Use of Medicinal Plants in the Process of Wound Healing: A Literature Review.

The literature on the use of medicinal plants in wound healing was comprehensively searched to obtain and assess the data. The data were procured via clinical studies that utilized medicinal plants and their compounds in vitro and in vivo for wound healing. This review collected data from electronic databases, including Google Scholar, PubMed, Science Direct, Web of Science, SciFinder, Thesis, and Scopus, using the search terms "natural products", "wound healing", and "natural compounds", along with the keywords "plants", "extracts", and "phytochemicals". Results from the last decade reveal a total of 62 families and 109 genera of medicinal plants, and their compounds have been studied experimentally both in vivo and in vitro and clinically found to effectively promote healing. This activity is related to the presence of secondary metabolites such as flavonoids, alkaloids, saponins, tannins, terpenoids, and phenolic compounds, which act at different stages through different mechanisms to exert anti-inflammatory, antimicrobial, and antioxidant effects, confirming that the use of medicinal plants could be an adequate alternative to current conventional practices for treating wounds.

Integrated management of HIV, diabetes, and hypertension in sub-Saharan Africa (INTE-AFRICA): a pragmatic cluster-randomised, controlled trial.

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.

Accuracy of upper respiratory tract samples to diagnose Mycobacterium tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Pulmonary tuberculosis due to Mycobacterium tuberculosis can be challenging to diagnose when sputum samples cannot be obtained, which is especially problematic in children and older people. We systematically appraised the performance characteristics and diagnostic accuracy of upper respiratory tract sampling for diagnosing active pulmonary tuberculosis. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Cinahl, Web of Science, Global Health, and Global Health Archive databases for studies published between database inception and Dec 6, 2022 that reported on the accuracy of upper respiratory tract sampling for tuberculosis diagnosis compared with microbiological testing of sputum or gastric aspirate reference standard. We included studies that evaluated the accuracy of upper respiratory tract sampling (laryngeal swabs, nasopharyngeal aspirate, oral swabs, saliva, mouth wash, nasal swabs, plaque samples, and nasopharyngeal swabs) to be tested for microbiological diagnosis of tuberculous (by culture and nucleic acid amplification tests) compared with a reference standard using either sputum or gastric lavage for a microbiological test. We included cohort, case-control, cross-sectional, and randomised controlled studies that recruited participants from any community or clinical setting. We excluded post-mortem studies. We used a random-effects meta-analysis with a bivariate hierarchical model to estimate pooled sensitivity, specificity, and diagnostics odds ratio (DOR; odds of a positive test with disease relative to without), stratified by sampling method. We assessed bias using QUADAS-2 criteria. This study is registered with PROSPERO (CRD42021262392). FINDINGS: We screened 10 159 titles for inclusion, reviewed 274 full texts, and included 71, comprising 119 test comparisons published between May 13, 1933, and Dec 19, 2022, in the systematic review (53 in the meta-analysis). For laryngeal swabs, pooled sensitivity was 57·8% (95% CI 50·5-65·0), specificity was 93·8% (88·4-96·8), and DOR was 20·7 (11·1-38·8). Nasopharyngeal aspirate sensitivity was 65·2% (52·0-76·4), specificity was 97·9% (96·0-99·0), and DOR was 91·0 (37·8-218·8). Oral swabs sensitivity was 56·7% (44·3-68·2), specificity was 91·3% (CI 81·0-96·3), and DOR was 13·8 (5·6-34·0). Substantial heterogeneity in diagnostic accuracy was found, probably due to differences in reference and index standards. INTERPRETATION: Upper respiratory tract sampling holds promise to expand access to tuberculosis diagnosis. Exploring historical methods using modern microbiological techniques might further increase options for alternative sample types. Prospective studies are needed to optimise accuracy and utility of sampling methods in clinical practice. FUNDING: UK Medical Research Council, Wellcome, and UK Foreign, Commonwealth and Development Office.

Pooling sputum testing to diagnose tuberculosis using xpert MTB/RIF and xpert ultra: a cost-effectiveness analysis.

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.

Corrigendum to "Cross-sectional analysis of students and school workers reveals a high number of asymptomatic SARS-CoV-2 infections during school reopening in Brazilian cities" [Heliyon 8 (11) (November 2022) Article e11368].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e11368.].

Pooling of sputum samples to increase tuberculosis diagnostic capacity in Brazil during the COVID-19 pandemic.

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.

Cross-sectional analysis of students and school workers reveals a high number of asymptomatic SARS-CoV-2 infections during school reopening in Brazilian cities.

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.

Pooling samples to increase testing capacity with Xpert Xpress SARS-CoV-2 during the Covid-19 pandemic in Lao People's Democratic Republic.

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.

Spatial clusters, social determinants of health and risk of COVID-19 mortality in Brazilian children and adolescents: A nationwide population-based ecological study.

Background: Data regarding the geographical distribution of cases and risk factors for COVID-19 death in children and adolescents are scarce. We describe the spatial distribution of COVID-19 cases and deaths in paediatric population and their association with social determinants of health in Brazil. Methods: This is a population-based ecological study with a spatial analysis of all cases and deaths due to COVID-19 in Brazil among children and adolescents aged 0-19 years from March 2020 to October 2021. The units of analysis were the 5570 municipalities. Data on COVID-19 cases and deaths, social vulnerability, health inequities, and health system capacity were obtained from publicly available databases. Municipalities were stratified from low to very high COVID-19 incidence and mortality using K-means clustering procedures, and spatial clusters and relative risks were estimated using spatial statistics with Poisson probability models. The relationship between COVID-19 estimates and social determinants of health was explored by using multivariate Beta regression techniques. Findings: A total of 33,991 COVID-19 cases and 2424 deaths among children and adolescents aged 0-19 years were recorded from March 2020 to October 2021. There was a spatial dependence for the crude mortality coefficient per 100,000 population in the paediatric population aged 0-19 years (I Moran 0·10; P < 0·001). Forty municipalities had higher mortality rates, of which 20 were in states from the Northeast region. Seven spatial clusters were identified for COVID-19 mortality, with four clusters in the Northeast region and three in the North region. Municipalities with higher social inequality and vulnerability had higher COVID-19 mortality in the paediatric population. Interpretation: The main clusters of risk for mortality among children and adolescents were identified in municipalities in the North and Northeast regions, which are the regions with the worst socioeconomic indicators and greatest health disparities in the country. Our findings confirmed the higher burden of COVID-19 for Brazilian paediatric population in municipalities with higher social inequality and vulnerability and worse socioeconomic indicators. To reduce the burden of COVID-19 on children, mass immunisation is necessary. Funding: None.

A prospective diagnostic evaluation of accuracy of self-taken and healthcare worker-taken swabs for rapid COVID-19 testing.

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.

A case report, bilateral spontaneous pneumothorax as a late complication for SARS CoV-2 infection.

The beta-coronavirus discovered in Wuhan in 2019 (COVID-19) provokes a series of affections from mild symptoms to life-threatening complications. There is evidence that associates the disease to spontaneous pneumothorax, however, the mechanism is unknown. The patient was a 45-year-old male with previous pneumonia due to COVID-19 who was attended the emergency department, where chest radiography was taken, confirming the diagnosis of right pneumothorax. However, the patient developed a new episode of pleuritic pain three days later, and a new radiograph showed left pneumothorax requiring a new chest tube. The simple tomography shows intraparenchymal bullae in the apical region of both lungs. The patient was kept under observation, and when improving, both endopleural chest drains were removed, and the patient was discharged. Spontaneous bilateral pneumothorax is a rare and potentially life-threatening complication. Identifying pulmonary bullae in patients with COVID-19 could be an early sign for these patients to develop spontaneous pneumothorax.

Piperacillin/tazobactam-resistant, cephalosporin-susceptible Escherichia coli bloodstream infections are driven by multiple acquisition of resistance across diverse sequence types.

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 ß-lactamases, and an S133G blaCTX-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.

SARS-CoV-2 enzyme-linked immunosorbent assays as proxies for plaque reduction neutralisation tests.

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 (PRNT80 > 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.

Pooled testing of sputum with Xpert MTB/RIF and Xpert Ultra during tuberculosis active case finding campaigns in Lao People's Democratic Republic.

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.

Clinical characteristics and risk factors for maternal deaths due to COVID-19 in Brazil: a nationwide population-based cohort study.

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 Informação de Vigilância Epidemiológica 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.

Twelve lateral flow immunoassays (LFAs) to detect SARS-CoV-2 antibodies.

BACKGROUND: There are an abundance of commercially available lateral flow assays (LFAs) that detect antibodies to SARS-CoV-2. Whilst these are usually evaluated by the manufacturer, externally performed diagnostic accuracy studies to assess performance are essential. Herein we present an evaluation of 12 LFAs. METHODS: Sera from 100 SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) positive participants were recruited through the FASTER study. A total of 105 pre-pandemic sera from participants with other infections were included as negative samples. RESULTS: At presentation sensitivity against RT-PCR ranged from 37.4 to 79% for IgM/IgG, 30.3-74% for IgG, and 21.2-67% for IgM. Sensitivity for IgM/IgG improved ≥ 21 days post symptom onset for 10/12 tests. Specificity ranged from 74.3 to 99.1% for IgM/IgG, 82.9-100% for IgG, and 75.2-98% for IgM. Compared to the EuroImmun IgG enzyme-linked immunosorbent assay (ELISA), sensitivity and specificity ranged from 44.6 to 95.4% and 85.4-100%, respectively. CONCLUSION: There are many LFAs available with varied sensitivity and specificity. Understanding the diagnostic accuracy of these tests will be vital as we come to rely more on the antibody status of a person moving forward, and as such manufacturer-independent evaluations are crucial.

Pooling sputum for Xpert MTB/RIF and Xpert Ultra testing during the Covid-19 pandemic in Lao People's Democratic Republic.

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.

Effects of the COVID-19 pandemic on routine pediatric vaccination in Brazil.

BACKGROUND: COVID-19 pandemic has disrupted health services, including vaccination demand. We describe the impact of the COVID-19 pandemic on routine pediatric vaccination in Brazil. METHODS: We conducted a retrospective analysis of all vaccine doses provided to children aged 0-6 years from January 2019 to December 2020. We obtained data stratified by age group (0 to 2 years and >2 to 6 years) and Brazilian region. Difference-in-difference (DiD) analyses were performed to compare vaccine uptake in the pre-pandemic (January-February), stay-at-home (March-June), and reopening (July-December) periods. RESULTS: The number of vaccine doses administered declined in the stay-at-home period. For children aged 0 to 2 years, the highest reductions were recorded in the North (-25.3%), Northeast (-16.8%) and Central-West (-10.2%) regions. For children aged >2 to 6 years, the highest decline was observed in the North (DiD = -27.2%) and South (DiD = -14.0%) regions. The number of vaccine doses administered in the reopening period has slightly increased in all regions. CONCLUSIONS: Vaccination decreased during the COVID-19 pandemic. Although the number of doses recovered in part during the reopening phase, additional strategies, such as increased public awareness and vaccination booster campaigns are required.