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Summary: Background: The efficacy of on-demand HIV pre-exposure prophylaxis (PrEP) for men in sub-Saharan Africa has not been evaluated, and the on-demand PrEP dosing requirement for insertive sex remains unknown. Methods: HIV-negative males 13–24 years, requesting voluntary medical male circumcision (VMMC), were enrolled into an open-label randomised controlled trial (NCT03986970), and randomised 1:1:1:1:1:1:1:1:1 to control arm or one of eight arms receiving emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) over one or two days, and circumcised 5 or 21 h thereafter. The primary outcome was foreskin p24 concentrations following ex vivo HIV-1BaL challenge. Secondary outcomes included peripheral blood mononuclear cell (PBMC) p24 concentration, and drug concentrations in foreskin tissue, PBMCs, plasma and foreskin CD4+/CD4-cells. In the control arm, post-exposure prophylaxis (PEP) activity of non-formulated tenofovir-emtricitabine (TFV-FTC) or TAF-FTC was assessed with ex vivo dosing 1, 24, 48 or 72 h post-HIV-1 challenge. Findings: 144 participants were analysed. PrEP with F/TDF or F/TAF prevented ex vivo infection of foreskins and PBMCs both 5 and 21 h after PrEP dosing. There was no difference between F/TDF and F/TAF (p24day15 geometric mean ratio 1.06, 95% confidence interval: 0.65–1.74). Additional ex vivo dosing did not further increase inhibition. In the control arm, PEP ex vivo dosing was effective up to 48 post-exposure diminishing thereafter, with TAF-FTC showing prolonged protection compared to TFV-FTC. Participants receiving F/TAF had higher TFV-DP concentrations in foreskin tissue and PBMCs compared with F/TDF, irrespective of dose and sampling interval; but F/TAF did not confer preferential TFV-DP distribution into foreskin HIV target cells. FTC-TP concentrations with both drug regimens were equivalent and ∼1 log higher than TFV-DP in foreskin. Interpretation: A double dose of either F/TDF or F/TAF given once either 5 or 21 h before ex vivo HIV-challenge provided protection across foreskin tissue. Further clinical evaluation of pre-coital PrEP for insertive sex is warranted. Funding: EDCTP2, Gilead Sciences, Vetenskapsrådet.

Introduction: Tight junctions (TJs) serve as permeability filters between the internal and external cellular environment. A large number of proteins have been identified to be localized at the TJs. Due to limitations in tissue collection, TJs in the male genital tract have been understudied. Methods: We analysed the transcriptomics of 132 TJ genes in foreskin tissue of men requesting voluntary medical male circumcision (VMMC) and enrolled in the Combined HIV Adolescent Prevention Study (CHAPS) trial conducted in South Africa and Uganda (NCT03986970). The trial evaluated the dose requirements for event-driven HIV pre-exposure prophylaxis (PrEP) with emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during insertive sex. A total of 144 participants were randomized to either control arm or one of 8 PrEP arms (n=16/arm), receiving oral FTC-TDF or FTC-TAF over one or two days. Following in vivo oral PrEP dosing and VMMC, the expression level of three important TJ proteins (CLDN-1, OCN and ZO-1) was measured ex vivo in foreskin tissue by Western blot. The expression of cytokine genes implicated in TJ regulation was determined. Non-parametric Kruskal-Wallis tests were used to compare TJ gene expression and protein levels by type of PrEP received, and Spearman's correlation coefficients were calculated to assess whether TJ gene expression levels were related to cytokine gene levels or to PrEP drug concentrations and their active intracellularly phosphorylated metabolites. Results: A high level of expression in foreskin tissue was found for 118 (of 132) TJ genes analysed; this finding contributed to create a map of TJ components within the male genital tract. Importantly, PrEP regimens tested in the CHAPS trial did not affect the expression of TJ genes and the analysed proteins in the foreskin; thus, further supporting the safety of this prevention strategy against HIV-1 transmission during insertive sex. Additionally, we identified the level of several cytokines' genes to be correlated to TJ gene expression: among them, IL-18, IL-33 and VEGF. Discussion: TJs can limit viral entry into target cells; to affect this biological function viruses can reduce the expression of TJ proteins. Our study, on the expression and regulation of TJs in the foreskin, contribute important knowledge for PrEP safety and further design of HIV-1 prophylaxis. [ABSTRACT FROM AUTHOR]

Background Tuberculosis (TB) preventive therapy (TPT) reduces the risk of TB disease in people with human immunodeficiency virus (HIV), yet uptake has been suboptimal in many countries. We assessed whether QuantiFERON Gold In-Tube (QGIT) during routine HIV care increased TB infection (TBI) testing and TPT prescriptions. Methods This parallel-arm, 1:1 cluster-randomized controlled trial compared the standard-of-care tuberculin skin test to QGIT in South Africa. We enrolled consenting, TPT-eligible adults diagnosed with HIV ≤30 days prior and used intention-to-treat analyses for the outcomes: proportion of patients with documented TBI results, proportion with documented TPT, and time from enrollment to outcomes. Findings We enrolled 2232 patients across 14 clinics from November 2014 to May 2017 (58% in intervention clinics). At 24 months of follow-up, more participants in intervention clinics had TBI results (69% vs 2%, P <.001) and TPT prescriptions (45% vs 30%, P =.13) than control clinics. Controlling for baseline covariates, intervention clinics had 60% (95% confidence interval, 51–68; P <.001) more participants with TBI results and 12% (95% confidence interval, −6 to 31; P =.18) more with TPT prescriptions. Among participants with results, those in intervention clinics received results and TPT faster (intervention: median of 6 and 29 days after enrollment vs control: 21 and 54 days, respectively). Interpretation In this setting, QGIT in routine HIV care resulted in more patients with TBI results. Clinicians also initiated more people with HIV on TPT in QGIT intervention clinics, and did so more quickly, than the control arm. Clinical Trials Registration NCT02119130. [ABSTRACT FROM AUTHOR]

With the onset of COVID-19, the development of ex vivo laboratory models became an urgent priority to study host-pathogen interactions in response to the pandemic. In this study, we aimed to establish an ex vivo mucosal tissue explant challenge model for studying SARS-CoV-2 infection and replication. Nasal or oral tissue samples were collected from eligible participants and explants generated from the tissue were infected with various SARS-CoV-2 strains, including IC19 (lineage B.1.13), Beta (lineage B.1.351) and Delta (lineage B.1.617.2). A qRT-PCR assay used to measure viral replication in the tissue explants over a 15-day period, demonstrated no replication for any viral strains tested. Based on this, the ex vivo challenge protocol was modified by reducing the viral infection time and duration of sampling. Despite these changes, viral infectivity of the nasal and oral mucosa was not improved. Since 67% of the enrolled participants were already vaccinated against SARS-CoV-2, it is possible that neutralizing antibodies in explant tissue may have prevented the establishment of infection. However, we were unable to optimize plaque assays aimed at titrating the virus in supernatants from both infected and uninfected tissue, due to limited volume of culture supernatant available at the various collection time points. Currently, the reasons for the inability of these mucosal tissue samples to support replication of SARS-CoV-2 ex vivo remains unclear and requires further investigation. [ABSTRACT FROM AUTHOR]

Healthcare utilization surveys contextualize facility-based surveillance data for burden estimates. We describe healthcare utilization in the catchment areas for sentinel site healthcare facilities during the first year of the COVID-19 pandemic. We conducted a cross-sectional healthcare utilization survey in households in three communities from three provinces (KwaZulu-Natal, Western Cape and North West). Field workers administered structured questionnaires electronically with the household members reporting influenza-like illness (ILI) in the past 30 days or severe respiratory illness (SRI) since March 2020. Multivariable logistic regression was used to identify factors associated with healthcare utilization among individuals that reported illness. From November 2020 through April 2021, we enrolled 5804 households and 23,003 individuals. Any respiratory illness was reported by 1.6% of individuals; 0.7% reported ILI only, 0.8% reported SRI only, and 0.1% reported both ILI and SRI. Any form of medical care was sought by 40.8% (95% CI 32.9% - 49.6%) and 71.3% (95% CI 63.2% - 78.6%) of individuals with ILI and SRI, respectively. On multivariable analysis, respiratory illness was more likely to be medically attended for individuals at the Pietermaritzburg site (aOR 3.2, 95% CI 1.1–9.5, compared to Klerksdorp), that were underweight (aOR 11.5, 95% CI 1.5–90.2, compared to normal weight), with underlying illness (aOR 3.2, 95%CI 1.2–8.5), that experienced severe illness (aOR 4.8, 95% CI 1.6–14.3) and those with symptom duration of ≥10 days (aOR 7.9, 95% CI 2.1–30.2, compared to <5 days). Less than half of ILI episodes and only 71% of SRI episodes were medically attended during the first two COVID-19 waves in South Africa. Facility-based data may underestimate disease burden during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

People with tuberculosis (TB) are often lost to follow-up during treatment transition to another facility. These losses may result in substantial morbidity and mortality but are rarely recorded. We conducted a record review on adults diagnosed with TB at 11 hospitals in Limpopo, South Africa, who were subsequently transferred to a local clinic to initiate or continue treatment. We then performed in-depth record reviews at the primary care clinic to which they were referred and called participants who could not be identified as starting treatment. Between August 2017 and April 2018, we reviewed records of 778 individuals diagnosed with TB in-hospital and later referred to local clinics for treatment. Of the 778, 88 (11%) did not link to care, and an additional 43 (5.5%) died. Compared to people without cough, those with cough had higher odds of linking to care (aOR = 2.01, 95% CI: 1.26–3.25, p = 0.005) and were also linked more quickly [adjusted Time Ratio (aTR) = 0.53, 95% CI:0.36–0.79, p<0.001], as were those diagnosed microbiologically (aOR = 1.86, 95% CI: 1.16–3.06, p = 0.012; aTR = 0.58, 95% CI: 0.34–0.98, p = 0.04). People diagnosed with TB in hospitals often disengage following referral to local clinics. Interventions to identify and re-engage people who do not present to local clinics within days of referral might close an important gap in the TB treatment cascade. [ABSTRACT FROM AUTHOR]

Background Missing or undiagnosed patients with tuberculosis (TB) or coronavirus disease 2019 (COVID-19) are of concern. Identifying both infections in patients with no diagnosis prior to death contributes to understanding the burden of disease. To confirm reports of global reduction in TB incidence, a 2012 autopsy study of adults dying at home of natural causes in a high-TB-burden setting was repeated, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assessments after the first COVID-19 surge in South Africa. Methods Adult decedents who died at home with insufficient information to determine cause of death, no recent hospitalization, and no current antemortem TB or COVID-19 diagnosis were identified between March 2019 and October 2020 with a 4-month halt during lockdown. A standardized verbal autopsy followed by minimally invasive needle autopsy (MIA) was performed. Biopsies were taken for histopathology from liver, bilateral brain and lung; bronchoalveolar lavage fluid was collected for Xpert (MTB/RIF) and mycobacterial culture, and blood for human immunodeficiency virus (HIV) polymerase chain reaction (PCR) testing. After the start of the COVID-19 pandemic, a nasopharyngeal swab and lung tissue were subjected to SARS-CoV-2 PCR testing. Results Sixty-six MIAs were completed in 25 men and 41 women (median age, 60 years); 68.2% had antemortem respiratory symptoms and 30.3% were people with HIV. Overall, TB was diagnosed in 11 of 66 (16.7%) decedents, and 14 of 41 (34.1%) in the COVID-19 pandemic were SARS-CoV-2 positive. Conclusions Undiagnosed TB in adults dying at home has decreased but remains unacceptably high. Forty percent of decedents had undiagnosed COVID-19, suggesting that estimates of excess deaths may underestimate the impact of SARS-CoV-2 on mortality. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) recommends systematic symptom screening for tuberculosis (TB). However, TB prevalence surveys suggest that this strategy does not identify millions of TB patients, globally. Undiagnosed or delayed diagnosis of TB contribute to TB transmission and exacerbate morbidity and mortality. We conducted a cluster-randomized trial of large urban and rural primary healthcare clinics in 3 provinces of South Africa to evaluate whether a novel intervention of targeted universal testing for TB (TUTT) in high-risk groups diagnosed more patients with TB per month compared to current standard of care (SoC) symptom-directed TB testing. Methods and findings: Sixty-two clinics were randomized; with initiation of the intervention clinics over 6 months from March 2019. The study was prematurely stopped in March 2020 due to clinics restricting access to patients, and then a week later due to the Coronavirus Disease 2019 (COVID-19) national lockdown; by then, we had accrued a similar number of TB diagnoses to that of the power estimates and permanently stopped the trial. In intervention clinics, attendees living with HIV, those self-reporting a recent close contact with TB, or a prior episode of TB were all offered a sputum test for TB, irrespective of whether they reported symptoms of TB. We analyzed data abstracted from the national public sector laboratory database using Poisson regression models and compared the mean number of TB patients diagnosed per clinic per month between the study arms. Intervention clinics diagnosed 6,777 patients with TB, 20.7 patients with TB per clinic month (95% CI 16.7, 24.8) versus 6,750, 18.8 patients with TB per clinic month (95% CI 15.3, 22.2) in control clinics during study months. A direct comparison, adjusting for province and clinic TB case volume strata, did not show a significant difference in the number of TB cases between the 2 arms, incidence rate ratio (IRR) 1.14 (95% CI 0.94, 1.38, p = 0.46). However, prespecified difference-in-differences analyses showed that while the rate of TB diagnoses in control clinics decreased over time, intervention clinics had a 17% relative increase in TB patients diagnosed per month compared to the prior year, interaction IRR 1.17 (95% CI 1.14, 1.19, p < 0.001). Trial limitations were the premature stop due to COVID-19 lockdowns and the absence of between-arm comparisons of initiation and outcomes of TB treatment in those diagnosed with TB. Conclusions: Our trial suggests that the implementation of TUTT in these 3 groups at extreme risk of TB identified more TB patients than SoC and could assist in reducing undiagnosed TB patients in settings of high TB prevalence. Trial registration: South African National Clinical Trials Registry DOH-27-092021-4901. In a cluster randomised trial of primary care clinics in South Africa, Neil Martinson and colleagues, investigate the value of targeted testing for Tuberculosis in those at highest risk. Author summary: Why was this study done?: Tuberculosis (TB) diagnosis is made by laboratory sputum testing usually prompted by the presence of at least 1 symptom of TB (cough, fever or night sweats, loss of weight). The World Health Organization promotes screening of entire groups of people at high risk of TB irrespective of symptoms. In South Africa, high-risk groups include people living with HIV, those who report being a close contact of someone with TB, and those who have had a recent episode of TB. There is little data on the usefulness of diagnostic assays as screening tests. Our trial assessed if targeted sputum testing of people at high risk without TB symptoms helped to identify undiagnosed TB. What did the researchers do and find?: A total of 62 large primary care clinics in South Africa were randomized to either our intervention—TB testing of sputum of all people in high-risk groups, or our control—to continue symptom directed testing for TB (the standard of care). The total number of TB cases diagnosed each month in all clinics was recorded. Comparisons were made between intervention and control clinics. In trial intervention clinics, 6,777 people were diagnosed with TB, an average of 20.7 patients per clinic month versus 6,750 in control clinics, an average of 18.8 patients with TB per clinic month. After adjusting for clustering, province, and the strata of average number of TB patients diagnosed per month in the last quarter of 2017, intervention clinics diagnosed 14% more patients with TB than control clinics, but this did not reach statistical significance. Secondary analyses, including data from the year prior to the intervention, demonstrated a statistically significant increase in TB diagnoses per month, reported as a 17% relative increase. What do these findings mean?: A strategy targeting high-risk groups for universal testing for TB (TUTT) may help to improve diagnostic rates of TB in areas where prevalence is high. Universal testing strategies could be be implemented in low-resource settings provided costs of testing were addressed, and other locally relevant high-risk groups for TB could be targeted. [ABSTRACT FROM AUTHOR]

Background We report the yield of targeted universal tuberculosis (TB) testing of clinic attendees in high-risk groups. Methods Clinic attendees in primary healthcare facilities in South Africa with one of the following risk factors underwent sputum testing for TB: human immunodeficiency virus (HIV), contact with a TB patient in the past year, and having had TB in the past 2 years. A single sample was collected for Xpert-Ultra (Xpert) and culture. We report the proportion positive for Mycobacterium tuberculosis. Data were analyzed descriptively. The unadjusted clinical and demographic factors' relative risk of TB detected by culture or Xpert were calculated and concordance between Xpert and culture is described. Results A total of 30 513 participants had a TB test result. Median age was 39 years, and 11 553 (38%) were men. The majority (n = 21734, 71%) had HIV, 12 492 (41%) reported close contact with a TB patient, and 1573 (5%) reported prior TB. Overall, 8.3% were positive for M. tuberculosis by culture and/or Xpert compared with 6.0% with trace-positive results excluded. In asymptomatic participants, the yield was 6.7% and 10.1% in symptomatic participants (with trace-positives excluded). Only 10% of trace-positive results were culture-positive. We found that 55% of clinic attendees with a sputum result positive for M. tuberculosis did not have a positive TB symptom screen. Conclusions A high proportion of clinic attendees with specific risk factors (HIV, close TB contact, history of TB) test positive for M. tuberculosis when universal testing is implemented. [ABSTRACT FROM AUTHOR]

Introduction: South Africa has the largest number of confirmed cases of COVID-19 in Africa. Data to inform public health strategies to mitigate the spread of new variants and severity of disease is needed, including information on knowledge, attitudes and practices (KAP) regarding COVID-19, factors associated with intention to get vaccinated, and viewpoints on reliable sources of data. Methods: we investigated these topics as part of the COVID-19 healthcare utilization and seroprevalence (HUTS) cross-sectional survey in three communities in South Africa: Mitchell's Plain (Western Cape Province), Pietermaritzburg (KwaZulu-Natal Province) and Klerksdorp (North West Province) during and after the second wave of COVID-19 prior to vaccine availability. Results: primary caregivers from 5799 households participated in the study, 41.1% from Pietermaritzburg, 34.2% from Klerksdorp and 24.7% from Mitchells Plain. Two-thirds and 94.7% of respondents had correct knowledge on the cause and spread of COVID-19, respectively. Knowledge measures were significantly associated with age less than 65 years, the highest level of education and site (Mitchells Plain). Desired preventive behaviors were associated with higher socio-economic status. While 64.7% of people intended to get vaccinated, those over 64 years of age were more likely to intend to vaccinate (aOR: 1.25, 95% CI: 1.06-1.47). Vaccine intention related to protection of self (58.4%) and family (40.0%). The most trusted source of COVID-19 information was television (59.3%) followed by radio (20.0%). Conclusion: these data can be used to design targeted public health campaigns for the current COVID-19 and future epidemics, ensuring that socio-economic constraints and preference for trusted information are considered. [ABSTRACT FROM AUTHOR]

Background Household contact investigation for people newly diagnosed with tuberculosis (TB) is poorly implemented, particularly in low- and middle-income countries. Conditional cash incentives may improve uptake. Methods We conducted a pragmatic, cluster-randomized, crossover trial of 2 TB contact investigation approaches (household-based and incentive-based) in 28 public primary care clinics in South Africa. Each clinic used 1 approach for 18 months, followed by a 6-month washout period, after which the opposite approach was used. Fourteen clinics were randomized to each approach. In the household-based arm, we conducted TB screening and testing of contacts at the household. In the incentive-based arm, both index patients and ≤10 of their close contacts (either within or outside the household) were given small cash incentives for presenting to study clinics for TB screening. The primary outcome was the number of people with incident TB who were diagnosed and started on treatment at study clinics. Results From July 2016 to January 2020, we randomized 28 clinics to each study arm, and enrolled 782 index TB patients and 1882 contacts in the household-based arm and 780 index patients and 1940 contacts in the incentive-based arm. A total of 1413 individuals started on TB treatment in the household-based arm and 1510 in the incentive-based arm. The adjusted incidence rate ratio of TB treatment initiation in the incentive- versus household-based arms was 1.05 (95% confidence interval:.97–1.13). Conclusions Incentive-based contact investigation for TB has similar effectiveness to traditional household-based approaches and may be a viable alternative or complementary approach to household-based investigation. [ABSTRACT FROM AUTHOR]

Background In South Africa, 19% of adults are living with human immunodeficiency virus (HIV; LWH). Few data on the influence of HIV on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) household transmission are available. Methods We performed a case-ascertained, prospective household transmission study of symptomatic adult index SARS-CoV-2 cases LWH and not living with HIV (NLWH) and their contacts from October 2020 to September 2021. Households were followed up 3 times a week for 6 weeks to collect nasal swabs for SARS-CoV-2 testing. We estimated household cumulative infection risk (HCIR) and duration of SARS-CoV-2 positivity (at a cycle threshold value <30 as proxy for high viral load). Results HCIR was 59% (220 of 373), not differing by index HIV status (60% LWH vs 58% NLWH). HCIR increased with index case age (35–59 years: adjusted OR [aOR], 3.4; 95% CI, 1.5–7.8 and ≥60 years: aOR, 3.1; 95% CI, 1.0–10.1) compared with 18–34 years and with contacts' age, 13–17 years (aOR, 7.1; 95% CI, 1.5–33.9) and 18–34 years (aOR, 4.4; 95% CI, 1.0–18.4) compared with <5 years. Mean positivity was longer in cases LWH (adjusted hazard ratio, 0.4; 95% CI,.1–.9). Conclusions Index HIV status was not associated with higher HCIR, but cases LWH had longer positivity duration. Adults aged >35 years were more likely to transmit and individuals aged 13–34 to be infected SARS-CoV-2 in the household. As HIV infection may increase transmission, health services must maintain HIV testing and antiretroviral therapy initiation. [ABSTRACT FROM AUTHOR]

Background Longitudinal pneumococcus colonization data in high human immunodeficiency virus (HIV) prevalence settings following pneumococcal conjugate vaccine introduction are limited. Methods In 327 randomly selected households, 1684 individuals were enrolled and followed-up for 6 to 10 months during 2016 through 2018 from 2 communities. Nasopharyngeal swabs were collected twice weekly and tested for pneumococcus using quantitative lytA real-time polymerase chain reaction. A Markov model was fitted to the data to define the start and end of an episode of colonization. We assessed factors associated with colonization using logistic regression. Results During the study period, 98% (1655/1684) of participants were colonized with pneumococcus at least once. Younger age (<5 years: adjusted odds ratio [aOR], 14.1; 95% confidence [CI], 1.8–111.3, and 5–24 years: aOR, 4.8, 95% CI, 1.9–11.9, compared with 25–44 years) and HIV infection (aOR, 10.1; 95% CI, 1.3–77.1) were associated with increased odds of colonization. Children aged <5 years had fewer colonization episodes (median, 9) than individuals ≥5 years (median, 18; P <.001) but had a longer episode duration (<5 years: 35.5 days; interquartile range, 17–88) vs. ≥5 years: 5.5 days (4–12). High pneumococcal loads were associated with age (<1 year: aOR 25.4; 95% CI, 7.4–87.6; 1–4 years: aOR 13.5, 95% CI 8.3–22.9; 5–14 years: aOR 3.1, 95% CI, 2.1–4.4 vs. 45–65 year old patients) and HIV infection (aOR 1.7; 95% CI 1.2–2.4). Conclusions We observed high levels of pneumococcus colonization across all age groups. Children and people with HIV were more likely to be colonized and had higher pneumococcal loads. Carriage duration decreased with age highlighting that children remain important in pneumococcal transmission. [ABSTRACT FROM AUTHOR]

The mucosal environment of the upper respiratory tract is the first barrier of protection against SARS-CoV-2 transmission. However, the mucosal factors involved in viral transmission and potentially modulating the capacity to prevent such transmission have not fully been identified. In this pilot proteomics study, we compared mucosal and systemic compartments in a South African cohort of vaccinated and unvaccinated individuals undergoing maxillofacial surgery with previous history of COVID-19 or not. Inflammatory profiles were analyzed in plasma, nasopharyngeal swabs, and nasal and oral tissue explant cultures, using Olink and Luminex technologies. SARS-CoV-2-specific antibody levels were measured in serum and tissue explants. An increased pro-inflammatory proteomic profile was measured in the nasal compartment compared to plasma. However, IP-10 and MIG levels were higher in secretions than in nasal tissue, and the opposite was observed for TGF-β. Nasal anti-SARS-CoV-2 spike IgG correlated with mucosal MIG expression for all participants. A further positive correlation was found with IP-10 in BioNTech/Pfizer-vaccinated individuals. Systemic levels of anti-SARS-CoV-2 spike IgG elicited by this vaccine correlated with plasma IL-10, IL-6 and HBD4. Proteomic profiles measured in mucosal tissues and secretions using combined technologies could reveal correlates of protection at the mucosal portals of viral entry. [ABSTRACT FROM AUTHOR]

We conducted 3 prospective cohort studies (2016-2018), enrolling persons from 2 communities in South Africa. Nasopharyngeal swab specimens were collected twice a week from participants. Factors associated with Bordetella pertussis incidence, episode duration, and household transmission were determined by using Poisson regression, Weibull accelerated time-failure, and logistic regression hierarchical models, respectively. Among 1,684 participants, 118 episodes of infection were detected in 107 participants (incidence 0.21, 95% CI 0.17-0.25 infections/100 person-weeks). Children <5 years of age who had incomplete vaccination were more likely to have pertussis infection. Episode duration was longer for participants who had higher bacterial loads. Transmission was more likely to occur from male index case-patients and persons who had >7 days infection duration. In both communities, there was high incidence of B. pertussis infection and most cases were colonized. [ABSTRACT FROM AUTHOR]

Background: Non-communicable diseases (NCDs) are an emerging global public health problem. Objectives: To assess the prevalence of NCDs and their risk factors among adults on antiretroviral therapy (ART). Method: This was a cross-sectional study (July 2019 – January 2020) in Limpopo, South Africa. Patients were enrolled if they were ≥ 40 years, HIV-positive, and virologically suppressed on ART. Data were analysed descriptively, and a binomial regression model was used to identify risk factors for NCDs. Results: The majority of participants (65%; 319/488) were women. Most (83%; 405/488) were aged 40–59 years; 60% (285/472) were overweight or obese. Based on self-report, 22% (107/488) were currently smokers. Almost half (44%) 213/488) reported daily consumption of vegetables and 65% (319/488) exercised regularly and 39% (190/488) reported treatment for another chronic disease. The leading comorbid conditions were hypertension (32%; 158/488) and diabetes mellitus (5%; 24/488). Risk factors for hypertension included age 60 years and older (relative risk [RR]: 1.72; 95% confidence interval [CI]: 1.29–2.30) diabetes (RR: 1.42; 95% CI: 1.08–1.87), overweight (RR: 1.32; 95% CI: 1.03–1.69) and obesity (RR: 1.69; 95% CI: 1.32–2.17). Conclusion: There is a high prevalence, both of risk factors for NCDs and multimorbidity (> 1 chronic disease) in patients who are ≥ 40 years and virologically suppressed on ART. [ABSTRACT FROM AUTHOR]

Background Household contact tracing for tuberculosis (TB) may facilitate diagnosis and access to TB preventive treatment (TPT). We investigated whether household contact tracing and intensive TB/human immunodeficiency virus (HIV) screening would improve TB-free survival. Methods Household contacts of index TB patients in 2 South African provinces were randomized to home tracing and intensive HIV/TB screening or standard of care (SOC; clinic referral letters). The primary outcome was incident TB or death at 15 months. Secondary outcomes included tuberculin skin test (TST) positivity in children ≤14 years and undiagnosed HIV. Results From December 2016 through March 2019, 1032 index patients (4459 contacts) and 1030 (4129 contacts) were randomized to the intervention and SOC arms. Of intervention arm contacts, 3.2% (69 of 2166) had prevalent microbiologically confirmed TB. At 15 months, the cumulative incidence of TB or death did not differ between the intensive screening (93 of 3230, 2.9%) and SOC (80 of 2600, 3.1%) arms (hazard ratio, 0.90; 95% confidence interval [CI],.66–1.24). TST positivity was higher in the intensive screening arm (38 of 845, 4.5%) compared with the SOC arm (15 of 800, 1.9%; odds ratio, 2.25; 95% CI, 1.07–4.72). Undiagnosed HIV was similar between arms (41 of 3185, 1.3% vs 32 of 2543, 1.3%; odds ratio, 1.02; 95% CI,.64–1.64). Conclusions Household contact tracing with intensive screening and referral did not reduce incident TB or death. Providing referral letters to household contacts of index patients is an alternative strategy to home visits. Clinical Trials Registration ISRCTN16006202. [ABSTRACT FROM AUTHOR]

Understanding the build-up of immunity with successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the epidemiological conditions that favor rapidly expanding epidemics will help facilitate future pandemic control. We analyzed high-resolution infection and serology data from two longitudinal household cohorts in South Africa to reveal high cumulative infection rates and durable cross-protective immunity conferred by prior infection in the pre-Omicron era. Building on the history of past exposures to different SARS-CoV-2 variants and vaccination in the cohort most representative of South Africa's high urbanization rate, we used mathematical models to explore the fitness advantage of the Omicron variant and its epidemic trajectory. Modeling suggests that the Omicron wave likely infected a large fraction (44 to 81%) of the population, leaving a complex landscape of population immunity primed and boosted with antigenically distinct variants. We project that future SARS-CoV-2 resurgences are likely under a range of scenarios of viral characteristics, population contacts, and residual cross-protection. SARS-CoV-2 in South Africa: Emerging SARS-CoV-2 variants bring questions as to their potential spread in populations. To analyze the spread of SARS-CoV-2 in South Africa, Sun et al. made use of detailed data from two household cohorts, one rural and one urban, who had longitudinal SARS-CoV-2 infection tests and serology assessments from July 2020 to August 2021. Their epidemiological analysis provides insights into the transmission dynamics of pre-Omicron SARS-CoV-2 variants and the population immunity landscape, and an additional modeling study evaluated the fitness advantage–fueled spread of Omicron and hypothetical future variants in this population. [ABSTRACT FROM AUTHOR]

HIV-1 pre-exposure prophylaxis (PrEP) relies on inhibition of HIV-1 replication steps. To understand how PrEP modulates the immunological environment, we derived the plasma proteomic profile of men receiving emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during the CHAPS trial in South Africa and Uganda (NCT03986970). The CHAPS trial randomized 144 participants to one control and 8 PrEP arms, differing by drug type, number of PrEP doses and timing from final PrEP dose to sampling. Blood was collected pre- and post-PrEP. The inflammatory profile of plasma samples was analyzed using Olink (N=92 proteins) and Luminex (N=33) and associated with plasma drug concentrations using mass spectrometry. The proteins whose levels changed most significantly from pre- to post-PrEP were CCL4, CCL3 and TNF-a; CCL4 was the key discriminator between pre- and post-PrEP samples. CCL4 and CCL3 levels were significantly increased in post-PrEP samples compared to control specimens. CCL4 was significantly correlated with FTC drug levels in plasma. Production of inflammatory chemokines CCL4 and CCL3 in response to short-term PrEP indicates the mobilization of ligands which potentially block virus attachment to CCR5 HIV-1 co-receptor. The significant correlation between CCL4 and FTC levels suggests that CCL4 increase is modulated as an inflammatory response to PrEP. [ABSTRACT FROM AUTHOR]