15 research outputs found

    Book Review: The Rise and Fall of the ANC Youth League

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    In The Rise and Fall of the ANC Youth League, the author intends to revive the activism of South Africa’s African National Congress Youth League (ANCYL) and end ‘the perception that the organisation is a get-rich-quick scheme’. The book is a commendable effort to tell the story of the dying organisation and is written by an insider (the author is a former member of the ANCYL National Task Team). The ANCYL has an illustrious history, having been founded by such ANC luminaries as Anton Lembede, Nelson Mandela, and Oliver Tambo in 1944. Buoyed by youthful militancy, one of the founding impulses of the Youth League was to make the ANC more accessible to ordinary South Africans who felt, more keenly and direly, the racial injustices that preceded apartheid and were codified into law after 1948

    Suboptimal patterns of provider initiated HIV testing and counselling, antiretroviral therapy eligibility assessment and referral in primary health clinic attendees in Blantyre, Malawi.

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    OBJECTIVE: To understand reasons for suboptimal and delayed uptake of antiretroviral therapy (ART) by describing the patterns of HIV testing and counselling (HTC) and outcomes of ART eligibility assessments in primary clinic attendees. METHODS: All clinic attendances and episodes of HTC were recorded at two clinics in Blantyre. A cohort of newly diagnosed HIV-positive adults (>15 years) was recruited and exit interviews undertaken. Logistic regression models were constructed to investigate factors associated with referral to start ART. Qualitative interviews were conducted with providers and patients. RESULTS: There were 2398 episodes of HTC during 18,021 clinic attendances (13.3%) between January and April 2011. The proportion of clinic attendees undergoing HTC was lowest in non-pregnant women (6.3%) and men (8.5%), compared with pregnant women (47.2%). Men had more advanced HIV infection than women (79.7% WHO stage 3 or 4 vs. 56.4%). Problems with WHO staging and access to CD4 counts affected ART eligibility assessments; only 48% completed ART eligibility assessment, and 54% of those reporting WHO stage 3/4 illnesses were not referred to start ART promptly. On multivariate analysis, HIV-positive pregnant women were significantly less likely to be referred directly for ART initiation (adjusted OR: 0.29, 95% CI: 0.13-0.63). CONCLUSIONS: These data show that provider-initiated testing and counselling (PITC) has not yet been fully implemented at primary care clinics. Suboptimal ART eligibility assessments and referral (reflecting the difficulties of WHO staging in primary care) mean that simplified eligibility assessment tools are required to reduce unnecessary delay and attrition in the pre-ART period. Simplified initiation criteria for pregnant women, as being introduced in Malawi, should improve linkage to ART

    Distribution of Rotavirus alphagastroenteritidis Strains in Blantyre, Malawi, During and After the COVID-19 Pandemic

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    Rotavirus alphagastroenteritidis remains the leading cause of severe gastroenteritis in children under five years, despite widespread vaccine use. The COVID-19 pandemic disrupted healthcare and vaccination delivery, while non-pharmacological interventions may have influenced R. alphagastroenteritidis transmission. We conducted hospital-based surveillance of R. alphagastroenteritidis gastroenteritis at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi, from October 2019 to October 2024. Children under five presenting with acute gastroenteritis were enrolled; 99.1% of vaccine-eligible participants had received at least one R. alphagastroenteritidis vaccine dose. Stool samples were tested for R. alphagastroenteritidis by enzyme immunoassay (EIA) and genotyped using RT-PCR. Among 1135 enrolled children, 29.1% (330/1135) were R. alphagastroenteritidis-positive. Cases occurred year-round except for December 2020–January 2021, when no R. alphagastroenteritidis infections were detected, and February–March 2023, when no samples were collected. The prevalence varied significantly by age group between children greater than 23 months of age to the rest of the age groups (&lt;6 months, 6–11 months, and 12–22 months) (p = 0.0046). The most common R. alphagastroenteritidis G-genotypes were G3 (38.7%), G2 (25.4%), and G12 (17.2%), with G2 emerging as the predominant strain from June 2023. G3P[8] was the most frequent G–P combination (25%). Its overall prevalence did not change during the pandemic; however, genotype distribution shifted compared to pre-COVID-19 patterns. Sustained surveillance and genomic analyses are essential to monitor evolving strain dynamics and inform vaccine policy.</p

    Exploring natural immune responses to shigella exposure using multiplex bead assays on dried blood spots in high burden countries: Protocol from a multisite diarrhea surveillance study

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    Background: Molecular diagnostics on human fecal samples have identified a larger burden of shigellosis than previously appreciated by culture. Evidence of fold changes in immunoglobulin G (IgG) to conserved and type-specific Shigella antigens could be used to validate the molecular assignment of type-specific Shigella as the etiology of acute diarrhea and support polymerase chain reaction (PCR)-based microbiologic end points for vaccine trials.Methods: We will test dried blood spots collected at enrollment and 4 weeks later using bead-based immunoassays for IgG to invasion plasmid antigen B and type-specific lipopolysaccharide O-antigen for Shigella flexneri 1b, 2a, 3a, and 6 and Shigella sonnei in Shigella-positive cases and age-, site-, and season-matched test-negative controls from all sites in the Enterics for Global Health (EFGH) Shigella surveillance study. Fold antibody responses will be compared between culture-positive, culture-negative but PCR-attributable, and PCR-positive but not attributable cases and test-negative controls. Age- and site-specific seroprevalence distributions will be identified, and the association between baseline antibodies and Shigella attribution will be estimated.Conclusions: The integration of these assays into the EFGH study will help support PCR-based attribution of acute diarrhea to type-specific Shigella, describe the baseline seroprevalence of conserved and type-specific Shigella antibodies, and support correlates of protection for immunity to Shigella diarrhea. These insights can help support the development and evaluation of Shigella vaccine candidates

    Acute rotavirus infection is associated with the induction of circulating memory CD4+ T cell subsets

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    Abstract Strong CD4+ T cell-mediated immune protection following rotavirus infection has been observed in animal models, but its relevance in humans remains unclear. Here, we characterized acute and convalescent CD4+ T cell responses in children who were hospitalized with rotavirus-positive and rotavirus-negative diarrhoea in Blantyre, Malawi. Children presenting with laboratory-confirmed rotavirus infection had higher proportions of effector and central memory T helper 2 cells during acute infection i.e., at disease presentation compared to convalescence, 28 days post-infection defined by a follow-up 28 days after acute infection. However, circulating cytokine-producing (IFN-γ and/or TNF-α) rotavirus-specific VP6-specific CD4+ T cells were rarely detectable in children with rotavirus infection at both acute and convalescent stages. Moreover, following whole blood mitogenic stimulation, the responding CD4+ T cells were predominantly non-cytokine producers of IFN-γ and/or TNF-α. Our findings demonstrate limited induction of anti-viral IFN-γ and/or TNF-α-producing CD4+ T cells in rotavirus-vaccinated Malawian children following the development of laboratory-confirmed rotavirus infection

    Leveraging Beneficial Off-Target Effects of Live-Attenuated Rotavirus Vaccines

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    Following the introduction of live-attenuated rotavirus vaccines in many countries, a notable reduction in deaths and hospitalisations associated with diarrhoea in children &lt;5 years of age has been reported. There is growing evidence to suggest that live-attenuated vaccines also provide protection against other infections beyond the vaccine-targeted pathogens. These so called off-target effects of vaccination have been associated with the tuberculosis vaccine Bacille Calmette Guérin (BCG), measles, oral polio and recently salmonella vaccines, and are thought to be mediated by modified innate and possibly adaptive immunity. Indeed, rotavirus vaccines have been reported to provide greater than expected reductions in acute gastroenteritis caused by other enteropathogens, that have mostly been attributed to herd protection and prior underestimation of rotavirus disease. Whether rotavirus vaccines also alter the immune system to reduce non targeted gastrointestinal infections has not been studied directly. Here we review the current understanding of the mechanisms underlying off-target effects of vaccines and propose a mechanism by which the live-attenuated neonatal rotavirus vaccine, RV3-BB, could promote protection beyond the targeted pathogen. Finally, we consider how vaccine developers may leverage these properties to improve health outcomes in children, particularly those in low-income countries where disease burden and mortality is disproportionately high relative to developed countries.</jats:p

    Universal testing and treatment as an HIV prevention strategy: research questions and methods.

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    Achieving high coverage of antiretroviral treatment (ART) in resource-poor settings will become increasingly difficult unless HIV incidence can be reduced substantially. Universal voluntary counselling and testing followed by immediate initiation of ART for all those diagnosed HIV-positive (universal testing and treatment, UTT) has the potential to reduce HIV incidence dramatically but would be very challenging and costly to deliver in the short term. Early modelling work in this field has been criticised for making unduly optimistic assumptions about the uptake and coverage of interventions. In future work, it is important that model parameters are realistic and based where possible on empirical data. Rigorous research evidence is needed before the UTT approach could be considered for wide-scale implementation. This paper reviews the main areas that need to be explored. We consider in turn research questions related to the provision of services for universal testing, services for immediate treatment of HIV-positives and the population-level impact of UTT, and the research methods that could be used to address these questions. Ideally, initial feasibility studies should be carried out to investigate the acceptability, feasibility and uptake of UTT services. If these studies produce promising results, there would be a strong case for a cluster-randomised trial to measure the impact of a UTT intervention on HIV incidence, and we consider the main design features of such a trial

    Rotavirus Genotypes in Hospitalized Children with Acute Gastroenteritis before and after Rotavirus Vaccine Introduction in Blantyre, Malawi, 1997-2019

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    Background: Rotavirus vaccine (Rotarix [RV1]) has reduced diarrhea-associated hospitalizations and deaths in Malawi. We examined the trends in circulating rotavirus genotypes in Malawi over a 22-year period to assess the impact of RV1 introduction on strain distribution. Methods: Data on rotavirus-positive stool specimens among children aged <5 years hospitalized with diarrhea in Blantyre, Malawi before (July 1997-October 2012, n = 1765) and after (November 2012-October 2019, n = 934) RV1 introduction were analyzed. Rotavirus G and P genotypes were assigned using reverse-transcription polymerase chain reaction. Results: A rich rotavirus strain diversity circulated throughout the 22-year period; Shannon (H′) and Simpson diversity (D′) indices did not differ between the pre- and postvaccine periods (H′ P <. 149; D′ P <. 287). Overall, G1 (n = 268/924 [28.7%]), G2 (n = 308/924 [33.0%]), G3 (n = 72/924 [7.7%]), and G12 (n = 109/924 [11.8%]) were the most prevalent genotypes identified following RV1 introduction. The prevalence of G1P[8] and G2P[4] genotypes declined each successive year following RV1 introduction, and were not detected after 2018. Genotype G3 reemerged and became the predominant genotype from 2017 onward. No evidence of genotype selection was observed 7 years post-RV1 introduction. Conclusions: Rotavirus strain diversity and genotype variation in Malawi are likely driven by natural mechanisms rather than vaccine pressure

    High SARS-CoV-2 seroprevalence in health care workers but relatively low numbers of deaths in urban Malawi

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    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.</ns3:p
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