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Objectives:

To define the incidence of clinically detected coronavirus disease 2019 (COVID-19) in people with HIV (PWH) in the United States and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19.

Design:

Observational study within the CFAR Network of Integrated Clinical Systems cohort in seven cities during 2020.

Methods:

We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4+ count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores.

Results:

Among 16 056 PWH in care, of whom 44.5% were black, 12.5% were Hispanic, with a median age of 52 years (IQR 40–59), 18% had a current CD4+ count less than 350, including 7% less than 200; 95.5% were on antiretroviral therapy (ART), and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and black PWH respectively, than non-Hispanic white PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or black identity, lowest historical CD4+ count less than 350 cells/μl (proxy for CD4+ nadir), current low CD4+ : CD8+ ratio, diabetes, and obesity.

Conclusion:

Our results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWH. PWH with immune exhaustion as evidenced by lowest historical CD4+ or current low CD4+ : CD8+ ratio had greater risk of COVID-19.

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Objective

The aim of this study was to assess the performance of kynurenine/tryptophan ratio for tuberculosis (TB) case-finding among antiretroviral therapy (ART)-naive people with HIV (PWH), and to investigate other factors associated with kynurenine/tryptophan ratio in this population.

Design

A nested case--control study based on a cohort of 812 ambulatory PWH in the Oromia region, Ethiopia.

Methods

At enrolment, all participants submitted sputum samples for bacteriological TB investigations. Concentrations of kynurenine and tryptophan in plasma were quantified using liquid chromatography-mass spectrometry. Receiver operator characteristic curves were constructed to assess diagnostic performance (area under the curve; AUC) for kynurenine, tryptophan, and kynurenine/tryptophan ratio. Sensitivity, specificity, and predictive values were calculated. Kynurenine/tryptophan ratios were correlated to plasma levels of nine inflammation mediators, plasma HIV RNA levels, CD4+ cell count, BMI, and mid-upper arm circumference (MUAC).

Results

We included 124 individuals with HIV-TB coinfection (HIV+/TB+) and 125 with HIV mono-infection (HIV+/TB-). Tryptophan levels were lower in HIV+/TB+ than in HIV+/TB- (median 19.5 vs. 29.8 μmol/l, P …

Objective:

Immune dysfunction and chronic inflammation are characteristic of HIV infection and diabetes mellitus (DM), with CD4+ T cell metabolism implicated in the pathogenesis of each disease. However, there is limited information on CD4+ T cell metabolism in HIV+ persons with DM. We examined CD4+ T cell glucose metabolism in HIV+ women with and without DM.

Design:

A case-control study was used to compare CD4+ T cell glucose metabolism in women with HIV with or without DM.

Methods:

Non-diabetic (HIV+DM–, N = 20) or type 2 diabetic HIV+ women with (HIV+DM+, N = 16) or without (HIV+DMTx+, N = 18) anti-diabetic treatment were identified from the WIHS and matched for age, race/ethnicity, smoking status and CD4 count. CD4+ T cell immunometabolism was examined by flow cytometry, microfluidic qRT-PCR of metabolic genes, and Seahorse extracellular flux analysis of stimulated CD4+ T cells.

Results:

HIV+DM+ displayed a significantly elevated proportion of CD4+ T cells expressing the immunometabolic marker GLUT1 compared to HIV+DMTx+ and HIV+DM– (p = 0.04 and p = 0.01, respectively). Relative expression of genes encoding key enzymes for glucose metabolism pathways were elevated in CD4+ T cells of HIV+DM+ compared to HIV+DMTx+ and HIV+DM–. TCR-activated CD4+ T cells from HIV+DM+ showed elevated glycolysis and oxidative phosphorylation compared to HIV+DM–.

Conclusions:

CD4+ T cells from HIV+DM+ have elevated glucose metabolism. Treatment of DM among women with HIV may partially correct CD4+ T cell metabolic dysfunction.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objective:

The primary objective was to explore weight and BMI changes in people with HIV (PWH) undergoing integrase strand transfer inhibitors (INSTI)-based regimens (vs. non-INSTI) in a large cohort and in the subsets of individuals without diabetes and insulin resistance (IR) at the time of switch to INSTI. The secondary objective was to identify risk factors for IR and cut-off of weight or BMI increase associated with IR in PWH switching to INSTI.

Design:

A longitudinal matched-cohort study including PWH attending Modena HIV Metabolic Clinic, Italy.

Methods:

PWH were divided into two groups: non-INSTI and INSTI-switch. The effect of switching to INSTI on weight and BMI change was tested through a linear mixed model. A mediation analysis explored the mediation effect of weight and BMI change in the association between the switch to INSTI and IR.

Results:

We analyzed 2437 PWH (1025 INSTI-switch, 1412 non-INSTI), in 54 826 weight assessments. Trends for weight increase were significantly higher in early-INSTI-switch (vs. early-non-INSTI), but no difference was observed in the late period after the switch. In the subset of 634 PWH without IR, switching to INSTI (vs. non-INSTI) was associated with a lower risk of IR (hazard ratio = 0.70, 95% confidence interval: 0.51, 0.98). A weight increase by 1% reduced the total protective effect of INSTI by 21.1% over 1 year of follow-up, which identifies a 5% weight increase as a clinically meaningful weight gain definition.

Conclusion:

A cut-off of 5% weight gain from the time of INSTI-switch is associated with IR, which may be a clinically meaningful endpoint to could be used in clinical and research settings.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Background:

Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) increases low-density lipoprotein cholesterol (LDL-C) and body weight. Metabolic effects of the opposite TAF-to-TDF switch are unknown.

Objectives:

To investigate the effect of TAF-to-TDF switch on plasma lipids, body weight, and atherosclerotic cardiovascular disease (ASCVD) risk score.

Design:

A retrospective chart review.

Methods:

One hundred and forty-six patients with TAF-to-TDF switch (Switch group) were compared with 146 patients matched for sex, age, and third antiretroviral agent class who continued unchanged TAF-containing regimen (Control group). Data were collected at approximately 1 year (follow-up FU-1) and 2 years (follow-up FU-2) after baseline values.

Results:

In Switch group at FU-1, total cholesterol (TC) and LDL-C decreased 12.1% and 12.4% (P …

Objective:

To investigate the association between HIV viremia exposure during antiretroviral therapy (ART) and cardiovascular disease (CVD) risk.

Design:

Nationwide observational cohort.

Methods:

Participants (age > 15 years) from the Swedish nationwide InfCareHIV register initiating ART 1996–2017 were categorized in a time-updated manner into four viremia categories, starting from 12 months after ART initiation: suppression (…

Objective:

The HIV Pre-exposure Prophylaxis Optimization Intervention (PrEP-OI) study evaluated the efficacy of a panel management intervention using PrEP Coordinators and a web-based panel management tool to support healthcare providers in optimizing PrEP prescription and ongoing PrEP care.

Design:

The PrEP-OI study was a stepped-wedge randomized clinical trial conducted across 10 San Francisco Department of Public Health primary care sites between November 2018 and September 2019. Each month, clinics one-by-one initiated PrEP-OI in random order until all sites received the intervention by the study team.

Methods:

The primary outcome was the number of PrEP prescriptions per month. Secondary outcomes compared pre- and post-intervention periods on whether PrEP was discussed and whether PrEP-related counseling (e.g., HIV risk assessment, risk reduction counseling, PrEP initiation/continuation assessment) was conducted. Prescription and clinical data were abstracted from the electronic health records. We calculated incidence rate ratios (IRR) and risk ratios (RR) to estimate the intervention effect on primary and secondary outcomes.

Results:

The number of PrEP prescriptions across clinics increased from 1.85/month (SD = 2.55) pre-intervention to 2.44/month (SD = 3.44) post-intervention (IRR = 1.34; 95% CI = 1.05–1.73; p = 0.021). PrEP-related discussions during clinic visits (RR = 1.13; 95% CI = 1.04–1.22; p = 0.004), HIV risk assessment (RR = 1.40; 95% CI = 1.14–1.72; p = 0.001), and risk reduction counseling (RR = 1.16; 95% CI = 1.03–1.30; p = 0.011) increased from the pre- to the post-intervention period. Assessment of PrEP initiation/continuation increased over time during the post-intervention period (RR = 1.05; 95% CI = 0.99–1.11; p = 0.100).

Conclusions:

A panel management intervention using PrEP Coordinators and a web-based panel management tool increased PrEP prescribing and improved PrEP-related counseling in safety-net primary care clinics.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objective:

Given the roll out of maternal antiretroviral therapy (ART) for prevention-of-perinatal-HIV-transmission, increasing numbers of children are perinatally HIV/ART exposed but uninfected (CAHEU). Some studies suggest CAHEU may be at increased risk for neurodevelopmental (ND) deficits. We aimed to assess ND performance among preschool CAHEU.

Design:

This cross-sectional study assessed ND outcomes among 3–6-year-old CAHEU at entry into a multicountry cohort study.

Methods:

We used the Mullen Scales of Early Learning (MSEL) and Kaufman Assessment Battery for Children (KABC-II) to assess ND status among 3–6-year-old CAHEU at entry into the PROMISE Ongoing Treatment Evaluation (PROMOTE) study conducted in Uganda, Malawi, Zimbabwe and South Africa. Statistical analyses (Stata 16.1) was used to generate group means for ND composite scores and subscale scores, compared to standardized test score means. We used multivariable analysis to adjust for known developmental risk factors including maternal clinical/socioeconomic variables, child sex, growth-for-age measurements, and country.

Results:

1647 children aged 3–6 years had baseline ND testing in PROMOTE; group-mean unadjusted Cognitive Composite scores on the MSEL were 85.8 (standard deviation [SD]: 18.2) and KABC-II were 79.5 (SD: 13.2). Composite score group-mean differences were noted by country, with South African and Zimbabwean children having higher scores. In KABC-II multivariable analyses, maternal age >40 years, lower education, male sex, and stunting were associated with lower composite scores.

Conclusions:

Among a large cohort of 3–6 year old CAHEU from eastern/southern Africa, group-mean composite ND scores averaged within the low-normal range; with differences noted by country, maternal clinical and socioeconomic factors.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Background:

Fracture rates have been reported to be higher among older women living with HIV (WLWH) than HIV− women. Hormone therapy with estrogen can reduce vasomotor symptoms (VMS) associated with menopause and prevent fractures. As data are limited on the benefits of hormone therapy use in WLWH, we examined associations of hormone therapy, use and fractures.

Methods:

A prospective study of 1765 (1350 WLWH and 415 HIV−) postmenopausal Women's Interagency HIV Study (WIHS) participants was performed, including self-reported hormone therapy, use and fracture data from 2003 to 2017. Proportional hazard models determined predictors of new fractures at any site or at typical fragility fracture sites (hip, spine, wrist).

Results:

At the first postmenopausal visit, the median (IQR) age of WLWH was slightly younger than HIV− women [49.8 (46.4–53) vs. 50.7 (47.5–54), P = 0.0002] and a smaller proportion of WLWH reported presence of VMS (17 vs. 26%, P …

We performed a calendar-matched, 12-month, before (November 27, 2017 to November 26, 2018) and after (November 27, 2018 to November 26, 2019) study, to assess the utility of an ED-based HIV screening program. There were 710 and 14,335 patients screened for HIV during the pre- and post-BPA periods, respectively, representing more than a 20-fold increase in HIV screening following BPA implementation. Total HIV positive tests increased 5-fold following BPA implementation.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objectives:

People living with HIV (PLWH) are at increased risk for premature cardiovascular disease (CVD). Clonal hematopoiesis (CH) is a common age-related condition that may be associated with increased CVD risk. The goal of this study was to determine the prevalence of CH and its association with chronic inflammation and CVD in PLWH.

Design:

Cross-sectional study utilizing archived specimens and data from 118 men (86 PLWH and 32 HIV-uninfected) from the Baltimore-Washington DC center of the Multicenter AIDS Cohort Study (MACS) who had had coronary computed tomography angiography (CTA) and measurement of 34 serologic inflammatory biomarkers.

Methods:

CH was assessed on peripheral blood mononuclear cells utilizing targeted error-corrected next generation sequencing (NGS) focused on 92 genes frequently mutated in hematologic malignancies. Clinical and laboratory data were obtained from the MACS database.

Results:

CH with a variant allele frequency (VAF) >1% was significantly more common in PLWH [20/86 (23.3%)] than in HIV-uninfected men [2/32 (6.3%)] (p = 0.035). PLWH with CH (VAF>1%) were more likely to have coronary artery stenosis ≥ 50% than those without CH (6/20 (30%) vs. 6/64 (9%); p = 0.021). Presence of CH was not significantly associated with serological inflammatory markers, except for significantly lower serum leptin levels; this was not significant after adjustment for abdominal or thigh subcutaneous fat area.

Conclusions:

CH was more common in PLWH and among PLWH was associated with the extent of coronary artery disease. Larger studies are needed to further examine the biological and clinical consequences of CH in PLWH.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objective:

Evaluating hepatic metabolic changes in people with HIV (PWH) with advanced disease, before and after antiretroviral therapy (ART) initiation, using [18F]-fluorodeoxyglucose (FDG) PET-computed tomography (PET/CT). FDG PET/CT noninvasively quantifies glucose metabolism in organs.

Design/methods:

Forty-eight viremic PWH (CD4+ counts…

Objectives:

To assess humoral responses to SARS-CoV-2 Delta-variant in people with HIV (PWH) after BNT162b2-vaccination.

Design:

Multicenter cohort study of PWH with CD4+ less than 500 cells/μl and viral load less than 50 copies/ml on stable antiretroviral therapy for at least 3 months.

Methods:

Anti-SARS-CoV-2 receptor-binding-domain IgG antibodies (anti-RBD IgG) were quantified and neutralization capacity was evaluated by ELISA/GenScript and virus-neutralization-test against the D614G-strain, beta and delta variants before vaccination (day 0) and 1 month after complete schedule (M1).

Results:

We enrolled 97 PWH, 85 received two vaccine shots. The seroconversion rate for anti-RBD IgG was 97% [95% confidence interval (CI) 90–100%] at M1. Median (IQR) anti-RBD IgG titer was 0.97 (0.97–5.3) BAU/ml at D0 and 1219 (602–1929) at M1. Neutralization capacity improved between D0 (15%; 50% CI 8–23%) and M1 (94%; 95% CI 87–98%) (P …

Background:

HIV-infected men who have sex with men (MSM) are at high risk to develop human papilloma virus (HPV)-related oropharyngeal cancer. The aim of our study was to assess the usefulness of a pilot oral dysplasia screening program and its correlation with an anal dysplasia screening program.

Methods:

This was a prospective study with HIV-infected MSM. Oral and anal screenings were performed based on HPV determination, liquid cytology, direct and microscopy oral examinations, high-resolution anoscopy and biopsies, if necessary.

Results:

A total of 103 patients were included. The mean age of the patients was 44.6 years, 55.3% were smokers, and 57.3% had a history of previous anal high-grade squamous intraepithelial lesions (HSILs).

The prevalence of oral HPV infections was 14% (9% HPV-high risk), the prevalence of abnormal cytology was 25.2%, and in 4.8% of the patients, oral examinations showed suspicious HSILs. Oral microscopy did not detect additional lesions that visual inspection. Five oral biopsies were performed and the results were normal. No risk factors for oral HPV infections were identified.

The prevalence of anal HPV infections was 88.3% (76.7% HPV-high risk), 52.9% of the patients had altered cytology, and in 45.6% anoscopy showed changes suggestive of HSILs. Seventy-two anal biopsies were performed, detecting 25 cases of HSILs (24.3%).

A poor correlation was observed between oral and anal HPV infections (κ = 0.037).

Conclusions:

The prevalence of oral HPV infections, abnormal cytology and lesions in HIV-infected MSM was low, and their correlation with anal HPV-related lesions was slight. These results confirm the current barriers to oral dysplasia screening techniques.

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Objective:

It remains unclear why HIV persists in most untreated individuals, and why a small minority of individuals can control the virus, either spontaneously or after an early treatment. Striking differences have been discovered between patient cohorts in CD4+ T-cell avidity but not in CD8+ T-cell avidity. The present work has the aim to explain the diverse outcome of infection and identify the key virological and immunological parameters predicting the outcome.

Design and method:

A mathematical model informed by these experiments and taking into account the details of HIV virology is developed.

Results:

The model predicts an arms race between viral dissemination and the proliferation of HIV-specific CD4+ helper cells leading to one of two states: a low-viremia state (controller) or a high-viremia state (progressor). Helper CD4+ cells with a higher avidity favor virus control. The parameter segregating spontaneous and posttreatment controllers is the infectivity difference between activated and resting CD4+ T cells. The model is shown to have a better connection to experiment that a previous model based on T-cell ‘exhaustion’.

Conclusion:

Using the model informed by patient data, the timing of antiretroviral therapy can be optimized.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objective:

People with HIV (PWH) have persistently elevated levels of inflammation and immune activation despite suppressive antiretroviral therapy (ART), with specific biomarkers showing associations with non-AIDS-defining morbidities and mortality. We investigated the potential role of the HIV-specific adaptive immune response, which also persists under ART, in driving levels of these clinically relevant biomarkers.

Design:

Cohort-based study.

Methods:

HIV-specific IFN-γ-producing T-cell responses and antibody concentrations were measured in blood at study entry in the ACTG A5321 cohort, following a median of 7 years of suppressive ART. HIV persistence measures including cell-associated (CA)-DNA, CA-RNA, and plasma HIV RNA (single-copy assay) were also assessed at study entry. Plasma inflammatory biomarkers and T-cell activation and cycling were measured at a pre-ART time point and at study entry.

Results:

Neither the magnitudes of HIV-specific T-cell responses nor HIV antibody levels were correlated with levels of the inflammatory or immune activation biomarkers, including hs-CRP, IL-6, neopterin, sCD14, sCD163, TNF-α, %CD38+HLA-DR+ CD8+ and CD4+ cells, and %Ki67+ CD8+ and CD4+ cells – including after adjustment for pre-ART biomarker level. Plasma HIV RNA levels were modestly correlated with CD8+ T-cell activation (r = 0.25, p = 0.027), but other HIV persistence parameters were not associated with these biomarkers. In mediation analysis, relationships between HIV persistence parameters and inflammatory biomarkers were not influenced by either HIV-specific T-cell responses or antibody levels.

Conclusions:

Adaptive HIV-specific immune responses do not appear to contribute to the elevated inflammatory and immune activation profile in persons on long-term ART.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objectives:

The aim of this study was to assess the impact of natural resource extraction projects on HIV transmission risks in local communities in sub-Saharan Africa.

Design:

Difference-in-differences design using repeated cross-sectional data from around newly opened mines.

Methods:

We combined data on mine openings with HIV data from the Demographic and Health Surveys (DHS). Using logistic regression models, we compared HIV related indicators between mining (i.e. up to 10 km distance from the mine) and comparison (i.e. 10–50 km) areas before and after mine opening to identify their impact on HIV prevalence, sexual behavior and HIV knowledge.

Results:

A total of 33,086 individuals across 39 mine openings were analyzed. Adjusting for baseline differences and temporal trends in the study regions, mine opening increased the odds of HIV infection almost two-fold (odds ratio (OR): 1.93, 95% confidence interval (CI): 1.19–3.14). Strongest effects were seen in high-prevalence countries and in the 20–29 years age group. In mining communities around operational mines there was a tendency towards lower HIV knowledge (OR: 0.81, 95% CI: 0.63–1.04). New mine openings increased the odds of risky sexual behaviors, such as having multiple sex partners (OR: 1.61, 95% CI: 1.02–2.55), high-risk sexual partners (OR: 1.45, 95% CI: 1.03–2.05) and unprotected sex with high-risk partners (OR: 1.77, 95% CI: 1.18–2.67).

Conclusion:

The findings suggest that in our sample of households surrounding industrial mines, HIV infection risks substantially increase upon mine opening. Existing strategies for addressing mining-related risks for HIV transmission seem to be insufficient. Further efforts for mitigating and monitoring impacts of mines are needed.

Video Abstract: http://links.lww.com/QAD/C557

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Over the course of the first year of COVID-19 vaccination, between Dec 8, 2020, and Dec 8, 2021, 8·33 billion doses were administered among 4·36 billion people globally.1 In their study in The Lancet Infectious Diseases, by fitting a mathematical model to excess mortality, Oliver J Watson and colleagues2 estimated that in 185 countries and territories 31·4 million COVID-19-related deaths would have occurred during this timeframe in the absence of COVID-19 vaccination. They estimated that 19·8 million deaths were averted by COVID-19 vaccination.

With rising incomes and the increased availability of antibiotics globally, per-capita consumption of antibiotics in middle-income countries is fast approaching the rates in high-income countries.1 Antimicrobial resistance has emerged as a major source of morbidity and mortality worldwide, and now is estimated to cause more deaths than malaria or HIV/AIDS.2 Existing and new vaccines could help avert a substantial proportion of current antibiotic use, and there is now considerable evidence linking vaccination with decreased use of antibiotics and averted cases of antimicrobial resistance.

COVID-19 vaccination has substantially altered the course of the pandemic, saving tens of millions of lives globally. However, inadequate access to vaccines in low-income countries has limited the impact in these settings, reinforcing the need for global vaccine equity and coverage.

In The Lancet Infectious Diseases, Aaron M Samuels and colleagues1 assessed the efficacy of fractional RTS,S/AS01E (hereafter referred to as RTS,S) vaccines doses against malaria. The study design of this clinical trial was based on findings from a phase 2a controlled human malaria infection (CHMI) study assessing vaccine efficacy in adults,2 and from a study evaluating the effect of a change in the vaccine regimen on the quality of antibody responses.3…

The Fx012-14 regimen was not superior to the standard regimen over 12 months after dose three. All RTS,S/AS01E regimens provided substantial, similar protection against clinical malaria, suggesting potential flexibility in the recommended dosing regimen and schedule. This, and the effect of annual boosters, will be further evaluated through 50 months of follow-up.

Counts of reported cases have been the key metric to monitor the COVID-19 pandemic. However, since the beginning, it has been clear that reported cases represent only a fraction of all SARS-CoV-2 infections.1 In The Lancet, COVID-19 Cumulative Infection Collaborators, writing on behalf of the Institute for Health Metrics and Evaluation, report a comprehensive set of global and location-specific estimates of daily and cumulative SARS-CoV-2 infections and the proportion of the population infected for 190 countries and territories up to Nov 14, 2021.

2 years into the COVID-19 pandemic, it is clear that gender differences exist, and that women, men, and gender minorities are differentially impacted by the pandemic.1 Emmanuela Gakidou and colleagues' Article2 in The Lancet provides additional data to reinforce this fact. Much of the research on the impacts of COVID-19 (outside of those whose work focuses on sex and gender differences) has focused on the direct health-related impacts of COVID-19, such as the fact that more men have been hospitalised and died from COVID-19-attributable causes than women.

During the COVID-19 pandemic health professionals have found themselves working in a landscape that has been utterly transformed, for good and ill. There have been remarkable advances, such as accelerated research to produce effective treatments and vaccines, and increased use of digital health care. There are also ongoing challenges in many health-care settings, such as staff shortages, the pressures of long waiting lists for routine care, and an exhausted health workforce. Yet whatever the innovations and adversities, compassion and connection remain fundamental to establishing a positive, healing relationship between health-care workers and patients.

1 month ago, North Korea declared its first COVID-19 cases. Information is scare, but the outbreak now appears to be huge, amid a food crisis and without mass vaccination. Talha Burki reports.

Monkeypox cases are increasing rapidly in the UK. The UK Health and Safety Agency (UKHSA) defines a probable case of monkeypox as “a person with an unexplained rash on any part of their body plus one or more classical symptom or symptoms of monkeypox infection since March 15, 2022 and either: has an epidemiological link to a confirmed or probable case of monkeypox in the 21 days before symptom onset; or reported a travel history to west or central Africa in the 21 days before symptom onset; or is a gay, bisexual or other man who has sex with men.

Christopher J L Murray and colleagues1 provide a compelling contribution to the understanding of the burden of disease attributable to bacterial antimicrobial resistance (AMR) in 2019. Focusing on 23 bacterial pathogens, they used two-stage spatiotemporal modelling to estimate this burden to be larger than diseases such as HIV and malaria, with the highest rates in sub-Saharan Africa. This new information should raise this issue higher on the global health agenda. They also, however, highlight the scarcity of high-quality data for infectious diseases and antibiotic consumption, with the authors having to rely on antibiotics sales data for an indication of antibiotic consumption.

Christopher J L Murray and colleagues1 provide a sobering analysis on the burden of common antimicrobial-resistant infections and a warning that, as a global community, we are rapidly surrendering any advantage we had on treating infections such as pneumonia and sepsis.2…

Christopher J L Murray and colleagues1 report on the dramatically high burden of antimicrobial resistance (AMR) worldwide, particularly in low-income and middle-income countries. The authors also emphasise the insufficient data on the prevalence of bacterial infections and AMR in low-resource settings. Although the figures presented are striking, they do not sufficiently depict the suffering of patients living in these locations and the frustration of clinicians unable to treat an infection that is typically easily curable elsewhere.

COVID-19 has already had a staggering impact on the world up to the beginning of the omicron (B.1.1.529) wave, with over 40% of the global population infected at least once by Nov 14, 2021. The vast differences in cumulative proportion of the population infected across locations could help policy makers identify the transmission-prevention strategies that have been most effective, as well as the populations at greatest risk for future infection. This information might also be useful for targeted transmission-prevention interventions, including vaccine prioritisation.

The most significant gender gaps identified in our study show intensified levels of pre-existing widespread inequalities between women and men during the COVID-19 pandemic. Political and social leaders should prioritise policies that enable and encourage women to participate in the labour force and continue their education, thereby equipping and enabling them with greater ability to overcome the barriers they face.

Science, Ahead of Print. …

Abstract

Introduction

The Bacille-Calmette–Guerin (BCG) vaccination remains the primary strategy to prevent severe disseminated TB in young children, particularly in high TB-burden countries such as Ethiopia. Accurate knowledge of vaccination coverage in small geographical areas is critically important to developing targeted immunization campaigns. Thus, this study aimed to investigate the spatiotemporal distributions and ecological level determinants of BCG vaccination coverage in Ethiopia.

Method

Bacille-Calmette–Guerin immunization coverage and geographical information data were obtained from five different Demographic and Health Surveys, conducted in Ethiopia between 2000 and 2019. Data for independent variables were obtained from publicly available sources. Bayesian geostatistical models were used to predict the spatial distribution of BCG vaccination coverage in Ethiopia.

Result

The overall national BCG vaccination coverage between 2000 and 2019 was 65.5%. The BCG vaccine coverage was 53.5% in 2000, 56.9% in 2005, 64.4% in 2011, 79.6% in 2016, and 79.0% in 2019. BCG vaccination coverage increased by 47.6% in Ethiopia from 2000 to 2019, but substantial geographical inequalities in BCG coverage remained at sub-national and local levels. High vaccination coverage was observed in northern, western, and central parts of Ethiopia. Climatic and demographic factors such as temperature, altitude, and population density were positively associated with BCG vaccination coverage. Whereas, healthcare access factors such as distance to health facilities and travel time to the nearest cities were negatively associated with BCG vaccine coverage in Ethiopia.

Conclusion

Despite substantial progress in national BCG vaccination coverage, marked spatial variation in BCG coverage persists throughout the country at sub-national and local levels. Healthcare access and climatic and demographic factors determined the spatial distribution of BCG vaccination coverage. Maintaining a high level of vaccination coverage across geographical areas is important to prevent TB in Ethiopia.

…

Abstract

Background

India has made considerable progress in malaria reduction over the past two decades, with government-sponsored indoor residual spraying (IRS) and insecticide-treated bed net (ITN) or long-lasting insecticidal nets (LLIN) distribution being the main vector-related prevention efforts. Few investigations have used non-participant observational methods to assess malaria control measures while they were being implemented, nor documented people’s perceptions and acceptance of IRS or LLINs in India, and none have done so in the northeast region. This study evaluated household (HH)-level operation of IRS and distribution of LLINs by India’s National Vector Borne Disease Control Programme (NVBDCP) in 50 villages of Meghalaya state, and documented their acceptance and use.

Methods

Study field teams accompanied the government health system teams during August-October, 2019 and 2020 to observe deployment of LLINs, and record HH-level data on LLIN numbers and use. In addition, NVBDCP spray teams were followed during 2019–2021 to observe IRS preparation and administration. HH members were interviewed to better understand reasons for acceptance or refusal of spraying.

Results

A total of 8386 LLINs were distributed to 2727 HHs in 24 villages from five Primary Health Centres, representing 99.5% of planned coverage. Interviews with 80 HH residents indicated that they appreciated the LLIN dissemination programme, and generally made regular and appropriate use of LLINs, except during overnight travel or when working in agricultural fields. However, HH-level IRS application, which was observed at 632 HHs, did not always follow standard insecticide preparation and safety protocols. Of 1,079 occupied HHs visited by the spray team, 632 (58.6%) refused to allow any spraying. Only 198 (18.4%) HHs agreed to be sprayed, comprising 152 (14.1%) that were only partly sprayed, and 46 (4.3%) that were fully sprayed. Reasons for refusal included: inadequate time to rearrange HH items, young children were present, annoying smell, staining of walls, and threat to bee-keeping or Eri silk moth cultivation.

Conclusions

These findings are among the first in India that independently evaluate people's perceptions and acceptance of ongoing government-sponsored IRS and LLIN programmes for malaria prevention. They represent important insights for achieving India's goal of malaria elimination by 2030.

…

Abstract

Background

Coronavirus disease 2019 (COVID-19) often causes atypical clinical manifestations similar to other infectious diseases. In malaria-endemic areas, the pandemic situation will very likely result in co-infection of COVID-19 and malaria, although reports to date are still few. Meanwhile, this disease will be challenging to diagnose in areas with low malaria prevalence because the symptoms closely resemble COVID-19.

Case presentation

A 23-year-old male patient presented to the hospital with fever, anosmia, headache, and nausea 1 week before. He was diagnosed with COVID-19 and treated for approximately 10 days, then discharged to continue self-quarantine at home. 2 weeks later, he returned to the hospital with a fever raised intermittently every 2 days and marked by a chilling-fever-sweating cycle. A laboratory test for malaria and a nasopharyngeal swab for SARS CoV-2 PCR were conducted, confirming both diagnoses. The laboratory examination showed markedly elevated D-dimer. He was treated with dihydroartemisinin-piperaquine (DHP) 4 tablets per day for 3 days and primaquine 2 tablets per day for 14 days according to Indonesian National Anti-malarial Treatment Guidelines. After 6 days of treatment, the patient had no complaints, and the results of laboratory tests had improved. This report describes the key points in considering the differential diagnosis and prompt treatment of malaria infection during the pandemic of COVID-19 in an endemic country to prevent the worse clinical outcomes. COVID-19 and malaria may also cause a hypercoagulable state, so a co-infection of those diseases may impact the prognosis of the disease.

Conclusion

This case report shows that considering the possibility of a co-infection in a COVID-19 patient who presents with fever can prevent delayed treatment that can worsen the disease outcome. Paying more attention to a history of travel to malaria-endemic areas, a history of previous malaria infection, and exploring anamnesis regarding the fever patterns in patients are important points in making a differential diagnosis of malaria infection during the COVID-19 pandemic.

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AbstractNative and invasive tick species pose a serious public health concern in the United States. Range expansion of several medically important tick species has resulted in an increasing number of communities at risk for exposure to ticks and tickborne pathogens.

ABSTRACTBackgroundThis United States-based study compared two candidate vaccines: RSV/ΔNS2/Δ1313/I1314L, attenuated by NS2 gene-deletion and temperature-sensitivity mutation in the polymerase gene; and RSV/276, attenuated by M2-2 deletion.MethodsRSV-seronegative children aged 6-24 months received RSV/ΔNS2/Δ1313/I1314L [106 plaque-forming units (PFU)], RSV/276 [105 PFU] or placebo intranasally. Participants were monitored for vaccine shedding, reactogenicity, and RSV serum antibodies, and followed over the subsequent RSV-season.ResultsEnrollment occurred September 2017-October 2019. During 28 days post-inoculation, upper respiratory illness (URI) and/or fever occurred in 64% of RSV/ΔNS2/Δ1313/I1314L, 84% RSV/276, and 58% placebo recipients. Symptoms were generally mild. Cough was more common in RSV/276 recipients than RSV/ΔNS2/Δ1313/I1314L (48% v. 12%; p = 0.012) or placebo recipients (17%; p = 0.084). There were no lower respiratory illness or serious adverse events. Eighty-eight and 96% of RSV/ΔNS2/Δ1313/I1314L and RSV/276 recipients were infected with vaccine (shed vaccine and/or had ≥4-fold rises in RSV antibodies). Serum RSV-neutralizing titers and anti-RSV F IgG titers increased ≥4-fold in 60% and 92% of RSV/ΔNS2/Δ1313/I1314L and RSV/276 vaccinees, respectively. Exposure to community RSV during the subsequent winter was associated with strong anamnestic RSV-antibody responses.ConclusionsBoth vaccines had excellent infectivity and were well-tolerated. RSV/276 induced an excess of mild cough. Both vaccines were immunogenic and primed for strong anamnestic responses.

AbstractInfection by the SARS-CoV-2 variant Omicron is usually asymptomatic or mild and appears to be poorly immunogenic at least in unvaccinated individuals. Here, we found that healthcare workers vaccinated with two doses of Sputnik V and a booster dose of ChAdOx1 mount a vigorous neutralizing-antibody response after Omicron breakthrough infection.

AbstractThe highly transmissible Omicron variant has caused high rates of breakthrough infections in those previously vaccinated with ancestral strain COVID-19 vaccines. Here, we demonstrate that a booster dose of UB-612 vaccine candidate delivered 7-9 months after primary vaccination increased neutralizing antibody levels by 131-, 61- and 49-fold against ancestral SARS-CoV-2, Omicron BA.1, and BA.2 variants, respectively. Based on the RBD protein-binding antibody responses, the UB-612 third dose booster may lead to an estimated ∼95% efficacy against symptomatic COVID-19 caused by the ancestral strain. Our results support UB-612 as a potential potent booster against current and emerging SARS-CoV-2 variants.

ABSTRACTTherapeutic drug monitoring (TDM) of beta-lactam antibiotics is recommended to address the variability in exposure observed in critical illness. However, the impact of TDM-guided dosing on clinical outcomes remains unknown. We conducted systematic review and meta-analysis on TDM-guided dosing and clinical outcomes (all-cause mortality, clinical cure, microbiological cure, treatment failure, hospital and ICU length of stay, target attainment, antibiotic-related adverse events, and emergence of resistance) in critically ill patients with suspected or proven sepsis. Eleven studies (n = 1463 participants) were included. TDM-guided dosing was associated with improved clinical cure (Relative Risk 1.17; 95% Confidence Interval [1.04, 1.31]), microbiological cure (1.14; [1.03, 1.27]), treatment failure (0.79; [0.66, 0.94]), and target attainment (1.85; [1.08, 3.16]). No associations with mortality and length of stay were found. TDM-guided dosing improved clinical and microbiological cure, and treatment response. Larger, prospective randomized trials are required to better assess the utility of beta-lactam TDM in critically ill patients.

AbstractBackgroundBlocking the transmission of parasites from humans to mosquitoes is a key component of malaria control. Tafenoquine exhibits activity against all stages of the malaria parasite and may have utility as a transmission blocking agent. We aimed to characterize the transmission blocking activity of low dose tafenoquine.MethodsHealthy adults were inoculated with P. falciparum 3D7-infected erythrocytes on day 0. Piperaquine was administered on days 9 and 11 to clear asexual parasitemia while allowing gametocyte development. A single 50 mg oral dose of tafenoquine was administered on day 25. Transmission was determined by enriched membrane feeding assays pre-dose and at 1, 4 and 7 days post-dose. Artemether-lumefantrine was administered following the final assay. Outcomes were the reduction in mosquito infection and gametocytemia post-tafenoquine, and safety parameters.ResultsSix participants were enrolled, and all were infective to mosquitoes pre-tafenoquine, with a median 86% (range: 22–98) of mosquitoes positive for oocysts and 57% (range: 4–92) positive for sporozoites. By day 4 post-tafenoquine, the oocyst and sporozoite positivity rate had reduced by a median 35% (IQR: 16–46) and 52% (IQR: 40–62), respectively, and by day 7, 81% (IQR 36–92) and 77% (IQR 52–98), respectively. The decline in gametocyte density post-tafenoquine was not significant. No significant participant safety concerns were identified.ConclusionLow dose tafenoquine (50 mg) reduces P. falciparum transmission to mosquitoes, with a delay in effect.