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The prevalence of epilepsy in sub-Saharan Africa seems to be higher than in other parts of the world, but estimates vary substantially for unknown reasons. We assessed the prevalence and risk factors of active convulsive epilepsy across five centres in this region. We did large population-based cross-sectional and case-control studies in five Health and Demographic Surveillance System centres: Kilifi, Kenya (Dec 3, 2007–July 31, 2008); Agincourt, South Africa (Aug 4, 2008–Feb 27, 2009); Iganga-Mayuge, Uganda (Feb 2, 2009–Oct 30, 2009); Ifakara, Tanzania (May 4, 2009–Dec 31, 2009); and Kintampo, Ghana (Aug 2, 2010–April 29, 2011). We used a three-stage screening process to identify people with active convulsive epilepsy. Prevalence was estimated as the ratio of confirmed cases to the population screened and was adjusted for sensitivity and attrition between stages. For each case, an age-matched control individual was randomly selected from the relevant centre's census database. Fieldworkers masked to the status of the person they were interviewing administered questionnaires to individuals with active convulsive epilepsy and control individuals to assess sociodemographic variables and historical risk factors (perinatal events, head injuries, and diet). Blood samples were taken from a randomly selected subgroup of 300 participants with epilepsy and 300 control individuals from each centre and were screened for antibodies to Toxocara canis, Toxoplasma gondii, Onchocerca volvulus, Plasmodium falciparum, Taenia solium, and HIV. We estimated odds ratios (ORs) with logistic regression, adjusted for age, sex, education, employment, and marital status. 586 607 residents in the study areas were screened in stage one, of whom 1711 were diagnosed as having active convulsive epilepsy. Prevalence adjusted for attrition and sensitivity varied between sites: 7·8 per 1000 people (95% CI 7·5–8·2) in Kilifi, 7·0 (6·2–7·4) in Agincourt, 10·3 (9·5–11·1) in Iganga-Mayuge, 14·8 (13·8–15·4) in Ifakara, and 10·1 (9·5–10·7) in Kintampo. The 1711 individuals with the disorder and 2032 control individuals were given questionnaires. In children (aged <18 years), the greatest relative increases in prevalence were associated with difficulties feeding, crying, or breathing after birth (OR 10·23, 95% CI 5·85–17·88; p<0·0001); abnormal antenatal periods (2·15, 1·53–3·02; p<0·0001); and head injury (1·97, 1·28–3·03; p=0·002). In adults (aged ≥18 years), the disorder was significantly associated with admission to hospital with malaria or fever (2·28, 1·06–4·92; p=0·036), exposure to T canis (1·74, 1·27–2·40; p=0·0006), exposure to T gondii (1·39, 1·05–1·84; p=0·021), and exposure to O volvulus (2·23, 1·56–3·19; p<0·0001). Hypertension (2·13, 1·08–4·20; p=0·029) and exposure to T solium (7·03, 2·06–24·00; p=0·002) were risk factors for adult-onset disease. The prevalence of active convulsive epilepsy varies in sub-Saharan Africa and that the variation is probably a result of differences in risk factors. Programmes to control parasitic diseases and interventions to improve antenatal and perinatal care could substantially reduce the prevalence of epilepsy in this region. Wellcome Trust, University of the Witwatersrand, and South African Medical Research Council.

Strengthening malaria surveillance is a key intervention needed to reduce the global disease burden. Reliable serological markers of recent malaria exposure could improve current surveillance methods by allowing for accurate estimates of infection incidence from limited data. We studied the IgG antibody response to 111 Plasmodium falciparum proteins in 65 adult travellers followed longitudinally after a natural malaria infection in complete absence of re-exposure. We identified a combination of five serological markers that detect exposure within the previous three months with >80% sensitivity and specificity. Using mathematical modelling, we examined the antibody kinetics and determined that responses informative of recent exposure display several distinct characteristics: rapid initial boosting and decay, less inter-individual variation in response kinetics, and minimal persistence over time. Such serological exposure markers could be incorporated into routine malaria surveillance to guide efforts for malaria control and elimination. Serological markers of recent Plasmodium falciparum infection could be useful to estimate incidence. Here, the authors identify a combination of five serological markers to detect exposure to infection within the previous three months with >80% sensitivity and specificity.

Human Papillomavirus (HPV) type variants have been classified into lineages and sublineages based upon their whole genome sequence. Here we have examined the specificity of antibodies generated following natural infection with lineage variants of oncogenic types (HPV16, 18, 31, 33, 45, 52 and 58) by testing serum samples assembled from existing archives from women residing in Africa, The Americas, Asia or Europe against representative lineage-specific pseudoviruses for each genotype. We have subjected the resulting neutralizing antibody data to antigenic clustering methods and created relational antigenic profiles for each genotype to inform the delineation of lineage-specific serotypes. For most genotypes, there was evidence of differential recognition of lineage-specific antigens and in some cases of a sufficient magnitude to suggest that some lineages should be considered antigenically distinct within their respective genotypes. These data provide compelling evidence for a degree of lineage specificity within the humoral immune response following natural infection with oncogenic HPV. Human Papillomaviruses (HPV) are classified in lineages based on their sequence. Here, the authors test neutralizing activity of sera from naturally infected women against vaccine-preventable HPV variants, delineating lineage-specific antibody responses.

Current vaccine strategies against the asexual blood stage of Plasmodium falciparum are mostly focused on well-studied merozoite antigens that induce immune responses after natural exposure, but have yet to induce robust protection in any clinical trial. Here we compare human-compatible viral-vectored vaccines targeting ten different blood-stage antigens. We show that the full-length P. falciparum reticulocyte-binding protein homologue 5 (PfRH5) is highly susceptible to cross-strain neutralizing vaccine-induced antibodies, out-performing all other antigens delivered by the same vaccine platform. We find that, despite being susceptible to antibody, PfRH5 is unlikely to be under substantial immune selection pressure; there is minimal acquisition of anti-PfRH5 IgG antibodies in malaria-exposed Kenyans. These data challenge the widespread beliefs that any merozoite antigen that is highly susceptible to immune attack would be subject to significant levels of antigenic polymorphism, and that erythrocyte invasion by P. falciparum is a degenerate process involving a series of parallel redundant pathways. At present there are no highly effective vaccines for Plasmodium falciparum . In this study, a vaccine raised against the P. falciparum reticulocyte-binding protein homologue 5 is shown to induce an IgG response in rabbits that could block the proliferation of multiple parasite strains in vitro .

The CEPI-Centralized Laboratory Network (CLN) has significantly contributed to the development of several approved SARS-CoV-2 vaccines by conducting over 70,000 clinical samples for testing from various vaccine developers. A centralized data management system was developed to track, review, store and share immunological clinical results generated from sample testing. The data system ensures the completeness and accuracy of submitted results and checks the set criteria in controls for each assay. Each testing facility within the network submits their results to a secure storage system using report forms with embedded data quality checks. Upon submission, a statistical program runs additional checks to identify errors in completeness and uniqueness. Any discrepancies or errors are shared with the testing facility to rectify. Reports are further reviewed by CEPI-CLN experts before releasing to the vaccine developer. Study results are then consolidated into an internal relational database management system, enabling CEPI to analyze the data through an interactive dashboard that visualizes control trends and sample results across all studies. This analysis facilitates the harmonization of immunological data and helps to inform CEPI’s programmatic and strategic decision making. Given the success of this approach with SARS-CoV-2 vaccines, the system will be adopted for new pathogens and assay types currently under development at CEPI-CLN.

Background: An effective vaccine against Nipah virus (NiV) is crucial due to its high fatality rate and recurrent outbreaks in South and Southeast Asia. Vaccine development is challenged by the lack of validated accessible neutralization assays, as virus culture requires BSL-4 facilities, restricting implementation in resource-limited settings. To address this, we standardized and validated a pseudotyped virus neutralization assay (PNA) for assessing NiV-neutralizing antibodies in BSL-2 laboratories. Methods: The NiV-PNA was validated following international regulatory standards, using a replication-defective recombinant Vesicular stomatitis virus (rVSV) backbone dependent pseudotyped virus. Assessments included sensitivity, specificity, dilutional linearity, relative accuracy, precision, and robustness. The assay was calibrated using the WHO International Standard for anti-NiV antibodies and characterized reference sera to ensure reliable performance. Findings: Preliminary evaluation of the developed NiV-PNA showed 100% sensitivity and specificity across 10 serum samples (5 positive, 5 negative), with a positive correlation to a calibrated reference assay (R2 = 0.8461). Dilutional linearity (R2 = 0.9940) and accuracy (98.18%) were confirmed across the analytical titer range of 11-1728 IU/mL. The assay also exhibited high precision, with intra-assay and intermediate precision geometric coefficients of variation of 6.66% and 15.63%, respectively. Robustness testing demonstrated minimal variation across different pseudotyped virus lots, incubation times, and cell counts. Conclusions: The validated NiV-PNA is a reproducible and scalable assay platform for quantifying NiV neutralizing antibodies, offering a safer alternative to virus culture. Its validation and integration into the CEPI Centralized Laboratory Network will enhance global capacity for vaccine evaluation and outbreak preparedness.

The complement system is required for innate immunity against Acinetobacter baumannii , an important cause of antibiotic resistant systemic infections. A. baumannii strains differ in their susceptibility to the membrane attack complex (MAC) formed from terminal complement pathway proteins, but the reasons for this variation remain poorly understood. We have characterized in detail the complement sensitivity phenotypes of nine A. baumannii clinical strains and some of the factors that might influence differences between strains. Using A. baumannii laboratory strains and flow cytometry assays, we first reconfirmed that both opsonization with the complement proteins C3b/iC3b and MAC formation were inhibited by the capsule. There were marked differences in C3b/iC3b and MAC binding between the nine clinical A. baumannii strains, but this variation was partially independent of capsule composition or size. Opsonization with C3b/iC3b improved neutrophil phagocytosis of most strains. Importantly, although C3b/iC3b binding and MAC formation on the bacterial surface correlated closely, MAC formation did not correlate with variations between A. baumannii strains in their levels of serum resistance. Genomic analysis identified only limited differences between strains in the distribution of genes required for serum resistance, but RNAseq data identified three complement-resistance genes that were differentially regulated between a MAC resistant and two MAC intermediate resistant strains when cultured in serum. These data demonstrate that clinical A. baumannii strains vary in their sensitivity to different aspects of the complement system, and that the serum resistance phenotype was influenced by factors in addition to the amount of MAC forming on the bacterial surface.

The CEPI Centralized Laboratory Network implemented key steps in the transfer and monitoring of the developed immunological SARS-CoV-2 assays to ensure standardization across all the facilities of the network. This comprehensive evaluation reinforces the reliability of the generated data and establishes a solid foundation for a standardized approach, enabling precise inter-laboratory comparisons and contributing to the overall integrity of our network’s clinical results. Herein, we will provide a brief elaboration on the specific measures and procedures implemented to standardize the transfer of assays across our network.

Antibody therapy may be an alternative treatment option for infections caused by the multi-drug resistant (MDR) bacterium Acinetobacter baumannii. As A. baumannii has multiple capsular serotypes, a universal antibody therapy would need to target conserved protein antigens rather than the capsular polysaccharides. We have immunized mice with single or multiple A. baumannii strains to induce antibody responses to protein antigens, and then assessed whether these responses provide cross-protection against a collection of genetically diverse clinical A. baumannii isolates. Immunized mice developed antibody responses to multiple protein antigens. Flow cytometry IgG binding assays and immunoblots demonstrated improved recognition of both homologous and heterologous clinical strains in sera from mice immunized with multiple strains compared to a single strain. The capsule partially inhibited bacterial recognition by IgG and the promotion of phagocytosis by human neutrophils. However, after immunization with multiple strains, serum antibodies to protein antigens promoted neutrophil phagocytosis of heterologous A. baumannii strains. In an infection model, mice immunized with multiple strains had lower bacterial counts in the spleen and liver following challenge with a heterologous strain. These data demonstrate that antibodies targeting protein antigens can improve immune recognition and protection against diverse A. baumannii strains, providing support for their use as an antibody therapy.

Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa. A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95%CI: 1.52-2.58, p<0.001), Toxocara canis (OR = 1.52; 95%CI: 1.23-1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95%CI: 1.04-1.56, p = 0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95%CI: 1.30-2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas. This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated.