Metagenomic next-generation sequencing (mNGS), the shotgun sequencing of RNA and DNA from clinical samples, has proved useful for broad-spectrum pathogen detection and the genomic surveillance of ...viral outbreaks. An additional target enrichment step is generally needed for high-sensitivity pathogen identification in low-titre infections, yet available methods using PCR or capture probes can be limited by high cost, narrow scope of detection, lengthy protocols and/or cross-contamination. Here, we developed metagenomic sequencing with spiked primer enrichment (MSSPE), a method for enriching targeted RNA viral sequences while simultaneously retaining metagenomic sensitivity for other pathogens. We evaluated MSSPE for 14 different viruses, yielding a median tenfold enrichment and mean 47% (±16%) increase in the breadth of genome coverage over mNGS alone. Virus detection using MSSPE arboviral or haemorrhagic fever viral panels was comparable in sensitivity to specific PCR, demonstrating 95% accuracy for the detection of Zika, Ebola, dengue, chikungunya and yellow fever viruses in plasma samples from infected patients. Notably, sequences from re-emerging and/or co-infecting viruses that have not been specifically targeted a priori, including Powassan and Usutu, were successfully enriched using MSSPE. MSSPE is simple, low cost, fast and deployable on either benchtop or portable nanopore sequencers, making this method directly applicable for diagnostic laboratory and field use.
Summary Background HIV-1 drug resistance to older thymidine analogue nucleoside reverse transcriptase inhibitor drugs has been identified in sub-Saharan Africa in patients with virological failure of ...first-line combination antiretroviral therapy (ART) containing the modern nucleoside reverse transcriptase inhibitor tenofovir. We aimed to investigate the prevalence and correlates of thymidine analogue mutations (TAM) in patients with virological failure of first-line tenofovir-containing ART. Methods We retrospectively analysed patients from 20 studies within the TenoRes collaboration who had locally defined viral failure on first-line therapy with tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI; nevirapine or efavirenz) in sub-Saharan Africa. Baseline visits in these studies occurred between 2005 and 2013. To assess between-study and within-study associations, we used meta-regression and meta-analyses to compare patients with and without TAMs for the presence of resistance to tenofovir, cytosine analogue, or NNRTIs. Findings Of 712 individuals with failure of first-line tenofovir-containing regimens, 115 (16%) had at least one TAM. In crude comparisons, patients with TAMs had lower CD4 counts at treatment initiation than did patients without TAMs (60·5 cells per μL IQR 21·0–128·0 in patients with TAMS vs 95·0 cells per μL 37·0–177·0 in patients without TAMs; p=0·007) and were more likely to have tenofovir resistance (93 81% of 115 patients with TAMs vs 352 59% of 597 patients without TAMs; p<0·0001), NNRTI resistance (107 93% vs 462 77%; p<0·0001), and cytosine analogue resistance (100 87% vs 378 63%; p=0·0002). We detected associations between TAMs and drug resistance mutations both between and within studies; the correlation between the study-level proportion of patients with tenofovir resistance and TAMs was 0·64 (p<0·0001), and the odds ratio for tenofovir resistance comparing patients with and without TAMs was 1·29 (1·13–1·47; p<0·0001) Interpretation TAMs are common in patients who have failure of first-line tenofovir-containing regimens in sub-Saharan Africa, and are associated with multidrug resistant HIV-1. Effective viral load monitoring and point-of-care resistance tests could help to mitigate the emergence and spread of such strains. Funding The Wellcome Trust.
According to the WHO report, a ninefold increase in dengue infection in Africa has been reported in 2023 as compared with 2019.4 As the misdiagnosis of dengue is common in Africa due to limited ...laboratory capacities, the numbers reported from the countries might be even higher. ...we strongly suggest countries make concerted efforts to proactively integrate the dengue outbreak preparedness and response activities into their public health surveillance systems and create an enabling environment and resources for the integration, including enhancing the diagnostic capacity. ...to effectively control the spread of cholera, the SADC recommended that the member states develop and implement a multisectoral response plan incorporating climatic effects on cholera re-emergence.7 Other African countries have also made several efforts to mitigate the spread and impacts of cholera in their countries, including cholera as one of their priority diseases, requiring public health surveillance and response and developing guidelines to support the implementation of multisectoral cholera prevention and control plans and strategies. Climate change is recognised as one of the most critical threats to attaining the ‘Agenda 2063: ...to mitigate and adapt to climate change impacts in Africa, the Africa Union developed a strategic plan (2022–2032) aiming at strengthening the adaptive capacity of affected communities and managing the risks related to climate change, pursuing equitable and transformative low emission, climate-resilient development pathways—enhancing Africa’s capacity to mobilise resources and improve access to and development of technology for ambitious climate action, and enhancing inclusion, alignment, cooperation, and ownership of climate strategies, policies, programmes and plans across all spheres of government and stakeholder groupings.10 As a leading and coordinating Pan-African Agency, Africa CDC has prioritised the One Health approach in its strategic plan (2023–2027) to prevent and control high-burden diseases adequately.11 However, translating these plans into practice is resource-intensive and requires concerted efforts and collaboration of national and international stakeholders.
Since the ignition of the HIV-1 group M pandemic in the beginning of the 20th century, group M lineages have spread heterogeneously throughout the world. Subtype C spread rapidly through sub-Saharan ...Africa and is currently the dominant HIV lineage worldwide. Yet the epidemiological and evolutionary circumstances that contributed to its epidemiological expansion remain poorly understood. Here, we analyse 346 novel pol sequences from the DRC to compare the evolutionary dynamics of the main HIV-1 lineages, subtypes A1, C and D. Our results place the origins of subtype C in the 1950s in Mbuji-Mayi, the mining city of southern DRC, while subtypes A1 and D emerged in the capital city of Kinshasa, and subtypes H and J in the less accessible port city of Matadi. Following a 15-year period of local transmission in southern DRC, we find that subtype C spread at least three-fold faster than other subtypes circulating in Central and East Africa. In conclusion, our results shed light on the origins of HIV-1 main lineages and suggest that socio-historical rather than evolutionary factors may have determined the epidemiological fate of subtype C in sub-Saharan Africa.
In addition to the direct effects of conflict on human and infrastructure loss, conflict-affected communities are also highly vulnerable to enormous public health threats including, but not limited ...to outbreaks, gender-based violence, mental and psycho-social problems, maternal and child health issues and nutritional problems.2 Wars and armed conflicts disrupt the health system and essential life-saving services are often jeopardised or not prioritised. ...conflict-affected communities make forced decisions to migrate internally or cross international borders—risking their lives and well-being.2 Moreover, global communities in general and African people specifically have been affected by the bi-directional interplay between war and climate change—wars and armed conflicts cause environmental degradation, and climate change in turn, aggravates armed conflicts. ...when conflict emerges, the unprepared health system cannot resist its impact. ...we call on local and international public health communities, including researchers, to exert concerted efforts to stand in solidarity, without any discrimination, with conflict-affected communities in their critical needs─possibly in preventing the conflicts and mitigating their impacts.
ABSTRACT
The aim of this study is to determine how stakeholder engagement can be adapted for the conduct of COVID‐19‐related clinical trials in sub‐Saharan Africa. Nine essential stakeholder ...engagement practices were reviewed: formative research; stakeholder engagement plan; communications and issues management plan; protocol development; informed consent process; standard of prevention for vaccine research and standard of care for treatment research; policies on trial‐related physical, psychological, financial, and/or social harms; trial accrual, follow‐up, exit trial closure and results dissemination; and post‐trial access to trial products or procedures. The norms, values, and practices of collectivist societies in Sub‐Saharan Africa and the low research literacy pose challenges to the conduct of clinical trials. Civil‐society organizations, members of community advisory boards and ethics committees, young persons, COVID‐19 survivors, researchers, government, and the private sector are assets for the implementation and translation of COVID‐19 related clinical trials. Adapting ethics guidelines to the socio‐cultural context of the region can facilitate achieving the aim of stakeholder engagement.
Fishing communities around Lake Victoria in sub-Saharan Africa have been characterised as a population at high risk of HIV-infection.
Using data from a cohort of HIV-positive individuals aged 13-49 ...years, enrolled from 5 fishing communities on Lake Victoria between 2009-2011, we sought to identify factors contributing to the epidemic and to understand the underlying structure of HIV transmission networks. Clinical and socio-demographic data were combined with HIV-1 phylogenetic analyses. HIV-1 gag-p24 and env-gp-41 sub-genomic fragments were amplified and sequenced from 283 HIV-1-infected participants. Phylogenetic clusters with ≥2 highly related sequences were defined as transmission clusters. Logistic regression models were used to determine factors associated with clustering.
Altogether, 24% (n = 67/283) of HIV positive individuals with sequences fell within 34 phylogenetically distinct clusters in at least one gene region (either gag or env). Of these, 83% occurred either within households or within community; 8/34 (24%) occurred within household partnerships, and 20/34 (59%) within community. 7/12 couples (58%) within households clustered together. Individuals in clusters with potential recent transmission (11/34) were more likely to be younger 71% (15/21) versus 46% (21/46) in un-clustered individuals and had recently become resident in the community 67% (14/21) vs 48% (22/46). Four of 11 (36%) potential transmission clusters included incident-incident transmissions. Independently, clustering was less likely in HIV subtype D (adjusted Odds Ratio, aOR = 0.51 95% CI 0.26-1.00) than A and more likely in those living with an HIV-infected individual in the household (aOR = 6.30 95% CI 3.40-11.68).
A large proportion of HIV sexual transmissions occur within house-holds and within communities even in this key mobile population. The findings suggest localized HIV transmissions and hence a potential benefit for the test and treat approach even at a community level, coupled with intensified HIV counselling to identify early infections.
Introduction
Young men who have sex with men (MSM) and transgender women (TGW) face stigmas that hinder access to healthcare. The aim of the study was to understand age‐related determinants of ...healthcare needs and engagement among MSM and TGW.
Methods
The TRUST/RV368 cohort provides integrated prevention and treatment services for HIV and other sexually transmitted infections (STIs) tailored to the needs of sexual and gender minorities. MSM and TGW aged ≥16 years in Abuja and ≥18 years Lagos, Nigeria, completed standardized behavioural questionnaires and were tested for HIV, Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) every three months for up to 18 months. Logistic regression was used to estimate adjusted odds ratios (aORs) for associations of age and other factors with outcomes of interest upon enrolment, including HIV care continuum steps – HIV testing, ART initiation and viral suppression <1000 copies/mL. Cox proportional hazards models were used to calculate adjusted hazard ratios (aHRs) for associations with incident infections.
Results
Between March 2013 and February 2019, 2123 participants were enrolled with median age 23 (interquartile range 21 to 27) years. Of 1745 tested, 865 (49.6%) were living with HIV. HIV incidence was 11.6/100 person‐years PY, including 23.1/100PY (95% CI 15.5 to 33.1) among participants aged 16 to 19 years and 23.8/100 PY (95% CI 13.6 to 39.1) among TGW. Compared to participants aged ≥25 years, those aged 16 to 19 years had decreased odds of prior HIV testing (aOR 0.40 95% CI 0.11 to 0.92), disclosing same‐sex sexual practices to healthcare workers (aOR 0.53 95% CI 0.36 to 0.77) and receiving HIV prevention information (aOR 0.60 95% CI 0.41 to 0.87). They had increased odds of avoiding healthcare (aOR 1.94 95% CI 1.3 to 2.83) and engaging in transactional sex (aOR 2.76 95% CI 1.92 to 3.71). Age 16 to 19 years was independently associated with increased incidence of HIV (aHR 4.09 95% CI 2.33 to 7.49), NG (aHR 3.91 95% CI 1.90 to 8.11) and CT (aHR 2.74 95% CI 1.48 to 5.81).
Conclusions
Young MSM and TGW demonstrated decreased healthcare engagement and higher incidence of HIV and other STIs as compared to older participants in this Nigerian cohort. Interventions to address unique obstacles to healthcare engagement by adolescents and young adults are needed to curb the spread of HIV and other STIs among MSM and TGW in Nigeria.
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