Molecular Tools for Helminth Control and Elimination: Time to Get them Out of the Laboratory and itno Programmes and Policies?

By Corrado Minetti

On my way back from Ghana, where we have been testing the molecular protocols for the detection of filarial parasites in mosquitoes, in the laboratory of Mike Osei-Atweneboana at the Council for Scientific and Industrial Research (CSIR) in Accra; I had some thoughts about how far molecular diagnostics has come but also questioned how can we make it a sustainable reality to assist effectively in disease control and elimination.

corrado-molecular-diagnostics-blog-post-08-11-2016

DNA extraction from pooled mosquitoes for the detection of filarial worms (on the left) and an example of amplification of parasite DNA (+) with the LAMP method (on the right) (Photo: Corrado Minetti)

In order to achieve the goals of the London Declaration on Neglected Tropical Diseases for the effective and sustainable control and long term elimination of Lymphatic Filariasis, onchocerciasis, soil-transmitted helminthiasis and schistosomiasis; the deployment of appropriate diagnostic tools is crucial at every stage of these disease control and elimination programmes from initial mapping to post-elimination surveillance. With the rapidly changing epidemiological scenario of these diseases due to the scaling up of mass drug administration, and the push towards more sustainable and cost-effective multi-disease interventions, the implementation of more sensitive and cost-effective diagnostic tools is a priority well recognized and advocated by the World Health organization.

Molecular diagnostics tools, including (multiplex) real-time polymerase chain reaction and more recent isothermal amplification assays such as loop-mediated isothermal amplification and recombinase polymerase amplification do offer increased sensitivity compared to traditional approaches but they are yet to be used in control and elimination programmes due to their cost and technical requirements. There are various gaps that need to be highlighted and solved in order to allow these approaches to become potentially embedded into disease control programmes & policies, and to inform decision-making.

In order to identify these much-needed gaps, we have recently published a review paper where we compared the features of published real-time PCR and isothermal amplification assays for the detection of Lymphatic Filariasis, onchocerciasis, soil-transmitted helminthiasis and schistosomiasis in clinical and vector/intermediate host samples. Despite the availability of a wide range of assays for both patient diagnosis and xenomonitoring (parasite detection in insect vectors or snails), little or no research has been devoted to estimate the real costs and logistics of implementing these approaches on a wider scale for control and elimination. We highlight the need for a major focus on the implementation aspects of these tools in developing countries, and how barriers for their full adoption in resource-poor settings could be overcome. Key issues are the technical requirements and the related need for capacity building, the abatement of costs and the economic sustainability of molecular screening over time. For example, diagnosing multiple parasites from the same clinical sample can heavily reduce the number of samples that a community may need to provide, resulting in a far less invasive procedure for the communities, as well as reducing significantly the cost of processing. A multi-disease approach to diagnostics will certainly benefit the health system as well, both logistically and economically.

Writing this review paper has been extremely valuable to get a clearer picture of the progress in the field so far and to identify the best and most cost-effective diagnostic approaches for our project. In a broader sense and within the COUNTDOWN research consortium, we hope this review could serve as a starting point of discussion in the NTDs control and elimination community, leading to a more comprehensive analysis of what molecular diagnostics can offer and how we can make sure these tools can finally get out from the laboratory becoming embedded into policy, to strengthen disease control and elimination programmes and the health system itself.

Find more information on COUNTDOWN’s activities visit us here.

COUNTDOWN goes Down Under for ICTMM 2016

By Prof. Russ Stothard, COUNTDOWN

Efforts to control NTDs typically require advice, support and coordination from several international networks. Like tropical medicine in general, the need to bring scientists and clinicians together regularly and discuss their findings is crucial to ensure that the best research is disseminated internationally and eventually translated into optimal control strategies. The International Congress for Tropical Medicine and Malaria (ICTMM) provides such a forum.

This year the 19th ICTMM took place from 18th to 22nd September in Brisbane, Australia. This brought together just over 1,500 delegates. The meeting was jointly organised by the Australian Society for Parasitology (ASP) and the Australasian Society for Infectious Diseases (ASID). I was especially honoured to be awarded a travelling lectureship from the ASP to present and also visit research groups in Australia to instigate future collaboration. This I did by visiting the laboratories of Robin Gasser and Don McManus at the University of Melbourne and Queens Institute of Medical Research (QIMR), Brisbane. Robin and Don each have a tremendous stature in veterinary and medical parasitology, respectively. Both seamlessly blend state-of-the-art molecular studies with field studies and have had significant research programmes advancing the health and well-being of those living in the tropics.

In Melbourne, I gave a departmental seminar and was able to discuss with Robin and his team our ongoing and future work in Ghana and Cameroon. The Gasser lab has been pioneering molecular surveillance of helminth diseases for over thirty years and one of their recent milestones was made by Dr Neil Young in publishing the genome of Schistosoma haematobium.  This Nature publication was a tremendous achievement bringing new focus to the control of urogenital schistosomiasis in Africa. Better knowledge of this genome has opened up new ways to study the population biology of this parasite, often revealing how it is able to cause such ill-health across the continent. Furthermore, a precise knowledge of this genome allows us to monitor significant evolutionary changes which may occur to mitigate our efforts to control it with preventive chemotherapy.

In Brisbane, I attended the ICTMM meeting and gave a keynote presentation on schistosomiasis, reporting our recent findings in Cameroon at Barombi Kotto and Mbo, as well as, two other presentations on treatment of pre-school-aged children with intestinal schistosomiasis and management of co-infections of schistosomiasis and giardiasis. Whilst at the conference our viewpoint article in was published which was a timely reminder of how much future work is needed to expand access of praziquantel to those children currently overlooked within control programmes.

Suzy Campbell gave a presentation on the focus of her PhD studies on WASH (Water, Sanitation and Hygiene) for Soil-Transmitted Helminthiasis (STH). It was also a great honour for me to be invited to serve on the IFTM expanded board so we can look forward to 20th ICTMM in 2020 hosted by the Parasitology and Tropical Medicine Association of Thailand.

A particular highlight was learning from Don the steps that his group had taken to develop and evaluate public health education materials used for control of soil-transmitted helminthiasis in China. I recommend that you view the ‘Magic Glasses’ animation and its associated impact has been reported in the New England Journal of Medicine. More broadly, we do not have adequate nor sufficient health education materials presently for use in African schools for several other NTDs. My own previous research on schistosomiasis in Zanzibar has shown that innovative approaches are very much needed to addressing this aspect of influencing positive behavioural change.

A Focus on Schistosomiasis and Soil-Transmitted Helminthiasis in Crater Lakes in Cameroon

By Deborah Sankey, Tim Day and Faye O’Hallaron

This blog describes some of the highlights and challenges of our work with Louis-Albert Tchuem-Tchuenté in Cameroon. We were privileged to learn a great deal about the day-to-day realities and practicalities of interventions against Neglected Tropical Diseases (NTD). Our experiences generated more stories than we have time to tell, but here is a brief overview about lakes Barombi Mbo and Kotto. We hope you enjoy reading this as much as we enjoyed our work with the team there.

Having attended several planning meetings and gaining local permissions in Kumba; our first day in the field involved getting ourselves and all our equipment to our first field site – the crater lake of Barombi Mbo. Getting there was challenging and our journey involved a one -hour commute each way in local hand-paddled canoes but was set within breath-taking scenery. We arrived on the other side of the lake and walked through the surrounding cocoa farms- the most valuable commodity of the region – to the village itself. After greeting several village elders, we were taken directly to the chief’s house to discuss our work. We requested their permissions and support to help us conduct our surveys and interviews.

pic-2-with-the-whole-team

At this point the team split, half going back to the lake in search of aquatic snails and the remainder based inside the village church hall to begin collection of samples and conduct interviews by questionnaire. As the community rushed to be involved, our workload on the first day was greater than expected. We faced challenges in French-speaking situations.  Meanwhile on the lake the malacological team were working under the full might of the African sun. Wearing their armour of waders and sporting only a simple kitchen sieve (Sainsbury’s RRP £4.99) and a pair of tweezers, the intrepid team delved into the shallows in search of the miniscule molluscs.

After both teams had completed their quota of samples for the day (the importance of applied statistics for you!), we regrouped and made our way back to Kumba setting to work analysing all our samples.

Several further days were spent in Barombi Mbo following a similar pattern of work, before moving on to our second study site Barombi Kotto. At Kotto, due to its rural location, we stayed in the vicinity of the second lake for the duration of the survey. This involved a three-hour journey along mud tracks, which was tricky even when dry and almost impassable on our return visit where two vehicles had succumbed to the mud.

We set up the lab in the local health centre, and were pleased to see a modern looking lab with clean white tiles and all the mod cons, minus however running water and electricity! Each day we collected water from the local stream and we had the foresight to bring a portable generator. Using this within the health centre meant entertainment was on hand for while we worked. The surrounding children could watch DVD films in the evening and adults charge phones in the health centre while we beavered away in the laboratory until the late hours of the evening. Deborah and Faye, being women, were lucky enough to enjoy the hospitality of a local family living within their vicinity. Tim and the male staff took up residence in the abandoned maternity ward. The family welcomed us with great kindness, cooking for us excellent meals every day, and ensuring we had everything we needed, we even joined the family for morning prayers.

The days followed a similar pattern of questionnaires, sample collection, and then analysis. The main difference was that the majority of the population lived in an isolated community on an island in the middle of the Lake Kotto. Unlike the clear waters of Mbo, the lake was smaller and much less enticing. The canoes were very rickety, made of half a hollowed-out tree patched-up with cement, making for interesting journeys across the lake. This community were less accustomed to foreign visitors and our supervisor was invited to spend a night on the island. We were lucky enough to be told stories by the community elders about the village’s history. It gave us a greater insight into the local culture and traditions and just how important the water of the lake was to their community identity and beliefs.

We faced many challenges throughout our trip and were pushed to our limit physically, mentally and digestively. With team work and perseverance we achieved our goals. We learned more than we can convey.

Read more

Anyone’s Disease: Ending Lymphatic Filariasis in Ghana

A Bed Net to Rule them all: Accelerating Lymphatic Filariasis Elimination through Malaria Control Programmes