Seasonal vaccination with RTS,S/AS01 vaccine with or without seasonal malaria chemoprevention in children up to the age of 5 years in Burkina Faso and Mali: a double-blind, randomised, controlled, phase 3 trial.

Background: Seasonal vaccination with the RTS,S/AS01 vaccine combined with seasonal malaria chemoprevention (SMC) prevented malaria in young children more effectively than either intervention given alone over a 3 year period. The objective of this study was to establish whether the added protection provided by the combination could be sustained for a further 2 years.

Methods: This was a double-blind, individually randomised, controlled, non-inferiority and superiority, phase 3 trial done at two sites: the Bougouni district and neighbouring areas in Mali and Houndé district, Burkina Faso.

Impact of seasonal RTS,S/AS01 vaccination plus seasonal malaria chemoprevention on the nutritional status of children in Burkina Faso and Mali.

Background: A recent trial in Burkina Faso and Mali showed that combining seasonal RTS,S/AS01 malaria vaccination with seasonal malaria chemoprevention (SMC) substantially reduced the incidence of uncomplicated and severe malaria in young children compared to either intervention alone. Given the possible negative effect of malaria on nutrition, the study investigated whether these children also experienced lower prevalence of acute and chronic malnutrition.

Methods: In Burkina Faso and Mali 5920 children were randomized to receive either SMC alone, RTS,S/AS01 alone, or SMC combined with RTS,S/AS01 for three malaria transmission seasons (2017-2019).

The Anti-Circumsporozoite Antibody Response of Children to Seasonal Vaccination With the RTS,S/AS01E Malaria Vaccine.

Background: A trial in African children showed that combining seasonal vaccination with the RTS,S/AS01E vaccine with seasonal malaria chemoprevention reduced the incidence of uncomplicated and severe malaria compared with either intervention given alone. Here, we report on the anti-circumsporozoite antibody response to seasonal RTS,S/AS01E vaccination in children in this trial.

Methods: Sera from a randomly selected subset of children collected before and 1 month after 3 priming doses of RTS,S/AS01E and before and 1 month after 2 seasonal booster doses were tested for anti-circumsporozoite antibodies using enzyme-linked immunosorbent assay.

Seasonal Malaria Vaccination with or without Seasonal Malaria Chemoprevention.

Background: Malaria control remains a challenge in many parts of the Sahel and sub-Sahel regions of Africa.

Methods: We conducted an individually randomized, controlled trial to assess whether seasonal vaccination with RTS,S/AS01 was noninferior to chemoprevention in preventing uncomplicated malaria and whether the two interventions combined were superior to either one alone in preventing uncomplicated malaria and severe malaria-related outcomes.

Results: We randomly assigned 6861 children 5 to 17 months of age to receive sulfadoxine-pyrimethamine and amodiaquine (2287 children [chemoprevention-alone group]), RTS,S/AS01 (2288 children [vaccine-alone group]), or chemoprevention and RTS,S/AS01 (2286 children [combination group]).

Nutritional status in young children prior to the malaria transmission season in Burkina Faso and Mali, and its impact on the incidence of clinical malaria.

Background: Malaria and malnutrition remain major problems in Sahel countries, especially in young children. The direct effect of malnutrition on malaria remains poorly understood, and may have important implications for malaria control. In this study, nutritional status and the association between malnutrition and subsequent incidence of symptomatic malaria were examined in children in Burkina Faso and Mali who received either azithromycin or placebo, alongside seasonal malaria chemoprevention.

The Duration of Protection from Azithromycin Against Malaria, Acute Respiratory, Gastrointestinal, and Skin Infections When Given Alongside Seasonal Malaria Chemoprevention: Secondary Analyses of Data from a Clinical Trial in Houndé, Burkina Faso, and Bougouni, Mali.

Background: Mass drug administration (MDA) with azithromycin (AZ) is being considered as a strategy to promote child survival in sub-Saharan Africa, but the mechanism by which AZ reduces mortality is unclear. To better understand the nature and extent of protection provided by AZ, we explored the profile of protection by time since administration, using data from a household-randomized, placebo-controlled trial in Burkina Faso and Mali.

Methods: Between 2014 and 2016, 30 977 children aged 3-59 months received seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine and either AZ or placebo monthly, on 4 occasions each year.

Seasonal malaria vaccination: protocol of a phase 3 trial of seasonal vaccination with the RTS,S/AS01 vaccine, seasonal malaria chemoprevention and the combination of vaccination and chemoprevention.

Introduction: Seasonal malaria chemoprevention (SMC), with sulphadoxine-pyrimethamine plus amodiaquine (SP+AQ) is effective but does not provide complete protection against clinical malaria. The RTS,S/AS01 malaria vaccine provides a high level of protection shortly after vaccination, but this wanes rapidly. Such a vaccine could be an alternative or additive to SMC.

Evaluation of seasonal malaria chemoprevention in two areas of intense seasonal malaria transmission: Secondary analysis of a household-randomised, placebo-controlled trial in Houndé District, Burkina Faso and Bougouni District, Mali.

Background: Seasonal malaria chemoprevention (SMC) is now widely deployed in the Sahel, including several countries that are major contributors to the global burden of malaria. Consequently, it is important to understand whether SMC continues to provide a high level of protection and how SMC might be improved. SMC was evaluated using data from a large, household-randomised trial in Houndé, Burkina Faso and Bougouni, Mali.

Serotype Profile of Nasopharyngeal Isolates of Obtained from Children in Burkina Faso before and after Mass Administration of Azithromycin.

Mass drug administration (MDA) with azithromycin (AZ) has been used successfully to control trachoma. However, several studies have shown that MDA with AZ has led to the emergence of resistance to AZ in The emergence of resistance to AZ has also been observed when this antibiotic was combined with the antimalarials used for seasonal malaria chemoprevention (SMC). The development of antibiotic resistance, including resistance to AZ, is sometimes associated with the emergence of a bacterial clone that belongs to a specific serotype.

Pregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.

Background: Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection.

Methods: A systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted.

Effect of adding azithromycin to the antimalarials used for seasonal malaria chemoprevention on the nutritional status of African children.

Objectives: Mass administration of azithromycin has reduced mortality in children in sub-Saharan Africa but its mode of action is not well characterised. A recent trial found that azithromycin given alongside seasonal malaria chemoprevention was not associated with a reduction in mortality or hospital admissions in young children. We investigated the effect of azithromycin on the nutritional status of children enrolled in this study.

Evaluation of Implementation of Intermittent Screening and Treatment for Control of Malaria in Pregnancy in Jharkhand, India.

This study evaluated intermittent screening and treatment during pregnancy (ISTp) for malaria using rapid diagnostic tests (RDTs) at antenatal care (ANC) compared with passive case detection within the routine health system. The mixed-method evaluation included two cross-sectional household surveys (pre- and post-implementation of ISTp), in-depth interviews with health workers, and focus group discussions (FGDs) with pregnant women. Differences in proportions between surveys for a number of outcomes were tested; 553 and 534 current and recently pregnant women were surveyed (pre- and post-implementation, respectively).

Impact of the addition of azithromycin to antimalarials used for seasonal malaria chemoprevention on antimicrobial resistance of Streptococcus pneumoniae.

Objective: A trial was conducted in Burkina Faso and Mali to investigate whether addition of azithromycin to the antimalarials used for seasonal malaria chemoprevention reduces mortality and hospital admissions of children. We tested the sensitivity of nasal isolates of Streptococcus pneumoniae obtained during this trial to azithromycin and other antibiotics.

Methods: Azithromycin or placebo was administered monthly, in combination with the antimalarials used for seasonal malaria chemoprevention, for four months, over the annual malaria transmission seasons of 2014, 2015, and 2016.

Effectiveness of intermittent screening and treatment for the control of malaria in pregnancy: a cluster randomised trial in India.

Background: The control of malaria in pregnancy (MiP) in India relies on testing women who present with symptoms or signs suggestive of malaria. We hypothesised that intermittent screening and treatment for malaria at each antenatal care visit (ISTp) would improve on this approach and reduce the adverse effects of MiP.

Methods: A cluster randomised controlled trial comparing ISTp versus passive case detection (PCD) was conducted in Jharkhand state.

Effect of Adding Azithromycin to Seasonal Malaria Chemoprevention.

Background: Mass administration of azithromycin for trachoma control led to a sustained reduction in all-cause mortality among Ethiopian children. Whether the addition of azithromycin to the monthly sulfadoxine-pyrimethamine plus amodiaquine used for seasonal malaria chemoprevention could reduce mortality and morbidity among African children was unclear.

Methods: We randomly assigned children 3 to 59 months of age, according to household, to receive either azithromycin or placebo, together with sulfadoxine-pyrimethamine plus amodiaquine, during the annual malaria-transmission season in Burkina Faso and Mali.

Efficacy of two artemisinin-based combinations for the treatment of malaria in pregnancy in India: a randomized controlled trial.

Background: In India, the recommended first-line treatment for malaria in the second and third trimester of pregnancy is artesunate + sulfadoxine-pyrimethamine (AS+SP). However, data on safety and efficacy of artemisinin-based combination therapy (ACT) in pregnancy is limited. This study assessed the safety and efficacy of AS+SP and artesunate + mefloquine (AS+MQ) for treatment of Plasmodium falciparum in pregnancy in India.

Seasonal vaccination against malaria: a potential use for an imperfect malaria vaccine.

In many parts of the African Sahel and sub-Sahel, where malaria remains a major cause of mortality and morbidity, transmission of the infection is highly seasonal. Seasonal malaria chemoprevention (SMC), which involves administration of a full course of malaria treatment to young children at monthly intervals during the high transmission season, is proving to be an effective malaria control measure in these areas. However, SMC does not provide complete protection and it is demanding to deliver for both families and healthcare givers.

Correct dosing of artemether-lumefantrine for management of uncomplicated malaria in rural Tanzania: do facility and patient characteristics matter?

Background: Use of artemisinin-based combination therapy (ACT), such as artemether-lumefantrine (AL), requires a strict dosing schedule that follows the drugs' pharmacokinetic properties. The quality of malaria case management was assessed in two areas in rural Tanzania, to ascertain patient characteristics and facility-specific factors that influence correct dosing of AL for management of uncomplicated malaria.

Methods: Exit interviews were conducted with patients attending health facilities for initial illness consultation.

Access to artemisinin-based anti-malarial treatment and its related factors in rural Tanzania.

Background: Artemisinin-based combination treatment (ACT) has been widely adopted as one of the main malaria control strategies. However, its promise to save thousands of lives in sub-Saharan Africa depends on how effective the use of ACT is within the routine health system. The INESS platform evaluated effective coverage of ACT in several African countries.

Safety and efficacy of the 10-day melarsoprol schedule for the treatment of second stage Rhodesiense sleeping sickness.

Objective: Assessment of the safety and efficacy of a 10-day melarsoprol schedule in second stage T.b. rhodesiense patients and the effect of suramin-pretreatment on the incidence of encephalopathic syndrome (ES) during melarsoprol therapy.

Clinical presentation of T.b. rhodesiense sleeping sickness in second stage patients from Tanzania and Uganda.

Background: A wide spectrum of disease severity has been described for Human African Trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense (T.b. rhodesiense), ranging from chronic disease patterns in southern countries of East Africa to an increase in virulence towards the north.

Comparative detection of trypanosomal DNA by loop-mediated isothermal amplification and PCR from flinders technology associates cards spotted with patient blood.

We analyzed DNA eluted from FTA (Flinders Technology Associates) cards spotted with blood from human African trypanosomiasis (HAT) patients admitted at Lwala Hospital in eastern Uganda and Kaliua Health Centre in northwestern Tanzania. The aims were to evaluate loop-mediated isothermal amplification (LAMP) for detection of trypanosomal DNA in clinical samples and to characterize the infecting trypanosomes to the subspecies level. LAMP targeting the Trypanozoon conserved random inserted mobile element (RIME-LAMP) and that for the serum resistance-associated (SRA) gene (SRA-LAMP) were performed.

Reflections on clinical research in sub-Saharan Africa.

The urgent need for new, safe and sustainable interventions against diseases that disproportionally affect the poor is finally receiving global attention and the funding landscape for development projects has significantly improved during the past decade. For the development of new drug and vaccine candidates, clinical trials have become the most important tool to assess their safety and efficacy. Recently, there has been a seismic shift in the number of clinical trials conducted in resource-limited settings.