Team:Hamburg/HP/Gold

Human Practice Interviews

As part of our Human Practices project we wanted to go further steps. Based on what we have found out, up until this point we carried out many interviews with research experts and public health officials involved with the topic.

We were able to integrate our knowledge we had gathered to specifically focus on topics important to improve our project further. For example we found out that a specific cell phone is used during field trips and we were able to adjust our 3D-printed lab-in-phone device to this phone. In the following you will find all of our interviews, in which we research our application scenario. Make sure to download our podcast!

Skype-Interview with Paul Courtright, PhD

Download the interview as a podcast.

PhD Paul Courtright established the Kilimanjaro Center for Community Ophthalmology (KCCO) in 2001 with his wife, supporting and training local doctors and government employees from all over Africa to effectively manage public health, with regards to eye care.

This interview was essential to us for understanding Trachoma treatment strategies in the field and laid the groundwork for our preparation visiting the BICO Ophthalmology Centre in Malawi.

Finding Chlamydory:
Introduction and description of our project.

Dr. Courtright:
You’re familiar with the point of care work that was done in the past by … it was Cambridge?

Kai:
No.

Dr. Courtright:
It was not successful, so that’s that. They did some point of care diagnostic work. I think they did it in Tanzania in our facility and we helped with some of that. In the end it was not successful and I can find some of that documentation and send it all to you.

Daniel C.:
That would be great.

Dr. Courtright:
BBC actually did a little piece, […] I was interviewed […] I look for that and send it all on to you. […]

Kai:
That would be cool. […] The reason we actually wanted to interview you, was because for the iGEM project we also have to do the so called Human Practices part. And we are trying to design an application scenario. So we want to just find out how well our device could be used in developing countries and if there is a need for a device like that.

Daniel C.:
We are doing some basic social studies to check the field and also see what kind of resources doctors in the field have available. So we can design our device accordingly. I’m actually looking at an article right now, where you are talking about Helen Lee and Claude-Edouard Michel from Cambridge […] In the article […] it says that the sensitivity was actually higher than previous diagnostic tests, so why did it fail?

Dr. Courtright:
It worked well when Claude […] assessed the specimens in the field, at that point of care time. But when they tried to train other people on assessing in the field it failed: it was too specific to one individual being able to read it in the field.

Kai:
Okay, so it was not reproducible?

Dr. Courtright:
Correct. What I can do is to find the documentation that addressed it. I don’t think they put it out as a publication. I think it came out more like some internal communication. What you probably find in the literature is where it was successful. What you probably not find is where it did not see any fare down the line, because the actual application was not successful. […]
    So I will give you a bit about my background. So I’m an epidemiology biologist by training. I have done primarily ocular epidemiology since my training. […] My background before doing my PhD was in the field of education and also in the field of international health. Since 2001 my wife and I established the Kilimanjaro Centre for Community Ophthalmology (KCCO). It was something we had wanted to do, because we had worked in Africa for five years between Ethiopia and Malawi in the late 80’s and early 90’s. We have gone back to and I worked at the university of British Columbia for a number of years. We always knew we wanted to return to Africa to set up the institute that really was focused on eye care not so much of training clinic. That’s because that was already placed, but in training people in operational research also in looking at a lot of […] the management aspects of providing eye care. In most developed countries the systems are in place and an epidemiologist can walk right in and provide eye care services.
   That’s not true of course within Africa so the institute we set up in Tanzania was really focused on training people from around Africa to providing mentorship so that they could run effective and efficiently managed eye care systems. So the research that we intended to do has been more on service delivery than it has been on the specifics of a particular disease. My doctoral work was actually on trachoma in Egypt back in the mid/late 80’s and of course I was involved in a lot of trachoma work. But truly that started more from 2009 because simply trachoma for many years was kind of dominated by a particular organization and until that organization underwent significant change on how they worked, it was not a field I wanted to spent lot of time in. So in 2009, and that was the initial trachoma initiative (ITI), the funders of ITI basically clenched down the old ITI and it was reopened in Atlanta under the task force with huge change in how it functions.
    It was that time when I was more involved in trachoma again. My current role is: I am the technical lead for all of the UK governments donor support for trachoma. That also includes the Queen Elizabeth Diamond Jubilee Trust support as well. It’s like an 80-million-pound program in nine countries and I provide the technical backup for all of this countries. I recently stepped down as director of KCCO, part of my semi-retirement plan. Still more semi than retirement but that’s the way it is. I lived in Africa about 20 years and only moved back to the US in April so we’re in the process of learning what it’s like to live in America which is at this current election period a bit scary. […]

Daniel C.:
Where did you live in Africa for those 20 years?

Dr. Courtright:
It would have been 1 year in Ethiopia, 4 years in Malawi, 11 years in Tanzania, 4 years in South Africa.

Daniel C.:
Then you really must have an overview of how the chlamydia endemic works in different countries within Africa?

Dr. Courtright:
Yeah, I have to visit all the nine countries which are Tanzania, Ethiopia, Uganda, Kenya, Mozambique, Malawi, Chad, Nigeria, and […] Zambia. I visit all these countries at least once a year and worked with all those folks for many, many years. I’m also involved with assisting Eritrea, Sudan, Yemen ... I’m now helping Vietnam to get their dossier for declaration of verification of elimination and the same for Nepal. So, yes, I have a pretty good sense on what is going on in the field.

Daniel C.:
It’s difficult for us to judge, so we want to ask you: What are the main factors actually contributing to chlamydia in those countries or the chlamydial infection?

Dr. Courtright:
Chlamydial infection … the transmission of course is very focal and if one looks throughout Africa, the mistake that was made in the past was to just […] paint all places red, if they found trachoma in one particular area within a country. That was an error, and only more recently the global trachoma mapping project is really clarifying where chlamydia transmission is really a problem where it’s not. As an example: in Tanzania there [are] around 150 districts but in fact right now there is probably only five districts in which transmission is at such a level that there needs to be considered effort at reducing transmission and tackling the disease. [In] Ethiopia, on the other hand, the number of districts that need intervention is probably over 150. So it’s very focal.
    I think that is one of the things we’ve had to learn, that we have to bring the programs down to an area by area. Even within an area we have to look much more carefully at where transmission is happening. So the programs that are in place, although they are focused on a district, and the district can be 100,000 to 300,000 people, there’s a bit of over treatment right now. In some areas, because the entire district does not really have problem but it is focally within that district so that is something […] we struggle with: that there is an overtreatment in some areas. But then in other areas undertreatments […] I’ll give you an example. Around Kilimanjaro we have districts that include the outland areas around Mount Kilimanjaro but then also the Masai step at the lower ends of Kilimanjaro. The population density is higher on the slopes of Kilimanjaro rather than down the flat lands, which is more of a hot dry area. […] Trachoma in those communities is a huge problem, but if you do a survey in the administrative district the findings from the slopes wash out the findings from the lower populated areas down below. So we’re actually missing populations that are not being treated. And this is a problem in several areas. I think that there are still a lot of lessons we need to learn if we are going to eliminate this disease. Our surveys although they are good for what they were designed for, they do miss out so we need to have other tools to make some decisions.

Daniel C.:
We read through some of that regional case study summaries and also the GET [Alliance for the Global Elimination of Trachoma] 2020 reports which also talked a lot about regions. […] You were also active in GET 2020. […] Can you tell us more or less about what you did associated with the WHO?

Dr. Courtright:
Well, GET 2020 is really an alliance. So, WHO leads the group but it’s an alliance of organizations […]. You have to talk about the past versus the present. The standpoint of the present GET 2020 is much more active and muscular, which is great, in terms of trying to provide the guidance, it doesn’t provide any money. It’s really the guidance for what programs and countries need to do to reach the elimination. There’s a new documentation on what a country needs to do to verify the elimination, for example. And that’s what GET 2020 does. GET 2020 […] also […] worked through organizations like KCCO to have scientific meetings: KCCO organized for GET 2020 the first and recently the second Global Trichiasis Scientific Meeting. […] So our role has been to provide some of the scientific backstopping and the coordination of overall GET 2020 activities.

Daniel C.:
Which means, that you probably have a very good overview of the progress GET 2020 has made? Global elimination of trachoma until 2020 is an ambitious goal. Do you think they will reach it?

Dr. Courtright:
Well, I would say yes and no. Yes, in many of the countries like Malawi, Mozambique and Nepal, in these countries, even Tanzania, […] they will achieve it by the year 2020. Some countries Ethiopia, for example, probably not, just because the problem there is so massive. Other countries like South Sudan that are still in a conflict stage, clearly it’s not, because there’s really nothing going on there or very little going on. If people say that global elimination means that every countries has to be at that level, then they are not going to achieve it. I don’t personally subscribe to that perspective because I think if the vast majority of countries have achieved it and we just have few countries left. And there’s a reason why it is not, […] I still think that celebration can occur.
    A fear of course is, that people start celebrating and then donors will say are saying: “Well then we don’t have to invest anymore”. Then we have a problem. That’s kind of what happened with leprosy back in the early 2000.

Daniel C.:
Back to talking about reasons why some countries still continue or might continue to have trachoma cases beyond 2020. What do you think are the main reasons, aside conflict in the South Sudan and other countries that this goal might not be achieved?

Dr. Courtright:
I don’t have an easy answer for that one. It’s a question that the whole trachoma community is struggling with particularly in terms of Ethiopia. As you might be aware the Amhara Region in Ethiopia has an antibiotic treatment in many of those districts for seven, eight, nine even ten years. And yet the prevalence of TF [follicular trachomatous inflammation] occurring in that regions is still quite high. The ministry of health in Ethiopia is really very concerned about it and rightfully so. So what is likely happen fairly soon is commissioning a much more in depth assessment of the situation to try to answer the question that you’re asking: Why is Amhara after so many years of antibiotic treatment not achieving lower prevalence rates of TF below the WHO threshold. I think many people would give you their idea why that’s the case, but I think getting kind of a global assessment of this will be helpful because it pulls in everybody’s perspectives on what is likely to be the gaps. My personal feeling the inadequate attention to transmission meaning that are the programs to reduce transmission whether it be through latrine construction, use of the latrines, you know clean phases, other approaches to reduce transmission. Are those approaches adequate? My sense is probably not. That’s said I see other countries that also don’t have, what I would call really robust wash programs and yet trachoma has decreased significantly. So what is unique about Amhara for example? I don’t have an easy answer for that right now, but I do think it has to do with transmission one way or the other. What is going on? That is still unclear.

Kai:
Would you think that for example our diagnostic device would be helpful to reduce the burden in such areas? Especially the financial burden? Because the major point is that it is affordable.

Dr. Courtright:
A little bit of history here. The ITI has supported the Carter Center to set up a laboratory facility [...] in order to run a whole bunch of laboratory tests to look at infection in that setting. It’s taken years and years and years to get it set up and I think it is operational now. However, we don’t have any real data coming up from it. To me that’s an indication of if you have overly technologically reliance systems that really require a lot of stuff and a lot of well-trained people and a good management system. If there is too much technical and management support that is needed. That things don’t really run well. We need systems and I’m hoping what you are talking about be something that is much easier to implement in the place like Ethiopia without having a huge overlay of technical backstopping and also a huge overlay of management backstopping.

Daniel C.:
That’s exactly the point of our project, which we hope is successful.

Dr. Courtright:
I do see there is a role for better tools for diagnosis of infection, particularly in settings where we are unclear as to what is going on. And Ethiopia stands out as the primary place for trying to figure out what is going on.

Daniel C.:
Can you give us rough outline of how that looks like in the field. I mean do you do general screenings of the population or do you do small samples? What’s the range of statistics that you gather?

Dr. Courtright:
Well it’s not that I’ve gathered. I mean the Carter Center with support from ITI has actually taken both approaches. Some initial small studies in focal areas but they have also, as part of their programs, collected specimens [...]. The initial challenge has been that the specimens have been stored for quite a while and as you might imagine there has been a breakdown in the composition of the specimen. So at the end of the day, when they run these specimens: Are we actually getting a correct reading or have the specimens been degraded so much that they are useless? How would one asses that? There’s a lot of data there, how meaningful the data is, how it can be used is completely open for question. So new tools in my mind would be most welcome.

Daniel C.:
When you were talking about specimens I just want to clarify what did you mean by that?

Dr. Courtright:
Well, in the settings in Ethiopia … I’m trying to remember now what type of specimens they took ...whether they were serum specimens or whether they took swabs. […] I can’t remember right now…but I would guess it would have been swabs simply because taking serum specimens would be much more invasive and would be much more challenging to do. […]

Daniel C.:
Talking about the range of data that is gathered in different regions to assess the chlamydial endemic. How does it look with funding? Is it tight in those programs? Do the decision makers have to decide which approach are we going, because we have to turn each dollar, we have to watch every expense?

Dr. Courtright:
Well, there’s different funding mechanisms in place. From the standpoint of the funding that is made possible through the UK government it is tied to doing impact surveys. And you can learn more about that through a program that is called Tropical Data and it's organized by the WHO. And that Tropical Data is really to provide the tools for doing impact surveys after multiple years of antibiotic treatment. If the prevalence of an area let’s say is 20% an impact survey is indicated after three years of antibiotic treatment. And then the decision on whether to continue treatment or to discontinue is based upon the findings of those surveys. The funding for additional distribution is generally backed in place either UK or US governments. And that’s all fine. The trouble is when we’re talking about like Amhara where it has continued way beyond the anticipated funding envelope there’s a challenge in getting additional money to continue [...]. Donors will say: “Wait a minute we have been paying for this for how many years now?!” For most countries it has not been an issue because they are seeing the prevalence of trachoma drop and so that the donors said: “Ok great, maybe one more year or a couple more years.” There has been no problem with donors bringing up the additional money. The problem has been in a place like Ethiopia where we have been looking at many, many more years of treatment. That’s where we have challenging issues now, that will become even more problematic in the future, if we don’t understand what is going on.

Daniel C.:
Thank you a lot. We just have one or two final questions, talking about awareness. Can you talk a little bit about how aware people are in the [United] States or western countries in general in contrast to developing countries for example? So is there a difference in the awareness of chlamydia?

Dr. Courtright:
Since I haven’t lived in America for so long it’s kind of hard to making a comment about here, but generally speaking there is not a lot of awareness about trachoma or chlamydia. I think most people are focused when they think about health care in developing countries it comes back to the “biggies” like Malaria, HIV, AIDS and TB. Chlamydia and trachoma don’t pop up on the radar screen. I always found it interesting in a lot of developing countries early on because there was money a long time ago focused on trachoma as a blinding condition that in many countries you’d ask them “What is your leading cause of blindness?” and they’d say “trachoma” and you go on “That is actually not true”. That is often because there was advocacy of identification of trachoma as a cause of blindness and for implementation of programs. I think there’s a much greater understanding of where trachoma fits in terms of causes of blindness in developing countries. But in industrialized countries I think there is very little understanding, […] I don’t think it deserves a huge amount of pressure for advocacy within the developed world. Simply because it is not the leading cause of blindness, it doesn’t kill people. I mean it’s probably speaking against my own better interests saying it’s not going to draw huge donor dollars and probably shouldn’t, because it’s not as big of a problem as many of the other health conditions that exist in these places.

Daniel C.:
Actually I was expecting you to say the opposite, because you were living in Africa for so long and we always imagine that maybe in the Western countries it is just underrepresented and in African countries it still affects people. […] And it’s easy to treat, but it just doesn’t have much attention.

Dr. Courtright:
When you say it is easy to treat: the technology is there yes, but when we say easy to treat I think many people in the industrialized world will get that a lot of what makes it difficult to treat is not the technology it’s the management systems and the health care systems that would support getting treated. Part of the reason why a tools such as you are developing has value is that the amounts of support it would need from within a health system, that are often rather weak, is going to be minimal. I’ll give you an example people have when promoting these diagnostic tools using mobile phones to look at the back of the eye for example. I bet you are familiar with some of this, but if you can use a mobile phone to look at the back of the eye and make some decisions about what is going on. That all sounds fine and cool and the technology is really attractive. But how you actually implement those is often a bigger challenge and let me go back to that statement: people are often happy to talk about a magic bullet, but in fact what we often need in many places in Africa is the magic gun. If you got magic bullets but you don’t have a magic gun the magic bullets frankly just stay on the shelf. So if we don’t invest in ensuring that the systems are strong enough to ensure it then it could end up just being a nice little piece of technology that doesn’t get used appropriately.

Daniel C.:
We also have a quick question about demographics. Because you were talking about different regions. So are there differences in infection between urban and rural areas or between the young and the old or something like that?

Dr. Courtright:
With trachoma certainly, yes. So it is a disease mostly in rural areas rather than urban. But even in rural areas it’s quite focal, so you would not just say rural areas and leave it at that. You really have to look more specifically. And certainly in terms of transmission we are looking at the highest transmission in preschool children, then it starts dropping when you are looking at the ages five, six and seven. There it’s dropping quite rapidly. Highest transmission rates are going to be in kids with three years of age rather than in the older children.

Daniel C.:
And what would be the reason for […] them to get more likely infected?

Dr. Courtright:
Children at that age […] don’t engage in any kind of personal hygienic practices, they don’t wash their face, they are not concerned about the flies that are landing on around their eyes. It requires somebody else to take to care of them. When a child gets five or six they generally start to talking on that rules for themselves. I think interesting thing you might be aware of is that although transmission in young children is pretty much the same for boys vs. girls. However, if you look at the prevalence of trichiasis (the inn turned eye lashes) in adults, women generally have about a 1.8 – 2 fold excess prevalence of trichiasis compared to men. The reason for that is that women get infected later in life by what’s going on with their children as their role of caretakers of the kids. So we have kind of two different periods when we have lot of infection between and amongst preschool children and then moms later on, when they are taking care of that preschool kids.

Kai:
[Our] last question would be if you would just focus on these two groups with a diagnostic tool and you just diagnose them eventhough you don’t have an indication would that be useful or would that just be a waste of money and time?

Dr. Courtright:
You mean, diagnosis without any other kind of other clinical signs? [...] I don’t know, that would be the quickest answer, because we often struggle to identify the connection between the clinical disease and the infection. Somebody may be infected but they are not manifesting with the clinical disease, yet. And at that point time there is definitely value in diagnosis of infection so it can be managed. At the same time, you might find plenty of clinical disease but there is no longer an infection, because the infection happened a considerable amount of time before. I think […] there are two different considerations here: one is the situation that we talked about in Ethiopia, what is going on in an area where we still have way too much infection and clinical disease. The other is as trachoma decreases. And when I say trachoma I mean the clinical disease. Do we end with focal conditions and where there is still infection going on and can we pick that up quickly to treat it quickly before it leads a recurrence of the disease? That is always the concern we have: we can see the prevalence of the clinical disease drop but we know it is not geographically even and there will be some areas where there’s still maybe more infection going on. Are there tools which can help identify those focal areas quickly and easily so that interventions can be done much quicker and therefore does not lead to a recurrence of the disease in an entire district for example.

Finding Chlamydory:
Thank you.

Useful links:

• Kilimanjaro Centre for Community Ophthalmology (KCCO): http://www.kcco.net
• Alliance for the Global Elimination of Trachoma (GET) 2020: http://www.who.int/blindness/causes/trachoma/en/
• Tropical Data: http://www.tropicaldata.org

Skype-Interview with Dr. Jeremy Keenan

Download the interview as a podcast.

Dr. Jeremy Keenan is the Director of International Programs at the Proctor Foundation for Research in Ophthalmology at the University of California San Francisco. He is part of the Proctor teams conducting randomized trials investigating trachoma elimination strategies in Ethiopia.

This interview helped us further understand the underlying problems with trachoma elimination strategies, concerning the behaviour of the target population

Finding Chlamydory:
Introduction and description of our project.

Dr. Keenan:
The World Health Organisation wants to eliminate trachoma by 2020. The way WHO does this is by treatment decisions. Did you guys hear of the SAFE strategy?

Kai, Daniel C.:
Yeah

Dr. Keenan:
So you know they base the SAFE strategy off of clinical signs in the field. So you go in and pick a sample of kids age 1-9, you flip their eye lids and look whether they look infected. So you look for inflammation and if the prevalence is above 5 % or above 2%, depending on if they got treatment before. Then you do mass treatment with an antibiotic, financed by NGOs to treat the whole community. So the question is how often do you have to treat? The WHO recommends once a year for a period of three to five years, depending on the baseline prevalence of the clinical signs TF and TT (Note: These signs are categorized in a symptomatic grading scale, indicating disease progress: Trachomatous Inflammation – TF, Trachomatous Inflammation – TI, Trachomatous Scarring – TS, Trachomatous Trichiasis (TT) in this area. However, the correlation between the clinical signs and the infection is not that great. In a lot of places where we work in Ethiopia [for example] the prevalences of the clinical signs stuck at pretty much around 40 % of the village, even though the infection rate when we do PCR tests is lower. [...]
   It is not really known why the TF doesn’t go down but our opinion is, that the clinical signs are probably not the best way for us to determine if we eliminated trachoma or not. We really should be looking for the chlamydial infection itself. That should guide treatment decisions, because the whole point of antibiotics is not to treat the clinical signs, but to treat the infection. The idea is that if you treat the infection, the clinical signs should get better. […] Currently, what we use in our research are just PCR tests, but the problem is in most of the places where trachoma is, they don’t have good labs where they can easily perform PCR tests. […] So a point-of-care test you could do in the field would be great. […] I think you guys are right on, because it sounds like the test you are developing is cheap. It has to be cheap. [...] Most of the trachoma programs in developing countries are based on donations [...] so it’s hard for them to afford testing. […] Important would be that it doesn't has to be frozen and that it would be easy to use also for a non-technical person to use, that would be ideal.

Daniel C.:
So what are your different projects concerning trachoma?

Dr. Keenan:
We do different things. We are looking at the frequency and the target-population as well using mathematical models. The WHO recommends giving antibiotics once a year, and we try to see if you give them more frequently to eliminate chlamydia quicker. So we have done randomized trials with villages to take antibiotics once a year, or twice a year, to see if this speeds up elimination. It is a disease you can get your whole life, and it‘s mostly kids who get infected. Kids are actually much easier to find in a community, because they are in the fields most of the time. So if you could get away with just treating the children only, that would be great. That would be much easier than have to treat the entire community, also due to the antibiotic cost. So that’s why we have done trials where we targeted our treatments only to kids […]. Basically we treat to see how we can get antibiotics better and usually in the context of an cost-optimized trial. [...] The other big trial we have done in the field is about WASH, so WAter, Sanitation, Hygiene. A lot of people think that if you don’t affect the underlying hygiene of the community, the antibiotics can only do so much. So we are trying to improve the hygiene with water points, doing hygiene education, to see if that can prevent trachoma.

Daniel C.:
And how are you implementing this? With whom are you cooperating in Ethiopia?

Dr. Keenan:
A NGO based in the US. They have offices all over the world, but they have a big office in Ethiopia.

Kai:
If you use so many antibiotics, isn’t there the risk of generating resistances?

Dr. Keenan:
There has never been resistance reported for chlamydia. It is an intracellular organism and some people think that kind of protects it, so that it is not subject to selection pressures and therefore doesn’t become resistant. It is not tested very often. But I think technically when people culture chlamydia in petri dishes they got resistant chlamydia that way. But in the field, no one has ever seen it yet. It is a concern for sure but it’s not something that seems to be as important as in other diseases, such as tuberculosis.

Daniel C.:
What do you think is the biggest problem in the fight against chlamydia?

Dr. Keenan:
So first of all, each place where trachoma occurs is different. Ethiopia has like the worst trachoma in the world. Another place where we do trials in West Africa is Niger and trachoma there seems to go away much easier than in Ethiopia. For some reason, trachoma in Ethiopia is just very resistant. Like after giving many rounds of antibiotic therapy there is still infection being detected within the community. The biggest problem is sort of knowing the end-game. Should we just keep treating forever or should we take some years off? The WHO gave recommendations for how you should treat, but we don’t have a good way to say how long we maintain long infection rates. [...] A big challenge is diagnostics for sure. […] Everything is completely dependent on Pfizer. The moment, when Pfizer decides they don’t want to donate anymore, […] that would be a huge problem because these countries won't be able to afford the antibiotics. […]

Daniel C.:
Do you think it is achievable to eliminate trachoma until 2020?

Dr. Keenan:
No.

Daniel C.:
How is the diagnosis being made in developing countries? Are there any immuno based methods to detect chlamydia?

Dr. Keenan:
[...] [Chlamydia] is not very symptomatic. It is not like you have a lot of people that are going to the clinic and saying that their eyes are bothering them. It’s more that we have that kind of subclinical information and that leads to scarring, and that leads to trichiasis and blindness later in life. But kids don’t complain that much anyway and there is often a lot of dust around these places so it’s like a facto of life that their eyes are bothering them a little bit, but they don’t complain about it. So it is not that they go to the clinic and have some test for chlamydia. The way it works is all through NGOs which have these programs and it is very public health-ish. It is based on a population and they make decisions based on what the prevalence is in the population. It doesn’t matter if yourself have the disease, all that matters is what’s the prevalence of the disease in your community.

Daniel C.:
It is not like the people go out to seek the doctors? So if we manage to develop this cheap diagnostic method, you would probably use it for mass screenings, right?

Dr. Keenan:
Yes. So what happens right now is that an NGO decides that it wants to do like a rapid assessment. And so they’ll pick a district and they’ll do clustering and sampling where they’ll pick a random number of communities and within that community they’ll pick a number of kids, age 1 to 9, and they go out and they just flick their lids and look for the signs. So you could easily do the same thing but just put a test in there. Just go in there and take a swab and test that way. But it is not really directed from the consumer. It is not like a goes to the clinic. I mean some people do, but only once they get trichiasis. Then they are uncomfortable. But a kid would never do that. A kid doesn’t tell its parents: „Oh my eyes are bothering me. Take me to the clinic to get tested.“ No, that will never happen. It is all gonna be directed by the programs, by the NGOs.

Kai:
Ok. Do you think that would change somehow if we were able to design a really cheap test that you could distribute to communities and they can just go to their local doctor and maybe get tested every year? Do you think that could impact somehow how you cope with the disease?

Dr. Keenan:
I don’t know. It is just not that symptomatic. You are asking a lot of people. If you are not symptomatic for the good of our community you should go every year and get tested? Sorry, but I don’t know if that is gonna happen. I think realistically it is gonna be directed from a program. It is not gonna come from the people themselves. It would honestly be nice to have a chlamydia test in the clinic. Not just for trachoma but also for sexually transmitted disease. I am not saying that it wouldn’t be useful, but in terms of like actually eliminating trachoma, I don’t know how much that would help. […] Even if you were an individual who went to the clinic, you wouldn’t be able to afford the azithromycine. It would be way to expensive for you. You could go for tetracycline, that you could afford I guess.

Daniel C.:
But is it that expensive? I mean, antibiotics are pretty cheap.

Dr. Keenan:
It is not available. It is unavailable in basically all countries that have trachoma. The only way for it to be available is through Pfizer’s donation.

Daniel C.:
But I mean that is more or less the government's fault, right? They could just import it.

Dr. Keenan:
Well, it is expensive. I mean it is just that people can not afford it. Trachoma happens at really poor places. People…they can’t afford lots of things. The government provides some medicines for free but it doesn’t make sense for them to provide azithromycine. It is just more expensive than domoxin or something like that.

Dominika:
You explained that there are many kids younger than 9 who get infected with chlamydia. Do you have an idea what’s the reason for that?

Dr. Keenan:
Well it is probably that there is some immunity that happens. In generally there is bad immunity for chlamydia and you get infected lots and lots of times but probably over the time you develop some sort of immunity. So even when you are exposed to chlamydia you won’t get the infection. And kids are just very active and they have their fingers in their eyes all the time, they play with other kids and they are not careful with their personal hygiene. They are much more likely to eat dirty and have chlamydia on their cloths and their fingers and faces and that is basically the source of transmission to other kids they are playing with.

Kai:
Do you have any idea why trachoma is such a big problem especially in Ethiopia?

Dr. Keenan:
No, actually people really don’t know why. I mean, the poverty there is pretty intense and people's personal hygiene is not great [like it is in other places] like for example Indonesia where we work. Probably that is because it is Muslim [unlike ethiopia] and there is just more focus on cleanliness and washing. There is definitely a difference. […] But I don’t know why Ethiopia is just that bad. […]

Daniel C.:
I found a paper of the WHO that dealt more or less with the estimated prevalence of chlamydia in African countries and on the top of the list was actually South Africa. 7

Dr. Keenan:
But you are talking about sexually transmitted chlamydia?

Daniel C.:
No, I am talking about chlamydia trachomatis in specific.

Dr. Keenan:
Talking about chlamydia, there are different serotypes. A, B, C that cause trachoma and there is G to K that cause sexually transmitted disease. There is no trachoma in South Africa. I am not sure about that paper. I am sure they have the sexually transmitted disease and you can get the sexually transmitted disease in your eye. But that’s not like a public health issue so much. It’s more like: „Uh oh, I have conjunctivitis and maybe a new sexual contact with chlamydia.“

Daniel C.:
I was thinking that people there are maybe more accustomed to going to the doctor and getting diagnosed so that they are treated before they actually get trachoma.

Dr. Keenan:
Well, I think there is definitely something to that. With development alone. For example: Europe, the US. We had trachoma and it went away by itself. It went away before we had antibiotics. A lot of people think it is because of improved hygiene and just better public health that it petered out and went away by itself. So development basically is the key to cure trachoma. So if you achieve to make everywhere developed, trachoma would go away on its own. And no one really knows why is that. Some people say it is the electricity, because if you have lights in your house you can see at nighttime so that you can wash your face. And some people say it is the roads, because they make water more accessible. One theory of development is that you get more access to antibiotics through development. And then you are taking antibiotics for other stuff, not for trachoma but for your cold, for your respiratory infection, but that treats more combating the chlamydia infection, too. So that is definitely true. If you have kids who might always have trachoma but get antibiotics for something else should have less trachoma.

Daniel C.:
Well, thank you Jeremy for that very insightful interview.

Dr. Keenan:
There are lots of trials that use chlamydia as their primary outcome for a clinical trial for trachoma. I am happy to send you a few papers. Basically, there are three big trachoma groups in the world. There is our group, there is the London School of Hygiene and then there is John Hopkins. All of these groups have recently done clinical trials with chlamydia. PCR for chlamydia is basically the standard outcome for any sort of clinical trial for trachoma. I think you mentioned that you have a hard time finding estimates. There definitely are estimates at least from Indonesia, Ethiopia, Tanzania, the Gambia and lots of other places.

Daniel C.:
Thanks a lot. We are definitely going to look into that. We actually have the means and the finances to go to Africa. Because we were thinking about seeing the conditions that the doctors and the NGOs are working for ourselves. And we wanted to ask if you have any contacts there that you can relegate us to.

Dr. Keenan:
Yeah. What are you interested in doing?

Daniel C.:
We would be very interested in to talk with public health professionals. Maybe NGOs working in the field, doing clinical trials and maybe with local doctors, if there are any from that specific country. In the clinics or outside in the field, where they are treating patients who have trachoma.

Kai:
So one aim would be to get information for us and for our project and the second aim would be to produce a small documentary to raise awareness and to show at the competition.

Daniel C.:
At that competition 3000 people are going to show up and they are mainly scientists or future scientist, students like us, who will be scientists in a few years. We want to show them not only the theoretical thought behind the whole application, but also the real-life- situation, the status quo and the main target of the application.

Dr. Keenan:
Well, so it sounds like it would be nice for you to have some meetings, for example in the capital or in another big city but you want to see the field conditions as well.

Daniel C., Dominika and Kai:
Yes.

Dr. Keenan:
I can certainly ask the Carter Center where we work in Ethiopia and also Indonesia. Although, I don’t know whether I can recommend Indonesia because of the security situation right now. Ethiopia is pretty dodgy also. But I think Ethiopia is fine. I don’t know.

Daniel C.:
It should be fine. I mean, as I believe, there are mostly demonstrations and if you keep away from those that can turn violent, you should be ok I guess.

Dr. Keenan:
Should be. The Carter Center has temporary canceled all travel to Ethiopia. So we are supposed to go there in December and then again January/February. So I am hoping that they will reverse that decision before. Anyhow, I can certainly ask them what they think. You know I am sure it would be tough for them to make a visit to the field just for you guys, but maybe it will work that they were going to be going anyway there for something, than you can tag along.

Daniel C., Dominika und Kai:
Ok.

Dr. Keenan:
What’s your timeline for that?

Daniel C.:
I am afraid our timeline is very unrealistic. We are going to the MIT to present (our project) at the end of October, like 27th to 31th. And we were planning to go to Africa before that, so maybe in two weeks or something.

Dr. Keenan:
Ok. I can still ask them. I mean you don’t work for the Carter Center. If you guys feel comfortable with Addis [Abeba] you can still do that on your own and at least talk to them in Addis Abeba. I am not sure, it might be difficult to arrange a trip out to the field. But they would definitely be happy to talk to you just in Addis Abeba. Let me just talk to them and see what they say. If you don’t hear from me in the next couple of days, will you e-mail me to see what’s up?

Daniel C.:
Yes, sure! No problem. We’ll just pester you until we get a response.

Laughter.

Dr. Keenan:
That is generally the best way.

Laughter.

Daniel C.:
Ok, great. Thanks a lot Jeremy.

Dr. Keenan:
Yeah, good luck with your test, I hope it works out. Good luck for the competition. And if you guys get it somewhere where you think it would be interesting to test out, let us know. It won’t be a big deal for us to take a few of them and compare it against the PCR test we are doing in the field anyway.

Daniel C.:
Yes, that would be great. Thanks! Have a nice day.

Everybody:
Bye!

Useful links:

• [1] The Regents of the University of California, Proctor Foundation Faculty, Jeremy Keenan: http://proctor.ucsf.edu/research/keenan
• [2] The SAFE strategy for the elimination of trachoma by 2020: will it work? (published by Robin Bailey & Tom Lietman) http://www.who.int/bulletin/archives/79(3)233.pdf

Interview with Emeritus Prof. Dr. Konrad Sachse

Download the interview as a podcast.

____

Emeritus Prof. Dr. Konrad Sachse is a renowned researcher at the University Jena who played an essential part in characterizing veterinary infections, such as Chlamydia psittaci, as well as developing and refining chlamydial diagnostic methods.

Finding Chlamydory:
Introduction and description of our project.

Prof. Sachse:
Just to handle the debate over the safety of GMOs, [if] they are released into the environment: Will they be able to replicate?

Daniel C.:
Yes they would, but even if we would get a working prototype [the project] would not be finished. We would still have to incorporate kill-switches before the deadline.

Prof. Sachse:
Well that is probably too much. It´s just that you need to find an answer. To show a way how to solve this problem if somebody puts up some regulatory issues, although they never will be pathogenic. I understand they are not pathogenic at all?

Daniel C.:
No, they are not. But officially they have the capacity to undergo mutation and they are E. coli so they can accept pathogenic plasmids. We are just trying to get the prototype working and we can add kill-switches later.

Kai:
And for the iGEM competition we have to do [...] a Human Practices Project. The whole competition is also to raise awareness for synthetic biology [...]. We got the idea to conduct interviews with Public Health Specialists and Researchers who worked on chlamydia detection. On the one side to help us in our project and on the other to get input. [...]

Prof. Sachse:
Talking about the importance of chlamydia one has to distinguish, of course, between the situation in the industrialised countries of the northern hemisphere and developing countries in Africa, Asia and South America. Situations are basically different there. While in the industrialised countries the situation is more or less monitored, in some countries it is better monitored, like the U.S. and Scandinavia, and in some countries it is not so well monitored, like in Germany and other European countries. The basic problem here with chlamydia infection in humans is the STDs of course, whereas in the developing world you have the Trachoma, which has millions of cases every year, as seen in the WHO statistics.
    Trachoma is a great issue and [very] serious. In some areas endemic disease and despite several international aid programs that have been on their way the problem persists. This is mainly due to the nature of chlamydia, that you can't just easily eradicate it with a single vaccination and the diagnosis is also not so easy, because you can't readily grow them like ordinary bacteria. So you face different problems. In a way bacterial infections with chlamydia are unique and quite different from the classical bacterial infections. These are factors that you have to consider in your project. But I understand that you have addressed all these peculiarities of the chlamydia, which includes the difficulty in growing them and the needs of an intracellular stage of culture and also the inability of easy eradication, neither by a single vaccination nor by antibiotics. Although antibiotics can give the patient a temporary relief and can also resolve single cases. But generally the chlamydia have a mechanism of just evading the action of classical antibiotics.

Kai:
Can you give us a quick overview over your work on chlamydia?

Prof. Sachse:
I have been involved in chlamydia research for more than 20 years and my main focus was the veterinary chlamydia infection, which is the chlamydia infection in animals. But among these infections in animals there are a few zoonotic infections as well, like the Psittacosis which has been known for more than a century. And you also have, for example, infections originating from sheep that can also affect humans. And in this work on chlamydia we also had to develop new diagnostic methods. My laboratory was the reference laboratory of the OIE, which is the counterpart of the WHO in veterinary medicine and in this function we had to provide always improved methods for laboratory diagnosis. And we had to implement also the latest state of the art in molecular diagnosis in order to be able to give advice to other laboratories and also to fulfill our role as a reference laboratory. So during these 20 years we became involved in several international frameworks, like the COST Action, which was a Pan European network of 18 countries where we coordinated the research activities of Chlamydia laboratories in virtually all european countries and some overseas countries as well. And we also got involved in a few research networks, or coordinated some of them. And these networks focused on pathogen-host interactions.
    So that was really a research into the mechanisms of disease. So in order to understand why the eradication or control is so difficult. And in these projects we managed to explain a few aspects, for instance the inability of controlling by use of classical antibiotics. And we also understood why it is so difficult to develop vaccines against chlamydia infections. The idea to develop a vaccine is very welcome and in the end it can provide a solution. But again it is not the same approach that might be working with classical bacterial infections. Because chlamydia are different.

Kai:
Could you talk about why it is so difficult to design vaccines against chlamydia?

Prof. Sachse:
The first point is that when investigating a course of infection in any way, in a human patient or an animal, you will notice that the humoral antibody response is not emerging in a straightforward way as it is in classical bacterial infections. There are even cases, depending on a certain bacterial level of the infection, when the patient or the infected animal will not develop a humoral response at all. So you can not achieve a protection or a protective level of antibody production. The second factor that I mentioned is that it is not well known how humoral antibody response is typically like. That is because there a many protein antigens contributing to the antibody response so the cocktail of these antigens is very different with different organisms. And we still donˋt understand why that is the case. And because of the complex difficulties we donˋt know how to generate with great certainty an antibody response that is 100 % emerging. There are, of course, vaccines used in the animal area but itˋs not guaranteed that the given vaccine will raise antibodies in each vaccinated animal. The performance of live vaccines is comparatively good. The performance of attenuated or inactivated vaccines is very poor, because you donˋt observe antibody response in the vast majority of cases.
    But on the other hand the use of the life vaccine is associated with problems, as life vaccines can [...] cause the disease, because the attenuation is not well defined. At least the vaccines that are being used now. So there are a lot of difficulties and people have of course been trying to use new technologies to produce subunit vaccines. And they were using promising protein antigens that have been investigated in-vitro and they were shown in vitro to work very well, but when used as a vaccine the performance was not satisfactory.
   This is the current state of affairs and people keep trying. But it probably needs another approach. The current molecular approach is not complete enough to generate the antibody response and the protection level that is required.

Kai:
Could you explain why it is so difficult to design good diagnosic methods?

Prof. Sachse:
Actually there are good laboratory tests that would be specifically enough but all these tests require extensive processing of the sample matrix, so you need DNA extraction or you need to produce a lysate. This might be enough for a diagnostic laboratory because they can handle the sample matrix and they can do the processing and they can even automate this to a certain degree. But in a field setting that you are envisioning this is unacceptable, it would be too much. In an area with poor infrastructure, where even electricity supply is not guaranteed, it would be too much to include another step of processing of your sample. The other issue is that when you process the sample you lose a certain degree of your sample amount due to the process. So you lose potentially some of your sensitivity as well and if you can avoid the pre-processing use the sample as it is, as you are trying to do, this is a potential advantage. This is on sensitivity. Currently the successful tests are based on PCR. Amplifying a few copies of DNA that is there, this is the way how they achieve the sensitivity, you canˋt do this and therefore you need to employ specific reactions or highly efficient binding reactions and, also as you do, include fluorescence, which is always a factor to enhance sensitivity because fluorescence can be measured at very sensitive levels. This is on sensitivity, but the specificity issue is different.
    In developed countries it is important to have species specific detection of Chlamydia. On the one hand it is important that you detect in the patient Chlamydia trachomatis and not another one so you can complete your diagnosis and can adapt the treatment accordingly. But in an area where the trachoma is endemic it is not important to bring the specificity to a certain level, because once you can establish that the patient has chlamydia the treatment will be the same. It will be sufficient for the physician to know that the patient has chlamydia in order to treat the patient properly. So there are certain areas where the species specificity is not such a big issue also in other areas where you have a single chlamydia species present like in certain animal infections.

Kai:
Which animals are affected by zoonotic infections? How are people infected?

Prof. Sachse:
Psittacosis has been there for centuries in South America. This chlamydia infection is by Chlamydia psittaci and is transmitted usually from parrots or other birds to humans. It is an air borne transmission, and can also be transmitted by direct contact between the bird and a patient. After infections the individual develops an atypical pneumonia [...] you see a typical X-ray picture, which is different from other pneumonias. The disease can be cured very quickly using certain antibiotics but the problem in many countries is - if there is no association between the patient and a bird [...] - if this association is not considered the possibility of the atypical pneumonia psittacosis will not be considered and the patient will not be given the right antibiotic. We even observe few fatalities every year, even in developed countries. Just because diagnosis is not done properly. Generally it is a pity that the detection of Chlamydia psittaci is not part of the routine diagnosis in the medical labs, while Chlamydia trachomatis and Chlamydia pneumoniae is part of the routine diagnosis. That's why certain cases can be overlooked. Awareness has been increasing in the last few years but there is still room for improvement. This is psittacosis.
    Another zoonosis is Chlamydia abortus the infection of pregnant women. Pregnant women can be infected by contact with lamming sheep, because sheep are often carriers of Chlamydia abortus Chlamydia abortus is often causing lamm loss or abortions in sheep and if a pregnant woman comes in contact with lamming sheep it can happen that she gets the infection and it will have serious consequences for the pregnancy. One has to say that this zoonosis is not encountered very often and the awareness has increased, so we observe only few cases. Yet often cases are poorly documented because for some reason even if the origin of the infection may have been established they are not properly documented so we have very few cases we can talk about. Another case of zoonotic transmission is in the Trachoma area. Until some years ago Chlamydia trachomatis was considered to be the only agent of trachoma [...]. But recent studies have shown that other chlamydia species can be involved, for example Chlamydia psittaci, Chlamydia pecorum and Chlamydia suis These other chlamydia [...] are acquired by contact with animals. People in endemic areas often live in close contact with their domestic animals. So it's easy to suggest transmission from those animals to the people. And if the proper hygiene is lacking it is easy to transfer the pathogen in your eye and get trachomatis. This is more or less the scope of the psittacosis caused by chlamydia.

Kai:
Is there an impact on the cultivation of animals? Do infections in herds result in economic damage?

Prof. Sachse:
Yes very much so and this is a factor that is underestimated worldwide. What people are aware of is the open and acute infections. Of course everybody knows that massive abortion of sheep flocks will cause economic damage and there are figures from the United Kingdom, for example showing this very dramatically. but apart from the acute infections we have a lot of endemic chlamydia with herd prevalences up to 60 % in the cattle population of Germany for example. The situation is the same in other countries and this is not noticed usually if there is no diagnosis especially undertaken. Because there are no dramatic outbreaks but the chlamydia infections persists throughout the life of the cattle from the calf until the end of the life of a dairy cow for example. We have been able to show that these persistent infections, although they are in rare cases causing open clinical signs, these persistent infections affect the performance of the animal like daily weight gain if it's feedlot cattle, so they should gain weight with time.
    This is measurably affected if you compare chlamydia free cattle with chlamydia infected cattle without clinical symptoms. And the same happens to milk productions. A cow herd that is affected by persistent subclinical chlamydiosis will produce less milk than a chlamydia free cow herd. So it really makes an economic sense to try to achieve a chlamydia free status. But we are very far from that. [...] The awareness has increased in the past few years but it's still a long way to achieve that. There is still another point on the subclinical chlamydia infections, as is said there are quite a few data on showing that the presence of chlamydia in domestic animal population is associated with loss of performance such as milk production and daily weight gain. I guess that something similar could happen in a human carriers of chlamydia as well. This is a factor that is currently not under consideration and I think there is no research on it but it seems straightforward to hypothesize that individuals, carriers of chlamydia who are not developing open clinical signs but remain carriers for a long time, these individuals may have their state of health deteriorated to a certain degree and in the end lose some of their performance. This is an important factor that should be addressed in future research.

Daniel C.:
Do you think that some strains are resistant to the antibiotics that are usually used to fight them and [therefore] persist in the body?

Prof. Sachse:
Chlamydia is an exceptional bacterium especially in regard to antibacterial resistance, because there is no resistance as such as in the other bacteria. There is only one species, where a few strands carrying a resistance gene have been detected, it's Chlamydia suis which is not of any importance to human health so generally speaking there are no antibiotic resistance genes in the chlamydia. But nevertheless you can control to a certain degree a chlamydia infection using certain efficient antibiotics but the mechanisms are different, and the mechanisms of control using antibiotics are more nonspecific than with other bacteria, because chlamydia have an ability to evade the impact of the antibiotic because of the absence of peptidoglycan but also because they have this biphasic developmental cycle, where they can reside for a certain period of their lifecycle in a cell in a vacuole so they are quite inaccessible to the action of the antibiotic.
    This is why you treat a chlamydial infections with antibiotics you will usually see a drop in infectivity for quite some time and in the short term the antibiotic seems to work, but what it does is just preventing the replication for a while and then, as the antibiotic can be administered for a long time, so when the time is over the chlamydia are still there, because they can survive intracellularly or in other forms so they can recover after the antibiotic is gone. So you will see a resurgence and a repeated infection can occur or at least the level of chlamydia load can be the same after the treatment. This is why in some cases you have to use antibiotics for treatment, to save the patient, but as a rule it will not eradicate the pathogen, it will still be there.

Daniel C.:
On the way here we read an abstract of your paper about chlamydia in poultry. Can you elaborate? What are the risks?

Prof. Sachse:
For poultry one can say that the prevalence of chlamydia is generally high in the poultry flocks and you can't get rid of them using antibiotics, as I just said. But again given the current practises of poultry productions and hygienic standards that are better than 100 years ago, there are not so many acute outbreaks anymore. It's just a case of the bacteria being there and being a constant threat for zoonotic transmission, because in birds there will usually be Chlamydia psittaci which is a health risk for human workers in the flocks. Additionally the presence of chlamydia is an economic factor because of the lowering of the performance due to subclinical infections, this is the same as with other animals. There is still another novel discovery from the last few years that needs to be mentioned.
    Until three years ago people thought that Chlamydia psittaci was the only pathogen present in birds and poultry, but now we know that there are at least three different chlamydiae like Chlamydia psittaci and Chlamydia gallinacea which is mainly in poultry and Chlamydia avium which is present in parrots and pigeons. So the spectrum of the pathogens is more complex that it was thought previously.

Daniel C.:
Going back to human pathogenity. In the beginning we were saying, not a lot of people know [about] chlamydia. It is not a well known STD. Do you think awareness in germany should be higher?

Prof. Sachse:
Yeah, definitely. There is still room for improvement, the awareness could be higher. There have been efforts to raise awareness in the last few years and I think to a certain degree these efforts have succeeded, but compared to other countries and in the first place I would like to mention Scandinavia, the awareness in Germany is not high enough.

Daniel C.:
[What is] your opinion about our project?

Prof. Sachse:
Having understood some of the details and the principle of your approach i would like to encourage you to follow your project because it is a new approach and of course risk is involved. [...] It's a promising approach. To me the central advantage is that your principle involves a great advantage of using directly the sample material. This is a great advantage of course in field setting, where you don't have laboratory infrastructure. But if this works it can be used in real diagnostic laboratories because it has a potential to be more economical and more rapid. The time consumption of your essay is extremely low and this is a very promising approach.

Kai:
We talked about species specificity. [...] Could you talk about what impact our diagnostic [method] would have?

Prof. Sachse:
Well, any rapid test will have an impact and will be welcomed, will be used by potential users, be it in established diagnostic laboratories or be it in the field. So if you manage to produce a test that is rapid and is sensitive enough with a limitation in specificity, which has to be declared, so people will know how to use your test and will also know the limitation, which as you said is not so important in certain settings and will be important for other applications but you have to declare this openly. Your main assets will be the simplicity, rapidity and sensitivity.

Daniel C.:
What has a higher prevalence? Chlamydial infections in animals or in humans?

Prof. Sachse:
Perhaps there are more animals infected but there is not a demand for the diagnosis to be done. [For a human diagnostic] test there will be money [...] but the animal owners or the production units of animals are under economic pressure and they will only do diagnosis when it is absolutely necessary. When it's vital for them. This was our problem too when I was head of the national reference laboratory. Advocating the importance of the infection is one thing but once the owners of the animals do not see the economic loss big enough that it hurts them they will not do the diagnosis.

Kai:
No prevalence of trachoma in developed countries. Why?

Prof. Sachse:
It is mainly the hygiene, of course climate could contribute to that but it's mainly the hygiene.

Daniel C.:
So the first aim should be to improve hygiene in underdeveloped countries

Prof. Sachse:
Yes.

Daniel C.:
Thank you for the interview

Prof. Sachse:
My pleasure.

Note:Concerning the discussion of the hypothetical distribution of the device, we decided a few days later against outsourcing the incapsulation to national centralized laboratories. Instead the devices would be prepared at the production center and then shipped with the diagnostic bacteria, to be distributed throughout the country.

Useful links:

• World Organisation for Animal Health (OIE): http://www.oie.int/
• Leaflet of the Centre for Food Security and Public Health: http://www.cfsph.iastate.edu/FastFacts/pdfs/chlamydiosis_F.pdf

Interview with Dr. Thomas Meyer

Download the interview as a podcast.

Dr. Thomas Meyer has studied and developed Chlamydia trachomatis diagnostic methods for clinical applications since 1990, working in the public as well as in the private sector. He is a foremost expert in the Chlamydia trachomatis life-cycle, working now as a researcher at the University Clinic Hamburg-Eppendorf.

Finding Chlamydory:
Introduction and description of our project.

Dr. Meyer:
The first question about your project. I think that it is a really good project and a really good idea and the technical procedure is absolutely trendy, to use microfluidic devices and to incorporate biosensors, another point is the test uses the point of care. It is a cheap assay, which it is exactly what is needed in some parts of the world, where the laboratory equipment, as we have it here in Germany is not present. It is important to have a device that can be used everywhere, if you look at Africa, Malawi, for example, there can be people that are infected that can not go to the next physician because they can be very far away and even if they do this long journey they will need the results immediately, they can not come back some days later when the results are present. So itˋs very important to have a point of testing and itˋs also important to have a point of treatment, because if the test is positive these patients must be treated immediately. So itˋs a really good way to address the problem in countries that don ́t have the laboratory structure and equipment like, for example in Europe.

Daniel C.:
Do you see difficulties in our project? What difficulties do you think could arise?

Dr. Meyer:
Yes of course, one should not be so naive to think, this is a very good idea, this is an interesting technical concept that will work, there may be a lot of problems that may become apparent. First of all, it is important to verify if the test is really specific for chlamydia, because if you have crossway activity with other bacteria even if you are analysing ocular samples this may appear, this will not be OK for using it as a point of care test. This is something that has to be checked first of all.

Daniel C.:
Do you think the usage of GMOs will be met with refusal?

Dr. Meyer:
This is not a problem, you can use GMOs for diagnostics. There is a certain prejudice in Germany towards GMOs but that belongs mainly to the organisms in the usage for food production but not the ones used in diagnostic test. You are intending to use your device mainly in countries outside of Germany, in those countries it will definitely not be a problem, because there is a great demand for this test and it will not have a negative impact.

Daniel C.:
Please tell us about your career.

Dr. Meyer:
Studied biology, a long time ago, in the 80ˋs in Germany in Bochum and then went to Hamburg to the University Hospital, this Hospital, and started my thesis on E.coli bacteria and finished it in the University of Würzburg and then I started a job in a private laboratory again in Hamburg and I have been working there for almost 20 years and that was very interesting because at that time in 1990 it was just beginning to introduce molecular tests in diagnostic of infectious diseases and then in 2008 I went back here to the University Hospital just because in the private laboratory there was only diagnostic testing and I was interested in other things, like developing new tests and also teaching students. And therefore I went back to the University Hospital and have been here in the University hospital for 8 years.

Daniel C.:
When did you start working with chlamydia?

Dr. Meyer:
The first time working with chlamydia was in 1990 in the private laboratory, where we developed an in house PCR test for detection of Chlamydia trachomatis. It was one of the first organisms we considered for PCR testing.

Daniel C.:
What is your experience with diagnostic methods for Chlamydia trachomatis? What kind of diagnostics are there at the moment?

Dr. Meyer:
Right now we are using primarily amplification tests for direct detection of the pathogen in different clinical materials and we are also using serology, testing for antibodies. There are certain diseases where serology may be helpful, this is not the acute infection of the global infection but there are some cases of chlamydia infection that may become chronic and result from ascending infections like for example reactive arthritis. And the department of pathology have sometimes questions and they send us samples for Chlamydia trachomatis for the testing of antibodies. So if you have no antibodies the joint disease is definitely not due to chlamydia, if you have antibodies it may be, but it is not definitely proved.

Daniel C.:
What are difficulties in developing chlamydia tests, maybe comparing industrial nations to developing nations.

Dr. Meyer:
First of all these pathogens are absolutely intracellular organisms, if you want to culture them you can not do this with conventional agar plates, you need an eukaryotic cell system. We have done chlamydia culturing in cell cultures in the private laboratory but stopped that in the late 1990ˋs because of the development of commercial PCR test it becomes much faster and more sensitive to detect chlamydia, so cell culture is no longer performed. This is a big problem for diagnostics. Now as amplification tests are quite easy to develop and can be obtained from different companies this is not a big problem but it begins with the development nucleic acid test. Many laboratories are depending on cultures and this is very difficult, it takes a lot of personnel, time and experience.

Daniel C.:
Are amplification tests used in developing countries?

Dr. Meyer:
Sometimes, I think most of them don't use amplification tests. This is a similar situation for HIV testing for example. If you think about a country like Cameroon for example they have very few laboratories that are doing amplification test and that would be the same for chlamydia.

Daniel C.:
What is the reason? The expense? Or the lack of proper laboratory equipment?

Dr. Meyer:
They don't have many laboratories in these countries and the laboratories that use the test are of course expensive and most of the patients that need this test are not able to pay for it and there is not something like a public insurance that will cover this cost.

Daniel C.:
How expensive would a test be?

Dr. Meyer:
Probably it's not the same like here in Germany. This is different in all countries. In Germany a chlamydia test would cost about 20 euro with a public insurance. This is not the same in other countries it could be even more, and if you have a private insurance it will be definitely more, so it may also be 30 or 40 euros or dollars for a chlamydia test. You can do this test in developing countries only if this is sponsored by NGOs.

Daniel C.:
We were browsing some of your papers to prepare ourselves. And we found a method for confirming chlamydial antigens, using fluorescence antibodies against LPS [lipopolysaccharides] and or DFA. And we were wondering: How can a fluorescent antibody against LPS be specific for chlamydia.

Dr. Meyer:
Yeah, definitely. There is still room for improvement, the awareness could be higher. There have been efforts to raise awareness in the last few years and I think to a certain degree these efforts have succeeded, but compared to other countries and in the first place I would like to mention Scandinavia, the awareness in Germany is not high enough.

Daniel C.:
[What is] your opinion about our project?

Dr. Meyer:
OK, this is a part of a review paper. Itˋs a test that has been used in the past very frequently and it is based on antibodies directed against the chlamydial LPS antigens and and these antibodies are labelled with fluorescent molecules. You are right, LPS is present in all gram-negative bacteria. But the LPS structure is different. The chlamydia do have a very special LPS that lacks the side chain and it is very truncated it is a very small one, but you are right, it might cause difficulties with specificity. The same is true with the antibody test that are based on LPS. You can get a lot of crossway activity due to antibodies against LPS of other bacteria. It is important to consider that all these antibodies directed against LPS may be associated with some kind of crossway activity.

Daniel C.:
More people are getting diagnosed with chlamydia. Is it because chlamydia spreads more, or the diagnostic methods are improving?

Dr. Meyer:
I think both are important. The improvement of the diagnostic method is one reason for increased reporting. Awareness about chlamydia may also be important. We have now screening systems in Germany and other european countries and the more people using these screening systems the more infections will be detected, so this may also cause an increase in numbers of infections, however this is just 10-12% of the target population that is really using the offer of screening. So that there could be much more. And I don't think that screening will be increased to 50% of the population. But if it does increase to 25% you must consider that there must be twice as much chlamydia infections.

Daniel C.:
What symptoms are usually associated with Chlamydia trachomatis?

Dr. Meyer:
The numbers are probably much higher because most infections do not produce symptoms, this is considered to be around 80%, maybe 90% in women and also in men the most infections do not produce symptoms, so if you have no symptoms, you will not go to a physician and there is no reason to take a test, only if you do participant screening programs these asymptomatic infections would be detected, but nevertheless, even if they are asymptomatic, they can be transferred to other people and other people may become infected and produce symptoms. So the asymptomatic infections is a good way for the chlamydia to spread.

Daniel C.:
How does one calculate the risk of Chlamydia trachomatis developing an antibiotic resistant strain?

Dr. Meyer:
So far, there has not been found antibiotic resistance in chlamydia, even though they were treated for a very long time with antibiotics. This may be due to the special life cycle of chlamydia, the intracellular life cycle, but you can never be sure that at some point there be a development of resistance, so it must be followed closely and therefore itˋs important to not only and exclusively use DNA amplification tests but there should be some laboratories, maybe the reference centers of chlamydia that from time to time should culture the bacteria in order to test antibiotic resistance. This is a bit more problematic for other bacteria because you have to use eukaryotic cell culture and itˋs not just putting the antibiotic in the agar medium and culture the bacterium and see if they grow or not, itˋs a bit more complicated but it can be done in special laboratories.

Daniel C.:
Could you tell us more about the life cycle of chlamydia?

Dr. Meyer:
This is a special form in chlamydia because we have at least two structures: they have infectious structures, so called elementary bodies, that bind to certain receptors on the target cell. They are incorporated, form an inclusion, and in this inclusion they are transformed into reticulate bodies and reticulate bodies are metabolically active and they propagate and divide in the inclusion body and when the inclusion body reaches a certain size they dedifferentiate into elementary bodies and these elementary bodies can be liberated by different mechanisms and they can infect other cell and individuals. So this is what you can see in cell culture under normal conditions. But there are probably other states. There is good evidence for a persisting state and this will happen when the immune system is targeted and the chlamydia infected cells, or if you use certain antibiotic you can induce these long time persistent structures. And this is likely to be an important mechanism to close these persistent infections.

Daniel C.:
Persistent infections are inclusion bodies that are metabolically less active?

Dr. Meyer:
Probably there are different forms together, even in a persistent infection there will be a low-grade production of infectious elementary bodies.

Daniel C.:
Is is known what metabolic reactions are going on with the inclusion bodies? How are they interacting with the cell?

Dr. Meyer:
There are some mechanisms that have been described. There is a lot of interaction between the chlamydia and the target cell. I don't know all these different mechanisms but there have been some experiments where you can find some ideas how the chlamydia is interacting with the eukaryotic cell, so itˋs chlamydia interfering with some mechanisms that allow persistence. They have to inhibit the apoptosis so that the cells are not eliminated. They also have to interfere with the immune system in order that those cells are not eliminated by cellular mechanisms. And they also have to interfere with some other physiological factors, so that some essential factors, like amino acids, are present and the chlamydia can use them for their own life cycle.

Daniel C.:
There is not much research on this question?

Dr. Meyer:
Some papers indicate some of these mechanisms, but I think that there will be much more in the future, because we have much more possibilities to analyse these mechanisms. There was a big shift for the research when the Chlamydia trachomatis genome was completely sequenced, it happened in 1998 and it was one of the first genomes, that was completely sequenced. And at that time it was known that the genome contains roughly one thousand different genes and a lot of the genes only have numbers. And it is now the big challenge to analyze what is the function of these genes and how do they interact. 1000 seems like a low number, but itˋs a lot to analyse.

Daniel C.:
Should the awareness of Chlamydia trachomatis be higher in Germany?

Dr. Meyer:
Of course the awareness should be higher. Even among physicians it is still not known everywhere that chlamydia can cause chronic infections and may also be responsible for infertility, for example. And among the general population even young people are not aware of chlamydia. Maybe it has improved a little bit, there are some activities in that direction, but most of the young people going to school, just in the age of 16-20 years don´t know what chlamydia are and what they are doing. Maybe you know the picture in an American STD clinic at the entrance, with a flower and it says: “chlamydia is NOT a tropical flower”.

Daniel C.:
[...]
Do you have any tips to be safe from chlamydial infections?

Dr. Meyer:
If you consider chlamydia infections in Europe you have to consider urogenital tract infections and chlamydia are transmitted by sexual contact. So you may say: If you donˋt have any sex, you will not become infected. There are some religious groups that follow this idea, but it is actually not possible to do that for everybody, so the other way is using condoms, that is an effective way of prevention, if condoms are not used the only way is to participate in the screening programs and to regularly test for chlamydia. If chlamydia are detected you can treat them. It is important to treat all partners in parallel or there will be re-infection. So awareness is a very important point. If you know that chlamydia can be transmitted by sexual contacts this is the very first important point. And then you can use condoms in order to prevent infection, and if itˋs not possible for certain reasons you should test yourself regularly and participate in screening programs and you can prevent chronic complications.

Daniel C.:
Thank you for the interview.

Dr. Meyer:
Oh, thank you.

Interview with Prof. Kalua - Director and Founder of BICO

Prof. Khumbo Kalua served many years as an ophthalmologist, before founding the Blantyre Institute for Community Ophthalmology in 2008. The Institute expanded rapidly, enganging with over 50 employees in multiple projects, such as the national Trachoma Elimination Project, an antibiotic effect study and assessing visual impairment in children. In the context of Trachoma elimination, BICO has organized Trachoma Impact, Surveillance and Drug Coverage surveys, as well as implemented mass-drug treatment (MDA) in collaboration with the Health Ministry from Malawi.

For our team, this interview gave us a clear understanding of the local circumstances, which helped us improve our diagnostic design. Also it was essential to us, whether our device would serve a use as such in the field.

Finding Chlamydory:
Introduction and description of our project.

Daniel C.:
[…] So this is more or less our project.

Prof. Kalua:
You are thinking of this more as a field-test?

Daniel C.:
Yeah. […] I mean, these are genetically modified bacteria, so the question of course is then if it is allowed to use [them] out in the open. They are incapsulated in alginic acid […] but if the device breaks, they might get out. They are not dangerous, but…

Prof. Kalua:
But you’ve got bacteria there.

Daniel C.:
Exactly.

Prof. Kalua:
So would you recommend this to be used in the lab then? That’s what I am asking.

Daniel C.:
Generally you could use it in the field. The problem is the perception of the people. Especially in the USA or from our judges from the competition. They say: „You can have an idea but you can’t take bacteria out in the field.“ […]

Prof. Kalua:
So in theory it is a rapid test, but it has to be done within the lab...

Samira:
Do you know whether there are any laws for using GMOs in Malawi?

Prof. Kalua:
Yes, there are very strict laws. If you mention in any study „genes“, you get a lot of rules. […] As long is it has a rapid turn-over of samples in the lab it’s fine, because when we are collecting the samples we collect close to 8000 samples a day. That’s why we end up freezing them and store them for many months. But we can’t let the patients wait, so we treat the patients and then a year later we find out it was not chlamydia. You know it’s too late. So if somebody would have at least a test that would take even a week [but have high throughput]. All the current tests – for example extracting the DNA – it takes time. […] The specimens we collected last year, they are all frozen. And even if we ship them to the US, they still say they need 6 months to look at the specimens. So that’s why I say it’s encouraging. People are trying [to develop] rapid tests.

Daniel C.:
We are still trying different reporter systems. Some take a few minutes, others take up to an hour. But it still is much faster and also cheap. We can grow the bacteria unlimited and these [microfluidic] devices are not expensive. They go for 10 [Euro]cents a piece.

Prof. Kalua:
Yes. How much work has been done into this device?

Daniel C.:
We are almost finished. We should have finished, until we went to Africa but in the lab not always everything goes according to plan.

Prof. Kalua:
I would like to ask you about the epidemiologies, the sensitivity/specificity of the test.

Daniel C.:
We weren’t able to validate yet.

Prof. Kalua:
One of the questions I would like to ask is if the test would be specific for chlamydia or react with other bacteria.

Daniel C.:
Yeah, so that’s actually something that we have to look into. The target of chlamydia – other bacterias have it too, but they build it into the cell-wall. So we can’t for example use urine samples, because the microbiome in the gut. The [bacteria] get degraded and then you have the degraded bacteria in your urine, so you also have a lot of the mDAP, the target in your urine. So [the test] would always show up positive. With conjunctiva swabs you shouldn’t have bacteria there, except you have an infection.

Kai:
But it’s also not […] species specific. You can detect chlamydia but [the test] doesn’t say if it’s Chlamydia trachomatis or any other [type of chlamydia].

Daniel C.:
It’s not limited to the serotype.

Prof. Kalua:
The issue is that a lot of the chlamydia react to Azithromycine. So for us it’s not an issue what sort of subspecies or serotype, because the treatment is actually the same. […] How expensive would the test be?

Daniel C.:
You mean, all in all?

Prof. Kalua:
Yes

Daniel C.:
If we would go into big production and have automated robots for 80.000 € in the clean lab, the device would not cost more than 0.10 €.

Prof. Kalua:
Okay. Because the current PCR that we are doing, one sample costs around 1 $ to process. Has this been tried elsewhere?

Daniel C.:
You mean this kind of system? No, it’s really new. It’s a new idea.

Prof. Kalua:
Why do you think it has not been tried?

Daniel C.:
Because it is a really new field. […] Also using GMOs for medical applications. And usually research groups have to publish everytime, so they can’t take any big risks. But we are students. We do this one year and don’t have any pressure to publish.

Prof. Kalua:
I suppose that’s true. I’m going to ask you one question […]: Do you know Mark Zuckerberg?

Everyone:
Yes.

Prof. Kalua:
Do you know the lawsuit involving him?

Everyone:
Yes.

Prof. Kalua:
So do I see a lawsuit in the future, saying: „I started this, I started this“?

Daniel C., Kai:
No, because it’s not a patentable idea. If we publish it at the MIT it has no licence. It’s free. […] We have no rights whatsoever on that design. No one has. Everyone can use it. It’s a big part of the competition, to make it open source.

Prof. Kalua:
[…] So as long as we are very clear on that. Because people…they may not do exactly the way you want it but they…

Kai, Daniel C.:
Yeah. But then it’s fine. We are not doing it for the money, it’s the research project for us. […] We want for someone to take it and make it work.

Prof. Kalua:
We are looking for anyone to take it up and we discussed at length. Some said: „Oh, what sort of students are they? Oh, maybe they just want to have fun.“ Maybe you only want to have fun, it’s fine. But if the idea is interesting, I’m aware of people who want these kind of things.

Kai:
Can you do a quick introduction into how it comes that your working at BICO and what BICO does?

Prof. Kalua:
Blantyre Institute for Community Ophthalmology, or as most people know it: BICO, has been around since 2008 and addressing community challenges in eye care. Not in the whole range of eye care, but with trachoma being a bigger focus. Working with the Ministry of Health and Universities to do operational research that is directly [brought] into practice. So we are not just clinical researchers doing the field work, research and publishing it, but also want to change the policy. So most of our work as projects, the Ministry of Health [adopts] them as national projects, but we always build in research in those ones. Most of our research may also not need ethical approval, because we are doing the treatment and everyone accepts that what we are doing is good. But we can also collect samples at the same time.

Kai:
How was it, that you started BICO?

Prof. Kalua:
My career started many years ago, this is now the end of my career. I studied medicine, specialised in Ophthalmology, working as an eye doctor and in the community I saw a lot of challenges where the profession as an eye doctor could not help me, because I needed funding and [organisational support]. So I decided to start BICO, to be able to actually help my profession. So at that time BICO was found on the idea of it being a source of personnel, material and equipment, but I always tried to improve my work in Ophthalmology. Ideas – as you start them – sometimes they die, sometimes they build up. When I started BICO, I started with two people, no funding and my idea was to maybe have four or five people. But along the course people got attracted. They linked up with me, started working with me and then we started having bigger projects, including clinical trials and ended up having a staff of over 50. Which was not in the original plan. […] When we started BICO, trachoma was not our main focus. Our main focus was on blindness in children. In general blindness, but eventually infectious diseases. […] This is where BICO has come from and it’s done well for Malawi with [the help] of NGOs. The NGOs are very international. You don’t get many locals who have international reputation. So BICO has worked with the London School of Hygiene and Tropical Medicine, as our main collaborator on the funded study. We also work with the task force for global health in Atlanta on trachoma studies and several other institutions. […] Overall in BICO we get 30 to 50 international visitors a year coming to see our project, like you do. […] Next week we have people coming from the US task force for global health coming about trachoma. We are doing the mass drug administration next week, so they are coming to observe the exercise. They are also bringing a photographer, to photograph the whole procedure.

Kai:
Can you talk about the impact trachoma has, on the people and the society?

Prof. Kalua:
Trachoma is an neglected tropical disease. It affects the poorest of the poor because of the conditions of poverty, lack of hygiene. So […] it is usually neglected. But for the few individuals who end up being in that bargain. When they get trachoma and it causes blindness, it is a lifelong bargain. It comparison to other diseases, that have at least some [possibility of] intervention, like cataract or age-related macular degeneration. There is a lot of things you can do with a lot of eye diseases. But trachoma, once you become blinded from it... you can’t do a cornea transplant, because the cornea becomes vascularized. So the impact on the [affected] becomes so huge. It is also a huge burden for the country. For every trachoma blind person, there is a child that is put out of school. Because the child has to physically take this person around. We don’t have social structures here. [...] And when the children don’t go to school, they just become poorer and poorer and poorer. It is a disease that is left with the eye care people, but its impact is on the whole economy.

Kai:
How would you rate the awareness of chlamydial infections in Malawi, especially in poorer regions?

Prof. Kalua:
Well, they are aware a little bit, mostry through our interventions. But before most of it has been explained through culture and beliefs. They think, something happened to you, to get trachoma. Some still believe, that if you fight with somebody you will get this disease. We explain to them that this is a bacteria, that has to with your environment and facial cleanliness. So they are aware to some state, but the challenge is the behavioural change. Because some of the factors that make chlamydia target the poor demographic, has to do with the behaviour. [...] We don’t believe in toilets as a culture. Culture-wise they don’t believe in having toilets. They think it’s not environmental friendly so they just use the bush. And this attracts a lot of flies which spread the trachoma. So the behavioural change is to convince them, to use toilets which is not very easy.

Dominika:
So you just told us about the misperceptions of the disease. So are there any educational programs at school for teaching?

Prof. Kalua:
Yes, there are some educational programs within the school curriculum dealing with trachoma. There are also NGO institutions, which focus specifically on facial cleanliness and environmental hygiene. Making posters, radio programs. Trying to teach the children to go out and teach their parents. So these are the programs that is happening as of now.

Dominika:
How are the laboratories equipped over here? You were talking about PCR tests...

Prof. Kalua:
Yes, we have very good laboratories, due to collaborations with international investors. So within the government system, most of the PCR facilities have been established because of the HIV epidemic. But as you know, when you use up to 2000 machines for HIV, you can just get another template for chlamydia. So the machines are there, we just get software for testing chlamydia. There are relatively good number of labs that have these 2000 machines, but when we get the software for diagnosing chlamydia, the cost is actually very high. It is very expensive. In such cases you question whether you should be spending money on drugs or on tests. As you know, we have an ointment which we give to babies. Costs about 0.30 $ and the PCR costs 1 $. So for every PCR that you do, you can actually buy treatment for three children. So as a policymaker sometimes you have lab-facilities but because they don’t provide the rapid results that you need, you may as well just buy the treatment. Currently we don’t have any rapid test to detect chlamydia.

Dominika:
When you diagnose for chlamydia. Is it done by medical professionals?

Prof. Kalua:
Yes, we have a group of medical professionals with a diploma in clinical medicine. They are called clinical officers and they are trained and certified to diagnose trachoma according to the WHO clinical diagnosis which is based mainly on the trachoma follicles and trachoma inflammation. This happens as a result of chlamydial inflammation. So with some experience you can say: This is trachoma. But you should be aware that there are other bacteria, which cause these follicles. So the diagnosis of trachoma can be confused sometimes with other conjunctivitis. But we trained the clinician to say to their best ability if this is trachoma or not trachoma. The diagnosis can only be confirmed by laboratory tests.

Dominika:
Who conducts the trachoma mapping?

Prof. Kalua:
The mapping is done by our trachoma team, led by an epidemiologist, using this standardized WHO mapping protocol. This is a global mapping project, so each country is doing the same mapping. Each country has a master trainer (which happens to be me). We mobilize the ophthalmic clinical officers and we train them using the active trachoma cases, we certify them and then they go through the exercise of diagnosing trachoma.

Samira:
What do you think are the main problems of diagnosing and treating chlamydial infections in Malawi?

Prof. Kalua:
In terms of the trachoma program. From the field based view you sometimes get situations where you are not sure, whether this is trachoma or not trachoma. The WHO cut is very specific: If you are below 5% you don’t treat, if you are above 5% you do treat. And you know the treatment for trachoma is a mass treatment. Everyone else in the community gets [treated]. But sometimes you are in a situation where you are not sure [...]. If you have a lab-based simple test to confirm the cases, that would be very good. In most cases if you suspect this is trachoma, you take the specimens or the swabs, you treat the community and then you later analyse the samples in the lab – 6 months or 1 year later – and you find out, oh it was not trachoma. And you know, drugs and antibiotics have got side-effects. So you subject the community to a lot of treatment. But also to verify that your treatment has worked. You give treatment [..] and you go back to do an assessment, and demonstrate with laboratory indicators, that the chlamydia have disappeared. Because your aim is to interrupt transmission. We have some literature to show that some trachoma follicles don’t disappear, even if you treat. So even if the chlamydia disappears, the follicles will still be there and you may end up saying: „Oh, there is still trachoma.“ and then treat again. This is the certainly the challenge that we are not backed up by a lab. The reason is that we don’t have a simple test for chlamydia that can be used in the field, or at least as a rapid test.

Samira:
Do you think our device would be helpful in your way of fighting chlamydial infections?

Prof. Kalua:
I think the idea is good. If the device would work, the idea would be very good, because of the time it will take to get the results. If we would have a simpler test like this, to be done in the lab then we could collect some samples. [...] The ones where you are not sure, the positives. You send them to the lab, while you are still doing research and then you get the results and you find out [...]. So it would be a very good idea [...] at least for the field work in Africa. This is the type of idea that you want, in the way that you have some test that is quick and [helps] in decision-making.

Samira:
You said you already discussed with your colleagues about our project. So where do you see the problems which might arise by using [our application]?

Prof. Kalua:
When I discussed it with my collaborators in London School [...] the question of course is sensitivity/specificity and the stability of the test. Can this test stand in field conditions? This needs to be taken into the equation. Is this test specific for serotype? And the issue of any genetically modified bacteria. [...] It needs to be thought through. [...]

Samira:
Do you think the use of GMOs for medical applications might be met with refusal?

Prof. Kalua:
In our culture, not very much. It’s a very different culture, that beliefs so much in the medical work. If there is evidence that it works, it’s much easier to convince the people. It may be that people don’t know what genes really are. The challenge is usually getting approval from the ministry or ethical board. The ones that would need to understand more. But when you go on the ground and ask people to get involved, then nobody would refuse. In general people would have no problem for this test to be done. The other issue I was going to ask is... [if it works] have you thought of this in form of a multiplex, where you test other things? [...]

Daniel C.:
The thing is, we are hoping to defeat chlamydia soon. GET2020 is somewhat optimistic but it would be really cool to have chlamydia eradicated by 2020. And then of course the company that would produce and distribute the test would have nothing else to sell. So the idea would be to diversify. I mean, it’s a new system. We already talked about that. So there is opportunity to find other markers and put the sensors for the markers – which is actually the more difficult part – in the bacteria and then it should for other markers. But they have to be specific. So that would be something that the company would have to do on the side, to keep making profit and being able to produce these tests. It’s very theoretical but it would be something that is definitely possible. [...] The work for producing the device is not that [big]. You can simply switch out the genes, we have them in modules. It would take only a few weeks. The difficult part is really just to research and to find those markers and sensors necessary. [...]

Samira:
Could you talk a bit about the financial aspect?

Prof. Kalua:
[...] We are at the endgame. When you reach the end, there is always going to be need to verify that you really wiped out chlamydia. What markers are you going to use, [to make sure] there is no chlamydia? Because of that there was an open call. We are looking for people who can give some indication. We don’t have any markers to certify that we have reached the endgame. The Task Force for Global Health searched for markers for the endgame study, asking collaborators to think of what isolates [could be used as markers]. That’s something we have been struggling with for the last two years. [...] There are several antigenes we are trying to look at. [...] US-Aid is also funding this. My understand is, these are not open or closed grants. As long as you have a good idea, you can apply for it. So the money is there [...] for people to investigate markers for the endgame. From mobile health to diagnostics to anything else. You can think of anything, as long as it will help. And that idea of taking a picture...it was discussed last year in the US in the workshop. It was an idea [...] flying to manufacturing companies to modify the camera [for use]. There is now a project, which you can read about. It’s called PEEK. Portable Eye Examination Kit, where they use an iPhone. If you go to the field, you don’t need a doctor [to examine the back of the eye]. Any technician can take the picture, [send] it to the UK or US and someone there can look at it and [diagnose]. [...] There is still an [ongoing] study, but the device is there and takes a picture of the back of the eye. Which is very cool. I don’t know how they’ve done it. [...] And people oversea are wondering, how can they build on that technology. The people who have done this are from the center for eye health in London. Someone is doing a PhD. It’s a PhD idea. [...] This is something that has attracted a lot of attention.

Samira:
We discussed if it would be helpful to connect the app for the chlamydial diagnosis with your app for the questionnaires.

Prof. Kalua:
Yes, we started our own app because I went to these conferences and sent the data to the US. [...] So I asked my guys: „Can you study their system? Can we not have that server here?“ And they said: „No, it’s possible.“ So we don’t have to sent the data to someone in the US. We collect it, upload it on the BICO server. The advantage of that is we can come up with any questionnaire and use it for data collection. So we are always looking for collaborators who can have ideas. And if they are good, we can then get funding. [...] I wish you good luck so that you can excel. If you [are successful], you can produce a few devices and try them in the field.

Daniel C.:
That would be really cool.

Prof. Kalua:
So who is funding you?

Daniel C., Samira:
We have different sponsors. Not your usual eye care sponsors. A lot from the funding comes from our university, from different funding programs, and then also a few sponsors from companies. We are talking like 200 or 500 $. And then also from the MIT, the associated institutes. And the funding for this Africa Interviews, is a special program from the european commission.

Prof. Kalua:
What program is that?

Samira, Kai:
It’s Synenergene, for synthetic biology.

Prof. Kalua:
We have Dr. Bagrey Ngwira, she is a molecular biologist. From London School [...] but she is based here and she is the one that works with me in the lab. We are doing another study with qPCR [...] with the guys from Seattle. Always looking at the statistic diagnostic, to have a more specific test. [...] We don’t have any protocol for it, but the idea is there. So you have time to look at other areas in Malawi?

Daniel C.:
Yeah, so we will also be interviewing Georg. But we thought it would be great to go to a community.

Prof. Kalua:
I think they are going to the community. Did you talk to David already? [...] He’s going to the field for trachoma. He’s going to the community to tell them of the drugs and the tests. Salomie will organize with you.

Useful links:

• Blantyre Institute for Community Ophthalmology (BICO): http://www.bicomalawi.org/
• BICO Updates on Facebook: https://www.facebook.com/bicomalawi.org/
• PEEK: http://www.peekvision.org/
• GET2020: http://www.who.int/trachoma/partnership/en/

Interview with Co-Director of the Health Ministry - Michael Masika - and the project manager of the trachoma mapping project in Malawi - David Chinyanya

In the district Chikwawa we met Michael Masika, Assistant Director of Clinical Services (Ophthalmology) under the Ministry of Health and David Chinyanya, Program Manager at the Blantyre Institute for Community Outreach (BICO). They were on their way to some villages in the district to examine the progress of BICOs Trust Project. The Trust Project contains the performance of TT Surgeries and Mass Drug Administrations. In our interview Mr. Chinyanya and Mr. Masika told us a lot about the implementation of the SAFE strategy in Malawi, possible reasons for chlamydial infections of the eye and problems in the fight against trachoma, including cultural as well as technical reasons like the absence of affordable diagnostic methods.

Daniel C.:
[talking about our device]...In the middle is the negative control, it will slightly glow, even when you donˋt put anything there, only very little, but it is still somewhat measurable. Then you also have the positive control, where you put in the solution of only the molecule, so you can compare it. So you have no control, all control and in the third you can put the patient sample and its´ signal is somewhere in between and you can guess, does the person have trachoma, is this person infected?

David Chinyanya
When you say “trachoma”, do you mean the chlamydia or the stages?

Daniel C.:
I mean the Chlamydia infection, not the final stage. Because, as you were saying, you started with the clinical signs, but they didnˋt work. So now you also do PCR based tests. But in Ethiopia they still do only clinical signs, I think.

David Chinyanya:
What we do now in Malawi is the whole SAFE strategy. That´s what we are dealing with. As I said, because when we just started dealing with the patients that are coming to the hospital, we knew, that there are others in the community that are not assisted. All the reposing factors they are still there, all the transmitting agencies are still there in the community. So with the support from other organisations we are trying to manage now to do the whole SAFE strategy.

Daniel C.:
How are you going along in Malawi?

David Chinyanya:
We are doing very well, because the first mass drug administration we did started in 2011 up to 2013, then we went back to the districts where we were doing the mass drug administration we found out that the prevalence of TF, trachoma follicles, was below the public health problem, below 5 %. But we realized that just bringing that is not enough. As I have already said, that the rural minister should do the whole SAFE strategy. Now with the coming of other organisations that are helping us like The Queen Elizabeth Diamond Jubilee Trust Fund. They are helping us to deal with the whole SAFE strategy; The surgeries, those that have got problems and are burden for the mass drug administration and F and E [SAFE-Strategy: S stands for surgery, A for antibiotics F stands for facial cleanliness and E for environmental improvements].

Daniel C.:
So you are doing progress?

David Chinyanya:
Yes, we are doing good progress.The impact survey that we have done this year, we found that almost all the districts the TF is less than 5%. In other districts it was 9.9 %, other up to 15 % those were we have done a few rounds of mass drug administration. But those that were above 5 %, where we have done the mass drug administration (MDA) we found that it is less than 5 %. Which is now not [a] public health problem [anymore]. But the problem that is going to be there is sustainability. We have to sustain that. Because we know that there are others in the incubation period. Others will still have the organism with them. Now if we donˋt do anything, if we don’t improve on the F and E, likely it will come back.

Daniel C.:
Is it true that the threshold of 5 % is for communities that have “new” trachoma, and there are about 2 % of communities that already had trachoma and are being reexamined?

David Chinyanya:
No, [that’s] not correct. Because we do random sampling in the community. We do random sampling of 30 households. We examine everybody in that house. As you know, random sampling can mislead you. You can miss a house, that has got the problem. But now, when you do the mass drug administration it includes everybody. Even those who had not been sampled. Assuming that they still have the chlamydia. We know that by doing the F and E and the antibiotic and the mass drug administration we are likely to win the battle.

Daniel C.:
It sounds like you are really doing some progress. It is better than I think in Ethiopia, because they really have problems.

David Chinyanya:
The problem that is in Ethiopia is that the prevalence rate in Ethiopia is very high. Other districts it is up to 45 % TF. So they need to treat for five years. And migration in Ethiopia is very big. And if I recall the instability as well of other communities because of their ethics, something like that. Which is not here in Malawi.

Daniel C.:
And they are treating, but itˋs not really regressing.

David Chinyanya:
No. According to the information that we have got. But I have not gone there yet to see if what they are saying is true. But in Malawi, this is where we are.

Daniel C.:
What exactly are we doing in the village now?

David Chinyanya:
Now the ITI (International Trachoma Initiative), the Chief executive Paul Wilson will come here after next week. Just to see how we are doing the self survey. Because of the progress Malawi has reported. Because even the mass drug administration, the lowest that we have reported is 90%. The reason is, we use the head of surveillance assistance, who are government employed people. They are in the community. The doctors in the community there, they know the people, they have the trust of the people. So when we are doing the mass drug administration, if someone has not taken the drug the head of surveillance already knows, that that particular patient on that corner didn´t take the drug, so they go back. So initial when we did the mass drug administration, we got less than 80 %. We are going to the mop up now these are the people that help in the mopping up of the people that didnˋt take the drug. So our coming here is the report that we have got as a country. Thatˋs why ITI would like to come and see. So if they come, they don’t want to see the whole SAFE strategy. So they are coming over here just to see the eyes of the community. That we have this high powered delegation people just to see what we are doing. There is not much that we are going to improve in what we are doing, because we are already doing that.

Michael Masika:
Just to add to what you said. So what we did is that, when you look at this. This is a simple register. This is a village known as Namila. This is the number of the household. Number of household members. These are four in total. The name of the household members. So this is the registration. This is for the trachoma MDA register. So we give this one to each one of the heads of surveillance assistance to register. So what we are doing here, we are actually doing registration. So in this household there are four people. And this is the date of their births, this is the sex. Of course we put the year, so 2016, 2017. So whatˋs happening during the actual mass drug administration, if Alina Caseinje shows up, then he is measured. His height is measured and the dosage is indicated here. So when he has finished during mop up, what he does is he goes to the register. He checks who has not taken the drug. So he follows them up on the server. So we actually make sure, that everyone takes the drug. Basically thatˋs what is happening here and additionally we are also coming to check which villages they can visit. Because we have been told that they shouldn’t be too far away from the district. But otherwise we would have taken them very far away so that they appreciate what is happening. So basically when they are coming, they observe the mass drug administration and they also observe surgeries. Trachomatous trichiasis surgeries which will take place at the district hospital and then from there they will be going back. So as BICO we are a partner that is coordinating the program. Now as a ministry, they are the beneficials of the program. Now the ITI is coming as a guest of the ministry. So the ministry representative has to see where the visitors are taken. You don’t take a visitor where you don’t even know...

Daniel C.:
So now you register and the next week you come back and you do the mass drug administration. Who does the mass drug administration?

David Chinyanya:
The head of surveillance assistant. Because they do a lot of work in the community. The organisation and the drugs, they are giving it to the people. So thatˋs the registration.

Daniel C.:
Sounds like a smooth operation.

Michael Masika:
Yes it is. So we start with this one and then we start with the trainings. So next week- lots of trainings, to make sure that we prepare them to make sure that we prepare them for the smooth implementation of the program. So [we] will come back to see that everyone is trained and then we will come to support the training. The drugs have already arrived, they are at the district hospital. And next week they will be distributed in all the facilities, and from the facilities they will be distributed to all areas which are headed by heads of surveillance assistance and then the head of surveillance assistance, with the support of the village volunteers go and administer the drug. And then after we will come back to get reports and then we document and then we close the chapter. The program is over. Then, of course, after two weeks we come back to do and make what we call coverage survey. This is an independent survey to ascertain and verify the report that came from the head office. So that’s done in the absence, we also do sampling. They go around. I think that’s the program that Salomie is conversant with. With the phone and the app thing. So we will come back to verify. And then six months we will come back with the impact survey to determine whether we still have the problem, or not. So in all the district where we were implementing, as BICO, we were in about nine districts and we did the impact surveys and we discovered that the problem is below 5%, which is the threshold. And perhaps you are asking you how do we sustain this? Because in Chikwawa, two years ago, we declared that trachoma is no longer a public health concern. Two years later, when we came for surveillance, we found that it has gone up again. So those are some of the challenges. So I think the emphasis for the first few years was on S and A, which is the clinical side of it and the issue of the environment was not taken on board. Unless this time were it is strongly recommended that we need to also do that.

Daniel C.:
How do you do that?

Michael Masika:
There is a program, which is also funded by the trust. But it is a small program. And we are also working closely with other partners, who are already doing WASH. They are normally doing F and E but they are doing WASH. So when they are doing Water, Sanitation and Hygiene promotion they are also doing F and E. So we are working closely with them like in the villages we visited. Itˋs not the money from the trust they are utilising, actually they are utilising the funds from other partners and they are declaring villages open defecation-free which is quite a positive omen. We believe that we should be able to combat the disease and perhaps celebrate that we are done with it. But as long as the risk factors, not have been taken aboard, the likelihood of the disease recurring is very high. For example here, when you look around, itˋs all dust, itˋs very dry. You have seen the cows, there is dung all around. And there are flies all around. Now if we can’t take care of our eyes properly with F and E we don’t have to expect any progress.

Daniel C.:
How does it look during rainy season?

Michael Masika:
It looks very different. During rainy season itˋs waterlogged. Well this place is flat, so itˋs waterlogged for some few months and then itˋs completely dry for some months. So itˋs always very damp. Sometimes, during the rainy season all the toilets are destroyed and the people donˋt have toilets. But when itˋs dry, they are constructing them again. Itˋs on and off. Thatˋs the problem with the two districts that we have here, Chikwawa and Nsanje. They are flat and they are also prone to flooding.

David Chinyanya:
Like we fixed the Chikwawa three rounds of MDA, that was in 2013. In 2014 the we had the worst floods maybe some of us have seen so there was water all over, so all the toilets had gone so now we are starting construct latrines at the lake. So it´s not easy.

Daniel C.:
When you map and diagnose the people, when do you use the clinical signs and when do you use PCR for diagnosing?

David Chinyanya:
In most cases we use the clinical signs, the PCR we are just using for the program. But when we are outdoor diagnosing patients we use the clinical signs. So whenever they get the clinical signs we treat them there and then and if they need to be referred, we refer them to a hospital, where they then do surgeries on the lid.

Daniel C.:
What is the demographic of the diagnosed people? What kind of people are especially prone to infection? And why?

Michael Masika:
Mostly women and children. As a country and as a culture, children stay with mothers. Now itˋs the children that have running eyes, discharges, eventually this will attract flies, that might transmit the chlamydia. So if the child is on the back of the mother and there are flies all over, the face is not clean. What you expect is that the flies will also jump to the mother and they also jump to other children that are around the mother. The men are not there. They are not staying with the children. Thatˋs why women are more affected.

David Chinyanya:
Itˋs our culture, we try to educate the people, that the men can also take care of the children. Even if you drive back to where I come from you see, that itˋs the mother that are caring for the children. The men are just walking around, or the men just leave in the morning, they go somewhere and chat with their friends and come back. Another thing is the culture as well, that if there are only a few litres of water in the home, it will be given to the father, or to the man of the household, not the mother. They like to give it to the father to use that water, the others can do as well without it. One of the messages we are trying to develop is to change the mindset. Which is not easy, but itˋs really the mindset. We give priority to the fathers. Thatˋs a big challenge, as a country and you know, culture is not easy to change and it takes time and it takes a lot of advocacy and awareness which is an ongoing thing. Thatˋs the challenge that we have to meet. And perhaps, the other thing which we should also mention is the issue of illiteracy. In Malawi the illiteracy is very high among women. Itˋs something also cultural. For example two children, a boy and a girl, are raised in a family and both of them get selected to go to school, but the preference will go to the boy, and the girl will get married and taken care of by the man. This is highly entrenched in our culture. So if you are a man you are raised thinking that you have to take care of a woman. So that’s the problem. Because of illiteracy acquisition of knowledge and technology is very slow. And also with other believes and needs associated with eye health it highly complicates matters. Thatˋs why women are affected by disease.

Daniel C.:
How is the distribution of doctors in the field? Do people in the villages go to the doctor when there is something wrong or do you have to go and check?

David Chinyanya:
They go if there is something wrong with them. Medical [...] behavior is not yet there entrenched in us.They usually go to a hospital with a problem. Nobody will come to a doctor to ask to get his eyes checked. During my practice nobody came to me to just get his eyes checked. When you see them coming to you, they have a problem. The other issue is why is it like that? Maybe doctors are very few. So if somebody comes to me and says: “I just wanted my eyes to be checked” I would say : “Please wait, I want to check on the one that is sick”.

Daniel C.:
So you often diagnose the disease when itˋs in a late stage?

Michael Masika:
Yes, because of the illiteracy thing that is there. A lot of them come to us when itˋs already late. But it is not supposed to be like that, because when someone comes to me with a corneal scar certainly to trichiasis they are not supposed to come to me at that stage. They should have seen the problem somewhere four, five years ago. But if the people come with that corneal scars secondary to trichiasis, it means that the thing has been there for some time. Because if they came earlier we would have corrected the trichiasis.

Daniel C.:
And then you have to operate.

Michael Masika:
Yes. If they come at that stage you have to operate just to relieve the symptoms and signs but not to regain the sight. But when they came earlier on,we could have prevented the progression of the disease.

David Chinyanya:
In addition to that, of course our health system is also growing, progressing. Eye health specialists or clinicians, [there] are not many in the country. Very few. He (Michael Masika) is in charge of that, he can actually count for you. At least at one point he told me, that there are 69. And about twenty district hospitals, but then we also have central hospitals, where we need more of those because of the referral system. So because of that most of them are [...] disenfranchised they have been dissuaded. They can not really say “letˋs go and get our eyes checked”, because they know that when they go, perhaps they may find nobody who can attend to them and that has been a problem. But there is a remarkably progress. [...] I think some few years ago, that was not the case. Now, because of that, some of them, who are old they may have developed trichiasis but they feel that it is time for them to be blind, because they are old. So those are some of the beliefs that are there. Even right now when we have the program where we are correcting (?) trichiasis the challenge is to persuade them to access this antibiotic service. So that’s the challenge.

Daniel C.:
Yes, it is surprising. Salomie showed in the questionnaire that people might refuse surgery. Do you have to persuade a lot?

Michael Masika:
Yes you have to persuade a lot. Most patients are afraid of surgeries.

David Chinyanya:
Others you try to persuade even say “No”. They tell you “What will you tell me I have to see what I haven’t already seen before? So it is better for me you leave me alone, Iˋll die. Iˋll die blind. My parents died blind. So this is hereditary”. You try to say that itˋs not hereditary, this is trichiasis, so this is contracted. But they say: “Leave me alone.” The other thing is the system of medical services[...]. The road that you have taken until here maybe is about 23 kilometers but this road will take you up to the border of Mozambique which is about 70 to 80 kilometers out of the town. To take a patient from there to use his or her own resources to go to the hospital and he finds that the ophthalmic clinician is out with us to the field. There is nobody to attend to him. If he goes back, do you think he will come back again? He won’t. He will say: “I went there, I suffered, I used the resources that I had and I didn’t find anybody. So just leave me alone”. You talk to them and they say: “Just leave me alone”.

Michael Masika:
Yes, that’s one of the symptoms of the few numbers [of clinicians]. If somebody comes and the clinician is away. Now he has pased through many of the head of facilities. The clinical officers, general clinical officers but there is no one for ophthalmic clinical medicine. So thatˋs where the problem is. [...] We just talked to the chief and he seems to be very aware of the challenges he is facing. He has actually encouraged everyone to register, so perhaps you can prevent it. This is one of the challenges we have to deal with. Our staff are not adequate and therefore they can not serve the growing population.

Daniel C.:
I have a question concerning our application. [...] These bacteria are genetically modified. Would there be acceptance for genetically modified organisms to be used in the field? Would that kind of medical application be accepted?

Michael Masika:
I donˋt see a problem with that. Provided, we sensitize the whole channel. Everybody knows what is happening. Because thatˋs an advancement in the management of the patient. We want the patient to be diagnosed at the earliest stage.

David Chinyanya:
Yes, I think he is the right person to answer that because that’s a political issue. And he is the right person. He’s from the government. [...].

Dominika:
We spoke with some Professors who are handling Chlamydia. They have a theory that transmissions over animals happen quite frequently. Have you looked into it yet? Is there any transmission possible?

Daniel C.:
It was theorized by one professor, who deals with Chlamydia in animals, that they might serve as a reservoir for the infection. It´s a mystery, why in some villages in Ethiopia infection always returns.

David Chinyanya:
Yes, even here, we are using it as a theory, because often when people are sleeping together in a house with animals, the incidence is high. So we think that one agent of chlamydia transmission is cow dung. That´s why I was showing you the cows. In areas, where people live in the same house with cows, that problem is high. We have tried to talk to the community that they have to improve on that, but they have got their own reasons why they keep the animals together with them in the same house. So here we are using the same theory, because [in] areas that are doing that, trachoma is a problem. And in areas, where they donˋt stay in the same house with animals the incidence is low.

Daniel C.:
That really plays for a study there, because we went through all the research papers and couldn’t find anything.

David Chinyanya:
Yes, we haven’t done any study it just shows, not as scientifical research, but you just observe, as you were saying, where you are seeing this dung, dusty, dirty places. Especially when the dung component overweights you find that there is a lot of trachoma there. If you have the chance of going up North of Malawi, where those things are not there we didnˋt find any trachoma. The people keep the animals away from the house. I went myself to the island in the lake Malawi, Likoma. I didnˋt see the animals like you are always seeing them here. I was there for four days, I didn’t even see one case of trachoma. Not even a case. So theoretically it might be along those lines. When you come down here, [the people say] because I am afraid of my animals that they can be away, outside my house, I put them in my house, the problem is there.

Daniel C.:
Thank you. This was very interesting.

Michael Masika:
Hope is the last thing to despair in life. Thatˋs why there are blind people that still come to the hospital because they hope to see again one day.

Salomie Mumderanji Balakasi - Data manager for BICO

Salomie was our first contact from BICO. As Prof. Kalua´s personal assistant and project assistant in data management as well as information and communication technology, she was able to give us deep insights into the day to day work at BICO. We also learned from Salomie how BICO collects and analyzes trachoma epidemiologic data and how that contributes to the fight against the disease in Malawi.

Finding Chlamydory:
We have a lot of general questions concerning your trachoma mapping efforts in Malawi and the general measures you take to fight the disease.

Salomi:
In short, I would say that BICO has a number of projects: [for example] the trachoma elimination program which is funded by the Queen Elizabeth Diamond Jubilee Trust and we have the low vision program where we do mass screenings at primary and secondary schools and provide glasses for those students who are visually impaired. At BICO I work as a personal assistant for Prof. Kalua but I also do data management and ICT (information and communications technology). So I am going to talk a lot on how we manage our data. […] I should say that previously we’ve been capturing all the trachoma data on hard copies but that way it was hard to keep all the questionnaires, to track them, to do analysis. […] So in 2015 we moved again to Open Data Kit, which involves capturing and collection of data through electronic questionnaires and the data is stored on a cloud server. Everyone can easily access it as long as they have the rights. We developed our own cloud server for BICO. Then we moved all our hard copy questionnaires onto the server. So whenever we want to go to the field to do research or data collection, we get the questionnaires from the server onto a phone and use apps to access it, which are either Task force Tropical Data or Task Force LINKS. […] For the trachoma elimination programs there are a number of things that we are doing: There is mass drug administration. We administer azithromycin, the trachoma drug. For this year we have done it in Dedza. This October we are able to do another mass drug administration in Chikwawa ditrict...

Daniel C.:
…which is an epidemic region?

Salomi:
Yes. [And] We also have trachoma trichiasis surgeries happen. So we have some questionnaire to capture the data for the trachoma trichiasis patients. The whole process starts with screening, trachoma trichiasis verification and then the actual operation. For all those processes we have questionnaires […].

Daniel C.:
What about your trachoma mapping efforts?

Salomi:
We do mapping in Mangochi. We had a baseline survey and we will have another mass drug administration in this district because it was confirmed to be a hotspot.

Daniel C.:
Who goes out into the field and does the actual mapping?

Salomi:
For the mapping its actually myself, other supervisors from the ministry of health, Prof. Kalua and enumerators. Usually when we have to conduct a survey, we invite the enumerators depending on how big the survey is. Usually they are trained for two to three days because we have to explain to them the project itself. Because when they go into the field they meet a lot of questions which they have to be able to address. We also need to introduce them to the app and make sure they collect the data correctly. Otherwise, if they mess up it means that also the data is messed up and we cannot rely on it. But we have a lot of enumerators so most of the times it’s just a refresher training because we have already trained a lot of them. Sometimes they have found jobs that’s why they can’t come and we have to train new enumerators.

For the surgeries, in case we organized a camp and want to do some trachomatous trichiasis operations, one of the BICO staff goes there before to capture the data. And the surgeons have also been trained on how to capture the data. So when they are doing the operation, they are also entering the data into the phone. Then the data is uploaded to the server and we can access it.

Daniel C.:
Wow. It sounds like a smooth operation. You don’t have to do any paperwork.

Salomi:
Yeah, there is no need for paperwork. And in case the project officers organize an operational research [project], we just ask him or her to give us the questions and we put them on the server and download them on the phone so they can use it.

Dominika:
Could you show us some of the questionnaires and the app?

Salomi:
Yeah sure. We are using Motorola MB865 phones for the surveys and data collection. For example, after mass drug administration we have to do coverage surveys to see if the people received the drug, or how many people received it. And then after six months there is the impact assessment survey. All that data is collected using these android phones.

Daniel C.:
How much data do you collect from one district for example?

Salomi:
It depends on how large the district is. For the impact assessment surveys, we usually have a sample size of 1090 children per district […].

Daniel C.:
I am really interested to see what questions are in the questionnaire.

Salomi:
Yeah we are going to show you. So this is the questionnaire that the surgeon fills out when he has finished the surgeries. He has to fill out the summaries like how many were males, how many where females, how many have been operated on both eyes, how many have been operated on just a single eye, how many were screened […].

Daniel C.:
After the surgeries, can the patients see again?

Salomi:
No they can’t. They [the surgents] are focusing on the eyelids. And the eyelids are now ok but people who were blind will not be able to see again.

Daniel C.:
So it can’t get worse but it won’t get better either?

Salomi:
Yes.

Daniel C.:
Can you show us the questionnaire for the trachoma mapping?

Salomi:
So the trachoma mapping questionnaire is actually not an interview but an examination […]. There are some general questions regarding the hygiene of the household. For example:

• What is your main source of drinking water?
• How long does it take to go there, get water and come back?
• In the dry season, what is the main source of water used for face washing?
• Where do you and other members of the household usually defecate?

[...] So that is the first questionnaire that is filled out when the enumerators arrive at the household. And then we have a trachoma grader who examines each and every resident of the household and fills another questionnaire.

Samira:
So when you do the mass screening for trachoma, do you just rely on symptomatic diagnosis or do you do some laboratory tests as well?

Salomi:
No, when we are screening we only focus on the symptoms - or I should rather say the signs of trachoma.

Dominika:
So there are a number of people who are refusing the surgery. What reasons do they have?

Salomi:
The main reason why people refuse surgeries is misconception of what happens in the theater and also fear. There are a lot of misconceptions about the surgery, that when you are in there the surgeon takes off your ear or your eye and then operates you and then puts it back. So it´s not easy to convince the people in the villages. Sometimes we use the people who have been operated to convince the others and to tell them what is done and that it only takes 15 minutes.

Dominika:
Do you have projects in schools for children to educate them on trachoma and how they can avoid it?

Salomi:
We have school projects but not necessary for trachoma. It’s the low vision project where we do a lot of screening and offer reading glasses for free […].

Daniel C.
[…] What about the SAFE strategy?

Salomi:
[…] It’s S for surgery, A for antibiotics, F for facial cleanliness and E for environmental improvements. Yeah we do it, but then our main focus as BICO is S and A we don’t do F and E […]. But trachoma cannot be treated if we focus on the S and A but we leave out the F and E, they all need to be working together. So we talk with them but it´s not our main focus. There are other organizations who are specifically working on F and E.

Interviewing George Moyo - Data Analyst for BICO

In the provincial Chikwawa we met George, who works as a data analyst for BICO. He just finished his Master thesis in community eye health at Cape Town University, in which he dealt with the data of the Global Trachoma Mapping Program (GTMP). In the interview George told us a lot about the challenges in terms of (global) trachoma data collection and analyses. Furthermore he confirmed that a cheap and fast detection method for chlamydia would be extremely helpful, possibly even the only way to completely eliminate global trachoma.

Daniel C.:
Introduces us and describes the project to George.

George:
When will this project be finished?

Daniel C.:
Pretty soon actually. [...] We’ve just got message that our bacteria are as good as finished. The device is also as good as finished, so now we are testing it.

George:
Oh that’s good! We are supposed to do [...] an operational study that should confirm that itˋs the real trachoma. So we will begin maybe next week. We are going to the field, collect some blood samples, take some swabs. [...] So if you can provide your device we want to use it, because we have a project already. [laughing] We have a budget and we train some people to collect the data, especially blood, how to keep [it], how to collect. So this could be nice. But at the moment the device is not ready [...] but this could be very good. Right now there is PCR [...] to [analyze] if there is chlamydia or if there is no chlamydia.

Daniel C. Dominika Samira:
But I understood it in this way that you only find out later, [after] the people have been treated, [whether they really had the infection].

George:
Yes.

Dominika:
Ok, then let’s start with your career. What has it been like until now and when did you start working on fighting trachoma?

George:
Yeah, [...] I am just new. [...] I am also a student. At the University of Cape Town. There I am doing my Master's in community eye health, but I started with Optometry. So I am an optometrist by profession. Then there was this opportunity by the Queen that some few people can do their Master’s in community eye health then I applied and I was lucky. So I have just finished my modules and my thesis. Because my study was in trachoma, they gave me the data for all the endemic countries in the world, so about 54 countries, [and] I had to analyse country by country. [...]. So that’s why I am found in the trachoma studies, but I am not an important person in the trachoma studies. I am also just learning.

Daniel C.:
But that’s interesting. Like all those 54 countries and you studied all of them, how old was the data?

George:
There is this program called GTMP, global trachoma mapping project. So at first data was not collected, like it was not available but then the people said oh, this disease we have to get eradicated and they started to think how could we organize our data and now we have one server. So all the data is on that server in Atlanta and when you collect data, usually in all these countries data is collected with android phones, so it is really easy, it is sent directly to the server. [...] In my study we could simply wait for the information of these countries. So you write a letter to Malawi: please provide us with data. [and] they provide you with data. [...] so from all the countries that accepted, I have the data.

Dominika:
What are you looking for?

George:
There have been some questions about trachoma. We are trying to find out. Some studies were showing that trachoma is more common in females than in males and then there were some systematic views and people came up to maybe 1.8 as a ratio. Say when you see one male [with trachoma] you expect 1.8 females. This data was mainly taken from very high endemic regions and my role is to make sure that I use all the data and say if the ratio is still the same. Even if we use very high prevalence and combine it with small prevalence we should have the same ratio at a global level. If I find one male then I find 1.8 females. So that was my job and apart from that I should find out why females [are more affected than males][…].

Dominika:
And what was the conclusion?

George:
It is difficult to answer this question. Because I was using secondary data. The data collected contains variables which don’t give a correct answer to the question why females? Because I hadn't planned the variables. I just found the variables in the secondary data and from the collected variables it is difficult to say why females. [...] Because when you come to the villages you find that they are exposed mainly to same things. So do you have water, do you have this, do you have that, and you find that maybe many things are common. [...] But I am thinking of doing another study where I should be conducting it, where I can go into the villages and see why.

Samira:
The ratio of 1.8 female to 1 male patient was similar in all countries you looked at?

George:
The 1.8 is not my [data] [...]. But in all countries you have [a] higher [prevalence] in females than in males. [...] The ratios might be changing but always it will be higher in females than in males, especially in adults. In the young ones [the prevalence in females and males] is almost the same.

Dominika:
So there are differences in the ages too?

George:
Yes. [...] When they are young, maybe because of their activities, they are similar. The prevalences [in females and males] are almost the same. But when they grow it [the prevalence] starts to differentiate to females more than males.

Dominika:
Are there any regional differences too?

George:
Yes. Trachoma is truly a disease of the poor, because it depends of the hygiene and feces. If we go now in the villages, before we examine we can say we will find trachoma in that child. [...] When you’re moving around and they [the people] look clean and you’re examine usually you don’t find [trachoma]. But those children [...] where you say Ah this one! This one is too dirty, maybe it is everyday like that. Many times you find [trachoma]. So It is more in rural than in the urban areas.

Dominika:
What can you tell us about the infection rate? Is it increasing or decreasing?

George:
It should be decreasing. Because something is happening. People are aware of the disease. They know how to control it. [...] In many areas it is eliminated [...].

Samira:
You seem to be an expert for the global mapping program. Maybe you can tell us a little bit about the trends between different countries? Because we always hear a lot about Ethiopia, that there is a huge problem [with trachoma] there compared to other countries. Can you tell us what’s the reason for that?

George:
I have never been to Ethiopia. I just have data for Ethiopia. So that’s why I told you that reasons are very difficult [to find]. [...] Maybe because of social [or] environmental [reasons]. I don’t know. [...] But what I know [is] when you look at their eyes there is a very high prevalence. [...] Just some few why's that I can answer is: it seems that they have many animals. Because of that there are many flies around. Those flies can easily transfer chlamydia from one to the other. There are children and there are flies coming to their faces. So that could be a reason why the prevalence there is high. Maybe their type of living. Maybe they live crowded. Because in other places they can be poor but because one family is here and the other one is there, they are separated. It can be a poor community but because of their non-communal life, the prevalence is lower. So culture affects [the prevalence] [...].

Daniel C.:
You looked at all these countries. Do you have like an estimate how the fight against trachoma is going in the countries in general?

George:
Yes. In all the countries where this project GTMP is there is a huge fight [...] against trachoma. [...] I can’t be very very detailed what they are being right now. But for Malawi we can say that we are eliminating trachoma by 2019 and many countries are the same, by 2020 might have eliminated trachoma.

Daniel C.:
[...] Do you think 2020 is realistic to eliminate global trachoma?

George:
Elimination as a disease and elimination as a public health problem is not the same. They are a little bit different. So what I think: people might try to eliminate it as a public health problem. Wherefore you say for something to be a public health problem [it] should be [...] less than 1 in 1000. And those are the targets we are fighting for. So if that is done and there could be some backlog and you see that people are not carrying the chlamydia, [but] it is still around. Of course they are doing something. There is this SAFE strategy so that the chlamydia can not find their way out [...]. But the project is really strengthening, especially in surveillance. In countries where they have reached less than the threshold and the surveillance is very active. [...] I think we can eliminate because there are many diseases that were very difficult looking but they were eliminated. The way trachoma is being managed, I think is very good. There is a very nice networking. You can see the eyes, you can have data [...], you can upload the data to the server. So if that is strengthened, especially the data, I think we can [eliminate trachoma]. But maybe the time has to be increased a little bit. By 2020 is possible [...].

Dominika:
What kind of data are you collecting all together?

George:
For PCR we are taking blood and swabs. These are the two samples that we use. [...] We believe, if chlamydia is not found there, the follicles that are found are not trachomatous follicles. And the other one is we have a standard in terms of follicles if we flip the lid and we see that there are almost five follicles on the center of the lid then we classify that this person has trachoma. We call that trachoma follicular (TF). If the conjunctiva is red also, we add this one has trachoma inflammation. So we call that trachoma TI. So if it’s TF that one could be inflamed or could not be inflamed but he has got some follicles on the lid, especially on the center part. So that’s what we use the most. But the PCR [...] is expensive. We only use it to confirm phenotype. Like Are you saying the truth? Let’s confirm! It´s the gold standard.

Samira:
And how long does it take to analyse the data? What’s the time between Ok, I think this person has trachoma and the treatment with antibiotics?

George:
From the time we say this one has trachoma to the time we give treatment? Usually trachoma has got stages and we can [recognize] trachoma All the stages are very easy. By just looking at you I will know, this one has trachoma. Than we treat right there, because some of them with trichiasis, the stage where the eyelashes are touching the globe, so it’s very easy. You only treat them. Just when some eyelashes are touching the globe, than you know this one has trachoma, then you straight away start treating with antibiotics. If they are children you don’t expect to have such signs because the trichiasis will only come when there is recurrence of infection. Recurrence, recurrence, recurrence. So in children you don’t expect trichiasis. [...] you flip the lid and see the follicles that I was talking about. [...] So that’s how we treat. So we train our clinicians. It doesn’t take long because according to the stages, how I said, if it’s trichiasis you just see the signs and you say this is trachoma. You do the surgery and you make sure you cut so that the lashes don’t touch the globe. If it’s in children you make sure you treat so that the bacteria should die.

Dominika:
What are some problems you encounter when you are collecting data or when you are analysing data?

George:
[...] I am used [to] my data package, so I don’t have too much problems. Maybe there are some softwares I need to pay. Maybe they will tell you for you to do this type of analysis you need to pay or you should be a member of this for you to do maybe to do all these results you need to pay less much or maybe you have a nice craft you need to pay or there is maybe a free version and they will tell you if you want to use this pay this. So maybe this are challenges but otherwise in the analysis I can analyse global data in five minutes. If you ask me now: tell us how many people of this and this? [acts like he is hacking] ENTER. And it shows me. So in terms of analysis, Itˋnot a really big challenge. So the only challenge might be experience. So it takes much time to understand one thing. But otherwise it’s not a very big challenge.

Dominika:
And in terms of collecting the data?

George:
n terms of collecting the data there are too many challenges. As you know it is hard to reach areas. [...] So distance is one of the problems of data collection. […] Other challenges we have managed to overcome them, because we want quality data [...].

Samira:
What sample size do you take when you go to one village? How many households do you test?

George:
Different countries use different numbers, but in Malawi, because of the nature of our districts, I think we use 1090 children per district. So those districts which are very big, we divided them so that they fit to the WHO criteria. Because WHO, they have their own district size. So our districts, some of them are big. So if you say in our district they maybe tell us to take 30 households. So we are allowed to take 30 households per district. Than according to our districts, they are too big. So we divide those districts into maybe three portions and from those three we take 30, 30, 30. So Malawi maybe has 26 districts, but in terms of trachoma it could be having 40 districts. Because we want to match with WHO saying in a district you can take 30 households.

Samira:
And we heard about that when a certain prevalence is reached when you do the sampling you do mass treatment for the whole village. So what is this prevalence?

George:
Prevalence, especially when you are dealing with trachoma, you are very much worried about the infection. The disease is active when it is trachoma follicle. So [...] in terms of TF, if you have got maybe nine per 1000, then you are thinking Oh, that’s a lot! In terms of trachoma trichiasis, if you find less than one per 1000 [...] BICO considers it as not very important.

Daniel C.:
Is there a difference in the thresholds between villages that have [...] chlamydiosis outbreak for the first time and villages which already have been treated? So are the thresholds different?

George:
No. Because if it is treated for you to have a survey you wait for maybe two years. So we have an impact survey that is ok. After we treated we just want to see what’s the prevalence now. So if you find it’s the same, you just use the same. Like Chikwawa. We treated now a few times. We treated and we think we are done. Then we come, so let’s go do impact survey. The medication we gave, what is it happening? Then we come and we find [that] there are maybe 30 TF per village and you see no reason. So you use the same guidelines whether you have treated or not. Because you wait for two years before you do the impact surveys [...].

Daniel C.:
So what are you doing at the moment programme-wise?

George:
[...] Here in Chikwawa, we want to give another mass drug administration. So what we are doing [...] [here], if you see those motorcycles, those are senior agencies. They call themselves disease control surveillance officers. [...] They are the ones who bring information to us. So today we are verifying to say: is the registration going on well? Have you giving us correct figures? When we have that, next week we will see how much medication we will need.

Daniel C.:
So let’s say now is 2019 and every region is under the threshold, what are your next steps? What does BICO have to do to make sure that trachoma won’t return? Do you have any plans?

George:
Yes. Currently, my role that they have given me as George is to make sure that I collect all the data that have ever been there for trachoma. Because the GTMP came when the data has already been collected. So my role is to make sure that I collect all the data from everywhere, all resources. Others are in hard copy, I have to put them in soft copy [until] I have every data. [...] Then I make a team that has a network. I could net Chikwawa clinicians, Sandama clinicians, Zomba clinicians. All the clinicians should be connected in a certain network. When they identify any case, these clinicians can easily tell this step and this step can easily notify. So in my case I will take guys that are not fireable. So any case would be very important then we follow that case. So that what we are trying to do so that we can say that we have it eliminated. Any place where trachoma is showing, we will intervene. So it will not mean that we will have reached elimination and we will stop. But otherwise it is that of surveillance where we see Oh these [...] people [...] have trachoma! We intervene. When one comes and says: Oh there is one here. we will deal with it like that. So with this information we will trying to be very fast and very clear. So that will be my role in BICO. The Ministry of health, [...] the trust, [...] the WHO they need this type of following up. Anything that comes up should be noticed. So we are taking over establishing that type of networking, especially with clinicians. If they see anything, they have to notify me and I am supposed to copy. Other people who are also doing some surveillance they also need to copy me. So I am supposed to find out who are those people keeping data. Like HIA’s. This is something they send it to my e-mail or they send it to this server of BICO. Something like that, so we know exactly what is happening.

Daniel C.:
How many months have you now been at BICO?

George:
Working for BICO? I can say one month [laughing]. [...] I was working full time in the Ministry of Health. Because these things are happening much in the southern part of Malawi, but I was working in the northern part, [...] they tried to make me come to this side. So to come here, it is just one month. So that’s why I said I am new [laughing].

Daniel C.:
But you also worked in this area when you were in the northern part.

George:
Yes.

Daniel C.:
And is it different, the northern part of Malawi and the southern part?

George:
Yes, very. Because in the North we don’t have [trachoma]. I come from there also and there is no such a disease. I was there, I talked to Prof. Kalua and I said: Why are you not coming to our region? and he said: Yeah George, we don’t have that disease at that side. And I said: No, no, no, I think we have. And then I think he sent some people to do the survey and they found that the disease is not there. So we hope it’s true that the disease is not there. That’s why we are thinking about is it culture? Is it what? Why is it not found there but it is found in other places? That is difficult to know. Because we can’t say in the North people are rich, or they are hygienic, or they are what. I don’t know is it culture?

Daniel C.:
So the toiletries are the main part why people get infected?

George:
It might be wrong to say that. Because correlating it with the toilet, I don’t think it comes directly proportional.

Daniel C.:
Or is it also the access to water?

George:
[No] access to water is poverty. So poverty is the thing. Access to water maybe, maybe not. But maybe hygiene. Water can be very far, but people can be hygienic. You can have water very close, but maybe you are not hygienic. So hygiene, if it’s promoted, the chlamydia cannot find space. Because we say even when you get chlamydia from this place, you take it to the city and it will not survive. [...] So that’s why we think that it’s just those places where there is less hygiene. Because when they move out those people, then the disease is not there.

Daniel C.:
Ok, then thank you so much for the interview George!

George:
If we would use [your] method to find chlamydia then we would know when we have to much chlamydia that it is rising. But now, since we are only using when the signs come up it is very difficult to have like incidents to know right there, right then.

Daniel C.:
Of course! Because sometimes people got chlamydia, got treated but still have signs left.

George:
Yes. So I think that method will help. If you do come to me I put a question about this STIs but it is not even on the list. People don’t even think about it.

Daniel C.:
Even not in Malawi? I mean in Malawi there is awareness of chlamydia or not?

George:
There is no.

Daniel C.:
There is no? People don’t know it?

Dominika:
We heard that there are educational programs in schools that are teaching about chlamydia and hygiene.

George:
That is about this where we are talking over the eyes. But the one [that is] transmitted by sexual what what is not viable. So it’s possible that people are having it in light numbers because there is no method of testing. The one we test, I donˋt think passes even through sexual intercourse, it passes through this hygiene things and then we test checking the eyes. This other type of chlamydia, you got the chlamydia maybe from your friend, that one is quiet. So maybe if we also do that type of study in Malawi it’s ok. Let’s collect some blood samples, then check chlamydia, I would send the data, we would find 90 %? Yeah, because nobody can claim to be tested for chlamydia, because it is very expensive. The method we have now is very expensive. PCR. You can’t say we want to test people who have chlamydia, we use PCR. It is extremely expensive. [...] That’s why elimination, as you said, is challenging because we are only looking at the signs. So if you are busy looking on the signs, how do you see it? How will you eliminate it by looking on the signs? It’s challenging, because you have to see from the blood do people have it? [...] But not by looking on the signs. What if you don’t see the signs but in the blood it is still there? That’s where I think much more needs to be done. [...] Some of us too think that we need to know if the person has the disease, rather than just the symptoms. So we are doing fine. Or not us, but the Queen people. The Queen is giving us all the resources. Yeah, so they are doing fine.

Daniel C.:
Yeah, they are actually doing a great job. I looked at the website of the trust foundation and they have so many countries that they are supporting, it is crazy.

George:
It is not just us they’re supporting. They do huge support in all these countries. At least the support is on fight of trachoma as a project. So you know if you are fighting as a project. Where it has got maybe the busiest then when the project ends you find...

Daniel C.:
...they peter out.

George:
But they are trying to sustain it so that even though the project should go but the villages should be at least equipped to say Ok, hygiene should be like that. So that’s what we are trying, but it is not easy.

Daniel C.:
Yeah, but I think that’s the end aim, to have the villages know what they are doing and taking care of themselves. Yes, I think you are right.

George:
Yes if that is done then itˋs just moving, giving medication, doing what we can not take cares away. But educating, or something like that. Yeah, something is happening.

Daniel C.:
Well, thanks again.

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