Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.

BACKGROUND: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).

Demography, maternal health and the epidemiology of malaria and other major infectious diseases in the rural department Tsamba-Magotsi, Ngounie Province, in central African Gabon.

BACKGROUND: Sub-Saharan Africa is undergoing an epidemiological transition from a predominance of infectious diseases to non-communicable and lifestyle related conditions. However, the pace of this transition and the pattern of disease epidemiology are uneven between affluent urban and rural poor populations. To address this question for a remote rural region located in the central African rainforest region of Gabon, this study was conducted to assess reasons for health care attendance and to characterize the epidemiology of malaria and other major infectious diseases for the department of Tsamba Magotsi. METHODS: Major causes for health care attendance were collected from local hospital records. Cross sectional population based surveys were performed for the assessment of local malaria epidemiology. Pregnant women attending antenatal care services were surveyed as a sentinel population for the characterization of chronic viral and parasitic infections in the community. RESULTS: Infectious diseases were responsible for 71% (7469) of a total of 10,580 consultations at the formal health care sector in 2010. Overall, malaria - defined by clinical syndrome - remained the most frequent cause for health care attendance. A cross sectional malaria survey in 840 asymptomatic individuals residing in Tsamba Magotsi resulted in a Plasmodium spp. infection prevalence of 37%. The infection rate in 2-10 year old asymptomatic children - a standard measure for malaria endemicity - was 46% (100 of 217) with P. falciparum as predominant species (79%). Infection with other plasmodial species (P. ovale and P. malariae) presented most commonly as coinfections (23.2%). Prevalence of HIV, HBV, and syphilis were 6.2, 7.3, and 2.5%, respectively, in cross-sectional assessments of antenatal care visits of pregnant women. Urogenital schistosomiasis and the filarial pathogens Loa loa and Mansonella perstans are highly prevalent chronic parasitic infections affecting the local population. CONCLUSIONS: Despite major improvements in the accessibility of Tsamba Magotsi over the past decade the epidemiological transition does not appear to have majorly changed on the spectrum of diseases in this rural Gabonese population. The high prevalence of Plasmodium infection indicates a high burden of malaria related morbidity. Infectious diseases remain one of the most important health issues and further research activities in the field of tropical medicine and infectious diseases could help improve health care for the local population.

HIV-exposed uninfected compared with unexposed infants show the presence of leucocytes, lower lactoferrin levels and antimicrobial-resistant micro-organisms in the stool.

Background: HIV-exposed uninfected (HEU)-infants have been shown to be particularly vulnerable to infections. In this population, disturbance of the gut micro-environment might increase their susceptibility to enteric diseases and even favour the translocation of bacteria in the bloodstream. Methods: The gastro-intestinal micro-environment was explored in 22 HEU infants and 16 HIV-unexposed (HU) infants aged 6-24 weeks. Faecal leucocytes, firmicutes (gram-positive bacteria) and gracilicutes (gram-negative bacteria) were assessed by cytology. Faecal lactoferrin and sIgA were measured by ELISA. The spectrum of micro-organisms in infants' stool was analysed by culturing. Results: HEU infants were 14 times more likely to have leucocytes in their stool than HU infants (p < 0.005). The lactoferrin level was significantly lower in HEU infants than in HU infants (p = 0.02). Potentially pathogenic bacteria such as Escherichia coli were more prevalent in HEU than in HU infants (64% vs 23.5%). Also, E. coli strains resistant to key antibiotics including co-trimoxazole, ß-lactam (cephalosporins included) and tetraclines were observed in some HEU infants. Conclusion: HEU infants are more likely to present an inflamed digestive tract as highlighted by the presence of leucocytes. In addition, there is a real risk of colonisation of HEU infants' microbiota by resistant micro-organisms.

Evaluation of the scientific impact of the Ebola epidemic: a systematic review.

OBJECTIVES: The Ebola outbreak prompted an extensive number of scientific publications, but little attention has been paid to the involvement of local scientists, distribution of research funding and related publications. We sought to systematically review publicly available information on the scientific impact of the Ebola epidemic. METHODS: A systematic review of literature on the Ebola outbreak was performed. Extracted information included origins of the authors, type and distribution of funding, and impact factors (IF) of related publications between 6 December 2013, and 22 December 2015. RESULTS: We identified 460 relevant articles out of 3281 references, which were mostly authored by American (46.6%) and European (28.4%) institutions; only 13.4% of authors were affiliated with African institutions. Most IF can be attributed to the Americas and Europe, with 43% (25 030.8 IF) and 34.5% (20 074.2 IF), respectively, compared with 17.9% (10 436.5 IF) in Africa. Funds were provided mainly by the Americas (31.8% of all funded studies) and Europe (17%). American and European funds were also distributed back, mainly to American (77.8%) and European (85.2%) institutions, respectively. CONCLUSIONS: The Ebola outbreak had a significant scientific impact and resulted in numerous publications in high IF journals. The main impact could be measured in the Americas and Europe, and was directly related to funding. African researchers were only marginally involved in the scientific processing (86.6% of all researchers were not African), probably because major research centres are located in America and Europe. Our results suggest the importance of promoting closer cooperation between regions.

Monoclonal antibodies for the treatment of Ebola virus disease.

INTRODUCTION: To date, the management of patients with suspected or confirmed Ebolavirus disease (EVD) depends on quarantine, symptomatic management and supportive care, as there are no approved vaccines or treatments available for human use. However, accelerated by the recent large outbreak in West Africa, significant progress has been made towards vaccine development but also towards specific treatment with convalescent plasma and monoclonal antibodies. Areas covered: We describe recent developments in monoclonal antibody treatment for EVD, encompassing mAb114 and the MB-003, ZMAb, ZMapp™ and MIL-77E cocktails. Expert opinion: Preventive measures, are, and will remain essential to curb EVD outbreaks; even more so with vaccine development progressing. However, research for treatment options must not be neglected. Small-scale animal and individual human case studies show that monoclonal antibodies (mAbs) can be effective for EVD treatment; thus justifying exploration in clinical trials. Potential limitations are that high doses may be needed to yield clinical efficacy; epitope mutations might reduce efficacy; and constant evolution of (outbreak-specific) mAb mixtures might be required. Interim advice based on the clinical experience to date is that treatment of patients with mAbs is sensible, provided those could be made available in the necessary amounts in time.