Elevated genital concentrations of HIV target cell-recruiting chemokines and a genital inflammatory profile contributes to the high risk of HIV acquisition in these African women.

BackgroundBetween 1995 and 2000, KwaZulu–Natal province, South Africa, experienced a marked increase in Plasmodium falciparum malaria, fuelled by pyrethroid and sulfadoxine-pyrimethamine resistance. In response, vector control was strengthened and artemether-lumefantrine (AL) was deployed in the first Ministry of Health artemisinin-based combination treatment policy in Africa. In South Africa, effective vector and parasite control had historically ensured low-intensity malaria transmission. Malaria is diagnosed definitively and treatment is provided free of charge in reasonably accessible public-sector health-care facilities.Methods and FindingsWe reviewed four years of malaria morbidity and mortality data at four sentinel health-care facilities within KwaZulu–Natal's malaria-endemic area. In the year following improved vector control and implementation of AL treatment, malaria-related admissions and deaths both declined by 89%, and outpatient visits decreased by 85% at the sentinel facilities. By 2003, malaria-related outpatient cases and admissions had fallen by 99%, and malaria-related deaths had decreased by 97%. There was a concomitant marked and sustained decline in notified malaria throughout the province. No serious adverse events were associated causally with AL treatment in an active sentinel pharmacovigilance survey. In a prospective study with 42 d follow up, AL cured 97/98 (99%) and prevented gametocyte developing in all patients. Consistent with the findings of focus group discussions, a household survey found self-reported adherence to the six-dose AL regimen was 96%.ConclusionTogether with concurrent strengthening of vector control measures, the antimalarial treatment policy change to AL in KwaZulu–Natal contributed to a marked and sustained decrease in malaria cases, admissions, and deaths, by greatly improving clinical and parasitological cure rates and reducing gametocyte carriage.

Background The utility of heated and humidified high-flow nasal oxygen (HFNO) for severe COVID-19-related hypoxaemic respiratory failure (HRF), particularly in s``ettings with limited access to intensive care unit (ICU) resources, remains unclear, and predictors of outcome have been poorly studied. Methods We included consecutive patients with COVID-19-related HRF treated with HFNO at two tertiary hospitals in Cape Town, South Africa. The primary outcome was the proportion of patients who were successfully weaned from HFNO, whilst failure comprised intubation or death on HFNO. Findings The median (IQR) arterial oxygen partial pressure to fraction inspired oxygen ratio (P a O2/FiO 2 ) was 68 (54–92) in 293 enroled patients. Of these, 137/293 (47%) of patients [P a O2/FiO 2 76 (63–93)] were successfully weaned from HFNO. The median duration of HFNO was 6 (3–9) in those successfully treated versus 2 (1–5) days in those who failed ( p <0.001). A higher ratio of oxygen saturation/FiO2 to respiratory rate within 6 h (ROX-6 score) after HFNO commencement was associated with HFNO success (ROX-6; AHR 0.43, 0.31–0.60), as was use of steroids (AHR 0.35, 95%CI 0.19–0.64). A ROX-6 score of ≥3.7 was 80% predictive of successful weaning whilst ROX-6 ≤ 2.2 was 74% predictive of failure. In total, 139 patents (52%) survived to hospital discharge, whilst mortality amongst HFNO failures with outcomes was 129/140 (92%). Interpretation In a resource-constrained setting, HFNO for severe COVID-19 HRF is feasible and more almost half of those who receive it can be successfully weaned without the need for mechanical ventilation.

Background Both T cell activation during early HIV-1 infection and soluble markers of immune activation during chronic infection are predictive of HIV disease progression. Although the acute phase of HIV infection is associated with increased pro-inflammatory cytokine production, the relationship between cytokine concentrations and HIV pathogenesis is unknown. Objectives To identify cytokine biomarkers measurable in plasma during acute HIV-1 infection that predict HIV disease progression. Design Study including 40 South African women who became infected with HIV-1 and were followed longitudinally from the time of infection. Methods The concentrations of 30 cytokines in plasma from women with acute HIV-1 infection were measured and associations between cytokine levels and both viral load set-point 12 months post-infection and time taken for CD4 counts to fall below 350 cells/μl were determined using multivariate and Cox proportional-hazards regression. Results We found that the concentrations of 5 plasma cytokines, IL-12p40, IL-12p70, IFN-γ, IL-7 and IL-15, in women with acute infection predicted 66% of the variation in viral load set-point 12 months post infection. IL-12p40, IL-12p70 and IFN-γ were significantly associated with lower viral load whereas IL-7 and IL-15 were associated with higher viral load. Plasma concentrations of IL-12p40 and GM-CSF during acute infection were associated with maintenance of CD4 counts above 350 cells/μl while IL-1α, eotaxin and IL-7 were associated with more rapid CD4 loss. Conclusions A small panel of plasma cytokines during acute HIV-1 infection was predictive of long-term HIV disease prognosis in this group of South African women.

Chlamydia was associated with the highest genital cytokine levels, followed by gonorrhoea, HSV-2, trichomoniasis, and BV. In regions where HIV is prevalent and STIs are managed syndromically, better STI/BV screening is urgently needed, as certain infections were found to be highly inflammatory.

Helen Cox and colleagues investigate the impact Xpert MTB/RIF for diagnosing patients with presumptive tuberculosis in a large primary care clinic in Khayelitsha, Cape Town. Please see later in the article for the Editors' Summary

Objective To determine the relationship between mortality risk and the CD4 cell response to antiretroviral therapy (ART). Design Observational community-based ART cohort in South Africa. Methods CD4 cell counts were measured 4 monthly, and deaths were prospectively ascertained. Cumulative person-time accrued within a range of updated CD4 cell count strata (CD4 cell-strata) was calculated and used to derive CD4 cell-stratified mortality rates. Results Patients (2423) (median baseline CD4 cell count of 105 cells/ml) were observed for up to 5 years of ART. One hundred and ninety-seven patients died during 3155 person years of observation. In multivariate analysis, mortality rate ratios associated with 0–49, 50–99, 100–199, 200–299, 300– 399, 400–499 and at least 500 cells/ml updated CD4 cell-strata were 11.6, 4.9, 2.6, 1.7, 1.5, 1.4 and 1.0, respectively. Analysis of CD4 cell count recovery permitted calculations of person-time accrued within these CD4 cell strata. Despite rapid immune recovery, high mortality in the first year of ART was related to the large proportion of person-time accrued within CD4 cell-strata less than 200 cells/ml. Moreover, patients with baseline CD4 cell counts less than 100 cells/ml had much higher cumulative mortality estimates at 1 and 4 years (11.6 and 16.7%) compared with those of patients with baseline counts of at least 100 cells/ml (5.2 and 9.5%) largely because of greater cumulative person-time at CD4 cell counts less than 200 cells/ml. Conclusion: Updated CD4 cell counts are the variable most strongly associated with mortality risk during ART. High cumulative mortality risk is associated with person-time accrued at low CD4 cell counts. National HIV programmes in resource-limited settings should be designed to minimize the time patients spend with CD4 cell counts less than 200 cells/ml both before and during ART.

Pharmacokinetic factors may contribute to the increased risk of sulfadoxine-pyrimethamine antimalarial treatment failure in young children. The current dose recommendations need revision. We predict that children aged 2 to 5 years should be treated with 1 g sulfadoxine/50 mg pyrimethamine to achieve drug concentrations equivalent to those in adults.