Investing in Africa's scientific future.

Africa bears a disproportionate burden of infectious diseases, accounting for a substantial percentage of global cases. Malaria, HIV/AIDS, tuberculosis, cholera, Ebola, Lassa fever, and other tropical diseases, such as dengue and chikungunya, have had a profound impact on morbidity and mortality. Various factors contribute to the higher prevalence and incidence of infectious diseases in Africa, including socioeconomic challenges, limited access to health care, inadequate sanitation and hygiene infrastructure, climate-related factors, and endemicity of certain diseases in specific regions. A skilled workforce is crucial to addressing these challenges. Unfortunately, many countries in Africa often lack the required resources, and aspiring scientists frequently seek educational and career opportunities abroad, leading to a substantial loss of talent and expertise from the continent. This talent migration, referred to as "brain drain," exacerbates the existing training gaps and hampers the sustainability of research within Africa.

Genomic assessment of invasion dynamics of SARS-CoV-2 Omicron BA.1.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) now arise in the context of heterogeneous human connectivity and population immunity. Through a large-scale phylodynamic analysis of 115,622 Omicron BA.1 genomes, we identified >6,000 introductions of the antigenically distinct VOC into England and analyzed their local transmission and dispersal history. We find that six of the eight largest English Omicron lineages were already transmitting when Omicron was first reported in southern Africa (22 November 2021). Multiple datasets show that importation of Omicron continued despite subsequent restrictions on travel from southern Africa as a result of export from well-connected secondary locations. Initiation and dispersal of Omicron transmission lineages in England was a two-stage process that can be explained by models of the country's human geography and hierarchical travel network. Our results enable a comparison of the processes that drive the invasion of Omicron and other VOCs across multiple spatial scales.

Implementation of an efficient SARS-CoV-2 specimen pooling strategy for high throughput diagnostic testing.

The rapid identification and isolation of infected individuals remains a key strategy for controlling the spread of SARS-CoV-2. Frequent testing of populations to detect infection early in asymptomatic or presymptomatic individuals can be a powerful tool for intercepting transmission, especially when the viral prevalence is low. However, RT-PCR testing-the gold standard of SARS-CoV-2 diagnosis-is expensive, making regular testing of every individual unfeasible. Sample pooling is one approach to lowering costs. By combining samples and testing them in groups the number of tests required is reduced, substantially lowering costs. Here we report on the implementation of pooling strategies using 3-d and 4-d hypercubes to test a professional sports team in South Africa. We have shown that infected samples can be reliably detected in groups of 27 and 81, with minimal loss of assay sensitivity for samples with individual Ct values of up to 32. We report on the automation of sample pooling, using a liquid-handling robot and an automated web interface to identify positive samples. We conclude that hypercube pooling allows for the reliable RT-PCR detection of SARS-CoV-2 infection, at significantly lower costs than lateral flow antigen (LFA) tests.

Global disparities in SARS-CoV-2 genomic surveillance.

Genomic sequencing provides critical information to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments and vaccines, and guide public health responses. To investigate the spatiotemporal heterogeneity in the global SARS-CoV-2 genomic surveillance, we estimated the impact of sequencing intensity and turnaround times (TAT) on variant detection in 167 countries. Most countries submit genomes >21 days after sample collection, and 77% of low and middle income countries sequenced <0.5% of their cases. We found that sequencing at least 0.5% of the cases, with a TAT <21 days, could be a benchmark for SARS-CoV-2 genomic surveillance efforts. Socioeconomic inequalities substantially impact our ability to quickly detect SARS-CoV-2 variants, and undermine the global pandemic preparedness.

Dolutegravir for first-line antiretroviral therapy in low-income and middle-income countries: uncertainties and opportunities for implementation and research.

A new first-line antiretroviral therapy (ART) regimen containing dolutegravir is being rolled out in low-income and middle-income countries (LMICs). In studies from predominantly high-income settings, dolutegravir-based regimens had superior efficacy, tolerability, and durability compared with existing first-line regimens. However, several questions remain about the roll out of dolutegravir in LMICs, where most people with HIV are women of reproductive age, tuberculosis prevalence can be high, and access to viral load and HIV drug resistance testing is limited. Findings from cohort studies suggest that dolutegravir is safe when initiated in pregnancy, but more data are needed to determine the risk of adverse birth outcomes when dolutegravir-based regimens are initiated before conception. Increasing access to viral load testing to monitor the effectiveness of dolutegravir remains crucial, but the best strategy to manage patients with viraemia is unclear. Furthermore, evidence to support the effectiveness of dolutegravir when given with tuberculosis treatment is scarce, particularly in programmatic settings in LMICs. Lastly, whether nucleoside reverse transcriptase inhibitor resistance will affect the long-term efficacy of dolutegravir-based regimens in first-line, and potentially second-line, ART is unknown. Clinical trials, cohorts, and surveillance of HIV drug resistance will be necessary to answer these questions and to maximise the benefits of this new regimen.

Brief Report: Virologic Monitoring Can Be a Cost-Effective Strategy to Diagnose Treatment Failure on First-Line ART.

CD4 count testing is perceived to be an affordable strategy to diagnose treatment failure on first-line antiretroviral therapy. We hypothesize that the superior accuracy of viral load (VL) testing will result in less patients being incorrectly switched to more expensive and toxic second-line regimens. Using data from a drug resistance cohort, we show that CD4 testing is approximately double the cost to make 1 correct regimen switch under certain diagnostic thresholds (CD4 = US $499 vs. VL = US $186 or CD4 = US $3031 vs. VL = US $1828). In line with World Health Organization guidelines, our findings show that VL testing can be both an accurate and cost-effective treatment monitoring strategy.

Implementing HIV-1 genotypic resistance testing in antiretroviral therapy programs in Africa: needs, opportunities, and challenges.

Tremendous progress has been made with the scale-up of antiretroviral therapy in Africa, with an estimated seven million people now receiving antiretroviral therapy in the region. The long-term success of antiretroviral therapy programs depends on appropriate strategies to deal with potential threats, one of which is the emergence and spread of antiretroviral drug resistance. Whilst public health surveillance forms the mainstay of the World Health Organization approach to antiretroviral drug resistance, there is likely to be increasing demand for access to drug resistance testing as programs mature and as HIV clinical management becomes more complex. African-owned research initiatives have helped to develop affordable resistance testing appropriate for use in the region, and have developed delivery models for resistance testing at different levels of the public health system. Some upper-middle-income countries such as Botswana and South Africa have introduced drug resistance testing for selected patient groups to guide clinical management. The scale-up of resistance testing will require substantial expansion of clinical and laboratory capacity in the region, but the expertise and resources exist in Africa to support this. The long-term population health impact and cost-effectiveness of resistance testing in the region will also require further investigation.

The HIV type 1 epidemic in Bulgaria involves multiple subtypes and is sustained by continuous viral inflow from West and East European countries.

Little is known about the HIV-1 epidemic in Balkan countries. To fill the gap, we investigated the viral genetic diversity in Bulgaria, by sequencing and phylogenetic characterization of 86 plasma samples collected between 2002 and 2006 from seropositive individuals diagnosed within 1986-2006. Analysis of pol gene sequences assigned 51% of the samples to HIV-1 subtype B and 27% to subtype A1. HIV-1 subtype C, F, G, H, and a few putative recombinant forms were also found. Phylogenetic and molecular clock analysis showed a continuous exchange of subtype A and B between Bulgaria and Western as well as other Eastern European countries. At least three separate introductions of HIV-1 subtype A and four of HIV-1 subtype B have occurred within the past 25 years in Bulgaria. The central geographic location of Bulgaria, the substantial genetic heterogeneity of the epidemic with multiple subtypes, and the significant viral flow observed to and from the Balkan countries have the potential to modify the current HIV-1 epidemiological structure in Europe and highlight the importance of more extensive and continuous monitoring of the epidemic in the Balkans.

Assessment of automated genotyping protocols as tools for surveillance of HIV-1 genetic diversity.

BACKGROUND: The routine use of drug resistance testing provides an abundant source of HIV-1 sequence data. However, it is not clear how reliable standard genotyping of these sequences is for describing HIV-1 genetic variation and for detecting novel genetic variants and epidemiological trends. OBJECTIVES: To compare assignment of HIV-1 resistance test sequences to reference strains across commonly used genotyping protocols. METHODS: Subtype assignments were compared across three standard genotyping protocols for 10 537 resistance test sequences, representing approximately one-fifth of all reported infections in the United Kingdom. Sequences that were inconsistently genotyped across methods, or that were unassigned by at least one method, were examined for evidence of recombination using sliding-window-based approaches. RESULTS: Although agreement across methods was high for subtypes B, C and H, it was generally much lower (< 50%) for other subtypes. Disagreement between methods typically involved closely related, but epidemiologically distinct, groups or involved a significant proportion ( approximately 12%) of divergent sequences in which analysis revealed widespread evidence of recombination and a remarkable diversity of unusual recombinant forms. CONCLUSIONS: With frequent long-distance transfer of viral strains and widespread recombination between them, genetic and epidemiological relationships within HIV-1 are becoming increasingly complex. Current methods of subtype assignment vary in their ability to identify novel genetic variants and to distinguish epidemiologically distinct strains. Capturing meaningful epidemiological information from resistance test data will require a critical understanding of the methodologies used in order to appreciate the possible sources of error and misclassification.