Human African Trypanosomiasis: Real Obstacles to Elimination

Abstract presented at: 5ème Congrès International de Pathologie Infectieuse et Parasitaire - en présence du Ministre de la Santé, Kinshasa, DRC, November 2009Significant progress has been made in controlling human African trypanosomiasis (HAT) caused by T.b. gambiense as evidenced by the clear decline in the number of reported cases in recent years. Now the prevailing discourse is about the possible elimination of HAT and the need to integrate treatment for it into existing health structures. However, “Hot spots” still exist and one of which is the northeastern region of Orientale Province in the Democratic Republic of Congo (DRC). In this region there is neither a monitoring system nor working health centres capable of diagnosing and treating patients.\ud An assessment carried out by the DRC’s national program to fight HAT and Doctors Without Borders/Médecins Sans Frontières (MSF) in 2004 discovered an alarming prevalence (2.1%) in the region. Between June 2007 and March 2009 MSF launched a HAT monitoring program in the Doruma, Ango, and Bili health zones. The overall prevalence was found to be 3.4%. Of the 46,601 people tested (18,559 through passive screening and 28,042 through active screening), 1,570 people were infected with T.b. gambiense. Of that group, 947 (60%) were in the first phase of HAT, indicating intense transmission of the disease. \ud Due to the acute insecurity in this region of the DRC, MSF had to suspend its projects in March 2009, even though the limits of the disease foci had not yet been reached. Moreover, the disease could spread further by the displacement of entire populations who are fleeing the insecurity and heading for areas that had been previously “cleaned” of HAT.\ud The intervention, which took place during a crisis situation, leads us to question the feasibility of eliminating HAT and integrating treatment in crisis areas where health services are at a minimum

Updated estimate of the duration of the meningo-encephalitic stage in gambiense human African trypanosomiasis

Background: The duration of the stages of HAT is an important factor in epidemiological studies and intervention planning. Previously, we published estimates of the duration of the haemo-lymphatic stage 1 and meningo-encephalitic stage 2 of the gambiense form of human African trypanosomiasis (HAT), in the absence of treatment. Here we revise the estimate of stage 2 duration, computed based on data from Uganda and South Sudan, by adjusting observed infection prevalence for incomplete case detection coverage and diagnostic inaccuracy. Findings: The revised best estimate for the mean duration of stage 2 is 252 days (95% CI 171–399), about half of our initial best estimate, giving a total mean duration of untreated gambiense HAT infection of approximately 2 years and 2 months. Conclusions: Our new estimate provides improved information on the transmission dynamics of this neglected tropical disease in Uganda and South Sudan. We stress that there remains considerable variability around the estimated mean values, and that one must be cautious in applying these results to other foci

The chronification of post-COVID condition associated with neurocognitive symptoms, functional impairment and increased healthcare utilization.

Post-COVID condition is prevalent in 10-35% of cases in outpatient settings, however a stratification of the duration and severity of symptoms is still lacking, adding to the complexity and heterogeneity of the definition of post-COVID condition and its oucomes. In addition, the potential impacts of a longer duration of disease are not yet clear, along with which risk factors are associated with a chronification of symptoms beyond the initial 12 weeks. In this study, follow-up was conducted at 7 and 15 months after testing at the outpatient SARS-CoV-2 testing center of the Geneva University Hospitals. The chronification of symptoms was defined as the continuous presence of symptoms at each evaluation timepoint (7 and 15 months). Adjusted estimates of healthcare utilization, treatment, functional impairment and quality of life were calculated. Logistic regression models were used to evaluate the associations between the chronification of symptoms and predictors. Overall 1383 participants were included, with a mean age of 44.3 years, standard deviation (SD) 13.4 years, 61.4% were women and 54.5% did not have any comorbidities. Out of SARS-CoV-2 positive participants (n = 767), 37.0% still had symptoms 7 months after their test of which 47.9% had a resolution of symptoms at the second follow-up (15 months after the infection), and 52.1% had persistent symptoms and were considered to have a chronification of their post-COVID condition. Individuals with a chronification of symptoms had an increased utilization of healthcare resources, more recourse to treatment, more functional impairment, and a poorer quality of life. Having several symptoms at testing and difficulty concentrating at 7 months were associated with a chronification of symptoms. COVID-19 patients develop post-COVID condition to varying degrees and duration. Individuals with a chronification of symptoms experience a long-term impact on their health status, functional capacity and quality of life, requiring a special attention, more involved care and early on identification considering the associated predictors

Clinical epidemiology, diagnosis and treatment of visceral leishmaniasis in the Pokot endemic area of Uganda and Kenya.

Between 2000 and 2010, Médecins Sans Frontières diagnosed and treated 4,831 patients with visceral leishmaniasis (VL) in the Pokot region straddling the border between Uganda and Kenya. A retrospective analysis of routinely collected clinical data showed no marked seasonal or annual fluctuations. Males between 5 and 14 years of age were the most affected group. Marked splenomegaly and anemia were striking features. An rK39 antigen-based rapid diagnostic test was evaluated and found sufficiently accurate to replace the direct agglutination test and spleen aspiration as the first-line diagnostic procedure. The case-fatality rate with sodium stibogluconate as first-line treatment was low. The VL relapses were rare and often diagnosed more than 6 months post-treatment. Post-kala-azar dermal leishmaniasis was rare but likely to be underdiagnosed. The epidemiological and clinical features of VL in the Pokot area differed markedly from VL in Sudan, the main endemic focus in Africa

Updated estimate of the duration of the meningo-encephalitic stage in gambiense human African trypanosomiasis.

BACKGROUND: The duration of the stages of HAT is an important factor in epidemiological studies and intervention planning. Previously, we published estimates of the duration of the haemo-lymphatic stage 1 and meningo-encephalitic stage 2 of the gambiense form of human African trypanosomiasis (HAT), in the absence of treatment. Here we revise the estimate of stage 2 duration, computed based on data from Uganda and South Sudan, by adjusting observed infection prevalence for incomplete case detection coverage and diagnostic inaccuracy. FINDINGS: The revised best estimate for the mean duration of stage 2 is 252 days (95% CI 171-399), about half of our initial best estimate, giving a total mean duration of untreated gambiense HAT infection of approximately 2 years and 2 months. CONCLUSIONS: Our new estimate provides improved information on the transmission dynamics of this neglected tropical disease in Uganda and South Sudan. We stress that there remains considerable variability around the estimated mean values, and that one must be cautious in applying these results to other foci

Eflornithine Is Safer than Melarsoprol for the Treatment of Second-Stage Trypanosoma brucei gambiense Human African Trypanosomiasis

Patients with second-stage human African trypanosomiasis treated with eflornithine (n = 251) in 2003 in Kiri, southern Sudan, had an adjusted relative risk of death of 0.2 and experienced significantly fewer cutaneous and neurological adverse effects than did patients who were treated with melarsoprol in 2001 and 2002 (n = 708

Tolerance and Safety of Nifurtimox in Patients with Chronic Chagas Disease

Background. Nifurtimox has been used to treat Chagas disease for 40 years, but tolerance and safety data in adults are scarce. We aimed to evaluate nifurtimox tolerance and safety in a cohort of Trypanosoma cruzi-infected adult patients in a country of nonendemicity. Methods. This observational study included all consecutive adults patients who were given a diagnosis of T. cruzi infection from June through December 2008. Eligible patients received nifurtimox at 10 mg/kg/day for 60 days, with regular medical and biological follow-up. Adverse events (AEs) were recorded according to Common Terminology Criteria for Adverse Events, version 3.0. Results. Eighty-one patients received nifurtimox. Eight were lost to follow-up during treatment, and 41 (56.2%) completed the 60-day course. All premature treatment terminations were caused by AEs; 97.5% of patients suffered from AEs, mostly expected (90.5%) and not severe. Gastrointestinal symptoms predominated. Six (7.4%) patients presented with a suspected unexpected serious adverse reaction: drug reaction with eosinophilia and systemic symptoms (n = 3), Quincke edema (n = 1), acute myocarditis (n = 1), and anaphylaxis (n = 1). Patients with 3 or more AEs had an increased risk of premature treatment termination (hazard ratio, 8.42; 95% confidence interval, 1.6-45.5). Conclusion. Nifurtimox is poorly tolerated among adults with chronic Chagas disease, resulting in a low treatment completion rate. Considering the significant risk of serious AEs, close monitoring is required, which may be difficult to implement in poor rural areas of countries of endemicity. The safety and efficacy of nifurtimox and benznidazole should be compared to improve current therapeutic recommendations, and pharmacovigilance systems should be enhance

Estimates of the duration of the early and late stage of gambiense sleeping sickness.

BACKGROUND: The durations of untreated stage 1 (early stage, haemo-lymphatic) and stage 2 (late stage, meningo-encephalitic) human African trypanosomiasis (sleeping sickness) due to Trypanosoma brucei gambiense are poorly quantified, but key to predicting the impact of screening on transmission. Here, we outline a method to estimate these parameters. METHODS: We first model the duration of stage 1 through survival analysis of untreated serological suspects detected during Médecins Sans Frontières interventions in Uganda and Sudan. We then deduce the duration of stage 2 based on the stage 1 to stage 2 ratio observed during active case detection in villages within the same sites. RESULTS: Survival in stage 1 appears to decay exponentially (daily rate = 0.0019; mean stage 1 duration = 526 days [95%CI 357 to 833]), possibly explaining past reports of abnormally long duration. Assuming epidemiological equilibrium, we estimate a similar duration of stage 2 (500 days [95%CI 345 to 769]), for a total of nearly three years in the absence of treatment. CONCLUSION: Robust estimates of these basic epidemiological parameters are essential to formulating a quantitative understanding of sleeping sickness dynamics, and will facilitate the evaluation of different possible control strategies.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Global health partnerships in the time of COVID-19: redefining the way we work

# Background The emergence of COVID-19 disrupted several global health partnerships, with people unable to travel, meetings and conferences cancelled, and many forced to work remotely. The aim of this study was to explore the impact of COVID-19 on global health partnerships learning from the activities of the Division of Tropical and Humanitarian Medicine (DTHM) at the Geneva University Hospitals (HUG). # Methods Five members of the DTHM team as well as five local partners from ongoing projects within the DTHM in Bosnia-Herzegovina, Kyrgyzstan, Nepal, Peru and Ukraine were interviewed. A qualitative approach was chosen employing an interpretive approach using Grounded Theory involving the application of inductive reasoning for the analysis. # Results Interviewees describe both positive and negative impacts of COVID-19 for the existing partnerships. The use of on-site visits was disrupted and replaced by extra remote monitoring. Digital tools enabled the continuity of interactions ensuring that the partnership could continue to operate. Online tools allowed access to a wider audience and advantages with regards to time, cost and the environment. However, going online was unable to fully replace human interactions and exchanges which are core components of any partnership. # Conclusions COVID-19 resulted in the DTHM and its partners needing to redefine and improve how partnerships were established and maintained. This change in how partnerships operated and adapted during the pandemic will require ongoing assessment to see the long-term impact of these changes in the ways partnerships function in a post-COVID-19 environment