Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression.

Innate lymphoid cells (ILCs) play a central role in the response to infection by secreting cytokines crucial for immune regulation, tissue homeostasis, and repair. Although dysregulation of these systems is central to pathology, the impact of HIV-1 on ILCs remains unknown. We found that human blood ILCs were severely depleted during acute viremic HIV-1 infection and that ILC numbers did not recover after resolution of peak viremia. ILC numbers were preserved by antiretroviral therapy (ART), but only if initiated during acute infection. Transcriptional profiling during the acute phase revealed upregulation of genes associated with cell death, temporally linked with a strong IFN acute-phase response and evidence of gut barrier breakdown. We found no evidence of tissue redistribution in chronic disease and remaining circulating ILCs were activated but not apoptotic. These data provide a potential mechanistic link between acute HIV-1 infection, lymphoid tissue breakdown, and persistent immune dysfunction.

Molecular Characterization of Corynebacterium diphtheriae Outbreak Isolates, South Africa, March-June 2015.

In 2015, a cluster of respiratory diphtheria cases was reported from KwaZulu-Natal Province in South Africa. By using whole-genome analysis, we characterized 21 Corynebacterium diphtheriae isolates collected from 20 patients and contacts during the outbreak (1 patient was infected with 2 variants of C. diphtheriae). In addition, we included 1 cutaneous isolate, 2 endocarditis isolates, and 2 archived clinical isolates (ca. 1980) for comparison. Two novel lineages were identified, namely, toxigenic sequence type (ST) ST-378 (n = 17) and nontoxigenic ST-395 (n = 3). One archived isolate and the cutaneous isolate were ST-395, suggesting ongoing circulation of this lineage for >30 years. The absence of preexisting molecular sequence data limits drawing conclusions pertaining to the origin of these strains; however, these findings provide baseline genotypic data for future cases and outbreaks. Neither ST has been reported in any other country; this ST appears to be endemic only in South Africa.

Ten years of ear, nose and throat (ENT) services in Southern Africa: a scoping review.

BACKGROUND: While ear, nose, and throat (ENT) diseases are a substantial threat to global health, comprehensive reviews of ENT services in Southern Africa remain scarce. OBJECTIVE: This scoping review provides a decade-long overview of ENT services in Southern Africa and identifies gaps in healthcare provision. From the current literature, we hope to provide evidence-based recommendations to mitigate the challenges faced by the resource-limited ENT service. DATA SOURCES: PubMed, Web of Science, EBSCOhost, Cochrane Library, Cochrane Library, and Scopus. REVIEW METHODS: On several databases, we conducted a comprehensive literature search on both quantitative and qualitative studies on ENT services in Southern Africa, published between 1 January 2014 and 27 February 2024. The extracted data from the analyzed studies was summarized into themes. RESULTS: Four themes in the fourteen studies included in the final analysis described the existing ENT services in Southern Africa: 1. Workforce scarcity and knowledge inadequacies, 2. Deficiencies in ENT infrastructure, equipment, and medication, 3. Inadequate ENT disease screening, management, and rehabilitation and 4. A lack of telehealth technology. CONCLUSION: The Southern African ENT health service faces many disease screening, treatment, and rehabilitation challenges, including critical shortages of workforce, equipment, and medication. These challenges, impeding patient access to ENT healthcare, could be effectively addressed by implementing deliberate policies to train a larger workforce, increase ENT funding for equipment and medication, promote telehealth, and reduce the patient cost of care.

Main findings: Ear, nose and throat (ENT) healthcare in Southern Africa faces critical shortages of workforce, equipment, and medication for disease screening, treatment and rehabilitation.Added knowledge: In this review, we identify challenges in the resource-limited Southern African ENT healthcare provision and provide evidence-based recommendations to mitigate these challenges.Global health impact for policy and action: Improving ENT service delivery in the resource-limited world requires deliberate policies that improve health worker training, expand financing and resource availability, incorporate new technology, and lower patient costs of care.

Corrigendum to "Availability of ENT Surgical Procedures and Medication in Low-Income Nation Hospitals: Cause for Concern in Zambia".

[This corrects the article DOI: 10.1155/2020/1980123.].

HIV specific CD8+ TRM-like cells in tonsils express exhaustive signatures in the absence of natural HIV control.

Lymphoid tissues are an important HIV reservoir site that persists in the face of antiretroviral therapy and natural immunity. Targeting these reservoirs by harnessing the antiviral activity of local tissue-resident memory (TRM) CD8+ T-cells is of great interest, but limited data exist on TRM-like cells within lymph nodes of people living with HIV (PLWH). Here, we studied tonsil CD8+ T-cells obtained from PLWH and uninfected controls from South Africa. We show that these cells are preferentially located outside the germinal centers (GCs), the main reservoir site for HIV, and display a low cytolytic and a transcriptionally TRM-like profile distinct from blood CD8+ T-cells. In PLWH, CD8+ TRM-like cells are expanded and adopt a more cytolytic, activated, and exhausted phenotype not reversed by antiretroviral therapy (ART). This phenotype was enhanced in HIV-specific CD8+ T-cells from tonsils compared to matched blood suggesting a higher antigen burden in tonsils. Single-cell transcriptional and clonotype resolution showed that these HIV-specific CD8+ T-cells in the tonsils express heterogeneous signatures of T-cell activation, clonal expansion, and exhaustion ex-vivo. Interestingly, this signature was absent in a natural HIV controller, who expressed lower PD-1 and CXCR5 levels and reduced transcriptional evidence of T-cell activation, exhaustion, and cytolytic activity. These data provide important insights into lymphoid tissue-derived HIV-specific CD8+ TRM-like phenotypes in settings of HIV remission and highlight their potential for immunotherapy and targeting of the HIV reservoirs.

HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells.

SARS-CoV-2 infects epithelial cells of the human gastrointestinal (GI) tract and causes related symptoms. HIV infection impairs gut homeostasis and is associated with an increased risk of COVID-19 fatality. To investigate the potential link between these observations, we analyzed single-cell transcriptional profiles and SARS-CoV-2 entry receptor expression across lymphoid and mucosal human tissue from chronically HIV-infected individuals and uninfected controls. Absorptive gut enterocytes displayed the highest coexpression of SARS-CoV-2 receptors ACE2, TMPRSS2, and TMPRSS4, of which ACE2 expression was associated with canonical interferon response and antiviral genes. Chronic treated HIV infection was associated with a clear antiviral response in gut enterocytes and, unexpectedly, with a substantial reduction of ACE2 and TMPRSS2 target cells. Gut tissue from SARS-CoV-2-infected individuals, however, showed abundant SARS-CoV-2 nucleocapsid protein in both the large and small intestine, including an HIV-coinfected individual. Thus, upregulation of antiviral response genes and downregulation of ACE2 and TMPRSS2 in the GI tract of HIV-infected individuals does not prevent SARS-CoV-2 infection in this compartment. The impact of these HIV-associated intestinal mucosal changes on SARS-CoV-2 infection dynamics, disease severity, and vaccine responses remains unclear and requires further investigation.

Availability of ENT Surgical Procedures and Medication in Low-Income Nation Hospitals: Cause for Concern in Zambia.

BACKGROUND: Ear, nose, and throat (ENT) diseases are an oft overlooked global health concern. Despite their high prevalence and associated morbidity and mortality, ENT diseases have remained neglected in health care delivery. In Zambia and many other low-income countries, ENT services are characterized by poor funding, unavailable surgical procedures, and erratic supply of essential drugs. OBJECTIVE: To investigate ENT service provision in Zambia with regard to availability of surgical procedures and supply of essential drugs. METHODS: A descriptive cross-sectional survey was conducted using a piloted structured questionnaire between 17 January 2017 and 2 January 2018. Included in the study were the 109 hospitals registered with the Ministry of Health (MoH) across the 10 provinces of Zambia. RESULTS: Of the participating hospitals, only 5.9% (n = 1) and 40% (n = 1) and 40% (n = 1) and 40% (n = 1) and 40% (n = 1) and 40% (n = 1) and 40% (n = 1) and 40% (n = 1) and 40% (n = 1) and 40% (n = 1) and 40% (n = 1) and 40% (n = 1) and 40% (. CONCLUSION: ENT service delivery in Zambia is limited with regard to performed surgical procedures and availability of essential drugs, necessitating urgent intervention. The findings from this study may be used to direct national policy on the improvement of provision of ENT services in Zambia.

Innate Lymphoid Cell Activation and Sustained Depletion in Blood and Tissue of Children Infected with HIV from Birth Despite Antiretroviral Therapy.

Innate lymphoid cells (ILCs) are important for response to infection and for immune development in early life. HIV infection in adults depletes circulating ILCs, but the impact on children infected from birth remains unknown. We study vertically HIV-infected children from birth to adulthood and find severe and persistent depletion of all circulating ILCs that, unlike CD4+ T cells, are not restored by long-term antiretroviral therapy unless initiated at birth. Remaining ILCs upregulate genes associated with cellular activation and metabolic perturbation. Unlike HIV-infected adults, ILCs are also profoundly depleted in tonsils of vertically infected children. Transcriptional profiling of remaining ILCs reveals ongoing cell-type-specific activity despite antiretroviral therapy. Collectively, these data suggest an important and ongoing role for ILCs in lymphoid tissue of HIV-infected children from birth, where persistent depletion and sustained transcriptional activity are likely to have long-term immune consequences that merit further investigation.

High-Frequency, Functional HIV-Specific T-Follicular Helper and Regulatory Cells Are Present Within Germinal Centers in Children but Not Adults.

Broadly neutralizing antibodies (bnAbs) against HIV-1 are an effective means of preventing transmission. To better understand the mechanisms by which HIV-specific bnAbs naturally develop, we investigated blood and lymphoid tissue in pediatric infection, since potent bnAbs develop with greater frequency in children than adults. As in adults, the frequency of circulating effector T-follicular helper cells (TFH) in HIV infected, treatment naïve children correlates with neutralization breadth. However, major differences between children and adults were also observed both in circulation, and in a small number of tonsil samples. In children, TFH cells are significantly more abundant, both in blood and in lymphoid tissue germinal centers, than in adults. Second, HIV-specific TFH cells are more frequent in pediatric than in adult lymphoid tissue and secrete the signature cytokine IL-21, which HIV-infected adults do not. Third, the enrichment of IL-21-secreting HIV-specific TFH in pediatric lymphoid tissue is accompanied by increased TFH regulation via more abundant regulatory follicular T-cells and HIV-specific CXCR5+ CD8 T-cells compared to adults. The relationship between regulation and neutralization breadth is also observed in the pediatric PBMC samples and correlates with neutralization breadth. Matching neutralization data from lymphoid tissue samples is not available. However, the distinction between infected children and adults in the magnitude, quality and regulation of HIV-specific TFH responses is consistent with the superior ability of children to develop high-frequency, potent bnAbs. These findings suggest the possibility that the optimal timing for next generation vaccine strategies designed to induce high-frequency, potent bnAbs to prevent HIV infection in adults would be in childhood.