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Previous infection with any SARS-CoV-2 variant provided some protection against symptomatic reinfection, and vaccination added to this protection. Vaccination provides low-to-moderate protection against symptomatic omicron infection, with waning protection after each dose, while hybrid immunity provided the most robust protection. Although more data are needed to investigate longer-term protection and protection against infection with new variants, these data question the need for additional booster vaccine doses for adolescents in populations with already high protection against SARS-CoV-2 infection.

Human infection with parvovirus B19 causes a range of clinical manifestations, including benign erythema infectiosum in children, arthralgias in adults, aplastic crisis in patients with bone marrow failure, and potentially fatal congenital hydrops fetalis. Persistent parvovirus B19 infection is a rare disease presentation mostly seen in adult women or immunocompromised individuals. Treatment options include corticosteroids and intravenous immunoglobulin; however, viral clearance is difficult to obtain and rarely maintained.

Since the start of the Coronavirus Disease 2019 (COVID-19) pandemic in early 2020, over 564 million confirmed cases and over 6 million deaths have been reported globally (July 22nd, 2022)(WHO, 2022a). In the Netherlands (total population: 17.6 million), 8.3 million inhabitants have officially been diagnosed with COVID-19 (WHO, 2022b). This number is an underestimation of the actual number of cases, since not all people were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.

We aimed to compare clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection.

To determine the impact of a booster dose on the humoral response in individuals inoculated with a complete schedule of any SARS-CoV-2 vaccine, we evaluated the neutralizing antibody (NAb) titers of homologous or heterologous booster doses over a 90-days period in CoronaVac vaccinees from three centers in Santiago, Chile.

A 33-year-old man presented at the hospital because of a left axillary adenitis which appeared one month before. He had no prior medical history and was up-to-date on his vaccinations. He had two dogs and had been in recent contact with cattle in the course of his work as a rat exterminator. Physical examination revealed a growing and inflammatory axillary lesion associated with a dry cough. Blood analysis revealed hypereosinophilia (eosinophils count: 2.53x109/L). The Gram staining of the lymph node aspiration showed Gram-variable filamentous branching rods (Fig.

We aimed to generate comprehensive estimates of the appropriateness of outpatient antibiotic prescriptions at primary healthcare facilities (PHFs) in China.

Objective: Women with HIV (WWH) have heightened heart failure (HF) risk. Plasma OPN (osteopontin) is a powerful predictor of HF outcomes in the general population. Limited data exist on relationships between plasma OPN and surrogates of HIV-associated HF risk.Design: Prospective, cross-sectionalMethods: We analyzed relationships between plasma OPN and cardiac structure/ function (assessed using cardiovascular magnetic resonance imaging) and immune activation (biomarkers and flow cytometry) among 20 WWH and 14 women without HIV (WWOH).Results: Plasma OPN did not differ between groups. Among WWH, plasma OPN related directly to the markers of cardiac fibrosis, growth differentiation factor-15 (ρ=0.51, P = 0.02) and soluble interleukin 1 receptor-like 1 (ρ=0.45, P = 0.0459). Among WWH (but not among WWOH or the whole group), plasma OPN related directly to both myocardial fibrosis (ρ=0.49, P = 0.03) and myocardial steatosis (ρ=0.46, P = 0.0487). Among the whole group and WWH (and not among WWOH), plasma OPN related directly to the surface expression of C-X3-C motif chemokine receptor 1 (CX3CR1) on non-classical (CD14-CD16+) monocytes (whole group:ρ=0.36, P = 0.04; WWH:ρ=0.46, P = 0.04). Further, among WWH and WWOH (and not among the whole group), plasma OPN related directly to the surface expression of CC motif chemokine receptor 2 (CCR2) on inflammatory (CD14+CD16+) monocytes (WWH:ρ=0.54, P = 0.01; WWOH:ρ=0.60, P = 0.03), and in WWH, this held even after controlling for HIV-specific parameters.Conclusions: Among WWH, plasma OPN, a powerful predictor of HF outcomes, related to myocardial fibrosis and steatosis and the expression of CCR2 and CX3CR1 on select monocyte subpopulations. OPN may play a role in HF pathogenesis among WWH.Clinicaltrials.gov Registration: NCT02874703Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objective: To investigate relationships between Life's Simple 7 (LS7), an assessment of cardiovascular health (CVH), and coronary plaque among people with HIV (PWH).Design: Cross-sectional.Methods: Coronary computed tomography angiography, immune/inflammatory biomarkers, and characterization of LS7 were collected among a subset of ART-treated PWH enrolled in REPRIEVE, a primary prevention trial. Analyses adjusted for cardiovascular disease risk (ASCVD score).Results: Median age of the 735 participants was 51(±6) years, 16% female, and median (Q1–Q3) CVD risk was 4.5% (2.6–6.9). Forty percentage had poor (≤2 ideal components), 51% had intermediate (three or four ideal components), and only 9% had ideal CVH (≥5). Coronary plaque was present in 357 (49%); 167 (23%) had ≥1 vulnerable plaque features, 293 (40%) had noncalcified plaque, and 242 (35%) had a coronary artery calcium score >0. All three phenotypes were increasingly more prevalent with poorer CVH and these relationships remained after adjusting for ASCVD risk. Poor CVH was associated with higher high-sensitivity C-reactive protein, oxidized low-density cholesterol, and interleukin-6. The relationship of LS7 to plaque remained after adjusting for these biomarkers.Conclusions: Among PWH, poor CVH as measured by LS7 was associated with coronary plaque presence, vulnerable features, and calcification. LS7 was also associated with selected biomarkers; adjustment for these and ASCVD score reduced but did not eliminate LS7's association with plaque, suggesting the possibility of additional protective mechanisms against atherogenesis and plaque remodeling. Clinical use of LS7 and further exploration of its relationships with coronary artery disease may enhance efforts to reduce cardiovascular morbidity and mortality in PWH.Clinical Trials Registration: NCT02344290Graphical abstract, http://links.lww.com/QAD/C694Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Objective: To study gut microbiota before and 24 weeks after a single antiretroviral agent switch.Design: HIV-positive subjects with efavirenz (EFV) or a protease inhibitor-based antiretroviral therapy (ART) were randomized to switch EFV or protease inhibitor to raltegravir (RAL group, n = 19) or to continue unchanged ART [EFV/protease inhibitor (EFV/PI) group, n = 22]. Age-matched and weight-matched HIV-negative subjects (n = 10) were included for comparison.Methods: Microbiota was analyzed using 16S rRNA sequencing. Serum intestinal fatty acid-binding protein (I-FABP) and serum lipopolysaccharide-binding protein (LBP) were measured as gut permeability markers. Three-day food diaries were collected.Results: At week 24, microbiota diversity (Chao1 index) was higher in RAL than EFV/PI group (P = 0.014), and RAL group did not differ from HIV-negative subjects. In subgroup analysis switching from EFV (P = 0.043), but not from a protease inhibitor to RAL increased Chao1. At week 24, RAL and EFV/PI group differed in the relative abundance of Prevotella 9 (higher in RAL, P = 0.01), Phascolarctobacterium and Bacteroides (lower in RAL, P = 0.01 and P = 0.03). Dietary intakes did not change during the study and do not explain microbiota differences. Also, I-FABP and LBP remained unchanged.Conclusion: Here we demonstrate that a single ART agent switch caused microbiota alterations, most importantly, an increase in diversity with EFV to RAL switch. Previously, we reported weight gain, yet reduced inflammation in this cohort. The observed microbiota differences between RAL and EFV/PI groups may be associated with reduced inflammation and/or increase in weight. Further studies are needed to evaluate inflammatory and metabolic capacity of microbiota with ART switches.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objective: Evaluating the vascular function in HIV+ compared to HIV- with assessment of body composition, inflammation, and gut integrity markers.Design: A non-invasive test that measures the endothelial function.Methods: We included participants ≥18 years, with peripheral arterial tonometry testing (EndoPAT2000) between 2014-2022. Persons living with HIV (PLWH) had documented infection, a stable ART regimen, and a Viral Load…

Objective: To describe the prevalence of diagnosed depression, anxiety, bipolar disorder, and schizophrenia in people with HIV (PWH) and the differences in HIV care continuum outcomes in those with and without mental health disorders (MHDs).Design: Observational study of participants in the North American AIDS Cohort Collaboration on Research and Design.Methods: PWH (≥18 years) contributed data on prevalent schizophrenia, anxiety, depressive, and bipolar disorders from 2008 to 2018 based on ICD code mapping. Mental health (MH) multimorbidity was defined as having ≥2 MHD. Log binomial models with generalized estimating equations estimated adjusted prevalence ratios (aPR) and 95% confidence intervals for retention in care (≥1 visit/year) and viral suppression (HIV RNA ≤200 copies/ml) by presence vs. absence of each MHD between 2016 and 2018.Results: Among 122 896 PWH, 67 643 (55.1%) were diagnosed with ≥1 MHD: 39% with depressive disorders, 28% with anxiety disorders, 10% with bipolar disorder, and 5% with schizophrenia. The prevalence of depressive and anxiety disorders increased between 2008 and 2018, whereas bipolar disorder and schizophrenia remained stable. MH multimorbidity affected 24% of PWH. From 2016 to 2018 (N = 64 684), retention in care was marginally lower among PWH with depression or anxiety, however those with MH multimorbidity were more likely to be retained in care. PWH with bipolar disorder had marginally lower prevalence of viral suppression (aPR = 0.98 [0.98–0.99]) as did PWH with MH multimorbidity (aPR = 0.99 [0.99–1.00]) compared with PWH without MHD.Conclusion: The prevalence of MHD among PWH was high, including MH multimorbidity. Although retention and viral suppression were similar to people without MHD, viral suppression was lower in those with bipolar disorder and MH multimorbidity.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Introduction: Studies examining hospitalization among infants with HIV in resource-limited settings, in the context of early infant diagnosis and early antiretroviral therapy (ART) initiation, are limited.Methods: We used routinely collected data on infants who initiated ART aged 1 hospitalization. Median age at ART initiation decreased from 57 days (interquartile range [IQR] 22–74; 2013–2015) to 19 days (IQR 5–54; 2016–2017). Early neonatal hospitalization (age…

Objective: To characterize the prevalence of anemia and risk factors between 2007 and 2017 for moderate/severe anemia among people with HIV (PWH) in North America who have initiated antiretroviral therapy (ART).Design: Observational study of participants in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).Methods: We estimated the annual prevalence between 1 January 2007 and 31 December 2017 of mild (11.0–12.9 g/dl men, 11.0–11.9 g/dl women), moderate (8.0–10.9 g/dl regardless of sex) and severe (1 year of ART) (aPR = 1.66 [1.61–1.72]).Conclusion: The prevalence of anemia among PWH is reduced after ART initiation but remains high. Risk factors differ by sex and include comorbidities and HIV disease severity. The persistent, substantial prevalence of anemia among PWH merits further investigation, targeted screening, and clinical interventions.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Ian Frazer, Douglas Lowy, and John Schiller have been recognised for their work on HPV vaccines, and Ralph DeFronzo wins for work on diabetes. Talha Burki reports.

Both bedaquiline-containing regimens, a 9-month oral regimen and a 6-month regimen with 8 weeks of second-line injectable, had superior efficacy compared with a 9-month injectable-containing regimen, with fewer cases of hearing loss.

A 45-year-old man presented to our department with a 5-month history of foamy urine and swollen legs. Previously, the patient had epilepsy, seronegative rheumatoid arthritis, and thyroid carcinoma. He was being prescribed the following medications: carbamazepine, levothyroxine, ezetimibe combined with simvastatin, calcitriol, ramipril, furosemide, and mesoglycan. On examination, the patient had moderate oedema of both lower limbs with no other atypical findings; his blood pressure was 140/85 mm Hg and heart rate was 76 beats per min.

SummaryMitochondria are the controllers of cell metabolism and are recognized as decision makers in cell death pathways, organizers of cytoplasmic signaling networks, managers of cellular stress responses and regulators of nuclear gene expression. Cells of the immune system are particularly dependent on mitochondrial resources, as they must swiftly respond to danger signals with activation, trafficking, migration, and generation of daughter cells. Analogously, faulty immune responses that lead to autoimmunity and tissue inflammation rely on mitochondria to supply energy, cell building blocks and metabolic intermediates. Emerging data endorse the concept that mitochondrial fitness, and the lack of it, is of particular relevance in the autoimmune disease rheumatoid arthritis (RA) where deviations of bioenergetic and biosynthetic flux affect T cells during early and late stages of disease. During early stages of RA, mitochondrial deficiency allows naïve RA T cells to lose self-tolerance, biasing fundamental choices of the immune system towards immune-mediated tissue damage and away from host protection. During late stages of RA, mitochondrial abnormalities shape the response patterns of RA effector T cells engaged in the inflammatory lesions, enabling chronicity of tissue damage and tissue remodeling. In the inflamed joint, autoreactive T cells partner with metabolically reprogrammed tissue macrophages that specialize in antigen-presentation and survive by adapting to the glucose-deplete tissue microenvironment. Here, we summarize recent data on dysfunctional mitochondria and mitochondria-derived signals relevant in the RA disease process that offer novel opportunities to deter autoimmune tissue inflammation by metabolic interference.

SummarySignal transducer and activator of transcription 1 (STAT1) is a well-known and pivotal molecule in the regulation of the Janus activating kinases (JAK)-STAT pathway, an extensive signalling pathway downstream of several cytokine receptors that plays an indispensable role in immune defence in humans. In the JAK-STAT pathway, STAT1 homodimer-dependent IFN-γ immunity is crucial for defence against intra-macrophagic bacteria, and STAT1/STAT2/IRF9 complex-dependent IFN-α/β immunity is essential for protection against viruses. STAT1 dysfunction causes a wide range of immune dysregulation phenotypes, which have been classified into four disease types, namely, (i) autosomal recessive (AR) complete STAT1 deficiency, (ii) AR partial STAT1 deficiency, (iii) autosomal dominant (AD) STAT1 deficiency, and (iv) AD STAT1 gain-of-function (GOF), based on their mode of inheritance and function. Disease types (i, ii, and iii) are caused by STAT1 loss-of-function (LOF) mutations, whereas disease type (iv) is caused by STAT1 GOF mutations. Notably, rapid and accurate diagnosis of these four diseases can be difficult. In particular, the differential diagnosis of AD STAT1 deficiency and AD STAT1 GOF, which are caused by LOF- and GOF-STAT1 mutations, respectively, can be complicated due to their overlapping clinical symptoms. In addition, more than 150 pathological mutations have been identified in STAT1 across all domains, making functional prediction of novel mutations difficult. Thus, the functional analysis of mutations is necessary for diagnosis. The recently proposed reference database of mutant STAT1 functions based on comprehensive alanine scanning is a useful tool for evaluating unknown STAT1 mutations with high accuracy.

AbstractBackgroundPersons with opioid use disorder (OUD) may present with infectious complications from injection drug use, thus ID physicians are uniquely positioned to treat OUD. Buprenorphine is safe and effective for OUD but remains underutilized. The prevalence and geographic distribution of ID physicians who are waivered to prescribe buprenorphine are unknown.MethodsThis cross-sectional study merged data from several publicly available datasets from November 1, 2021 to January 15, 2022. Our primary outcome was proportion of ID physicians possessing buprenorphine waivers in the United States. We identified individual and county-level characteristics associated with buprenorphine waiver possession. We then used geospatial analysis to determine geographic distribution of waivered ID physicians.ResultsWe identified 6372 ID physicians in the US, among whom 170 (2.7%) possessed waivers. Most ID physicians (97.3%) practiced in metropolitan counties. In our multivariable analysis, ID physicians had lower odds of having a waiver for every 10-year increase since graduating medical school (OR 0.79, 95% CI 0.68-0.91). ID physicians practicing in counties with higher proportion of uninsured residents had lower odds of having a waiver (OR 0.75, 95% CI 0.62-0.90). Among counties with at least one ID physician (n = 729), only 11.2% had at least one waivered ID physician.ConclusionsWe found an extremely low prevalence and skewed geographic distribution of ID physicians with buprenorphine waivers. Our findings suggest an urgent need to increase the workforce of ID physicians waivered to prescribe buprenorphine and a call for increased integration of OUD education into ID training and continuing medical education.

NIH10.13039/100000002NIDCR10.13039/100000072…

Proceedings of the National Academy of Sciences, Volume 119, Issue 48, November 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 48, November 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 48, November 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 48, November 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 48, November 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 48, November 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 48, November 2022.

AbstractBiological dinitrogen (N2) fixation supplies nitrogen to the oceans, supporting primary productivity, and is carried out by some bacteria and archaea referred to as diazotrophs. Cyanobacteria are conventionally considered to be the major contributors to marine N2 fixation, but non-cyanobacterial diazotrophs (NCDs) have been shown to be distributed throughout ocean ecosystems. However, the biogeochemical significance of marine NCDs has not been demonstrated. This review synthesizes multiple datasets, drawing from cultivation-independent molecular techniques and data from extensive oceanic expeditions, to provide a comprehensive view into the diversity, biogeography, ecophysiology, and activity of marine NCDs. A NCD nifH gene catalog was compiled containing sequences from both PCR-based and PCR-free methods, identifying taxa for future studies. NCD abundances from a novel database of NCD nifH-based abundances were colocalized with environmental data, unveiling distinct distributions and environmental drivers of individual taxa. Mechanisms that NCDs may use to fuel and regulate N2 fixation in response to oxygen and fixed nitrogen availability are discussed, based on a metabolic analysis of recently available Tara Oceans expedition data. The integration of multiple datasets provides a new perspective that enhances understanding of the biology, ecology, and biogeography of marine NCDs and provides tools and directions for future research.

Abstract Background Eosinophilia is defined as a blood eosinophil count > 500/mcL with etiology usually an allergic reaction or parasitic infection which can lead to serious organ damage. Case presentation A patient being treated for hardware infection develops eosinophilia while on daptomycin in the setting of a positive strongyloides antibody. The patient was on chronic steroids prior to admission for epitheliopathy which complicated care. The daptomycin was discontinued, ivermectin initiated to treat strongyloidiasis, and high dose steroids initiated simultaneously. Eosinophilia resolved and patient discharged home after two months in the hospital. Conclusion Multifactorial eosinophilia poses question of steroid harm in the setting of parasitic infection. Patient was treated for both strongyloides and daptomycin induced eosinophilia with improvement and discharge from the hospital. …

Abstract The Mycobacterium abscessus complex (MABC) is a group of acid-fast, rapidly dividing non-tuberculous mycobacteria (NTM) that include a number of clinically important subspecies, including M. abscessus, M. bolletii, and M. massiliense. These organisms are prevalent in the environment and are primarily associated with human pulmonary or skin and skin structure infections (SSSI) but may cause more deep-seeded disseminated infections and bacteremia in the immunocompromised. Importantly, these NTM are resistant to most first-line anti-tuberculous agents and, due to intrinsic or acquired resistance, exhibit exceedingly low, variable, and geographically distinct susceptibilities to commonly used antibacterial agents including older tetracyclines, macrolides, aminoglycosides, cephalosporins, carbapenems, and sulfamethoxazole-trimethoprim. Omadacycline is a novel third-generation member of the tetracycline family of antibacterials that has recently been demonstrated to have potent anti-NTM effects and clinical efficacy against MABC, including M. abscessus. The purpose of this review is to present a comprehensive and up-to-date assessment on the body of literature on the role of omadacycline for M. abscessus infections. Specifically, the in vitro and in vivo microbiology, mechanisms of action, mechanisms of resistance, clinical pharmacokinetics, clinical efficacy, adverse effects, dosage and administration, and place in therapy of omadacycline in management of M. abscessus infections will be detailed.…

Abstract Background The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies. Methods To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle. Results 180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57–73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61–2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63–2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively. Conclusions Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020 …

Abstract Background In Bangladesh, safely managed sanitation (SMS) coverage is low, and diarrheal disease is a significant health problem. This study estimated the inequality in access to SMS facilities at the national and sub-national levels and assessed the prevalence of diarrheal diseases in connection with these improved facilities. Methods Data were extracted from the Bangladesh Demographic and Health Survey, conducted during 2017–2018. SMS was defined as using an improved sanitation facility, which designed to hygienically separate excreta from human contact and include the use of a flush toilet connected to piped sewer system, septic tank, ventilated improved pit latrine, pit latrine with a slab, and composting toilet. The slope index of inequality (SII) and multi-level regression models were used for inequality and risk factors of SMS respectively. Results The national coverage of SMS was 44.0% (45.3% and 43.5% in urban and rural areas, respectively). At the sub-national level, the lowest and highest coverage of SMS was observed in Mymensingh (32.9%) and Chittagong (54.1%) divisions, respectively. The national level SII indicated that wealthy households had access to higher SMS by 60.8 percentage points than poor households. Additionally, greater inequality was observed in rural areas, which was 71.9 percentage points higher in the richest households than in the poorest households. The coverage gap between the rich and poor was highest in the Sylhet division (85.3 percentage points higher in rich than in poor) and lowest in Dhaka (34.9 percentage points). Old and highly educated household heads and richest households had better access to higher levels of adequate sanitation. After adjusting for confounding variables, the prevalence of diarrheal disease was 14.0% lower in the SMS user group than in their counterparts. Conclusion Substantial inequalities in access to SMS exist at both national and sub-national levels of Bangladesh, with the prevalence of diarrhea being lower among SMS users. These findings may help to prioritize resources for reducing inequality and expanding the coverage of improved sanitation in Bangladesh. …

Abstract Background This retrospective cohort study assessed benefits and risks of bedaquiline treatment in multidrug-resistant-tuberculosis (MDR-TB) combination therapy by evaluating safety, effectiveness, drug utilization and emergence of resistance to bedaquiline. Methods Data were extracted from a register of South African drug-resistant-tuberculosis (DR-TB) patients (Electronic DR-TB Register [EDRWeb]) for newly diagnosed patients with MDR-TB (including pre-extensively drug-resistant [XDR]-TB and XDR-TB and excluding rifampicin-mono-resistant [RR]-TB, as these patients are by definition not multidrug-resistant), receiving either a bedaquiline-containing or non-bedaquiline-containing regimen, at 14 sites in South Africa. Total duration of treatment and follow-up was up to 30 months, including 6 months’ bedaquiline treatment. WHO treatment outcomes within 6 months after end-of-treatment were assessed in both patient groups. Longer term mortality (up to 30 months from treatment start) was evaluated through matching to the South African National Vital Statistics Register. Multivariable Cox proportional hazards analyses were used to predict association between receiving a bedaquiline-containing regimen and treatment outcome. Results Data were extracted from EDRWeb for 5981 MDR-TB patients (N = 3747 bedaquiline-treated; N = 2234 non-bedaquiline-treated) who initiated treatment between 2015 and 2017, of whom 40.7% versus 80.6% had MDR-TB. More bedaquiline-treated than non-bedaquiline-treated patients had pre-XDR-TB (27.7% versus 9.5%) and XDR-TB (31.5% versus 9.9%) per pre-2021 WHO definitions. Most patients with treatment duration data (94.3%) received bedaquiline for 6 months. Treatment success (per pre-2021 WHO definitions) was achieved in 66.9% of bedaquiline-treated and 49.4% of non-bedaquiline-treated patients. Death was reported in fewer bedaquiline-treated (15.4%) than non-bedaquiline-treated (25.6%) patients. Bedaquiline-treated patients had increased likelihood of treatment success and decreased risk of mortality versus non-bedaquiline-treated patients. In patients with evaluable drug susceptibility testing data, 3.5% of bedaquiline-susceptible isolates at baseline acquired phenotypic resistance. Few patients reported bedaquiline-related treatment-emergent adverse events (TEAEs) (1.8%), TEAE-related bedaquiline discontinuations (1.4%) and QTcF values > 500 ms (2.5%) during treatment. Conclusion Data from this large cohort of South African patients with MDR-TB showed treatment with bedaquiline-containing regimens was associated with survival and effectiveness benefit compared with non-bedaquiline-containing regimens. No new safety signals were detected. These data are consistent with the positive risk–benefit profile of bedaquiline and warrant continued implementation in combination therapy for MDR-TB treatment. …

Abstract Background Malaria is a priority global health disease with high morbidity and mortality especially among children under-five and pregnant women. Malaria elimination requires an effective surveillance system. The malaria surveillance system in Benue State was evaluated to assess its attributes and performance in line with set objectives. Methods The updated United States Centers for Disease Control and Prevention guideline for evaluating surveillance systems was used. The surveillance system’s key attributes was quantitatively and qualitatively assessed. Semi-structured questionnaires were administered to all Local Government Area (LGA) Roll Back Malaria (RBM) focal persons and five key informants were interviewed at the State level. The Benue State District Health Information System-2 (DHIS-2) malaria data and monthly summary forms were reviewed from January 2015 to December 2019. Results A total of 46 RBM focal persons and 5 key-informants participated. About 56.9% were males, the mean-age 43.8 (SD ± 9.3) years and 32 (62.8%) had ≥ 20-year experience on malaria surveillance with mean-year-experience 20.8 (SD ± 7.8) years. All 46 (100%) RBMs understood the case definition; 43 (93.5%) found it easy-to-fill the standardized data tools and understood the data flow channels. The malaria surveillance system in Benue is simple, acceptable and useful to all stakeholders, 36 (70.6%) found switching from the paper-based to the electronic-data tools with ease and 45 (88.2%) stated that analysed data were used for decision-making. Data flow from LGA to State is clearly defined, however majority of the data is collected from public health facilities through the DHIS-2 Platform. The overall timeliness and completeness of reporting was 76.5% and 95.7%, respectively, which were below the ≥ 80% and 100% targets, respectively. Conclusions The malaria surveillance system in Benue State is simple, useful, acceptable, and flexible, but it is not representative and timely. Public–private and public-public-partnerships should be strengthened to encourage reporting from both private and tertiary health facilities and improve representativeness, and frequent feedback to improve reporting timeliness. …

Abstract Background Malaria is an infectious disease which has been globally targeted for elimination in at least 35 of 90 endemic countries by 2030. Most successful malaria elimination country programmes have engaged the private health sector in an effort to identify, document, investigate, provide effective treatment, and follow-up cases. However, there has been limited rigorous research showing evidence of adherence among healthcare providers of the formal private health sector to national malaria diagnosis and treatment guidelines in Ethiopia, starting from malaria control to elimination phases. The aims of this study were to investigate and explain the level of adherence to malaria diagnosis and treatment guidelines among healthcare providers working in formal private health facilities in north-western Ethiopia. Methods An explanatory sequential mixed method design was conducted in the West Gojjam Zone of Ethiopia. Quantitative data were extracted from 1650 medical records of adult uncomplicated malaria outpatients served in 11 private-for-profit health facilities. In addition, using a qualitative approach, 33 in-depth interviews (IDIs) with healthcare providers were conducted. All interviews were audio-recorded, transcribed verbatim, and analysed using eight steps. Results Of 1650 suspected malaria cases in adult outpatients, 80.6% (1330/1650) were screen tested using microscopy and the remainder 19.4% (320/1650) were tested using multispecies rapid diagnosis tests (RDTs). Hence, the results revealed that private healthcare providers universally adhered to diagnosis guidelines. In addition, after following-up and excluding other causes of fever, 4.1% (56/1376) patients were clinically diagnosed with uncomplicated malaria. Despite this, the proportion of private healthcare provider adherence with confirmed malaria case treatment guidelines was 20.9% (69/330). In addition, 1320 (95.9%) of adult outpatients with negative laboratory results were not treated. Some of the identified determinant factors for sub-optimal adherence of healthcare providers to malaria guidelines were interruptions in supply and lack of availability of recommended anti-malarial drugs, lack of availability of quality assured laboratory supplies, and poor knowledge of the recommendations of the national standards. Conclusions Private healthcare providers adhered to universal parasitological diagnosis, providing comprehensive counseling, and linking patients with community health workers. In addition, almost all laboratory negative patients were not treated with anti-malarial drugs. However, only one-fifth of confirmed patients were treated in line with national guideline recommendations. Malaria control and elimination efforts across Ethiopia could be improved through establishing a collaborative function of a win-win public private mix partnership model. In addition, including the data of the private health sector in the health information system could show real malaria burden and use the information to improve the adherence to malaria diagnosis, treatment, and reporting standards within the targeted era of elimination. Therefore, building the capacity of private healthcare providers and ensuring the availability of all nationally recommended drugs and supplies in private health sector facilities is recommended to improve the quality of services. …

New England Journal of Medicine, Ahead of Print.