Treatment options for visceral leishmaniasis (VL) in East Africa are far from satisfactory due to cost, toxicity, prolonged treatment duration or emergence of parasite resistance. Hence there is a need to explore alternative treatment protocols such as miltefosine alone or in combinations including miltefosine, sodium stibogluconate (SSG) or liposomal amphotericin B. The aim of this trial is to identify regimen(s) which are sufficiently promising for future trials in East Africa.

Trachoma has been endemic in The Gambia for decades. National trachoma control activities have been in place since the mid-1980's, but with no mass antibiotic treatment campaign. We aimed to assess the prevalence of active trachoma and of actual ocular Chlamydia trachomatis infection as measured by polymerase chain reaction (PCR) in the two Gambian regions that had had the highest prevalence of trachoma in the last national survey in 1996 prior to planned national mass antibiotic treatment distribution in 2006.

Mycobacterium tuberculosis (M. tuberculosis) produces a diverse range of antigenic proteins in its dormant phase. The cytokine profiles of CD4+ T cell responses, especially subsets other than Th1 type (non-Th1 type), against these latency-associated M. tuberculosis antigens such as α-crystallin (Acr), heparin-binding hemagglutinin (HBHA), and mycobacterial DNA-binding protein 1 (MDP-1) remain elusive in relation to the clinical stage of M. tuberculosis infection. In the present study, peripheral blood mononuclear cells (PBMCs) collected from different stages of M. tuberculosis-infected cases and control PBMCs were stimulated with these antigens and ESAT-6/CFP-10. Cytokine profiles of CD4+ T cells were evaluated by intracellular cytokine staining using multicolor flow cytometry. Our results demonstrate that Th1 cytokine responses were predominant after TB onset independent of the type of antigen stimulation. On the contrary, non-Th1 cytokine responses were preferentially induced by latency-associated M. tuberculosis antigens, specifically IL-10 response against Acr in latent M. tuberculosis infection. From these results, we surmise a shift in the CD4+ T cell response from mixed non-Th1 to Th1 dominant type during TB progression.

Since the approval of medical abortion in Cambodia in 2010, the proportion of women reporting an abortion has increased. We describe the characteristics and contraceptive outcomes of women seeking medical abortion compared to surgical abortion at four reproductive health clinics in Cambodia.

Bubonic plague is the primary manifestation of infection with Yersinia pestis, accounting for 90% of all plague cases and with 75% of global cases reported in Madagascar. All drugs in use for treating plague are registered based on experimental data and anecdotal evidence, and no regimen currently recommended is supported by a randomized clinical trial. The IMASOY trial intends to fill this knowledge gap by comparing two 10-day regimens included in the national guidelines in Madagascar. The primary objective of the trial is to test the hypothesis that ciprofloxacin monotherapy is non-inferior to streptomycin followed by ciprofloxacin for the treatment of bubonic plague, thus avoiding the need for injectable, potentially toxic, aminoglycosides.

Mass drug administration (MDA) treatment of active trachoma with antibiotic is recommended to be initiated in any district where the prevalence of trachoma inflammation, follicular (TF) is ≥ 10% in children aged 1-9 years, and then to continue for at least three annual rounds before resurvey. In The Gambia the PRET study found that discontinuing MDA based on testing a sample of children for ocular Chlamydia trachomatis(Ct) infection after one MDA round had similar effects to continuing MDA for three rounds. Moreover, one round of MDA reduced disease below the 5% TF threshold. We compared the costs of examining a sample of children for TF, and of testing them for Ct, with those of MDA rounds.

A recent study has shown that treatment of visceral leishmaniasis (VL) with the standard dose of 15 mg/kg/day of paromomycin sulphate (PM) for 21 days was not efficacious in patients in Sudan. We therefore decided to test the efficacy of paramomycin for a longer treatment duration (15 mg/kg/day for 28 days) and at the higher dose of 20 mg/kg/day for 21 days.

AmBisome® is an efficacious, safe anti-leishmanial treatment. There is growing interest in its use, either as a single dose or in combination treatments. In East Africa, the minimum optimal single-dosage has not been identified.

Anti-leishmanial drug regimens that include a single dose AmBisome could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown.

The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.

There is concern that untreated individuals in mass drug administration (MDA) programs for neglected tropical diseases can reduce the impact of elimination efforts by maintaining a source of transmission and re-infection.

Alternative treatments for visceral leishmaniasis (VL) are required in East Africa. Paromomycin sulphate (PM) has been shown to be efficacious for VL treatment in India.

Among the many collaterals of the COVID-19 pandemic is the disruption of health services and vital clinical research. COVID-19 has magnified the challenges faced in research and threatens to slow research for urgently needed therapeutics for Neglected Tropical Diseases (NTDs) and diseases affecting the most vulnerable populations. Here we explore the impact of the pandemic on a clinical trial for plague therapeutics and strategies that have been considered to ensure research efforts continue.

Although the burden of diphtheria has declined greatly since the introduction of vaccines, sporadic outbreaks continue to be reported. WHO recommends booster doses after a primary series, but questions remain about the optimal interval between these doses. We conducted a systematic review and quantitative data analysis to quantify the duration of protective immunity after different numbers of doses. Fifteen cross-sectional seroprevalence studies provided data on geometric mean concentration (GMC). Single-year age-stratified GMCs were analyzed using a mixed-effect linear regression model with a random intercept incorporating the between-country variability. GMC was estimated to decline to 0.1 IU/ml in 2.5 years (95% CI: 0.9-4.0), 10.3 years (95% CI: 7.1-13.6), and 25.1 years (95% CI: 7.6-42.6) after receiving three, four and five doses, respectively. The results drawn from cross-sectional data collected in countries with different epidemiologies, vaccines, and schedules had several limitations. However, these analyses contribute to the discussion of optimal timing between booster doses of diphtheria toxoid-containing vaccine.

Trachoma, caused by ocular Chlamydia trachomatis infection, is the leading infectious cause of blindness, but its prevalence is now falling in many countries. As the prevalence falls, an increasing proportion of individuals with clinical signs of follicular trachoma (TF) is not infected with C. trachomatis. A recent study in Tanzania suggested that other bacteria may play a role in the persistence of these clinical signs.

Blinding trachoma, caused by ocular infection with Chlamydia trachomatis, is targeted for global elimination by 2020. Knowledge of risk factors can help target control interventions.

With user fees now seen as a major hindrance to universal health coverage, many countries have introduced fee reduction or elimination policies, but there is growing evidence that adherence to reduced fees is often highly imperfect. In 2004, Kenya adopted a reduced and uniform user fee policy providing fee exemptions to many groups. We present data on user fee implementation, revenue and expenditure from a nationally representative survey of Kenyan primary health facilities. Data were collected from 248 randomly selected public health centres and dispensaries in 2010, comprising an interview with the health worker in charge, exit interviews with curative outpatients, and a financial record review. Adherence to user fee policy was assessed for eight tracer conditions based on health worker reports, and patients were asked about actual amounts paid. No facilities adhered fully to the user fee policy across all eight tracers, with adherence ranging from 62.2% for an adult with tuberculosis to 4.2% for an adult with malaria. Three quarters of exit interviewees had paid some fees, with a median payment of US dollars (USD) 0.39, and a quarter of interviewees were required to purchase additional medical supplies at a later stage from a private drug retailer. No consistent pattern of association was identified between facility characteristics and policy adherence. User fee revenues accounted for almost all facility cash income, with average revenue of USD 683 per facility per year. Fee revenue was mainly used to cover support staff, non-drug supplies and travel allowances. Adherence to user fee policy was very low, leading to concerns about the impact on access and the financial burden on households. However, the potential to ensure adherence was constrained by the facilities' need for revenue to cover basic operating costs, highlighting the need for alternative funding strategies for peripheral health facilities.

Mass drug administration (MDA) with azithromycin, carried out for the control of blinding trachoma, has been linked to reduced mortality in children. While the mechanism behind this reduction is unclear, it may be due, in part, to improved nutritional status via a potential reduction in the community burden of infectious disease. To determine whether MDA with azithromycin improves anthropometric indices at the community level, we measured the heights and weights of children aged 1 to 4 years in communities where one (single MDA arm) or three annual rounds (annual MDA arm) of azithromycin had been distributed.

Visceral leishmaniasis (VL) in human immunodeficiency virus (HIV) co-infected patients requires special case management. AmBisome monotherapy at 40 mg/kg is recommended by the World Health Organization. The objective of the study was to assess if a combination of a lower dose of AmBisome with miltefosine would show acceptable efficacy at the end of treatment.

Equitable access to health care is a key health systems goal, and is a particular concern in low-income countries. In Kenya, public facilities are an important resource for the poor, but little is known on the equity of service provision. This paper assesses whether poorer areas have poorer health services by investigating associations between public facility characteristics and the poverty level of the area in which the facility is located.