Background Tuberculosis (TB) is a leading cause of death from a single infectious agent, and triage tests based on biomarkers may help to improve the diagnosis. This study aims to determine whether C-reactive protein (CRP), interferon-γ-inducible protein 10 (IP-10), α1-acid glycoprotein (AGP), and α1-anti-trypsin (AAT) could be useful for a screening test in patients with presumptive TB disease. Methods CRP, IP-10, AGP, and AAT were measured in plasma samples from 277 patients with presumptive TB disease in the Republic of Moldova in a prospective study. Results In general, the levels of all the biomarkers were higher in patients with TB than in the other groups ( p < 0.05). Receiver operating characteristic curve analyses showed an area under the curve lower than 0.7 for all the biomarkers, and low correlations (Spearman's r < 0.6) were found between biomarkers. Conclusion The levels of the tested biomarkers were different throughout the patient groups studied, but their suboptimal diagnostic performance either as individual biomarkers or in combination does not favor their use for triage testing.

COVID 19 is a highly contagious disease, and health care workers are especially vulnerable. The novel virus has continued to wreak havoc in various countries around the world, particularly among the unvaccinated population. The study aimed to assess health workers' knowledge, risk perception, and willingness to receive the COVID 19 vaccine. This study utilized a cross-sectional design carried out among Primary Health Care Workers in the Federal Capital Territory (FCT) Abuja. A two-stage sampling technique was used to recruit 284 participants for the study. We adapted the Extended Parallel Process Model questionnaire to determine respondents’ knowledge, risk perception, and willingness to COVID 19 vaccine uptake. Data were analysed using SPSS version 23, and statistical significance was set at p<0.005. The average age of the study participants was 36 years. The study revealed, slightly more than half 167(58.8%) of respondents have a good knowledge of COVID 19. The relationship between sex and knowledge of coronavirus disease was statistically significant (p = 0.014). Most of respondents 260 (91.5%) were aware of the coronavirus vaccine. The majority of the respondents reported a lack of trust in government 140 (49.3%) and religion 33 (11.6%) as a reason for vaccine hesitancy. In our study, we found that HCWs' knowledge of COVID 19 was suboptimal, and their risk perception was low. Though vaccine willingness was high, vaccine hesitancy was primarily due to a lack of trust in the government.

Background: Adherence to Infection prevention and control standard practice protocol is critical in minimizing the risk of contracting COVID-19 infection among healthcare workers.With the increasing trend of nosocomial transmission of COVID-19 among healthcare workers during the pandemic in Nigeria, we assessed the status of IPC in facilities in the Federal Capital Territory (FCT), Abuja during the COVID-19 pandemic.Methods: A cross-sectional study design was conducted from March to April 2020 in the Federal Capital Territory (FCT), Abuja.A semi-structured intervieweradministered checklist adapted from the World Health Organization (WHO) IPC scorecard for health facilities was used.IPC focal persons for each health facility visited were interviewed on the twelve IPC domains.Data was analyzed using the IBM Statistical Package for Social Sciences (SPSS) version 26.A p<0.05 was considered statistically significant for all statistical tests.Result: Four hundred fifty-eight facilities took part in the study.The majority of the facilities 320 (69.9%) were public/ government owned, with more than half 315 (68.8%) being secondary health facilities.The overall IPC status was good in 408 (89.0%) of the health institutions.However, there was a statistically significant difference in IPC practices between private and public facilities in the majority of IPC domains: Functional IPC Committee (p0.001), facility triaging (p0.001), temporary holding area (THA) (P0.001),PPE (P0.001),Waste disposal (p=0.023),hospital sterilization (p=0.008), and hospital decontamination (p=0.004).Conclusion: The study found a satisfactory level of IPC protocol operationalization status in mostly public health facilities in the Federal Capital Territory (FCT), Abuja.Nevertheless, there is a need for interventions targeting mostly private health facilities to address the disparity and gaps identified in IPC practices.

Structured summaryBackgroundPulmonary tuberculosis (PTB) due toMycobacterium tuberculosis(Mtb) can be challenging to diagnose because of difficulty obtaining samples, and suboptimal sensitivity of existing tests. We investigated the performance characteristics and diagnostic accuracy of upper respiratory tract tests for diagnosing PTB and hypothesised they would have sufficient accuracy and utility to improve PTB diagnosis.MethodsA systematic review and meta-analysis was conducted by searching MEDLINE, Cinahl, Web of Science, Global Health, and Global Health Archive databases up to 31/01/2021, a second search was conducted for the period 1/1/2021 - 27/5/2022 (subsequently extended to 6/12/2022) to identify studies that reported on the accuracy of upper respiratory tract sampling for TB diagnosis compared to microbiological reference standards. We used a random-effects meta-analysis with a bivariate hierarchical model to estimate pooled sensitivity and specificity, stratified by sampling method. Bias was assessed using QUADAS- 2 criteria. Study registered with PROSPERO (CRD42021262392).Findings10,159 titles were screened for inclusion, 274 studies were assessed for full text review, and 71, comprising 119 test comparisons published between 1933 and 2022 were included in the systematic review (53 in meta-analysis). For laryngeal swabs, pooled sensitivity was 57.8% (95% CI 50.5-65.0%), specificity was 93.8% (95% CI 88.4-96.8%) and diagnostic odds ratio (DOR) was 20.7 (95% CI 11.1-38.8). Nasopharyngeal aspirate sensitivity was 65.2% (95% CI 52.0-76.4%), specificity was 97.9% (95% CI 96.0-99.0%) and DOR was 91.0 (95% CI 37.8-218.8). Oral swabs sensitivity was 56.7% (95% CI 44.3-68.2%), specificity was 91.3% (95% CI 81.0-96.3%), and DOR was 13.8 (95% CI 5.6-34.0).InterpretationUpper respiratory tract sampling holds promise to expand access to TB diagnosis, including for people who can’t produce sputum. Exploring historical methods using modern microbiological techniques may further increase the options for alternative sample types.Prospective studies are needed to optimise accuracy and utility of sampling methods in clinical practice.FundingHRS is funded by the MRC through the MRC DTP programme at LSTM [Grant number MR/N013514/1].Research in contextEvidence before this studyGlobally in 2021, an estimated 4.2 million of 10.6 million people with incident tuberculosis (TB) disease went undiagnosed, emphasising the urgent need for new diagnostic methodologies. Most TB diagnostics are performed on sputum samples, but people who need TB tests are often unable to produce sputum. Upper respiratory tract sampling for TB diagnosis was widely used historically and holds promise to expand non-sputum-based diagnosis.Added value of this studyWe systematically reviewed and synthesised through meta-analysis diagnostic accuracy evaluations of upper respiratory tract sampling for TB. Historically, upper respiratory tract sampling for TB diagnosis was commonly used, with 39/71 studies conducted before 1970, although in recent years there has been a resurgence of interest in oral sampling. We show that upper respiratory tract samples have acceptable sensitivity and specificity compared to sputum culture, and, if testing is optimised using newer molecular and culture-based methods, may be capable of meeting WHO target produce profiles.Implications of all the available evidenceUpper respiratory tract sampling methodologies for TB (oral sampling, and sampling from the larynx and nasopharynx) may hold promise to expand access to TB diagnosis, including for people who can’t produce sputum. These sampling strategies can be optimised using modern microbiological techniques to increase access to diagnostics for TB.

OBJECTIVES:We assessed whether combining (pooling) four individual's samples and testing with Xpert Ultra has the same accuracy as testing samples individually as a more efficient testing method.METHODS:We conducted a cross-sectional study of individuals with presumptive tuberculosis attending primary health care or general hospital facilities in Alagoas, Brazil. The sputum samples of four consecutive individuals were pooled and the pool and individual samples were tested with Xpert Ultra. The agreement of the tests was compared using kappa statistics. We estimated the sensitivity and specificity of pooling using the individual test as the reference standard and potential cartridge savings.RESULTS:A total of 396 participants were tested. A total of 95 (24.0%) individual samples were Mycobacterium tuberculosis (MTB)-positive, 300 (75.8%) "MTB not detected", including 20 "MTB trace", and one reported an error. A total of 99 pools of four samples were tested, of which 62 (62.6%) had MTB detected and 37 (37.4%) MTB not detected, including six (6.1%) with MTB trace. The agreement between individual and pooled testing was 96.0%. Pooling had a sensitivity of 95.0% (95% confidence interval 86.9-99%), specificity of 97.1% (95% confidence interval 85.1-99.9%), and kappa of 0.913. The method saved 12.4% of cartridge costs.CONCLUSION:The pooled testing of specimens had a high level of agreement with individual testing. The pooling of samples for testing improves the efficiency of testing, potentially enabling the screening and testing of larger numbers of individuals more cost-effectively.

Background The World Health Organization (WHO) recommends the diagnosis of tuberculosis (TB) using molecular tests, such as Xpert MTB/RIF (MTB/RIF) or Xpert Ultra (Ultra). These tests are expensive and resource-consuming, and cost-effective approaches are needed for greater coverage. Methods We evaluated the cost-effectiveness of pooling sputum samples for TB testing by using a fixed amount of 1,000 MTB/RIF or Ultra cartridges. We used the number of people with TB detected as the indicator for cost-effectiveness. Cost-minimization analysis was conducted from the healthcare system perspective and included the costs to the healthcare system using pooled and individual testing. Results There was no significant difference in the overall performance of the pooled testing using MTB/RIF or Ultra (sensitivity, 93.9% vs. 97.6%, specificity 98% vs. 97%, p-value > 0.1 for both). The mean unit cost across all studies to test one person was 34.10 international dollars for the individual testing and 21.95 international dollars for the pooled testing, resulting in a savings of 12.15 international dollars per test performed (35.6% decrease). The mean unit cost per bacteriologically confirmed TB case was 249.64 international dollars for the individual testing and 162.44 international dollars for the pooled testing (34.9% decrease). Cost-minimization analysis indicates savings are directly associated with the proportion of samples that are positive. If the TB prevalence is ≥ 30%, pooled testing is not cost-effective. Conclusion Pooled sputum testing can be a cost-effective strategy for diagnosis of TB, resulting in significant resource savings. This approach could increase testing capacity and affordability in resource-limited settings and support increased testing towards achievement of WHO End TB strategy.

BACKGROUND:The use of molecular amplification as-says for TB diagnosis is limited by their costs and cartridge stocks. Pooling multiple samples to test them together is reported to have similar accuracy to individual testing and to save costs. METHODS:Two surveys of individuals with presumptive TB were conducted to assess the performance of pooled testing using Xpert® MTB/RIF (MTB/RIF) and Xpert® Ultra (Ultra). RESULTS:A total of 500 individuals were tested using MTB/RIF, with 72 (14.4%) being MTB-positive. The samples were tested in 125 pools, with 50 pools having ⩾1 MTB-positive and 75 only MTB-negative samples: 46/50 (92%, 95% CI 80.8-97.8) MTB-positive pools tested MTB-positive and 71/75 (94.7%, 95% CI 86.9-98.5) MTB-negative pools tested MTB-negative in the pooled test (agreement: 93.6%, κ = 0.867). Five hundred additional samples were tested using Ultra, with 60 (12%) being MTB-positive. Samples were tested in 125 pools, with 42 having ⩾1 MTB-positive and 83 only MTB-negative samples: 35/42 (83.6%, 95% CI 68.6-93.0) MTB-positive pools tested MTB-positive and 82/83 (98.8%, 95% CI 93.5-100.0) MTB-negative pools tested MTB-negative in the pooled test (agreement: 93.6%, κ = 0.851; P > 0.1 between individual and pooled testing). Pooled testing saved 35% (MTB/RIF) and 46% (Ultra) of cartridges. CONCLUSIONS:Pooled and individual testing has a high level of agreement and improves testing efficiency.

BACKGROUND:In sub-Saharan Africa, health-care provision for chronic conditions is fragmented. The aim of this study was to determine whether integrated management of HIV, diabetes, and hypertension led to improved rates of retention in care for people with diabetes or hypertension without adversely affecting rates of HIV viral suppression among people with HIV when compared to standard vertical care in medium and large health facilities in Uganda and Tanzania. METHODS:In INTE-AFRICA, a pragmatic cluster-randomised, controlled trial, we randomly allocated primary health-care facilities in Uganda and Tanzania to provide either integrated care or standard care for HIV, diabetes, and hypertension. Random allocation (1:1) was stratified by location, infrastructure level, and by country, with a permuted block randomisation method. In the integrated care group, participants with HIV, diabetes, or hypertension were managed by the same health-care workers, used the same pharmacy, had similarly designed medical records, shared the same registration and waiting areas, and had an integrated laboratory service. In the standard care group, these services were delivered vertically for each condition. Patients were eligible to join the trial if they were living with confirmed HIV, diabetes, or hypertension, were aged 18 years or older, were living within the catchment population area of the health facility, and were likely to remain in the catchment population for 6 months. The coprimary outcomes, retention in care (attending a clinic within the last 6 months of study follow-up) for participants with either diabetes or hypertension (tested for superiority) and plasma viral load suppression for those with HIV (>1000 copies per mL; tested for non-inferiority, 10% margin), were analysed using generalised estimating equations in the intention-to-treat population. This trial is registered with ISCRTN 43896688. FINDINGS:Between June 30, 2020, and April 1, 2021 we randomly allocated 32 health facilities (17 in Uganda and 15 in Tanzania) with 7028 eligible participants to the integrated care or the standard care groups. Among participants with diabetes, hypertension, or both, 2298 (75·8%) of 3032 were female and 734 (24·2%) of 3032 were male. Of participants with HIV alone, 2365 (70·3%) of 3365 were female and 1000 (29·7%) of 3365 were male. Follow-up lasted for 12 months. Among participants with diabetes, hypertension, or both, the proportion alive and retained in care at study end was 1254 (89·0%) of 1409 in integrated care and 1457 (89·8%) of 1623 in standard care. The risk differences were -0·65% (95% CI -5·76 to 4·46; p=0·80) unadjusted and -0·60% (-5·46 to 4·26; p=0·81) adjusted. Among participants with HIV, the proportion who had a plasma viral load of less than 1000 copies per mL was 1412 (97·0%) of 1456 in integrated care and 1451 (97·3%) of 1491 in standard care. The differences were -0·37% (one-sided 95% CI -1·99 to 1·26; pnon-inferiority<0·0001 unadjusted) and -0·36% (-1·99 to 1·28; pnon-inferiority<0·0001 adjusted). INTERPRETATION:In sub-Saharan Africa, integrated chronic care services could achieve a high standard of care for people with diabetes or hypertension without adversely affecting outcomes for people with HIV. FUNDING:European Union Horizon 2020 and Global Alliance for Chronic Diseases.

Resistance to piperacillin/tazobactam (TZP) in Escherichia coli has predominantly been associated with mechanisms that confer resistance to third-generation cephalosporins. Recent reports have identified E. coli strains with phenotypic resistance to piperacillin/tazobactam but susceptibility to third-generation cephalosporins (TZP-R/3GC-S). In this study we sought to determine the genetic diversity of this phenotype in E. coli (n=58) isolated between 2014–2017 at a single tertiary hospital in Liverpool, UK, as well as the associated resistance mechanisms. We compare our findings to a UK-wide collection of invasive E. coli isolates (n=1509) with publicly available phenotypic and genotypic data. These data sets included the TZP-R/3GC-S phenotype (n=68), and piperacillin/tazobactam and third-generation cephalosporin-susceptible (TZP-S/3GC-S, n=1271) phenotypes. The TZP-R/3GC-S phenotype was displayed in a broad range of sequence types, which was mirrored in the same phenotype from the UK-wide collection, and the overall diversity of invasive E. coli isolates. The TZP-R/3GC-S isolates contained a diverse range of plasmids, indicating multiple acquisition events of TZP resistance mechanisms rather than clonal expansion of a particular plasmid or sequence type. The putative resistance mechanisms were equally diverse, including hyperproduction of TEM-1, either via strong promoters or gene amplification, carriage of inhibitor-resistant β-lactamases, and an S133G bla CTX-M-15 mutation detected for the first time in clinical isolates. Several of these mechanisms were present at a lower abundance in the TZP-S/3GC-S isolates from the UK-wide collection, but without the associated phenotypic resistance to TZP. Eleven (19%) of the isolates had no putative mechanism identified from the genomic data. Our findings highlight the complexity of this cryptic phenotype and the need for continued phenotypic monitoring, as well as further investigation to improve detection and prediction of the TZP-R/3GC-S phenotype from genomic data.

Brazil experienced one of the most prolonged periods of school closures, and reopening could have exposed students to high rates of SARS-CoV-2 infection. However, the infection status of students and school workers at the time of the reopening of schools located in Brazilian cities is unknown. Here we evaluated viral carriage by RT-PCR and seroprevalence of anti-SARS-CoV-2 antibodies (IgM and IgG) by immunochromatography in 2259 individuals (1139 students and 1120 school workers) from 28 schools in 28 Brazilian cities. We collected the samples within 30 days after public schools reopened and before the start of vaccination campaigns. Most students (n = 421) and school workers (n = 446) had active (qRT-PCR + IgM- IgG- or qRT-PCR + IgM + IgG-/+) SARS-CoV-2 infection. Regression analysis indicated a strong association between the infection status of students and school workers. Furthermore, while 45% (n = 515) of the students and 37% (n = 415) of the school workers were neither antigen nor antibody positive in laboratory tests, 16% of the participants (169 students and 193 school workers) were oligosymptomatic, including those reinfected. These individuals presented mild symptoms such as headache, sore throat, and cough. Notably, most of the individuals were asymptomatic (83.9%). These results indicate that many SARS-CoV-2 infections in Brazilian cities during school reopening were asymptomatic. Thus, our study highlights the need to promote a coordinated public health effort to guarantee a safe educational environment while avoiding exacerbating pre-existent social inequalities in Brazil, reducing social, mental, and economic losses for students, school workers, and their families.

Introduction Active case finding (ACF) of individuals with tuberculosis (TB) is a key intervention to find the 30% of people missed every year. However, ACF requires screening large numbers of individuals who have a low probability of positive results, typically <5%, which makes using the recommended molecular tests expensive. Methods We conducted two ACF surveys (in 2020 and 2021) in high TB burden areas of Lao PDR. Participants were screened for TB symptoms and received a chest X-ray. Sputum samples of four consecutive individuals were pooled and tested with Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) (Xpert-MTB/RIF) (2020) or Xpert-Ultra (2021). The agreement of the individual and pooled samples was compared and the reasons for discrepant results and potential cartridge savings were assessed. Results Each survey included 436 participants, which were tested in 109 pools. In the Xpert-MTB/RIF survey, 25 (sensitivity 89%, 95% CI 72.8% to 96.3%) of 28 pools containing MTB-positive samples tested positive and 81 pools containing only MTB-negative samples tested negative (specificity 100%, 95% CI 95.5% to 100%). In the Xpert-Ultra survey, all 32 (sensitivity 100%, 95% CI 89.3% to 100%) pools containing MTB-positive samples tested positive and all 77 (specificity 100%, 95% CI 95.3% to 100%) containing only MTB-negative samples tested negative. Pooling with Xpert-MTB/RIF and Xpert-Ultra saved 52% and 46% (227/436 and 199/436, respectively) of cartridge costs alone. Conclusion Testing single and pooled specimens had a high level of agreement, with complete concordance when using Xpert-Ultra. Pooling samples could generate significant cartridge savings during ACF campaigns.

The COVID-19 pandemic created the need for large-scale testing of populations. However, most laboratories do not have sufficient testing capacity for mass screening. We evaluated pooled testing of samples, as a strategy to increase testing capacity in Lao PDR. Samples of consecutive patients were tested in pools of four using the Xpert Xpress SARS CoV-2 assay. Positive pools were confirmed by individual testing, and we describe the performance of the test and savings achieved. We also diluted selected positive samples to describe its effect on the assays CT values. 1,568 patients were tested in 392 pools of four. 361 (92.1%) pools were negative and 31 (7.9%) positive. 29/31 (93.5% (95%CI 77–99%) positive pools were confirmed by individual testing of the samples but, in 2/31 (6.5%) the four individual samples were negative, suggesting contamination. Pools with only one positive sample had higher CT values (lower RNA concentrations) than the respective individual samples, indicating a dilution effect, which suggested an increased risk of false negative results with dilutions >1:10. However, this risk may be low if the prevalence of infection is high, when pools are more likely to contain more than one positive sample. Pooling saved 67% of cartridges and substantially increased testing capacity. Pooling samples increased SARS-CoV-2 testing capacity and resulted in considerable cartridge savings. Given the need for high-volume testing, countries may consider implementation of pooling for SARS-CoV-2 screening.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread globally since its emergence in 2019. Most SARS-CoV-2 infections generate immune responses leading to rising levels of immunoglobulins (Ig) M, A and G which can be detected using diagnostic tests including enzyme-linked immunosorbent assays (ELISA). Whilst implying previous SARS-CoV-2 infection, the detection of Ig by ELISA does not guarantee the presence of neutralising antibodies (NAb) that can prevent the virus infecting cells. Plaque reduction neutralisation tests (PRNT) detect NAb, but are not amenable to mass testing as they take several days and require use of SARS-CoV-2 in high biocontainment laboratories. We evaluated the ability of IgG and IgM ELISAs targeting SARS-CoV-2 spike subunit 1 receptor binding domain (S1-RBD), and spike subunit 2 (S2) and nucleocapsid protein (NP), at predicting the presence and magnitude of NAb determined by PRNT. IgG S2 + NP ELISA was 96.8% [95% CI 83.8–99.9] sensitive and 88.9% [95% CI 51.8–99.7] specific at predicting the presence of NAbs (PRNT 80 > 1:40). IgG and IgM S1-RBD ELISAs correlated with PRNT titre, with higher ELISA results increasing the likelihood of a robust neutralising response. The IgM S1-RBD assay can be used as a rapid, high throughput test to approximate the magnitude of NAb titre.

The global Covid-19 pandemic has limited access to molecular TB diagnostics and National Programmes are struggling to maintain essential services. The pooling method (testing several samples together) could reduce the number of cartridges and staff time needed for TB diagnosis but has not been tested within the pandemic. We conducted two independent cross-sectional surveys. Pools composed of four sputum samples were tested using either Xpert-MTB/RIF or Xpert-Ultra. Pooled and individual results were compared to determine the level of agreement. Each survey included 840 participants and 210 pools. In the Xpert MTB/RIF survey, 77/81 (sensitivity 95.1%, 95%CI 87.8%-98.6%) pools containing ≥1 positive sample tested MTB-positive and 4/81 (4.9%, 95%CI 1.4%-12.2%) tested MTB-negative. All 129/129 pools containing MTB-negative samples tested MTB-negative (specificity 100%, 95%CI 97.2%-100%), with 98.1% agreement (Kappa: 0.959). In the Xpert-Ultra survey, 70/70 (sensitivity 100%, 95%CI 94.9%-100%) pools containing ≥ 1 MTB-positive sample tested MTB-positive and 140/140 (specificity 100%, 95%CI 97.4%-100%) pools containing only MTB-negative samples tested MTB-negative, with 100% agreement (Kappa: 1). Pooled testing with Xpert-MTB/RIF and Xpert-Ultra saved 38.3% and 41.7% (322/840 and 350/840, respectively) in cartridge costs alone. The pooling method with Xpert-MTB/RIF and Xpert-Ultra has similar performance to individual testing and can reduce the number of cartridges needed. These efficiencies can facilitate maintenance of stocks and sustain essential services as countries face difficulties for laboratory procurement during the pandemic and will provide cost and time savings post-pandemic.

Background Monitoring the characteristics and associated factors for death among pregnant and postpartum women with coronavirus disease 19 (COVID-19) is necessary. We investigated the clinical characteristics and risk factors associated with maternal deaths in a nationwide cohort of Brazil. Methods This was a population-based cohort of all pregnant and postpartum women hospitalised with COVID-19 notified to the Sistema de Informacao de Vigilancia Epidemiologica da Gripe of Brazil (SIVEP-Gripe), from February 2020 to September 2021. The primary outcome was time to in-hospital death, with risk factors analysed with univariable and multivariable Cox proportional hazards regression models. Results Cumulative observation time was 248 821 person-days from hospital admission to the end of follow-up for 15 105 individuals. There were 1858 deaths (12.3%) for a maternal mortality rate of 7.5 (95% CI 7.1-7.8) per 1000 patients-days. The cumulative mortality increased over time. Black/Brown ethnicity had a higher risk of death than women self-identifying as White. Women in the North, Northeast, Central-West and Southeast regions had higher risk of death than women in the South region. The characteristics independently associated with death were a postpartum status on admission [adjusted hazard ratio, HR 1.4 (95% confidence interval, CI 1.2-1.6)], pre-existing clinical conditions [adjusted HRs 1.2 (95%CI 1.1-1.3) for one and 1.3 (95%CI 1.1-1.5) for two comorbidities], hypoxaemia on admission [adjusted HR 1.2 (95%CI 1.1-1.4)] and requiring non-invasive [adjusted HR 2.6 (95%CI 2.1-3.3)] or invasive ventilatory support [adjusted HR 7.1 (95%CI 5.6-9.2)]. Conclusion In Brazil, the in-hospital maternal mortality rate due to COVID-19 is high and the risk of death increases with the length of hospitalisation. Socio-demographic and biological factors are associated with an increased risk of maternal death. The presence of respiratory signs and symptoms should be considered early markers of disease severity and an adequate management is necessary. Our findings reinforce the need for vaccination of pregnant and postpartum women against COVID-19.

Correspondence to Jacob Bigio; jacob. bigio@ protonmail. com © Author(s) (or their employer(s)) 2022. Reuse permitted under CC BYNC. No commercial reuse. See rights and permissions. Published by BMJ. INTRODUCTION In countries with a high burden of tuberculosis (TB), private pharmacies are often the first point of care seeking for individuals with TB symptoms, making them ideally placed to assist in the early detection of TB. However, the quality of TB care by pharmacies in lowincome and middleincome countries (LMICs) is often low, with lack of TB knowledge among pharmacy staff, inappropriate sales of antibiotics and antiTB medications, and lack of systems to facilitate referrals for TB testing. Most pharmacies are not linked to national tuberculosis programmes (NTPs) but establishing structured mechanisms for the referral of individuals with presumptive TB from pharmacies to private or NTPassociated facilities for testing could help to identify the estimated 4.1 million individuals who developed TB in 2020 but were not diagnosed and reported to NTPs. Between 2010 and June 2020, the Stop TB Partnership’s TB REACH initiative funded 26 interventions in 15 LMICs which engaged pharmacies to improve TB case detection, with the aim of demonstrating whether they are effective entry points to identify individuals with TB and whether they could subsequently be scaled up and transferred to a sustainable model either by other donor agencies or with monitoring and assistance from NTPs. An analysis of quantitative outcomes of the interventions will be published separately. For this publication, we discussed operational characteristics of the interventions with grantee implementors of 19 of these projects, and with members of the TB REACH initiative involved in providing technical support to the projects (table 1). We summarise the three main themes and operational lessons which emerged from these discussions as follows. The term pharmacy is used here broadly to refer to any provider engaged in the selling of Summary box

BACKGROUND:Rapid diagnostic tests (RDTs) developed for point of care detection of SARS-CoV-2 antigen are recommended by WHO to use trained health care workers to collect samples. We hypothesised that self-taken samples are non-inferior for use with RDTs to diagnose COVID-19. We designed a prospective diagnostic evaluation comparing self-taken and healthcare worker (HCW)-taken throat/nasal swabs to perform RDTs for SARS-CoV-2, and how these compare to RT-PCR. METHODS:Eligible participants 18 years or older with symptoms of COVID-19. 250 participants recruited at the NHS Test and Trace drive-through community PCR testing site (Liverpool, UK); one withdrew before analysis. Self-administered throat/nasal swab for the Covios® RDT, a trained HCW taken throat/nasal sample for PCR and HCW comparison throat/nasal swab for RDT were collected. RDT results were compared to RT-PCR, as the reference standard, to calculate sensitivity and specificity. FINDINGS:Seventy-five participants (75/249, 30.1%) were positive by RT-PCR. RDTs with self-taken swabs had a sensitivity of 90.5% (67/74, 95% CI: 83.9-97.2), compared to 78.4% (58/74, 95% CI: 69.0-87.8) for HCW-taken swabs (absolute difference 12.2%, 95% CI: 4.7-19.6, p = 0.003). Specificity for self-taken swabs was 99.4% (173/174, 95% CI: 98.3-100.0), versus 98.9% (172/174, 95% CI: 97.3-100.0) for HCW-taken swabs (absolute difference 0.6%, 95% CI: 0.5-1.7, p = 0.317). The PPV of self-taken RDTs (98.5%, 67/68, 95% CI: 95.7-100.0) and HCW-taken RDTs (96.7%, 58/60, 95% CI 92.1-100.0) were not significantly different (p = 0.262). However, the NPV of self-taken swab RDTs was significantly higher (96.1%, 173/180, 95% CI: 93.2-98.9) than HCW-taken RDTs (91.5%, 172/188, 95% CI 87.5-95.5, p = 0.003). INTERPRETATION:In conclusion, self-taken swabs for COVID-19 testing offer an accurate alternative to healthcare worker taken swabs for use with RDTs. Our results demonstrate that, with no training, self-taken throat/nasal samples can be used by lay individuals as part of rapid testing programmes for symptomatic adults. This is especially important where the lack of trained healthcare workers restricts access to testing.

Orviz et al.1 report that Monkeypox in Spain is associated with person-to-person transmission and that infected individuals are more likely to have concomitant sexually transmitted infections, pointing to a potential sexual transmission. Monkeypox, is the most prevalent orthopoxvirus2 since the eradication of smallpox and has long been reported from Africa, with outbreaks in Central and West Africa, corresponding to the Congo Basin and the West African clades (renamed clades 1 and 2, respectively).