Resisting Immune Exhaustion in HIV-1 Infection

Sarah Rowland-Jones and Thushan de Silva discuss a new study describing the fate of cytotoxic T lymphocytes responding to HIV-1 from very early through to chronic infection

Antiretroviral Therapy for HIV-2 Infection: Recommendations for Management in Low-Resource Settings

HIV-2 contributes approximately a third to the prevalence of HIV in West Africa and is present in significant amounts in several low-income countries outside of West Africa with historical ties to Portugal. It complicates HIV diagnosis, requiring more expensive and technically demanding testing algorithms. Natural polymorphisms and patterns in the development of resistance to antiretrovirals are reviewed, along with their implications for antiretroviral therapy. Nonnucleoside reverse transcriptase inhibitors, crucial in standard first-line regimens for HIV-1 in many low-income settings, have no effect on HIV-2. Nucleoside analogues alone are not sufficiently potent enough to achieve durable virologic control. Some protease inhibitors, in particular those without ritonavir boosting, are not sufficiently effective against HIV-2. Following review of the available evidence and taking the structure and challenges of antiretroviral care in West Africa into consideration, the authors make recommendations and highlight the needs of special populations

Immune Reconstitution Inflammatory Syndrome and the Influence of T Regulatory Cells: A Cohort Study in the Gambia

The factors associated with the development of immune reconstitution inflammatory syndrome in HIV patients commencing antiretroviral therapy have not been fully elucidated. Using a longitudinal study design, this study addressed whether alteration in the levels of T regulatory cells contributed to the development of IRIS in a West African cohort of HIV-1 and HIV-2 patients. Seventy-one HIV infected patients were prospectively recruited to the study and followed up for six months. The patients were categorized as IRIS or non-IRIS cases following published clinical guidelines. The levels of T regulatory cells were measured using flow cytometry at baseline and all follow-up visits. Baseline cytokine levels of IL-2, IL-6, IFN-(Gamma), TNF-(Alpha), MIP-1(Beta), IL-1, IL-12, IL-13, and IL-10 were measured in all patients

HIV-1 subtype distribution in the Gambia and the significant presence of CRF49_cpx, a novel circulating recombinant form

Background: Detailed local HIV-1 sequence data are essential for monitoring the HIV epidemic, for maintaining sensitive sequence-based diagnostics, and to aid in designing vaccines.Results: Reported here are full envelope sequences derived from 38 randomly selected HIV-1 infections identified at a Gambian clinic between 1991 and 2009. Special care was taken to generate sequences from circulating viral RNA as uncloned products, either by limiting dilution or single genome amplification polymerase chain reaction (PCR). Within these 38 isolates, eight were subtyped as A and 18 as CRF02_AG. A small number of subtype B, C, D viruses were identified. Surprising, however, was the identification of six isolates with subtype J-like envelopes, a subtype found normally in Central Africa and the Democratic Republic of the Congo (DRC), with gag p24 regions that clustered with subtype A sequences. Near full-length sequence from three of these isolates confirmed that these represent a novel circulating recombinant form of HIV-1, now named CRF49_cpx.Conclusions: This study expands the HIV-1 sequence database from the Gambia and will provide important data for HIV diagnostics, patient care, and vaccine development

Molecular epidemiology of endemic Human T-Lymphotropic virus 1 (HTLV-1) in a community in rural Guinea-Bissau

No abstract available

Protocol for the COG-UK hospital-onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in UK NHS hospitals

OBJECTIVES: Nosocomial transmission of SARS-CoV-2 has been a significant cause of mortality in National Health Service (NHS) hospitals during the COVID-19 pandemic. The COG-UK Consortium Hospital-Onset COVID-19 Infections (COG-UK HOCI) study aims to evaluate whether the use of rapid whole-genome sequencing of SARS-CoV-2, supported by a novel probabilistic reporting methodology, can inform infection prevention and control (IPC) practice within NHS hospital settings. DESIGN: Multicentre, prospective, interventional, superiority study. SETTING: 14 participating NHS hospitals over winter–spring 2020/2021 in the UK. PARTICIPANTS: Eligible patients must be admitted to hospital with first-confirmed SARS-CoV-2 PCR-positive test result >48 hour from time of admission, where COVID-19 diagnosis not suspected on admission. The projected sample size is 2380 patients. INTERVENTION: The intervention is the return of a sequence report, within 48 hours in one phase (rapid local lab processing) and within 5–10 days in a second phase (mimicking central lab), comparing the viral genome from an eligible study participant with others within and outside the hospital site. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes are incidence of Public Health England (PHE)/IPC-defined SARS-CoV-2 hospital-acquired infection during the baseline and two interventional phases, and proportion of hospital-onset cases with genomic evidence of transmission linkage following implementation of the intervention where such linkage was not suspected by initial IPC investigation. Secondary outcomes include incidence of hospital outbreaks, with and without sequencing data; actual and desirable changes to IPC actions; periods of healthcare worker (HCW) absence. Health economic analysis will be conducted to determine cost benefit of the intervention. A process evaluation using qualitative interviews with HCWs will be conducted alongside the study. TRIAL REGISTRATION NUMBER: ISRCTN50212645. Pre-results stage. This manuscript is based on protocol V.6.0. 2 September 2021

Potential impact of influenza vaccine roll-out on antibiotic use in Africa

Background Influenza infections result in both inappropriate and appropriate antibiotic prescribing. There is a huge burden of both influenza and infections caused by antimicrobial-resistant pathogens in Africa. Influenza vaccines have the potential to reduce appropriate antibiotic use, through reduction of secondary bacterial infections, as well as to reduce levels of influenza misdiagnosed and treated as a bacterial infection (inappropriate). Objectives To estimate potential reductions in antibiotic use that are achievable by introducing an influenza vaccine into various African settings. Methods Influenza incidence was combined with population size, vaccine and health system characteristics. Results We estimated that the direct impact of vaccination could avert more than 390 prescriptions per 100 000 population per year if a 50% efficacious influenza vaccine at 30% coverage was introduced to adults >65 years old in South Africa or children 2–5 years old in Senegal. Across Africa, purely through reducing the number of severe acute respiratory infections, the same vaccine characteristics could avert at least 24 000 antibiotic prescriptions per year if given to children <5 years old. Conclusions The introduction of an influenza vaccine into multiple African settings could have a dramatic indirect impact on antibiotic usage. Our values are limited underestimates, capturing only the direct impact of vaccination in a few settings and risk groups. This is owing to the huge lack of epidemiological information on antibiotic use and influenza in Africa. However, it is likely that influenza vaccination in Africa could substantially impact antibiotic usage in addition to influenza-related mortality and morbidity

Maternal proviral load and vertical transmission of Human T cell Lymphotropic Virus type 1 in Guinea-Bissau

The relative importance of routes of transmission of human T cell lymphotropic virus type 1 (HTLV-1) in Guinea-Bissau is largely unknown; vertical transmission is thought to be important, but there are very few existing data. We aimed to examine factors associated with transmission in mothers and children in Guinea-Bissau, where HTLV-1 is endemic (prevalence of 5% in the adult population). A cross-sectional survey was performed among mothers and their children (aged <15 years) in a rural community in Guinea-Bissau. A questionnaire to identify risk factors for infection and a blood sample were obtained. HTLV-1 proviral load in peripheral blood was determined and PCR was performed to compare long terminal repeat (LTR) sequences in mother-child pairs. Fourteen out of 55 children (25%) of 31 HTLV-1-infected mothers were infected versus none of 70 children of 30 uninfected mothers. The only factor significantly associated with HTLV-1 infection in the child was the proviral load of the mother; the risk of infection increased significantly with the log(10) proviral load in the mother's peripheral blood (OR 5.5, 95% CI 2.1-14.6, per quartile), adjusted for weaning age and maternal income. HTLV-1 sequences of the LTR region obtained from mother-child pairs were identical within pairs but differed between the pairs. Vertical transmission plays an important role in HTLV-1 transmission in this community in Guinea-Bissau. The risk of transmission increases with the mother's proviral load in the peripheral blood. Identical sequences in mother-child pairs give additional support to the maternal source of the children's infectio

Effect of intra-partum azithromycin on the development of the infant nasopharyngeal microbiota: A post hoc analysis of a double-blind randomized trial.

BACKGROUND: Sepsis is a leading cause of neonatal death. Intrapartum azithromycin reduces neonatal nasopharyngeal carriage of potentially pathogenic bacteria, a prerequisite for sepsis. Early antibiotic exposure has been associated with microbiota perturbations with varying effects. This study aims to understand the effect of intrapartum azithromycin intervention on the developing nasopharyngeal microbiota of the child. METHODS: Using 16S rRNA gene sequencing, we analysed the microbiota of 343 nasopharyngeal samples collected from birth to 12 months from 109 healthy infants selected from a double-blind randomized placebo-controlled clinical trial conducted in the Gambia (PregnAnZI-1). In the trial, 829 women were given 2g oral azithromycin or placebo (1:1) during labour with the objective of reducing bacterial carriage in mother and child during the neonatal period. The post-hoc analysis presented here assessed the effect of the intervention on the child nasopharyngeal microbiota development. FINDINGS: 55 children were from mothers given azithromycin and 54 from mothers given placebo. Comparing arms, we found an increase in alpha-diversity at day-6 (p = 0·018), and a significant effect on overall microbiota composition at days 6 and 28 (R2 = 4.4%, q = 0·007 and R2 = 2.3%, q = 0·018 respectively). At genus level, we found lower representation of Staphylococcus at day-6 (q = 0·0303) and higher representation of Moraxella at 12 months (q = 0·0443). Unsupervised clustering of samples by microbial community similarity showed different community dynamics between the intervention and placebo arms during the neonatal period. INTERPRETATION: These results indicate that intrapartum azithromycin caused short-term alterations in the nasopharyngeal microbiota with modest overall effect at 12 months of age. Further exploration of the effects of these variations on microbiome function will give more insight on the potential risks and benefits, for the child, associated with this intervention. FUNDING: This work was jointly funded by the Medical Research Council (UK) (MC_EX_MR/J010391/1/MRC), Bill & Melinda Gates Foundation (OPP1196513), and MRCG@LSHTM Doctoral Training Program