Background In low-income countries, like Malawi, important public health measures including social distancing or a lockdown, have been challenging to implement owing to socioeconomic constraints, leading to predictions that the COVID-19 pandemic would progress rapidly. However, due to limited capacity to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, there are no reliable estimates of the true burden of infection and death. We, therefore, conducted a SARS-CoV-2 serosurvey amongst health care workers (HCW) in Blantyre city to estimate the cumulative incidence of SARS-CoV-2 infection in urban Malawi. Methods Five hundred otherwise asymptomatic HCWs were recruited from Blantyre City (Malawi) from 22nd May 2020 to 19th June 2020 and serum samples were collected all participants. A commercial ELISA was used to measure SARS-CoV-2 IgG antibodies in serum. We run local negative samples (2018 - 2019) to verify the specificity of the assay. To estimate the seroprevalence of SARS CoV-2 antibodies, we adjusted the proportion of positive results based on local specificity of the assay. Results Eighty-four participants tested positive for SARS-CoV-2 antibodies. The HCW with a positive SARS-CoV-2 antibody result came from different parts of the city. The adjusted seroprevalence of SARS-CoV-2 antibodies was 12.3% [CI 9.0-15.7]. Using age-stratified infection fatality estimates reported from elsewhere, we found that at the observed adjusted seroprevalence, the number of predicted deaths was 8 times the number of reported deaths. Conclusion The high seroprevalence of SARS-CoV-2 antibodies among HCW and the discrepancy in the predicted versus reported deaths, suggests that there was early exposure but slow progression of COVID-19 epidemic in urban Malawi. This highlights the urgent need for development of locally parameterised mathematical models to more accurately predict the trajectory of the epidemic in sub-Saharan Africa for better evidence-based policy decisions and public health response planning.

Background: In low-income countries, like Malawi, important public health measures including social distancing or a lockdown have been challenging to implement owing to socioeconomic constraints, leading to predictions that the COVID-19 pandemic would progress rapidly. However, due to limited capacity to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, there are no reliable estimates of the true burden of infection and death.  We, therefore, conducted a SARS-CoV-2 serosurvey amongst health care workers (HCWs) in Blantyre city to estimate the cumulative incidence of SARS-CoV-2 infection in urban Malawi. Methods: We recruited 500 otherwise asymptomatic HCWs from Blantyre City (Malawi) from 22nd May 2020 to 19th June 2020 and serum samples were collected from all participants. A commercial ELISA was used to measure SARS-CoV-2 IgG antibodies in serum. Results: A total of 84 participants tested positive for SARS-CoV-2 antibodies. The HCWs with positive SARS-CoV-2 antibody results came from different parts of the city. The adjusted seroprevalence of SARS-CoV-2 antibodies was 12.3% [CI 8.2 - 16.5]. Using age-stratified infection fatality estimates reported from elsewhere, we found that at the observed adjusted seroprevalence, the number of predicted deaths was eight times the number of reported deaths. Conclusions: The high seroprevalence of SARS-CoV-2 antibodies among HCWs and the discrepancy in the predicted versus reported deaths suggests that there was early exposure but slow progression of COVID-19 epidemic in urban Malawi. This highlights the urgent need for development of locally parameterised mathematical models to more accurately predict the trajectory of the epidemic in sub-Saharan Africa for better evidence-based policy decisions and public health response planning.

Plasmodium falciparum is unique among human malarias in its ability to sequester in post-capillary venules of host organs. The main variant antigens implicated are the P. falciparum erythrocyte membrane protein 1 (PfEMP1), which can be divided into three major groups (A–C). Our study was a unique examination of sequestered populations of parasites for genetic background and expression of PfEMP1 groups. We collected post-mortem tissue from twenty paediatric hosts with pathologically different forms of cerebral malaria (CM1 and CM2) and parasitaemic controls (PC) to directly examine sequestered populations of parasites in the brain, heart and gut. Use of two different techniques to investigate this question produced divergent results. By quantitative PCR, group A var genes were upregulated in all three organs of CM2 and PC cases. In contrast, in CM1 infections displaying high levels of sequestration but negligible vascular pathology, there was high expression of group B var. Cloning and sequencing of var transcript tags from the same samples indicated a uniformly low expression of group A-like var. Generally, within an organ sample, 1–2 sequences were expressed at dominant levels. 23% of var tags were detected in multiple patients despite the P. falciparum infections being genetically distinct, and two tags were observed in up to seven hosts each with high expression in the brains of 3–4 patients. This study is a novel examination of the sequestered parasites responsible for fatal cerebral malaria and describes expression patterns of the major cytoadherence ligand in three organ-derived populations and three pathological states.

Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we characterise patients hospitalised with suspected (PCR-negative/IgG-positive) or confirmed (PCR-positive) COVID-19, and healthy community controls (PCR-negative/IgG-negative). PCR-positive COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-negative/IgG-positive and PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants exhibited a nasal and systemic cytokine signature analogous to PCR-positive COVID-19 participants, predominated by chemokines and neutrophils and distinct from PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants had increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. PCR-negative/IgG-positive individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies.