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Understanding the clinical spectrum of SARS-CoV-2 infection, including the asymptomatic fraction, is important as asymptomatic individuals are still able to infect other individuals and contribute to ongoing transmission. The WHO Unity Household transmission investigation (HHTI) protocol provides a platform for the prospective and systematic collection of high-quality clinical, epidemiological, serological and virological data from SARS-CoV-2 confirmed cases and their household contacts. These data can be used to understand key severity and transmissibility parameters-including the asymptomatic proportion-in relation to local epidemic context and help inform public health response. We aimed to estimate the asymptomatic proportion of SARS-CoV-2 Omicron variant infections in Unity-aligned HHTIs. We conducted a systematic review and meta-analysis in alignment with the PRISMA 2020 guidelines and registered our systematic review on PROSPERO (CRD42022378648). We searched EMBASE, Web of Science, MEDLINE and bioRxiv and medRxiv from 1 November 2021 to 22 August 2023. We identified 8368 records, of which 98 underwent full text review. We identified only three studies for data extraction, with substantial variation in study design and corresponding estimates of the asymptomatic proportion. As a result, we did not generate a pooled estimate or I2 metric. The limited number of quality studies that we identified highlights the need for improved preparedness and response capabilities to facilitate robust HHTI implementation, analysis and reporting, to better inform national, regional and global risk assessments and policymaking.
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Infecções Assintomáticas , COVID-19 , Características da Família , SARS-CoV-2 , Humanos , Infecções Assintomáticas/epidemiologia , COVID-19/epidemiologia , COVID-19/transmissão , COVID-19/virologia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificaçãoRESUMO
[This corrects the article DOI: 10.1016/j.lanwpc.2022.100573.].
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Women in malaria-endemic areas receive sulphadoxine-pyrimethamine (SP) as Intermittent Preventive Treatment in Pregnancy (IPTp) to reduce malaria. While dihydroartemisinin-piperaquine (DP) has superior antimalarial properties as IPTp, SP is associated with superior fetal growth. As maternal inflammation influences fetal growth, we investigated whether SP alters the relationship between inflammation and birth outcomes. We measured C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP) at enrollment (16-28 gestation weeks (gw)), visit 3 (24-36 gw) and delivery in 1319 Malawian women randomized to receive monthly SP, DP, or DP and single-dose azithromycin (AZ) in the IMPROVE trial (NCT03208179). Logistic regression was used to assess the relationship between adverse outcomes, inflammation, and treatment arm. Elevated AGP at enrollment was associated with adverse birth outcome (aRR 1.40, 95% CI: 1.15, 1.70), with similar associations observed across treatment arms, exceptions being that elevated AGP was associated with low maternal weight gain in SP recipients (aRR 1.94, 95% CI: 1.36, 2.76) and with small for gestational age in DP+AZ recepients (aRR 1.49, 95% CI 1.02, 2.17). At visit 3 there were few associations between inflammation andoutcomes. At delivery, women with elevated AGP receiving either DP or DP+AZ had an increased risk of adverse birth outcomes (aRR 1.60, 95% CI: 1.28, 2.00), including low birth weight, pre-term birth and foetal loss, this was not seen in women receiving SP (aRR 0.82, 95% CI: 0.54, 1.26). The risk of an association between elevated AGP and adverse birth outcome was higher in those receiving DP or DP+AZ compared to those receiving SP (aRR 1.95, 95% CI: 1.21, 3.13). No clear associations between CRP and adverse outcomes were observed. AGP identified women at risk of adverse pregnancy outcomes. SP modifies the relationship between inflammatory biomarkers and adverse outcomes. Our findings provide insights into potential mechanisms by which SP may improve pregnancy outcomes.
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Background: Desirability of outcome ranking (DOOR) is an emerging approach to clinical trial outcome measurement using an ordinal scale to incorporate efficacy and safety endpoints. Methods: We applied a previously validated DOOR endpoint to a cohort of CAMERA2 trial participants with methicillin-resistant Staphylococcus aureus bacteremia (MRSAB). Participants were randomly assigned to standard therapy, or to standard therapy plus an antistaphylococcal ß-lactam (combination therapy). Each participant was assigned a DOOR category, within which they were further ranked according to their hospital length of stay (LOS) and duration of intravenous antibiotic treatment. We calculated the probability and the generalized odds ratio of participants receiving combination therapy having worse outcomes than those receiving standard therapy. Results: Participants assigned combination therapy had a 54.5% (95% confidence interval [CI], 48.9%-60.1%; P = .11) probability and a 1.2-fold odds (95% CI, .95-1.50; P = .12) of having a worse outcome than participants on standard therapy. When further ranked according to LOS and duration of antibiotic treatment, participants in the combination group had a 55.6% (95% CI, 49.5%-61.7%) and 55.3% (95% CI, 49.2%-61.4%) probability of having a worse outcome than participants in the standard treatment group, respectively. Conclusions: When considering both efficacy and safety, treatment of MRSAB with a combination of standard therapy and a ß-lactam likely results in a worse clinical outcome than standard therapy. However, a small benefit of combination therapy cannot be excluded. Most likely the toxicity of combination therapy outweighed any benefit from faster clearance of bacteremia.
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BACKGROUND: Reducing antibiotic use in Australia, and the subsequent impact on antimicrobial resistance, requires multiple, sustained approaches with appropriate resources and support. Additional strategies to reduce antibiotic prescribing include effective vaccines, against pathogens such as Streptococcus pyogenes, the most common bacterial cause of sore throat. As part of efforts towards assessing the benefits of introducing new strategies to reduce antimicrobial prescribing, we aimed to determine the burden of antimicrobial prescribing for sore throat in general practice. METHODS: General practice activity data from 2013 - 2017 derived from the first 8 practices participating in the 'Primary Care Audit, Teaching and Research Open Network' (Patron) program were analysed according to reason for visit (upper respiratory tract infection, URTI, or sore throat) and antibiotic prescription. The main outcome measures were percentage of sore throat or URTI presentations with antibiotic prescription by age. RESULTS: A total of 722,339 visits to general practice were made by 65,449 patients; 5.7% of visits were for URTI with 0.8% meeting the more specific criteria for sore throat. 66.1% of sore throat visits and 36.2% of URTI visits resulted in antibiotic prescription. Penicillin, the recommended antibiotic for sore throat when indicated, was the antibiotic of choice in only 52.9% of sore throat cases prescribed antibiotics. Broader spectrum antibiotics were prescribed more frequently in older age groups. CONCLUSIONS: Frequency of antibiotic prescribing for sore throat is high and broad, despite Australian Therapeutic guideline recommendations. Multiple, sustained interventions to reduce prescribing, including availability of effective S. pyogenes vaccines that could reduce the incidence of streptococcal pharyngitis, could obviate the need to prescribe antibiotics and support ongoing efforts to promote antimicrobial stewardship.
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Faringite , Vacinas , Humanos , Idoso , Estudos Retrospectivos , Austrália , Faringite/tratamento farmacológico , Faringite/epidemiologia , Faringite/microbiologia , Antibacterianos/uso terapêutico , Prescrições de Medicamentos , Atenção Primária à Saúde , Vacinas/uso terapêuticoRESUMO
INTRODUCTION: Longitudinal studies can provide timely and accurate information to evaluate and inform COVID-19 control and mitigation strategies and future pandemic preparedness. The Optimise Study is a multidisciplinary research platform established in the Australian state of Victoria in September 2020 to collect epidemiological, social, psychological and behavioural data from priority populations. It aims to understand changing public attitudes, behaviours and experiences of COVID-19 and inform epidemic modelling and support responsive government policy. METHODS AND ANALYSIS: This protocol paper describes the data collection procedures for the Optimise Study, an ongoing longitudinal cohort of ~1000 Victorian adults and their social networks. Participants are recruited using snowball sampling with a set of seeds and two waves of snowball recruitment. Seeds are purposively selected from priority groups, including recent COVID-19 cases and close contacts and people at heightened risk of infection and/or adverse outcomes of COVID-19 infection and/or public health measures. Participants complete a schedule of monthly quantitative surveys and daily diaries for up to 24 months, plus additional surveys annually for up to 48 months. Cohort participants are recruited for qualitative interviews at key time points to enable in-depth exploration of people's lived experiences. Separately, community representatives are invited to participate in community engagement groups, which review and interpret research findings to inform policy and practice recommendations. ETHICS AND DISSEMINATION: The Optimise longitudinal cohort and qualitative interviews are approved by the Alfred Hospital Human Research Ethics Committee (# 333/20). The Optimise Study CEG is approved by the La Trobe University Human Ethics Committee (# HEC20532). All participants provide informed verbal consent to enter the cohort, with additional consent provided prior to any of the sub studies. Study findings will be disseminated through public website (https://optimisecovid.com.au/study-findings/) and through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05323799.
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COVID-19 , Adulto , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Estudos Longitudinais , Quarentena , AustráliaRESUMO
BACKGROUND: The first few 'X' (FFX) studies provide evidence to guide public health decision-making and resource allocation. The adapted WHO Unity FFX protocol for COVID-19 was implemented to gain an understanding of the clinical, epidemiological, virological and household transmission dynamics of the first cases of COVID-19 infection detected in Juba, South Sudan. METHODS: Laboratory-confirmed COVID-19 cases were identified through the national surveillance system, and an initial visit was conducted with eligible cases to identify all close contacts. Consenting cases and close contacts were enrolled between June 2020 and December 2020. Demographic, clinical information and biological samples were taken at enrollment and 14-21 days post-enrollment for all participants. RESULTS: Twenty-nine primary cases and 82 contacts were included in the analyses. Most primary cases (n = 23/29, 79.3%) and contacts (n = 61/82, 74.4%) were male. Many primary cases (n = 18/29, 62.1%) and contacts (n = 51/82, 62.2%) were seropositive for SARS-CoV-2 at baseline. The secondary attack rate among susceptible contacts was 12.9% (4/31; 95% CI: 4.9%-29.7%). All secondary cases and most (72%) primary cases were asymptomatic. Reported symptoms included coughing (n = 6/29, 20.7%), fever or history of fever (n = 4/29, 13.8%), headache (n = 3/29, 10.3%) and shortness of breath (n = 3/29, 10.3%). Of 38 cases, two were hospitalised (5.3%) and one died (2.6%). CONCLUSIONS: These findings were used to develop the South Sudanese Ministry of Health surveillance and contract tracing protocols, informing local COVID-19 case definitions, follow-up protocols and data management systems. This investigation demonstrates that rapid FFX implementation is critical in understanding the emerging disease and informing response priorities.
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COVID-19 , Masculino , Humanos , Feminino , COVID-19/epidemiologia , SARS-CoV-2 , Sudão do Sul/epidemiologia , Busca de Comunicante , IncidênciaRESUMO
Introduction: Antiretroviral therapy for people living with HIV-1 must be taken lifelong due to the persistence of latent virus in long-lived and proliferating CD4+ T cells. Vitamin D3 is a steroidal gene transcription regulator which exerts diverse effects on immune and epithelial cells including reductions in CD4+ T cell proliferation and improvement in gut barrier integrity. We hypothesised that a high dose of vitamin D3 would reduce the size of the HIV-1 reservoir by reducing CD4+ T cell proliferation. Methods: We performed a randomised placebo-controlled trial evaluating the effect of 24 weeks of vitamin D3 (10,000 international units per day) on the HIV-1 reservoir and immunologic parameters in 30 adults on antiretroviral therapy; participants were followed for 12 weeks post-treatment. The primary endpoint was the effect on total HIV-1 DNA at week 24. Parameters were assessed using mixed-effects models. Results: We found no effect of vitamin D3 on the change in total HIV-1 DNA from week 0 to week 24 relative to placebo. There were also no changes in integrated HIV-1 DNA, 2-long-terminal repeat (2-LTR) circles or cell-associated HIV-1 RNA. Vitamin D3 induced a significant increase in the proportion of central memory CD4+ and CD8+ T cells, a reduction in the proportion of senescent CD8+ T cells and a reduction in the natural killer cell frequency at all time points including week 36, 12 weeks after the study drug cessation. At week 36, there was a significant reduction in total HIV-1 DNA relative to placebo and persistently elevated 25-hydroxyvitamin D levels. No significant safety issues were identified. Conclusions: Vitamin D3 administration had a significant impact on the T cell differentiation but overall effects on the HIV-1 reservoir were limited and a reduction in HIV-1 DNA was only seen following cessation of the study drug. Additional studies are required to determine whether the dose and duration of vitamin D3 can be optimised to promote a continued depletion of the HIV-1 reservoir over time. Trial registration: ClinicalTrials.gov NCT03426592.
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BACKGROUND: The World Health Organization recommends that primaquine should be given once weekly for 8-weeks to patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but data on its antirelapse efficacy and safety are limited. METHODS: Within the context of a multicentre, randomised clinical trial of two primaquine regimens in P. vivax malaria, patients with G6PD deficiency were excluded and enrolled into a separate 12-month observational study. They were treated with a weekly dose of 0.75 mg/kg primaquine for 8 weeks (PQ8W) plus dihydroartemisinin piperaquine (Indonesia) or chloroquine (Afghanistan, Ethiopia, Vietnam). G6PD status was diagnosed using the fluorescent spot test and confirmed by genotyping for locally prevalent G6PD variants. The risk of P. vivax recurrence following PQ8W and the consequent haematological recovery were characterized in all patients and in patients with genotypically confirmed G6PD variants, and compared with the patients enrolled in the main randomised control trial. RESULTS: Between July 2014 and November 2017, 42 male and 8 female patients were enrolled in Afghanistan (6), Ethiopia (5), Indonesia (19), and Vietnam (20). G6PD deficiency was confirmed by genotyping in 31 patients: Viangchan (14), Mediterranean (4), 357A-G (3), Canton (2), Kaiping (2), and one each for A-, Chatham, Gaohe, Ludhiana, Orissa, and Vanua Lava. Two patients had recurrent P. vivax parasitaemia (days 68 and 207). The overall 12-month cumulative risk of recurrent P. vivax malaria was 5.1% (95% CI: 1.3-18.9) and the incidence rate of recurrence was 46.8 per 1000 person-years (95% CI: 11.7-187.1). The risk of P. vivax recurrence was lower in G6PD deficient patients treated with PQ8W compared to G6PD normal patients in all treatment arms of the randomised controlled trial. Two of the 26 confirmed hemizygous males had a significant fall in haemoglobin (>5g/dl) after the first dose but were able to complete their 8 week regimen. CONCLUSIONS: PQ8W was highly effective in preventing P. vivax recurrences. Whilst PQ8W was well tolerated in most patients across a range of different G6PD variants, significant falls in haemoglobin may occur after the first dose and require clinical monitoring. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT01814683).
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Deficiência de Glucosefosfato Desidrogenase , Malária Vivax , Humanos , Feminino , Masculino , Primaquina/uso terapêutico , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/genética , Malária Vivax/tratamento farmacológico , Afeganistão , BioensaioRESUMO
Background: The Combination Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus (CAMERA2) trial ceased recruitment in July 2018, noting that a higher proportion of patients in the intervention arm (combination therapy) developed acute kidney injury (AKI) compared to the standard therapy (monotherapy) arm. We analyzed the long-term outcomes of participants in CAMERA2 to understand the impact of combination antibiotic therapy and AKI. Methods: Trial sites obtained additional follow-up data. The primary outcome was all-cause mortality, censored at death or the date of last known follow-up. Secondary outcomes included kidney failure or a reduction in kidney function (a 40% reduction in estimated glomerular filtration rate to <60â mL/minute/1.73 m2). To determine independent predictors of mortality in this cohort, adjusted hazard ratios were calculated using a Cox proportional hazards regression model. Results: This post hoc analysis included extended follow-up data for 260 patients. Overall, 123 of 260 (47%) of participants died, with a median population survival estimate of 3.4 years (235 deaths per 1000 person-years). Fifty-five patients died within 90 days after CAMERA2 trial randomization; another 68 deaths occurred after day 90. Using univariable Cox proportional hazards regression, mortality was not associated with either the assigned treatment arm in CAMERA2 (hazard ratio [HR], 0.84 [95% confidence interval [CI], .59-1.19]; P = .33) or experiencing an AKI (HR at 1 year, 1.04 [95% CI, .64-1.68]; P = .88). Conclusions: In this cohort of patients hospitalized with methicillin-resistant S aureus bacteremia, we found no association between either treatment arm of the CAMERA2 trial or AKI (using CAMERA2 trial definition) and longer-term mortality.
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Background: The COVID-19 pandemic has global impacts but is relatively understudied in developing countries. Mongolia, a lower-middle-income country, instituted strict control measures in early 2020 and avoided widespread transmission until vaccines became available in February, 2021. Mongolia achieved its 60% vaccination coverage goal by July 2021. We investigated the distribution and determinants of SARS-CoV-2 seroprevalence in Mongolia over 2020 and 2021. Methods: We performed a longitudinal seroepidemiologic study aligned with WHO's Unity Studies protocols. We collected data from a panel of 5000 individuals in four rounds between October 2020 and December 2021. We selected participants through local health centres across Mongolia by age-stratified multi-stage cluster sampling. We tested serum for the presence of total antibodies against SARS-CoV-2 receptor-binding domain, and levels of anti-SARS-CoV-2 spike IgG and neutralising antibodies. We linked participant data with national mortality, COVID-19 case, and vaccination registries. We estimated population seroprevalence and vaccine uptake, as well as unvaccinated population prior-infection prevalence. Findings: At the final round in late 2021, 82% (n = 4088) of participants completed follow-up. Estimated seroprevalence increased from 1.5% (95% CI: 1.2-2.0), to 82.3% (95% CI: 79.5-84.8) between late-2020 and late-2021. At the final round an estimated 62.4% (95% CI: 60.2-64.5) of the population were vaccinated, and of the unvaccinated population 64.5% (95% CI: 59.7-69.0) had been infected. Cumulative case ascertainment in the unvaccinated was 22.8% (95% CI: 19.1%-26.9%) and the overall infection-fatality ratio was 0.100% (95% CI: 0.088-0.124). Health workers had higher odds for being COVID-19 confirmed cases at all rounds. Males (1.72 (95% CI: 1.33-2.22)) and adults aged 20 and above (12.70 (95% CI: 8.14-20.26)) had higher odds for seroconverting by mid-2021. Among the seropositive, 87.1% (95% CI: 82.3%-90.8%) had SARS-CoV-2 neutralising antibodies by late 2021. Interpretation: Our study enabled tracking of SARS-CoV-2 serological markers in the Mongolian population over one year. We found low SARS-CoV-2 seroprevalence in 2020 and early 2021, with seropositivity increasing over a 3-month interval in 2021 due to vaccine roll out and rapid infection of most of the unvaccinated population. Despite high seroprevalence in Mongolia amongst both vaccinated and unvaccinated individuals by end-2021, the SARS-CoV-2 Omicron immune escape variant caused a substantial epidemic. Funding: World Health Organization, WHO UNITY Studies initiative, with funding by the COVID-19 Solidarity Response Fund and the German Federal Ministry of Health (BMG) COVID-19 Research and development. The Ministry of Health, Mongolia partially funded this study.
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Background: Household transmission investigations (HHTIs) contribute timely epidemiologic knowledge in response to emerging pathogens. HHTIs conducted in the context of the COVID-19 pandemic in 2020-21 reported variable methodological approaches, producing epidemiological estimates that vary in meaning, precision and accuracy. Because specific tools to assist with the optimal design and critical appraisal of HHTIs are not available, the aggregation and pooling of inferences from HHTIs to inform policy and interventions may be challenging. Methods: In this manuscript, we discuss key aspects of the HHTI design, provide recommendations for the reporting of these studies and propose an appraisal tool that contributes to the optimal design and critical appraisal of HHTIs. Results: The appraisal tool consists of 12 questions that explore 10 aspects of HHTIs and can be answered 'yes', 'no' or 'unclear'. We provide an example of the use of this tool in the context of a systematic review that aimed to quantify the household secondary attack rate from HHTIs. Conclusion: We seek to fill a gap in the epidemiologic literature and contribute to standardised HHTI approaches across settings to achieve richer and more informative datasets.
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COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Características da FamíliaRESUMO
Participation of people from culturally and linguistically diverse (CALD) communities in public health research is often limited by challenges with recruitment, retention and second-language data collection. Consequently, people from CALD communities are at risk of their needs being marginalised in public health interventions. This paper presents intrinsic case analyses of two studies which were adapted to increase the cultural competence of research processes. Both cases were part of the Optimise study, a major mixed methods research study in Australia which provided evidence to inform the Victorian state government's decision-making about COVID-19 public health measures. Case study 1 involved the core Optimise longitudinal cohort study and Case study 2 was the CARE Victorian representative survey, an Optimise sub-study. Both case studies engaged cultural advisors and bilingual staff to adjust the survey measures and research processes to suit target CALD communities. Reflexive processes provided insights into the strengths and weaknesses of the inclusive strategies. Selected survey results are provided, demonstrating variation across CALD communities and in comparison to participants who reported speaking English at home. While in most cases a gradient of disadvantage was evident for CALD communities, some patterns were unexpected. The case studies demonstrate the challenge and value of investing in culturally competent research processes to ensure research guiding policy captures a spectrum of experiences and perspectives.
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COVID-19 , Saúde Pública , Humanos , Vitória/epidemiologia , Estudos Longitudinais , Projetos de Pesquisa , Diversidade Cultural , COVID-19/epidemiologia , LinguísticaRESUMO
BACKGROUNDS AND AIMS: We investigated associations between hepatitis B virus (HBV) genome-length haplotype number (HN) at baseline in subjects with HBeAg-positive chronic hepatitis B (CHB), and the likelihood of achieving functional cure during direct-acting antiviral therapy METHOD: We analysed 86 HBeAg-positive baseline samples from patients with HBV genotypes A and D who were enrolled in a Phase II trial of tenofovir disoproxil fumarate (TDF) to determine if HN was a biomarker of HBsAg loss during therapy. Findings were validated using baseline samples from 181 patients with HBV genotypes A and D from an independent clinical trial utilising TDF or tenofovir alafenamide therapy in HBeAg-positive CHB. RESULTS: In the HBeAg-positive test cohort, patients with genotypes A or D and ≤2 haplotypes had a minimum of 21-fold higher likelihood of achieving HBsAg loss on TDF. Baseline HN (p < 0.0001) was a stronger predictor of HBsAg loss on therapy than HBsAg titre (p = 0.03), HBeAg titre (p = 0.0002), or the presence of HBV basal core promoter (A1762T, p = 0.0379 and G1764A, p = 0.0176) or G1896A precore mutations (p = 0.0218). This finding was validated in the independent validation cohort. HN was statistically higher in patients with HBV genotypes B or C infection compared to genotypes A and D. CONCLUSION: Baseline HN ≤2 predicts which patients with HBV genotypes A or D will more likely progress to functional cure on current direct-acting antiviral therapy, with greater accuracy than current biomarkers including baseline HBsAg and HBeAg titre.
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Hepatite B Crônica , Hepatite C Crônica , Humanos , Vírus da Hepatite B/genética , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/genética , Antígenos E da Hepatite B/genética , Antígenos de Superfície da Hepatite B/genética , Antivirais/uso terapêutico , Haplótipos , Hepatite C Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Genótipo , DNA Viral/genética , DNA Viral/análiseRESUMO
BACKGROUND: Clinical risk factors for nephrotoxicity in Staphylococcus aureus bacteraemia remain largely undetermined, despite its common occurrence and clinical significance. In an international, multicentre, prospective clinical trial (CAMERA2), which compared standard therapy (vancomycin monotherapy) to combination therapy (adding an anti-staphylococcal beta-lactam) for methicillin-resistant S. aureus bacteraemia, significantly more people in the combination therapy arm experienced acute kidney injury compared with those in the monotherapy arm (23% vs 6%). OBJECTIVE: The aim of this post hoc analysis was to explore in greater depth the risk factors for acute kidney injury from the CAMERA2 trial. METHODS: Among participants of the CAMERA2 trial, demographic-related, infection-related and treatment-related risk factors were assessed for their relationship with acute kidney injury by univariable and multivariable logistic regression. Acute kidney injury was defined by a modified-KDIGO (Kidney Disease: Improving Global Outcomes) criteria (not including urinary output). RESULTS: Of the 266 participants included, age (p = 0.04), randomisation to combination therapy (p = 0.002), vancomycin area under the concentration-time curve (p = 0.03) and receipt of (flu)cloxacillin as the companion beta-lactam (p < 0.001) were significantly associated with acute kidney injury. On a multivariable analysis, concurrent use of (flu)cloxacillin increased the risk of acute kidney injury over four times compared with the use of cefazolin or no beta-lactam. The association of vancomycin area under the concentration-time curve with acute kidney injury also persisted in the multivariable model. CONCLUSIONS: For participants receiving vancomycin for S. aureus bacteraemia, use of (flu)cloxacillin and increased vancomycin area under the concentration-time curve were risk factors for acute kidney injury. These represent potentially modifiable risk factors for nephrotoxicity and highlight the importance of avoiding the use of concurrent nephrotoxins.
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Injúria Renal Aguda , Bacteriemia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Injúria Renal Aguda/induzido quimicamente , Antibacterianos/efeitos adversos , Bacteriemia/tratamento farmacológico , Bacteriemia/induzido quimicamente , beta-Lactamas/efeitos adversos , Cefazolina/uso terapêutico , Cloxacilina/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/induzido quimicamente , Staphylococcus aureus , Vancomicina/efeitos adversosRESUMO
Background: First Few "X" (FFX) studies provide a platform to collect the required epidemiological, clinical and virological data to help address emerging information needs about the COVID-19 pandemic. Methods: We adapted the WHO FFX protocol for COVID-19 to understand severity and household transmission dynamics in the early stages of the pandemic in Australia. Implementation strategies were developed for participating sites; all household members were followed for 14 days from case identification. Household contacts completed symptom diaries and had multiple respiratory swabs taken irrespective of symptoms. We modelled the spread of COVID-19 within households using a susceptible-exposed-infectious-recovered-type model, and calculated the household secondary attack rate and key epidemiological parameters. Findings: 96 households with 101 cases and 286 household contacts were recruited into the study between April-October 2020. Forty household contacts tested positive for SARS-CoV-2 in the study follow-up period. Our model estimated the household secondary attack rate to be 15% (95% CI 8-25%), which scaled up with increasing household size. Our findings suggest children were less infectious than their adult counterparts but were also more susceptible to infection. Interpretation: Our study provides important baseline data characterising the transmission of early SARS-CoV-2 strains from children and adults in Australia, against which properties of variants of concern can be benchmarked. We encountered many challenges with respect to logistics, ethics, governance and data management. Continued efforts to invest in preparedness research will help to test, refine and further develop Australian FFX study protocols in advance of future outbreaks. Funding: Australian Government Department of Health.
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Background: Whole genome sequencing (WGS) is increasingly used by tuberculosis (TB) programs to monitor Mycobacterium tuberculosis (Mtb) transmission. We aimed to characterise the molecular epidemiology of TB and Mtb transmission in the low-incidence setting of Victoria, Australia, and assess the utility of WGS. Methods: WGS was performed on all first Mtb isolates from TB cases from 2017 to 2020. Potential clusters (≤12 single nucleotide polymorphisms [SNPs]) were investigated for epidemiological links. Transmission events in highly-related (≤5 SNPs) clusters were classified as likely or possible, based on the presence or absence of an epidemiological link, respectively. Case characteristics and transmission settings (as defined by case relationship) were summarised. Poisson regression was used to examine associations with secondary case number. Findings: Of 1844 TB cases, 1276 (69.2%) had sequenced isolates, with 182 (14.2%) in 54 highly-related clusters, 2-40 cases in size. Following investigation, 140 cases (11.0% of sequenced) were classified as resulting from likely/possible local-transmission, including 82 (6.4%) for which transmission was likely. Common identified transmission settings were social/religious (26.4%), household (22.9%) and family living in different households (7.1%), but many were uncertain (41.4%). While household transmission featured in many clusters (n = 24), clusters were generally smaller (median = 3 cases) than the fewer that included transmission in social/religious settings (n = 12, median = 7.5 cases). Sputum-smear-positivity was associated with higher secondary case numbers. Interpretation: WGS results suggest Mtb transmission commonly occurs outside the household in our low-incidence setting. Further work is required to optimise the use of WGS in public health management of TB. Funding: The Victorian Tuberculosis Program receives block funding for activities including case management and contact tracing from the Victorian Department of Health. No specific funding for this report was received by manuscript authors or the Victorian Tuberculosis Program, and the funders had no role in the study design, data collection, data analysis, interpretation or report writing.
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Distinct bacterial trophic networks exist in the gut microbiota of individuals in industrialized and non-industrialized countries. In particular, non-industrialized gut microbiomes tend to be enriched with Prevotella species. To study the development of these Prevotella-rich compositions, we investigated the gut microbiota of children aged between 7 and 37 months living in rural Gambia (616 children, 1,389 stool samples, stratified by 3-month age groups). These infants, who typically eat a high-fibre, low-protein diet, were part of a double-blind, randomized iron intervention trial (NCT02941081) and here we report the secondary outcome. We found that child age was the largest discriminating factor between samples and that anthropometric indices (collection time points, season, geographic collection site, and iron supplementation) did not significantly influence the gut microbiome. Prevotella copri, Faecalibacterium prausnitzii and Prevotella stercorea were, on average, the most abundant species in these 1,389 samples (35%, 11% and 7%, respectively). Distinct bacterial trophic network clusters were identified, centred around either P. stercorea or F. prausnitzii and were found to develop steadily with age, whereas P. copri, independently of other species, rapidly became dominant after weaning. This dataset, set within a critical gut microbial developmental time frame, provides insights into the development of Prevotella-rich gut microbiomes, which are typically understudied and are underrepresented in western populations.