Malaria and other infections induce polyreactive antibodies that impact SARS-CoV-2 seropositivity estimations in endemic settings.

Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence is used to estimate the proportion of individuals within a population previously infected, to track viral transmission, and to monitor naturally and vaccine-induced immune protection. However, in sub-Saharan African settings, antibodies induced by higher exposure to pathogens may increase unspecific seroreactivity to SARS-CoV-2 antigens, resulting in false positive responses. To investigate the level and type of unspecific seroreactivitiy to SARS-CoV-2 in Africa, we measured immunoglobulin G (IgG), IgA, and IgM to a broad panel of antigens from different pathogens by Luminex in 602 plasma samples from African and European subjects differing in coronavirus disease 2019, malaria, and other exposures. Seroreactivity to SARS-CoV-2 antigens was higher in prepandemic African than in European samples and positively correlated with antibodies against human coronaviruses, helminths, protozoa, and especially Plasmodium falciparum. African subjects presented higher levels of autoantibodies, a surrogate of polyreactivity, which correlated with P. falciparum and SARS-CoV-2 antibodies. Finally, we found an improved sensitivity in the IgG assay in African samples when using urea as a chaotropic agent. In conclusion, our data suggest that polyreactive antibodies induced mostly by malaria are important mediators of the unspecific anti-SARS-CoV-2 responses, and that the use of dissociating agents in immunoassays could be useful for more accurate estimates of SARS-CoV-2 seroprevalence in African settings.

Excess mortality during the COVID-19 pandemic in low-and lower-middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Although the COVID-19 pandemic claimed a great deal of lives, it is still unclear how it affected mortality in low- and lower-middle-income countries (LLMICs). This review summarized the available literature on excess mortality during the COVID-19 pandemic in LLMICs, including methods, sources of data, and potential contributing factors that might have influenced excess mortality. METHODS: We conducted a systematic review and meta-analysis on excess mortality during the COVID-19 pandemic in LLMICs in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines We searched PubMed, Embase, Web of Science, Cochrane Library, Google Scholar, and Scopus. We included studies published from 2019 onwards with a non-COVID-19 period of at least one year as a comparator. The meta-analysis included studies reporting data on population size, as well as observed and expected deaths. We used the Mantel-Haenszel method to estimate the pooled risk ratio with 95% confidence intervals. The protocol was registered in PROSPERO (ID: CRD42022378267). RESULTS: The review covered 29 countries, with 10 countries included in the meta-analysis. The pooled meta-analysis included 1,405,128,717 individuals, for which 2,152,474 deaths were expected, and 3,555,880 deaths were reported. Calculated excess mortality was 100.3 deaths per 100,000 population per year, with an excess risk of death of 1.65 (95% CI: 1.649, 1.655, p < 0.001). The data sources used in the studies included civil registration systems, surveys, public cemeteries, funeral counts, obituary notifications, burial site imaging, and demographic surveillance systems. The primary techniques used to estimate excess mortality were statistical forecast modelling and geospatial analysis. One out of the 24 studies found higher excess mortality in urban settings. CONCLUSION: Our findings demonstrate that excess mortality in LLMICs during the pandemic was substantial. However, estimates of excess mortality are uncertain due to relatively poor data. Understanding the drivers of excess mortality, will require more research using various techniques and data sources.

Factors associated with skilled birth attendance in 37 low-income and middle-income countries: a secondary analysis of nationally representative, individual-level data.

BACKGROUND: Progress on skilled birth attendance (SBA) has been very uneven across low-income and middle-income countries (LMICs). There is scant empirical evidence on the role of fundamental development processes in explaining differences in SBA outcomes across world regions over time in these settings. We therefore aimed to estimate how these processes have contributed to observed changes in SBA across Latin America and the Caribbean, South Asia, Southeast Asia, and sub-Saharan Africa. METHODS: We pooled all available Demographic and Health Survey (DHS) rounds that contained detailed birth attendance information. The compiled data covers about 1·1 million births (1·1 million female individuals) from 103 DHS rounds in 37 countries. We estimated the determinants of SBA using multivariable regression techniques and Oaxaca-Blinder decompositions for different world regions and time periods (1990s, 2000s, and 2010s). FINDINGS: We show that progress in SBA is associated with improvements in terms of household-level wealth, mothers' education, urbanisation, contraceptive knowledge, and proxies of female empowerment. Furthermore, we show that changes in the underlying relationship between SBA and specific development indicators (wealth, education, and rural residence status) have further contributed to the observed rise in SBA across LMICs. Our findings further suggest that certain determinants of improvements in SBA are region-specific (eg, importance of rural residence status in sub-Saharan Africa), whereas some of the studied processes (eg, poverty, maternal education, and urbanisation) have become less predictive for the uptake of SBA over time. INTERPRETATION: Although substantial progress has been made in increasing SBA rates over the past three decades across LMICs, further efforts for continued progress are still needed to achieve international targets on SBA as part of the Sustainable Development Goals, the Every Newborn Action Plan, and the Ending Preventable Maternal Mortality initiative. According to our findings, these efforts can include general policies (eg, female empowerment) and region-specific policies (eg, poverty reduction programmes in Southeast Asia). FUNDING: Bernhard Nocht Institute for Tropical Medicine. TRANSLATIONS: For the French and Indonesian translations of the abstract see Supplementary Materials section.

Excess mortality during the COVID-19 pandemic in low-income and lower middle-income countries: protocol for a systematic review and meta-analysis.

INTRODUCTION: The COVID-19 pandemic has been marked by a massive death toll. However, the overall effect of the pandemic, including potential unintended negative impacts of some control measures, on mortality remains poorly understood in low-income and lower middle-income countries (LLMICs). This review aims to summarise the available literature on excess mortality in LLMICs, focusing on the methods and data sources used in estimating excess mortality and the drivers of excess mortality. METHODS AND ANALYSIS: We will review the available literature and report results in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis. Searches will be conducted in PubMed, Embase, Web of Science, Cochrane Library, Google Scholar and Scopus. All published studies that report on the estimates of excess mortality in populations of LLMICs will be included. This will include those with a publication date from 2019 onwards and those with at least a 1-year non-COVID-19 period as the comparator in the estimation of excess mortality during the pandemic. There will be no language restrictions on the search. The meta-analysis will include studies with extractable data on excess mortality, methods, population size, and observed and expected deaths. We will use the Mantel-Haenszel method to estimate the pooled risk ratio with 95% CIs. ETHICS AND DISSEMINATION: As there is no primary data collection, there is no requirement for ethical review. The results will be disseminated through peer-reviewed journal publication and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022378267.

Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): a population-based study.

BACKGROUND: Typhoid Fever remains a major cause of morbidity and mortality in low-income settings. The Severe Typhoid in Africa programme was designed to address regional gaps in typhoid burden data and identify populations eligible for interventions using novel typhoid conjugate vaccines. METHODS: A hybrid design, hospital-based prospective surveillance with population-based health-care utilisation surveys, was implemented in six countries in sub-Saharan Africa. Patients presenting with fever (≥37·5°C axillary or ≥38·0°C tympanic) or reporting fever for three consecutive days within the previous 7 days were invited to participate. Typhoid fever was ascertained by culture of blood collected upon enrolment. Disease incidence at the population level was estimated using a Bayesian mixture model. FINDINGS: 27 866 (33·8%) of 82 491 participants who met inclusion criteria were recruited. Blood cultures were performed for 27 544 (98·8%) of enrolled participants. Clinically significant organisms were detected in 2136 (7·7%) of these cultures, and 346 (16·2%) Salmonella enterica serovar Typhi were isolated. The overall adjusted incidence per 100 000 person-years of observation was highest in Kavuaya and Nkandu 1, Democratic Republic of the Congo (315, 95% credible interval 254-390). Overall, 46 (16·4%) of 280 tested isolates showed ciprofloxacin non-susceptibility. INTERPRETATION: High disease incidence (ie, >100 per 100 000 person-years of observation) recorded in four countries, the prevalence of typhoid hospitalisations and complicated disease, and the threat of resistant typhoid strains strengthen the need for rapid dispatch and implementation of effective typhoid conjugate vaccines along with measures designed to improve clean water, sanitation, and hygiene practices. FUNDING: The Bill & Melinda Gates Foundation.