Age-dependent acquisition of IgG antibodies to Shigella serotypes-a retrospective analysis of seroprevalence in Kenyan children with implications for infant vaccination.

Background: Shigellosis mainly affects children under 5 years of age living in low- and middle-income countries, who are the target population for vaccination. There are, however, limited data available to define the appropriate timing for vaccine administration in this age group. Information on antibody responses following natural infection, proxy for exposure, could help guide vaccination strategies. Methods: We undertook a retrospective analysis of antibodies to five of the most prevalent Shigella serotypes among children aged <5 years in Kenya. Serum samples from a cross-sectional serosurvey in three Kenyan sites (Nairobi, Siaya, and Kilifi) were analyzed by standardized ELISA to measure IgG against Shigella sonnei and Shigella flexneri 1b, 2a, 3a, and 6. We identified factors associated with seropositivity to each Shigella serotype, including seropositivity to other Shigella serotypes. Results: A total of 474 samples, one for each participant, were analyzed: Nairobi (n = 169), Siaya (n = 185), and Kilifi (n = 120). The median age of the participants was 13.4 months (IQR 7.0-35.6), and the male:female ratio was 1:1. Geometric mean concentrations (GMCs) for each serotype increased with age, mostly in the second year of life. The overall seroprevalence of IgG antibodies increased with age except for S. flexneri 6 which was high across all age subgroups. In the second year of life, there was a statistically significant increase of antibody GMCs against all five serotypes (p = 0.01-0.0001) and a significant increase of seroprevalence for S. flexneri 2a (p = 0.006), S. flexneri 3a (p = 0.006), and S. sonnei (p = 0.05) compared with the second part of the first year of life. Among all possible pairwise comparisons of antibody seropositivity, there was a significant association between S. flexneri 1b and 2a (OR = 6.75, 95% CI 3-14, p < 0.001) and between S. flexneri 1b and 3a (OR = 23.85, 95% CI 11-54, p < 0.001). Conclusion: Children living in low- and middle-income settings such as Kenya are exposed to Shigella infection starting from the first year of life and acquire serotype-specific antibodies against multiple serotypes. The data from this study suggest that Shigella vaccination should be targeted to infants, ideally at 6 or at least 9 months of age, to ensure children are protected in the second year of life when exposure significantly increases.

Cross-sectional prevalence and pattern of non-anaemia severe malaria among 2-10 year olds in Sokoto in Northwestern Nigeria.

Malaria is highly prevalent in Nigeria and accounts for approximately 40% of global malaria mortality. However, most reports on severe malaria in Nigeria are from hospital-based studies without accurate information from communities; thus, malaria-related deaths in the community are left untracked. This study aimed to describe the prevalence and pattern of severe malaria in a community in Northwestern Nigeria. A cross-sectional study was conducted among 2-10-year-old children in Sokoto, in August and December 2016, to determine the endemicity of malaria based on Plasmodium falciparum prevalence rate (PfPR2-10) and to describe the disease pattern. Severe malaria was diagnosed according to the World Health Organisation criteria. Data were described using Stata version 15. The prevalence of non-anaemia severe malaria was higher than expected (2.6%), considering the endemicity pattern which was mesoendemic based on a PfPR2-10 of 34.8%. The mean age of children with severe malaria was 3.73 years, and the male-female ratio was 2:1. However, 54.0% of the patients had hyperparasitaemia. A relatively high prevalence of non-anaemia severe malaria was found in Wamakko. This finding suggests the need to identify and treat cases in the community using modifications of current strategies, particularly seasonal malaria chemoprophylaxis.

Antibodies Elicited by the Shigella sonnei GMMA Vaccine in Adults Trigger Complement-Mediated Serum Bactericidal Activity: Results From a Phase 1 Dose Escalation Trial Followed by a Booster Extension.

Shigella is the second most deadly diarrheal disease among children under five years of age, after rotavirus, with high morbidity and mortality in developing countries. Currently, no vaccine is widely available, and the increasing levels of multidrug resistance make Shigella a high priority for vaccine development. The single-component candidate vaccine against Shigella sonnei (1790GAHB), developed using the GMMA technology, contains the O antigen (OAg) portion of lipopolysaccharide (LPS) as active moiety. The vaccine was well tolerated and immunogenic in early-phase clinical trials. In a phase 1 placebo-controlled dose escalation trial in France (NCT02017899), three doses of five different vaccine formulations (0.06/1, 0.3/5, 1.5/25, 3/50, 6/100 µg of OAg/protein) were administered to healthy adults. In the phase 1 extension trial (NCT03089879), conducted 2-3 years following the parent study, primed individuals who had undetectable antibody levels before the primary series received a 1790GAHB booster dose (1.5/25 µg OAg/protein). Controls were unprimed participants immunized with one 1790GAHB dose. The current analysis assessed the functionality of sera collected from both studies using a high-throughput luminescence-based serum bactericidal activity (SBA) assay optimized for testing human sera. Antibodies with complement-mediated bactericidal activity were detected in vaccinees but not in placebo recipients. SBA titers increased with OAg dose, with a persistent response up to six months after the primary vaccination with at least 1.5/25 µg of OAg/protein. The booster dose induced a strong increase of SBA titers in most primed participants. Correlation between SBA titers and anti-S. sonnei LPS serum immunoglobulin G levels was observed. Results suggest that GMMA is a promising OAg delivery system for the generation of functional antibody responses and persistent immunological memory.

Where have all the parasites gone? Unusual Plasmodium falciparum monoparasitaemia in a cross-sectional malariometric survey in northern Nigeria.

Background: Malaria is caused by one of five currently known Plasmodium parasite species causing disease in humans. While modelling has provided information of the vector, the same is not entirely the case for the parasite. The World Malaria reports of 2014 to 2016 reported 100% of confirmed cases from Nigeria being due to Plasmodium falciparum. Generally, about 98% of cases of uncomplicated malaria in most regions surveyed in Nigeria recently is due to P. falciparum, with the remainder being due to P. malariae. This study aimed to determine the proportions of Plasmodium parasites causing uncomplicated malaria in Wamakko Local Government Area of Sokoto State, north-western Nigeria. Methods: The study was a descriptive, cross-sectional study conducted during the rainy season and dry season in north-western Nigeria. The area has a 'local steppe' climate and Sudanian Savannah vegetation. Sampling was via multistage cluster sampling. Selected participants were examined for pallor, palpable splenomegaly and signs of complicated malaria. Blood samples were also taken for rapid diagnosis of malaria and thick and thin films to identify parasitaemia and the parasite species. Participants found to have malaria were treated with Artemether/Lumefantrine and those with complicated malaria were referred to the nearest hospital.  Results: We found a parasite prevalence of 34.8% overall, which was higher in the rainy season (49.3%) than in the dry season (20.2%). There was monoparasitaemia of Plasmodium falciparum throughout the study area, irrespective of the clinical status of the participant. Mapping of the parasite was extended throughout the Local Government Area and the State. Conclusions: Despite the intermediate endemicity in the area. P. falciparum monoparasitaemia affirms theories of disappearance of other parasite species, either due to faltering control of P. falciparum or more efficient control of other species.

A validation of the Malaria Atlas Project maps and development of a new map of malaria transmission in Sokoto, Nigeria: a cross-sectional study using geographic information systems.

BACKGROUND: Malaria remains a major cause of morbidity and mortality among children in Africa. There is inadequate information regarding malaria transmission-intensity in some of the worst-affected parts of sub-Saharan Africa (SSA). The Malaria Atlas Project (MAP) was developed in 2006, to project estimates of malaria transmission intensity where this data is not available, based on the vector behaviour for malaria. Data from malariometric studies globally were obtained and modelled to provide prevalence estimates. The sensitivity of these maps, however, reduces with unavailability of data. This necessitates a validation of these maps locally, and investigation into alternative methods of predicting prevalence to guide malaria control interventions and improve their efficiency and effectiveness. This study was conducted to compare the true estimates in Sokoto, Nigeria, with the MAP projections for north-western Nigeria, and it proposes an alternative way of mapping malaria intensity in Nigeria and beyond. METHODS: A malariometric survey was conducted including children aged 2-10 years in communities in Wamakko Local Government Area (LGA) of Sokoto State, Nigeria. Children had blood examinations for the presence of malaria parasitaemia and a physical examination for the signs of clinical malaria. All the sites from which children were included in the study were geo-located using a hand-held Global Positioning System (GPS) device and compared this to MAP maps of the same area. A mapping software was also used to generate a malaria prevalence map of the study area, considering the average flight distances of the vector. RESULTS: The prevalence among children 2 to 10 years was found to be 34.8% which was within the 30-40% projected prevalence for the study area by MAPs. However, it was much lower than the projection during the dry season (20.2%) and higher than the projected estimate during the rainy season (49.3%). There was monoparasitaemia of Plasmodium falciparum throughout the study area, although the study was not specifically designed to identify other species. The prevalence of parasitaemia and splenomegaly were similar when overall and when considered by age of the participants. The study also generated a map of malaria transmission, which mapped out areas where the prevalence was confirmed or likely to be to be within the range of 30-40%, based on the sites which constituted the study area for this study. CONCLUSION: The study concludes that the prevalence of malaria and its transmission intensity in Sokoto are similar to Malaria Atlas Project predictions for the area and that, for malaria control planning purposes, the projections may be utilized, with more efforts at validation of the MAPs in other locations and terrains. Also, the vector behaviour may be used to map transmission of malaria and other vector-transmitted diseases, where this information is lacking.