Antibodies to PfEMP1 and variant surface antigens: Protection after controlled human malaria infection in semi-immune Kenyan adults.

Objectives: Acquisition of antibodies to Plasmodium falciparum variant surface antigens (VSA) expressed on infected red blood cells (iRBCs) is associated with naturally acquired immunity to malaria. We have previously shown that antibodies to VSA on iRBCs are associated with protection against parasite growth in the context of controlled human malaria infection (CHMI). This study explored whether antibodies to recombinant antigens derived from PfEMP1 domains were independently associated with protection during CHMI in semi-immune Kenyan adults.

Antibody-Dependent Respiratory Burst against Merozoites in Individuals Living in an Area with Declining Malaria Transmission.

Malaria transmission intensity affects the development of naturally acquired immunity to malaria. An absolute correlate measure of protection against malaria is lacking. However, antibody-mediated functions against correlate with protection against malaria.

Breadth of Antibodies to Variant Surface Antigens Is Associated With Immunity in a Controlled Human Malaria Infection Study.

Background: variant surface antigens (VSAs) contribute to malaria pathogenesis by mediating cytoadhesion of infected red blood cells to the microvasculature endothelium. In this study, we investigated the association between anti-VSA antibodies and clinical outcome in a controlled human malaria infection (CHMI) study.

Method: We used flow cytometry and ELISA to measure levels of IgG antibodies to VSAs of five heterologous and one homologous parasite isolates, and to two PfEMP1 DBLβ domains in blood samples collected a day before the challenge and 14 days after infection.

The burden of neurological impairments and disability in older children measured in disability-adjusted life-years in rural Kenya.

Neurological impairment (NI) and disability are common in sub-Saharan Africa (SSA), but the overall burden in terms of morbidity and mortality in older children remains unknown. We estimated the burden of NI in disability-adjusted life years (DALYs), years of life lost to premature mortality (YLLs), and years lived with disability (YLDs) for older children in a defined rural setting in Kenya. We used empirical and literature estimates to model the overall burden for children aged 5-14 years in five domains: epilepsy (lifetime and active) and moderate/severe cognitive, hearing, motor, and visual impairments.

Neurological impairment and disability in children in rural Kenya.

Aim: To investigate geographical change over time in the burden of neurological impairments in school-aged children in a demographic surveillance area.

Method: We investigated changes in neurological impairment prevalence in five domains (epilepsy and cognitive, hearing, vision, and motor impairments) using similar two-phase surveys conducted in 2001 (n=10 218) and 2015 (n=11 223) and determined changes in location-level prevalence, geographical clustering, and significant risk factors for children aged 6 to 9 years (mean 7y 6mo, SD 1y) of whom 50.4% were males.

Tracking the introduction and spread of SARS-CoV-2 in coastal Kenya.

Genomic surveillance of SARS-CoV-2 is important for understanding both the evolution and the patterns of local and global transmission. Here, we generated 311 SARS-CoV-2 genomes from samples collected in coastal Kenya between 17 March and 31 July 2020. We estimated multiple independent SARS-CoV-2 introductions into the region were primarily of European origin, although introductions could have come through neighbouring countries.

Premature Mortality, Risk Factors, and Causes of Death Following Childhood-Onset Neurological Impairments: A Systematic Review.

Neurological impairment (NI) and disability are associated with reduced life expectancy, but the risk and magnitude of premature mortality in children vary considerably across study settings. We conducted a systematic review to estimate the magnitude of premature mortality following childhood-onset NI worldwide and to summarize known risk factors and causes of death. We searched various databases for published studies from their inception up to 31st October 2020.

Enhancing fieldworkers' performance management support in health research: an exploratory study on the views of field managers and fieldworkers from major research centres in Africa.

Introduction: Fieldworkers are part of the system that promotes scientific and ethical standards in research, through data collection, consenting and supporting research, due to their insider cultural knowledge and fluency in local languages. The credibility and integrity of health research, therefore, rely on how fieldworkers adhere to institutional and research procedures and guidelines.

Objectives: This study mapped out existing practices in training, support and performance management of fieldworkers in Africa, described fieldworkers' and their managers' experiences, and lessons learnt.

Premature mortality in children aged 6-9 years with neurological impairments in rural Kenya: a cohort study.

Background: Neurological impairments might significantly contribute to reduced life expectancy in low-income and middle-income countries (LMICs). There are no empirical studies of premature mortality in children with neurological impairments in Africa. This study estimated the risk of premature mortality in children with neurological impairments and identified risk factors and causes of death.

KILchip v1.0: A Novel Merozoite Protein Microarray to Facilitate Malaria Vaccine Candidate Prioritization.

Passive transfer studies in humans clearly demonstrated the protective role of IgG antibodies against malaria. Identifying the precise parasite antigens that mediate immunity is essential for vaccine design, but has proved difficult. Completion of the genome revealed thousands of potential vaccine candidates, but a significant bottleneck remains in their validation and prioritization for further evaluation in clinical trials.

A threshold concentration of anti-merozoite antibodies is required for protection from clinical episodes of malaria.

Antibodies to selected Plasmodium falciparum merozoite antigens are often reported to be associated with protection from malaria in one epidemiological cohort, but not in another. Here, we sought to understand this paradox by exploring the hypothesis that a threshold concentration of antibodies is necessary for protection. We analyzed data from two independent cohorts along the Kenyan coast, one in which antibodies to AMA1, MSP-2 and MSP-3 were associated with protection from malaria (Chonyi) and another in which this association was not observed (Junju).

Strengthening the informed consent process in international health research through community engagement: The KEMRI-Wellcome Trust Research Programme Experience.

Samson Muchina Kinyanjui and colleagues from the KEMRI-Wellcome Trust Research Programme discuss how they modified their informed consent processes by taking into account local social, cultural, and economic contexts in the design and administration of consent forms.

Effect of HIV infection on the acute antibody response to malaria antigens in children: an observational study.

Background: In sub-Saharan Africa, the distributions of malaria and HIV widely overlap. Among pregnant and non-pregnant adults, HIV affects susceptibility to malaria, its clinical course and impairs antibody responses to malaria antigens. However, the relationship between the two diseases in childhood, when most deaths from malaria occur, is less clear.

What you see is not what you get: implications of the brevity of antibody responses to malaria antigens and transmission heterogeneity in longitudinal studies of malaria immunity.

Background: A major handicap in developing a malaria vaccine is the difficulty in pinpointing the immune responses that protect against malaria. The protective efficacy of natural or vaccine-induced immune responses against malaria is normally assessed by relating the level of the responses in an individual at the beginning of a follow-up period and the individual's experience of malaria infection or disease during the follow-up. This approach has identified a number of important responses against malaria, but their protective efficacies vary considerably between studies.

IgG antibody responses to Plasmodium falciparum merozoite antigens in Kenyan children have a short half-life.

Background: Data suggest that antibody responses to malaria parasites merozoite antigens are generally short-lived and this has implications for serological studies and malaria vaccine designs. However, precise data on the kinetics of these responses is lacking.

Methods: IgG1 and IgG3 responses to five recombinant Plasmodium falciparum merozoite antigens (MSP-119, MSP-2 type A and B, AMA-1 ectodomain and EBA-175 region II) among Kenyan children were monitored using ELISA for 12 weeks after an acute episode of malaria and their half-lives estimated using an exponential decay model.

Plasmodium falciparum antigenic variation: relationships between in vivo selection, acquired antibody response, and disease severity.

Background: Variant surface antigens (VSA) on Plasmodium falciparum-infected erythrocytes are potentially important targets of immunity to malaria. We previously identified a VSA phenotype--VSA with a high frequency of antibody recognition (VSA(FoRH))--that is associated with young host age and severe malaria. We hypothesized that VSA(FoRH) are positively selected by host molecules such as intercellular adhesion molecule 1 (ICAM1) and CD36 and dominate in the absence of an effective immune response.

Protection against clinical malaria by heterologous immunoglobulin G antibodies against malaria-infected erythrocyte variant surface antigens requires interaction with asymptomatic infections.

Erythrocytes infected with mature stages of Plasmodium falciparum express variant surface antigens (VSAs) of parasite origin, including P. falciparum erythrocyte membrane protein 1. Anti-VSA antibodies protect against clinical malaria caused by parasites bearing VSAs to which they are specific (homologous), but their role in protecting against heterologous infection is unclear.

The use of cryopreserved mature trophozoites in assessing antibody recognition of variant surface antigens of Plasmodium falciparum-infected erythrocytes.

Mature stages of Plasmodium falciparum insert variant antigens (VSA) into the surface of infected erythrocytes, and antibodies against such antigen provide variant-specific protection against malaria. Because mature P. falciparum trophozoites normally sequester away from the peripheral circulation, parasites for anti-VSA antibody studies are obtained from patients as ring trophozoites, cryopreserved, and cultured to maturity when required.

Kinetics of antibody responses to Plasmodium falciparum-infected erythrocyte variant surface antigens.

The kinetics of antibody responses to the Plasmodium falciparum malaria parasite-induced erythrocyte surface antigens (PIESAs) in 26 Kenyan children were examined by use of flow cytometry and agglutination assays. Although 19 of the 26 children mounted a primary antibody response to PIESAs within 2 weeks of experiencing an acute episode and maintained high antibody levels for at least 12 weeks, the remaining 7 children had responses that were weak and brief. Resistance to reparasitization was decreased in the children with short-lived responses.