Early June, Mali enrolled its first patient in the ANTICOV clinical trial, a pan-African collaborative scientific study whose objective is to find treatments that can prevent mild-to-moderate COVID-19 cases from becoming severe.

Dr Samba SowThe Principal Investigator of the ANTICOV trial in Mali is Dr Samba Sow. He is a medical doctor, epidemiologist and Director of the Centre pour les Vaccins en Développement (CVD-Mali) du Ministère de la Santé du Mali, a public organization doing research and training on infectious diseases.

Dr Sow is a widely-recognized public health authority in the region: he was Minister of Health and Public Hygiene for Mali from 2017 to 2019 and was appointed in 2020 WHO Special envoy for COVID-19 in West Africa.

Dr Sow, what is the impact of the COVID-19 pandemic in Mali right now, in June 2021?

It is having a huge impact, not only in our daily lives but also on the delivery of primary care and on our healthcare system – which were already under major stress. We were not ready for such an emergency. Key health care activities such as maternal and child health, prenatal visits, childbirth, etc., delivery of treatments for tuberculosis, HIV, leprosy, malaria, or national programmes such as the one against blindness have been disrupted.

The repercussions on public health will be frightening and I am very worried for the future. To rebuild our healthcare system, it will require lots of time, efforts, energy, and collaborations.

I am also concerned by the attitude of many Malians, who seem to think that since vaccines now exist, the pandemic is over. The exact contrary is happening – it is getting worse. An aggravating factor is that our screening and pandemic surveillance activities are not working properly, which means we have trouble to evaluate the epidemiological situation.

What should be Mali’s answer to this massive public health crisis?

We need to open as many collaborations as possible. In the global fight against infectious diseases, a country can never go alone. Even a continent cannot go alone. The answer should be global. This is why ANTICOV is so important.

Even the most remote places, from every corner of the world, must join this global effort as early as possible, from the research phase, to become part of the solution. This is what my own country, Mali, must do.

We can see that vaccine research, for example, started in countries with high incomes and that this effort converted very fast into public health responses. The more deeply a country is involved in medical research, the easier it is to rapidly develop a response – because the results from this research are informing recommendations, policies, and public health decisions. If you do not conduct research from the start, you end up at the back of the queue. This is why Mali joined ANTICOV.

Could you explain your role in the ANTICOV trial?

I am the principal investigator, which means I am in charge of following, coordinating, and supervising all scientific, technical, administrative, and communication activities of the trial. A principal investigator is a linchpin of the trial and must spend a lot of time on the field, to work with his team and talk to the communities. A principal investigator cannot do anything without a strong team, and I am lucky to have one! Approximately 40 people are working directly on the ANTICOV trial in Mali.

‘In the global fight against infectious diseases, a country can never go alone. The answer should be global. This is why ANTICOV is so important.’

Dr Samba Sow

What are your expectations for the trial?

It is critical that ANTICOV succeeds. A success will be crucial for Mali and for all Africa – not only for the 13 participating countries.

ANTICOV’s objective is to find treatments for mild to moderate cases of COVID. These  are the most frequent cases we are seeing, and they are fuelling most community transmission. The number of beds in intensive care units in Mali is very limited, which means we must cure patients before their symptoms become severe. This is why this study is important.

Today, when we are talking treatments or vaccines, Africa is not in a good position. It is very important that Africans and African research organizations join the global effort to conduct trials.

How you do gain trust with your communities, to ensure that they will participate in the trial?

This is a very important question.  Without communities’ trust and support, even with the best study protocol of the world, you will go nowhere.

Fortunately, at the CVD-Mali, we are working closely and very early on with communities: we discuss with them the trial protocols as soon as they are approved. In every village, neighbourhood, or ‘commune’ we meet with representatives such as traditional or religious leaders, presidents of cultural, youth or women associations, etc.

Sometimes, during those meetings, people express doubts and have difficult questions. So we open our labs to them, we show them what we do with the samples we collected, we explain them the drugs we will distribute. These are truly transparency operations.

This is how we can convince communities that they will be the first to benefit from the research we do with them.

Photo credit: Kenny Mbala-DNDi, CVD-Mali

On Friday 18 June, the first Kenyan patient was enrolled in the ANTICOV clinical trial. Kenya is the 5th country after the Republic of Guinea, the Democratic Republic of Congo, Mali and Ghana to start this large pan-African, collaborative scientific study whose objective is to identify treatments for mild to moderate cases of COVID-19.

The Principal Investigator supervising the trial in Kenya is Dr Bernhards Ogutu. He is a trained paediatrician, clinical pharmacologist, Chief Research Officer at the Kenya Medical Research Institute (KEMRI) and Director of the Centre for Research in Therapeutic Sciences (CREATES) at Strathmore University, Nairobi.

Dr Ogutu, how is the COVID-19 situation in Kenya today?

I am worried. Hospitals have been observing more admissions than previously, with a number of people with severe disease coming in. The test positivity rate still remains high and is averaging 10%. But schools and parts of the economy have reopened, and we don’t know how the situation will pan out.

Despite this worrying trend, it is still difficult to convince people to adopt appropriate precautionary measures. Initially, when the first wave hit, people were a bit scared, and they listened when the first prevention measures were put in place. But now, some people feel they are safe since a few have been vaccinated; other still believe that only urban areas are affected and they are not at risk in rural areas – which is not true.

The vaccination situation is not good: we have only limited doses and the supplies are not forthcoming.  We need much more.

We need to continue looking for other health tools, in particular treatments to cure patients already infected with COVID-19.

This is why the ANTICOV clinical trial is so important.

Could you explain your role in the trial?

I am leading the ANTICOV study in Kenya. I need to ensure all the stakeholders are engaged and that all the questions the communities might have are answered. It is very important to explain to the public why we need ANTICOV right now, even though vaccines are coming.

ANTICOV researchers are focusing their efforts on mild to moderate cases, to find treatments that could prevent them from becoming severe. This is closer to prevention, because treating mild cases early can be much cheaper and effective than treating severe cases later. And it could save lives, especially in environments with limited ICU capacities.

‘A positive or a negative result from the trial will go a long way in shaping the policies of how COVID-19 is managed on the continent.’

Dr Bernhards Ogutu

What are your expectations for the ANTICOV trial?

There are many, but the main one is that ANTICOV will generate data to inform national guidelines. I sit on the National Task Force for COVID-19, and we are looking at a number of ways to treat patients. Unfortunately, we have no clear data on what treatment works for mild to moderate cases.

That is why we need to generate this data to inform the governments and the Ministries of Health on what really works and what does not, so they can make the appropriate decisions and adopt the right guidelines for their populations.

This is critical. A positive or a negative result from the trial will go a long way in shaping the policies of how COVID-19 is managed on the continent.

What will you do to gain trust with communities?

We are maintaining close contact with the communities especially in the region where the study is being carried out. We have been discussing the study with community leaders and we are ready. We also share transparently with the media all the information about ANTICOV to prevent any negative reaction. We have been explaining that we need to generate scientific data to know what drugs work for us, and that we do this for the public good.

People are more receptive because everybody knows somebody who suffered or died from COVID-19. A few sceptics still remain, but the majority are ready to listen. We had a number of appearances with media and televisions, some people wrote opeds, to make sure the communities understand the disease.

We will also explain to each participating patient to the trial that we are looking for a treatment that is tailored to their needs and that will work in their communities. It is crucial to detail the rigorous system that has been put in place to review the results and to ensure that the research we do is ethical, appropriate, and done well. This robust system of review and evaluation ensures that no one can do anything that would harm the population.

I think such sustained and positive communication is going to be key to build and maintain the trust of communities.

Any last words?

First, I would like to highlight the fact that this is the first time we are using an adaptive design as a platform for a large-scale clinical study in Kenya. Analysing the outcomes will be very interesting to evaluate how this new type of study design can be useful and can accelerate the development of knowledge. If it goes well, the findings of ANTICOV will be a very important milestone in the framework of clinical trials and in managing future pandemics.

Finally, this study shows that even in a pandemic, the global community can come together at short notice, set up a platform in a framework that is cost-effective, and develop and evaluate medicines for a new disease, in less than a year. This could create a new way of looking at how we can develop medicines for these urgent situations.

Photo credit: KEMRI, DNDi

Last Friday evening, listeners of one of France’s most venerable radio stations were treated to an hour-long tribute to the Congolese and international researchers that have dedicated their lives to ending sleeping sickness.

Veteran health reporter Tara Schlegel from France Culture accompanied our NTD Director Dr Nathalie Strub-Wourgaft to the Democratic Republic of Congo (DRC) to witness how the first all-oral treatment for sleeping sickness, fexinidazole, is being rolled out in the country. Her trip, from the capital Kinshasa to a remote rural hospital, was also a trip down Congo’s tumultuous past, where outbreaks of this deadly parasitic disease have ebbed and flowed over time.

Now, as Tara explains, we are finally on the verge of potentially eliminating this disease. The documentary is available in its entirety here.

France Culture is a well-known public radio and news outlet that has built an excellent reputation by broadcasting detailed and well-researched stories on important yet-sometimes overlooked topics. Topics such as neglected diseases. ‘Patients often have no political clout. Affected communities cannot afford treatment and are therefore of little interest to clinical research’, Tara writes in her account of the trip.

Tara landed in Kinshasa on April 11 and started by visiting our DRC regional office, a ‘pretty white house’, with a ‘hand-painted logo’ on the wall, surrounded by ‘blue lizards with red head and tails’, and a ‘large red iron gate; that the driver needs to honk at in order to open’. There she met Dr Wilfried Mutombo Kalonji, our Sleeping Sickness Trial Coordinator, whom she described in colorful terms: ‘a rugby physique, a love of French songs, and a passion for the political history of the Congo and the struggle for independence.’

The DNDi Regional Office in Kinshasa – Photo credit: T.S. – Radio France

Dr Wilfried helped Tara understand the nightmare reputation that sleeping sickness has in his country. Speaking with Tara, he said ‘Some sleep all day. Some have problems with language, behavior, walking. Some also become very aggressive, one spat on my face, another hit the nurse. But I’m not angry: this is because of the disease. They are my friends.‘ If left untreated, patients with sleeping sickness will die.

Dr Wilfried

She also met the legendary Dr Victor Kande: who has devoted his entire career to the fight against sleeping sickness. He described how patients were treated with melarsoprol, the only treatment available to physicians at the time. Derived from arsenic, melarsoprol is so toxic it killed one in 20 patients:  ‘At that time we had up to ten or twenty thousand patients… can you imagine when 5% of them died?

Tara then accompanied Dr Nathalie, DNDi’s DRC Head of Office Chirac Bulanga Milemba, and Dr Wilfried to Bandundu province, one of the regions most affected by sleeping sickness. The team visited the hospital in Baundundu city,  where DNDi, Sanofi, and various international and Congolese partners carried crucial clinical trials to develop fexinidazole, the simple oral pill that is revolutionizing the treatment of the disease.

Fexinidazole tablet

Near the village of Mushie, Tara met a mobile screening unit – these health workers travel deep into the most remote areas of the DRC to test entire villages for sleeping sickness. ‘This is a very difficult job,’  explained Alexandre Mbukatoto, the unit head. ‘Each month we spend 20 days far from our family and our children, always on the road. Some of us got divorced. The roads are not in good condition, we usually sleep in a villager’s house, or a class room, or a church.‘ But this job is crucial : this screening is necessary to eliminate the last reservoirs of the disease.

Reporter interviewing healthcare worker
Tara Schlegel interviewing Alexandre Mbukatoto

As Dr Nathalie explains in the documentary, ‘the journey from a promising drug candidate to obtaining the authorization to commercialize it took almost ten years.’ And our partnerships are going ever further, as we are developing acoziborole, a new, single-dose, easy to administer pill that holds tremendous promises.

If you speak French – or are learning – please discover more about this fantastic journey by listening to this fabulous audio-documentary.

Photo credit: Nathalie Strub-Wourgaft-DNDi, T.S. – Radio France, Sandrine Francine Ngalula-DNDi

by da Silva RA, Wanderley DMV, Forsyth C, Leite RM, Luna EJdA, Carneiro JN, Shikanai-Yasuda MA. Revista do Instituto de Medicina Tropical de São Paulo 2020; 62: e39. doi: 10.1590/s1678-9946202062039.

Summary: In this study, the authors describe the socioeconomic characteristics of Bolivian immigrants in Sao Paulo, their knowledge of Chagas disease, and the implications for access to health care. Using a structured questionnaire with 472 adults, the authors found that levels of familiarity with Chagas disease were low in this population. Raising awareness of the disease through specific communication strategies should be an essential component of public health programmes to reduce the burden of Chagas disease in this and other vulnerable populations.

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by da Rocha Siriano L, Marchiol A, Pereira Certo M, Cubides J-C, Forsyth C, Augusto de Sousa F. Tropical Medicine and Infectious Disease 2020, 5:92. doi: 10.3390/tropicalmed5020092.

Summary: The lack of public health measures aimed at the epidemiological surveillance of chronic Chagas cases constitutes a significant barrier for patients to access appropriate diagnosis, management, and follow-up, and hampers the planning of necessary activities within health systems. The authors present the design and implementation process for a policy for compulsory notification of chronic Chagas disease in the Brazilian state of Goiás. This notification policy allows authorities to determine the real magnitude of Chagas disease in the population, so that an appropriate public health response can be mounted to meet the needs of affected people, thereby ending the epidemiological silence of Chagas disease.

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by Alcântara LM, Ferreira TCS, Fontana V, Chatelain E, Moraes CB, Freitas-Junior LH. Molecules 2020, 25(11): 2551. doi: 10.3390/molecules25112551.

Summary: Development of broad-spectrum antileishmanial drugs is challenging due to the high genetic and phenotypic variability of the parasite. Screening panels consisting of several diverse Leishmania species can be useful for prioritizing compounds based on their spectrum of activity. The authors developed a robust and reproducible high content assay and screened 1280 small molecules against L. amazonensis, L. braziliensis, and L. donovani. The results highlight the reduced number of compound classes with pan-leishmanial activity that might be available from diversity libraries, emphasizing the need to screen active compounds against a panel of species and strains. This assay may be adapted to virtually any Leishmania species in order to facilitate the discovery of broad spectrum anti-leishmanial agents.

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by Eberhardt E, Hendrickx R, Van den Kerkhof M, Monnerat S, Alves F, Hendrickx S, Maesa L, Caljona G. Journal of Microbiological Methods 2020, 173:105935. doi: 10.1016/j.mimet.2020.105935

Summary: Molecular detection techniques using peripheral blood are preferred over invasive tissue aspiration for the diagnosis and post-treatment follow-up of visceral leishmaniasis patients. The authors compared the stabilizing capacities of six different commercially available reagents to prevent DNA and RNA degradation during storage and transport to specialized laboratories where molecular diagnosis is performed. The recommended stabilizing reagents are compatible with RNA- and DNA-based Leishmania detection in peripheral blood in a visceral leishmaniasis hamster model and spiked human blood. The findings of this study may be applied to human visceral leishmaniasis clinical studies, facilitating the use of less invasive molecular detection techniques.

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by Adriaensen W, Cuypers B, Cordero CF, Mengasha B, Blesson S, Cnops L, Kaye PM, Alves F, Diro E, van Griensven J. EBioMedicine 2020, 55: 102748. doi: 10.1016/j.ebiom.2020.102748

Summary: Visceral leishmaniasis treatment in HIV patients often fails, resulting in extended treatment time followed by high relapse and case-fatality rates. It is essential to assess treatment efficacy, but this currently involves repeated invasive and painful aspiration from infected organs. In order to develop a less invasive alternative, the authors studied changes in the whole blood transcriptional profile of VL-HIV patients during treatment. They identified a simple blood-based signature that could accurately discriminate treatment outcome. This signature holds significant promise for the facilitation of treatment efficacy monitoring in R&D and could provide an alternative test-of-cure to guide patient management in VL-HIV patients.

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by Abeijon C, Alves F, Monnerat S, Mbui J, Viana AG, Almeida RM, Bueno LL, Fujiwara RT, Campos-Neto A. PLOS Neglected Tropical Diseases 2020, 14(4): e0008246. doi: 10.1371/journal.pntd.0008246

Summary: There is still a need for a simple, non-expensive, sensitive, and specific test for visceral leishmaniasis that can be used both for accurate diagnosis and to monitor treatment efficacy. The authors describe a new test that can circumvent most of the drawbacks of existing approaches. It detects six leishmanial proteins or biomarkers that are eliminated in the urine of patients with visceral leishmaniasis. An initial clinical validation demonstrated that the test has a sensitivity of ≥93% and specificity of 100%. This new and accurate monoclonal antibody-based multiplexed assay could be a useful resource to diagnose most clinical forms and/or the severity of the disease. The test is ready for upscaling and validation for clinical use.

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by Molina R, Jiménez M, García-Martínez J, San Martín JV, Carrillo E, Sánchez C, Moreno J, Alvar JPLOS Neglected Tropical Diseases 2020, 14(4): e0008253. doi: 10.1371/journal.pntd.0008253

Summary: Visceral leishmaniasis is caused by Leishmania infantum in the Mediterranean region, with dog as the primary domestic reservoir. In this study, the authors investigate the role of the human host in disease transmission. They conclude that infected asymptomatic individuals and immunocompetent patients treated for visceral leishmaniasis have no epidemiological impact on the transmission of Linfantum. The impact of immunocompetent patients with untreated active visceral leishmaniasis is limited, whilst immunosuppressed patients are the most infectious towards the sand fly vector. The authors recommend screening for latent Leishmania infection in HIV-infected patients in scenarios where transmission occurs.

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