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The ratio of COVID-19-attributable deaths versus "true" COVID-19 deaths depends on the synchronicity of the epidemic wave with population mortality; duration of test positivity, diagnostic time window, and testing practices close to and at death; infection prevalence; the extent of diagnosing without testing documentation; and the ratio of overall (all-cause) population mortality rate and infection fatality rate. A nomogram is offered to assess the potential extent of over- and under-counting in different situations. COVID-19 deaths were apparently under-counted early in the pandemic and continue to be under-counted in several countries, especially in Africa, while over-counting probably currently exists for several other countries, especially those with intensive testing and high sensitization and/or incentives for COVID-19 diagnoses. Death attribution in a syndemic like COVID-19 needs great caution. Finally, excess death estimates are subject to substantial annual variability and include also indirect effects of the pandemic and the effects of measures taken. [ABSTRACT FROM AUTHOR]

Reports on a study which evaluated whether the amount of randomised clinical research on various medical conditions is related to the burden of disease and health needs of the local population in sub-Saharan Africa. Design; Setting; Main outcome measures; Results; Conclusion that few clinical trials are done in sub-Saharan Africa and that clinical research in that part of the world should focus more on the major contributors to burden of disease.

Objectives: To assess the evidence on the presence of antibodies cross-reactive with SARS-CoV-2 antigens in prepandemic samples from African populations., Methods: We performed a systematic review and meta-analysis of studies evaluating prepandemic African samples using pre-set assay-specific thresholds for SARS-CoV-2 seropositivity., Results: In total, 26 articles with 156 datasets were eligible, including 3437 positives among 29,923 measurements (11.5%) with large between-dataset heterogeneity. Positivity was similar for anti-nucleocapsid (14%) and anti-spike antibodies (11%), higher for anti-spike1 (23%), and lower for anti-receptor-binding domain antibodies (7%). Positivity was similar, on average, for immunoglobulin M and immunoglobulin G. Positivity was seen prominently in countries where malaria transmission occurs throughout and in datasets enriched in malaria cases (14%, 95% confidence interval, 12-15% vs 2%, 95% confidence interval 1-2% in other datasets). Substantial SARS-CoV-2 reactivity was seen in high malaria burden with or without high dengue burden (14% and 12%, respectively), and not without high malaria burden (2% and 0%, respectively). Lower SARS-CoV-2 cross-reactivity was seen in settings of high HIV seroprevalence. More sparse individual-level data showed associations of higher SARS-CoV-2 cross-reactivity with Plasmodium parasitemia and lower SARS-CoV-2 cross-reactivity with HIV seropositivity., Conclusion: Prepandemic samples from Africa show high levels of anti-SARS-CoV-2 seropositivity. At the country level, cross-reactivity tracks especially with malaria prevalence., Competing Interests: Declarations of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes., Methods and Findings: We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling., Conclusions: Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.

Objective: This study aimed to assess whether randomized controlled trials conducted in Africa with collaborators from outside Africa were more closely associated with health conditions that have a burden of disease that is of specific importance to Africa than with conditions of more general global importance or with conditions important to developed countries. We also assessed whether the source of funding influenced a study's relevance to Africa., Methods: We compared randomized controlled trials performed in Africa that looked at diseases specifically relevant to Africa (as determined by burden of disease criteria) with trials classified as looking at diseases of global importance or diseases important to developed countries in order to assess differences in collaboration and funding., Findings: Of 520 trials assessed, 347 studied diseases that are specifically important to Africa; 99 studied globally important diseases and 74 studied diseases that are important to developed countries. The strongest independent predictor of whether a study was of specifically African or global importance was the corresponding author's country of origin: African importance was negatively associated with a corresponding author being from South Africa (odds ratio (OR) = 0.04; 95% confidence interval (CI) = 0.02-0.10) but there was little difference between corresponding authors from other African countries and corresponding authors from countries outside Africa. The importance of a study to Africa was independently associated with having more non-African authors (OR per author = 1.31; 95% CI = 1.08-1.58), fewer trial sites (OR per site = 0.69; 95% CI = 0.50-0.96), and reporting of funding (OR = 2.14; 95% CI = 1.15-4.00). Similar patterns were present in the comparisons of trials studying diseases important to Africa versus those studying diseases important to developed countries with stronger associations overall. When funding was reported, private industry funding was negatively associated with African importance compared with global importance (OR = 0.31, P= 0.008 for African importance and OR = 0.51, P= 0.57 for importance for developed countries)., Conclusion: The relevance to Africa of trials conducted in Africa was not adversely affected by collaboration with non-African researchers but funding from private industry was associated with a decreased emphasis on diseases relevant to Africa.