Evaluating completion rates of COVID-19 contact tracing surveys in New York City.

IMPORTANCE: Contact tracing is the process of identifying people who have recently been in contact with someone diagnosed with an infectious disease. During an outbreak, data collected from contact tracing can inform interventions to reduce the spread of infectious diseases. Understanding factors associated with completion rates of contact tracing surveys can help design improved interview protocols for ongoing and future programs. OBJECTIVE: To identify factors associated with completion rates of COVID-19 contact tracing surveys in New York City (NYC) and evaluate the utility of a predictive model to improve completion rates, we analyze laboratory-confirmed and probable COVID-19 cases and their self-reported contacts in NYC from October 1st 2020 to May 10th 2021. METHODS: We analyzed 742,807 case investigation calls made during the study period. Using a log-binomial regression model, we examined the impact of age, time of day of phone call, and zip code-level demographic and socioeconomic factors on interview completion rates. We further developed a random forest model to predict the best phone call time and performed a counterfactual analysis to evaluate the change of completion rates if the predicative model were used. RESULTS: The percentage of contact tracing surveys that were completed was 79.4%, with substantial variations across ZIP code areas. Using a log-binomial regression model, we found that the age of index case (an individual who has tested positive through PCR or antigen testing and is thus subjected to a case investigation) had a significant effect on the completion of case investigation - compared with young adults (the reference group,24 years old < age < = 65 years old), the completion rate for seniors (age > 65 years old) were lower by 12.1% (95%CI: 11.1% - 13.3%), and the completion rate for youth group (age < = 24 years old) were lower by 1.6% (95%CI: 0.6% -2.6%). In addition, phone calls made from 6 to 9 pm had a 4.1% (95% CI: 1.8% - 6.3%) higher completion rate compared with the reference group of phone calls attempted from 12 and 3 pm. We further used a random forest algorithm to assess its potential utility for selecting the time of day of phone call. In counterfactual simulations, the overall completion rate in NYC was marginally improved by 1.2%; however, certain ZIP code areas had improvements up to 7.8%. CONCLUSION: These findings suggest that age and time of day of phone call were associated with completion rates of case investigations. It is possible to develop predictive models to estimate better phone call time for improving completion rates in certain communities.

Reduction of airborne and surface-borne bacteria in a medical center burn intensive care unit using active, upper-room, germicidal ultraviolet (GUV) disinfection.

OBJECTIVE: To determine the effectiveness of active, upper-room, germicidal ultraviolet (GUV) devices in reducing bacterial contamination in patient rooms in air and on surfaces as a supplement to the central heating, ventilation, and air conditioning (HVAC) air handling unit (AHU) with MERV 14 filters and UV-C disinfection. METHODS: This study was conducted in an academic medical center, burn intensive care unit (BICU), for 4 months in 2022. Room occupancy was monitored and recorded. In total, 402 preinstallation and postinstallation bacterial air and non-high-touch surface samples were obtained from 10 BICU patient rooms. Airborne particle counts were measured in the rooms, and bacterial air samples were obtained from the patient-room supply air vents and outdoor air, before and after the intervention. After preintervention samples were obtained, an active, upper-room, GUV air disinfection system was deployed in each of the patient rooms in the BICU. RESULTS: The average levels of airborne bacteria of 395 CFU/m3 before GUV device installation and 37 CFU/m3 after installation indicated an 89% overall decrease (P < .0001). Levels of surface-borne bacteria were associated with a 69% decrease (P < .0001) after GUV device installation. Outdoor levels of airborne bacteria averaged 341 CFU/m3 in March before installation and 676 CFU/m3 in June after installation, but this increase was not significant (P = .517). CONCLUSIONS: Significant reductions in air and surface contamination occurred in all rooms and areas and were not associated with variations in outdoor air concentrations of bacteria. The significant decrease of surface bacteria is an unexpected benefit associated with in-room GUV air disinfection, which can potentially reduce overall bioburden.

Community transmission of SARS-CoV-2 during the Delta wave in New York City.

BACKGROUND: Understanding community transmission of SARS-CoV-2 variants of concern (VOCs) is critical for disease control in the post pandemic era. The Delta variant (B.1.617.2) emerged in late 2020 and became the dominant VOC globally in the summer of 2021. While the epidemiological features of the Delta variant have been extensively studied, how those characteristics shaped community transmission in urban settings remains poorly understood. METHODS: Using high-resolution contact tracing data and testing records, we analyze the transmission of SARS-CoV-2 during the Delta wave within New York City (NYC) from May 2021 to October 2021. We reconstruct transmission networks at the individual level and across 177 ZIP code areas, examine network structure and spatial spread patterns, and use statistical analysis to estimate the effects of factors associated with COVID-19 spread. RESULTS: We find considerable individual variations in reported contacts and secondary infections, consistent with the pre-Delta period. Compared with earlier waves, Delta-period has more frequent long-range transmission events across ZIP codes. Using socioeconomic, mobility and COVID-19 surveillance data at the ZIP code level, we find that a larger number of cumulative cases in a ZIP code area is associated with reduced within- and cross-ZIP code transmission and the number of visitors to each ZIP code is positively associated with the number of non-household infections identified through contact tracing and testing. CONCLUSIONS: The Delta variant produced greater long-range spatial transmission across NYC ZIP code areas, likely caused by its increased transmissibility and elevated human mobility during the study period. Our findings highlight the potential role of population immunity in reducing transmission of VOCs. Quantifying variability of immunity is critical for identifying subpopulations susceptible to future VOCs. In addition, non-pharmaceutical interventions limiting human mobility likely reduced SARS-CoV-2 spread over successive pandemic waves and should be encouraged for reducing transmission of future VOCs.

Planning For The Next Pandemic: Lab Systems Need Policy Shift To Speed Emerging Infectious Disease Warning And Tracking.

Early detection and ongoing monitoring of infectious diseases depends on diagnostic testing. The US has a large, diverse system of public, academic, and private laboratories that develop new diagnostic tests; perform routine testing; and conduct specialized reference testing, such as genomic sequencing. These laboratories operate under a complex mix of laws and regulations at the federal, state, and local levels. The COVID-19 pandemic exposed major weaknesses in the nation's laboratory system, some of which were seen again during the global mpox outbreak in 2022. In this article we review how the US laboratory system has been designed to detect and monitor emerging infections, describe what gaps were revealed during COVID-19, and propose specific steps that policy makers can take both to strengthen the current system and to prepare the US for the next pandemic.

Excess burden of respiratory and abdominal conditions following COVID-19 infections during the ancestral and Delta variant periods in the United States: An EHR-based cohort study from the RECOVER Program.

Importance: The frequency and characteristics of post-acute sequelae of SARS-CoV-2 infection (PASC) may vary by SARS-CoV-2 variant. Objective: To characterize PASC-related conditions among individuals likely infected by the ancestral strain in 2020 and individuals likely infected by the Delta variant in 2021. Design: Retrospective cohort study of electronic medical record data for approximately 27 million patients from March 1, 2020-November 30, 2021. Setting: Healthcare facilities in New York and Florida. Participants: Patients who were at least 20 years old and had diagnosis codes that included at least one SARS-CoV-2 viral test during the study period. Exposure: Laboratory-confirmed COVID-19 infection, classified by the most common variant prevalent in those regions at the time. Main Outcomes and Measures: Relative risk (estimated by adjusted hazard ratio [aHR]) and absolute risk difference (estimated by adjusted excess burden) of new conditions, defined as new documentation of symptoms or diagnoses, in persons between 31-180 days after a positive COVID-19 test compared to persons with only negative tests during the 31-180 days after the last negative test. Results: We analyzed data from 560,752 patients. The median age was 57 years; 60.3% were female, 20.0% non-Hispanic Black, and 19.6% Hispanic. During the study period, 57,616 patients had a positive SARS-CoV-2 test; 503,136 did not. For infections during the ancestral strain period, pulmonary fibrosis, edema (excess fluid), and inflammation had the largest aHR, comparing those with a positive test to those with a negative test, (aHR 2.32 [95% CI 2.09 2.57]), and dyspnea (shortness of breath) carried the largest excess burden (47.6 more cases per 1,000 persons). For infections during the Delta period, pulmonary embolism had the largest aHR comparing those with a positive test to a negative test (aHR 2.18 [95% CI 1.57, 3.01]), and abdominal pain carried the largest excess burden (85.3 more cases per 1,000 persons). Conclusions and Relevance: We documented a substantial relative risk of pulmonary embolism and large absolute risk difference of abdomen-related symptoms after SARS-CoV-2 infection during the Delta variant period. As new SARS-CoV-2 variants emerge, researchers and clinicians should monitor patients for changing symptoms and conditions that develop after infection.

Advancing detection and response capacities for emerging and re-emerging pathogens in Africa.

Recurrent disease outbreaks caused by a range of emerging and resurging pathogens over the past decade reveal major gaps in public health preparedness, detection, and response systems in Africa. Underlying causes of recurrent disease outbreaks include inadequacies in the detection of new infectious disease outbreaks in the community, in rapid pathogen identification, and in proactive surveillance systems. In sub-Saharan Africa, where 70% of zoonotic outbreaks occur, there remains the perennial risk of outbreaks of new or re-emerging pathogens for which no vaccines or treatments are available. As the Ebola virus disease, COVID-19, and mpox (formerly known as monkeypox) outbreaks highlight, a major paradigm shift is required to establish an effective infrastructure and common frameworks for preparedness and to prompt national and regional public health responses to mitigate the effects of future pandemics in Africa.

Contact tracing reveals community transmission of COVID-19 in New York City.

Understanding SARS-CoV-2 transmission within and among communities is critical for tailoring public health policies to local context. However, analysis of community transmission is challenging due to a lack of high-resolution surveillance and testing data. Here, using contact tracing records for 644,029 cases and their contacts in New York City during the second pandemic wave, we provide a detailed characterization of the operational performance of contact tracing and reconstruct exposure and transmission networks at individual and ZIP code scales. We find considerable heterogeneity in reported close contacts and secondary infections and evidence of extensive transmission across ZIP code areas. Our analysis reveals the spatial pattern of SARS-CoV-2 spread and communities that are tightly interconnected by exposure and transmission. We find that locations with higher vaccination coverage and lower numbers of visitors to points-of-interest had reduced within- and cross-ZIP code transmission events, highlighting potential measures for curtailing SARS-CoV-2 spread in urban settings.

The effect of a proof-of-vaccination requirement, incentive payments, and employer-based mandates on COVID-19 vaccination rates in New York City: a synthetic-control analysis.

BACKGROUND: COVID-19 vaccines have been available to all adults in the USA since April, 2021, but many adults remain unvaccinated. We aimed to assess the joint effect of a proof-of-vaccination requirement, incentive payments, and employer-based mandates on rates of adult vaccination in New York City (NYC). METHODS: We constructed a synthetic control group for NYC composed of other counties in the core of large, metropolitan areas in the USA. The vaccination outcomes for NYC were compared against those of the synthetic control group from July 26, 2021, to Nov 1, 2021, to determine the differential effects of the policies. Analyses were conducted on county-level vaccination data reported by the Centers for Disease Control and Prevention. The synthetic control group was constructed by matching on county-level preintervention vaccination outcomes, partisanship, economic attributes, demographics, and metropolitan area population. Statistical inference was conducted using placebo tests for non-treated counties. FINDINGS: The synthetic control group resembled NYC across attributes used in the matching process. The cumulative adult vaccination rate for NYC (in adults aged 18 years or older who received at least one dose of an authorised COVID-19 vaccine) increased from 72·5% to 89·4% (+16·9 percentage points [pp]) during the intervention period, compared with an increase from 72·5% to 83·2% (+10·7 pp) for the synthetic control group, a difference of 6·2 pp (95% CI 1·4-10·7), or 410 201 people (90 966-706 532). Daily vaccinations for NYC were consistently higher than those in the synthetic control group, a pattern that started shortly after the start of the intervention period. INTERPRETATION: The combination of a proof-of-vaccination requirement, incentive payments, and vaccine mandates increased vaccination rates among adults in NYC compared with jurisdictions that did not use the same measures. Whether the impact of these measures occurred by inducing more people to get vaccinated, or by accelerating vaccinations that would have occurred later, the increase in vaccination rates likely averted illness and death. FUNDING: None.

Comparison of national antimicrobial treatment guidelines, African Union.

OBJECTIVE: To identify and compare antimicrobial treatment guidelines from African Union (AU) Member States. METHODS: We reviewed national government agency and public health institutes' websites and communicated with country or regional focal points to identify existing treatment guidelines from AU Member States. We included guidelines if they contained disease-, syndrome- or pathogen-specific treatment recommendations and if those recommendations included antimicrobial name or class, dosage and therapy duration. The scope of the review was limited to infections and clinical syndromes that often have a bacterial cause. We assessed treatment guidelines for alignment with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. We compared treatment recommendations for various common bacterial infections or clinical syndromes described across national guidelines and those described in three World Health Organization guidelines. FINDINGS: We identified 31 treatment guidelines from 20 of the 55 (36%) AU Member States; several countries had more than one treatment guideline that met our inclusion criteria. Fifteen (48%) guidelines from 10 countries have been published or updated since 2015. Methods used to develop the guidelines were not well described. No guidelines were developed according to the GRADE approach. Antimicrobial selection, dosage and duration of recommended therapies varied widely across guidelines for all infections and syndromes. CONCLUSION: AU Member States lack antimicrobial treatment guidelines that meet internationally accepted methods and that draw from local evidence about disease burden and antimicrobial susceptibility.

COVID-19 Infections Among Students and Staff in New York City Public Schools.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19) pandemic led many jurisdictions to close in-person school instruction. METHODS: We collected data about COVID-19 cases associated with New York City (NYC) public schools from polymerase chain reaction testing performed in each school on a sample of asymptomatic students and staff and from routine reporting. We compared prevalence from testing done in schools to community prevalence estimates from statistical models. We compared cumulative incidence for school-associated cases to all cases reported to the city. School-based contacts were monitored to estimate the secondary attack rate and possible direction of transmission. RESULTS: To assess prevalence, we analyzed data from 234 132 persons tested for severe acute respiratory syndrome coronavirus 2 infection in 1594 NYC public schools during October 9 to December 18, 2020; 986 (0.4%) tested positive. COVID-19 prevalence in schools was similar to or less than estimates of prevalence in the community for all weeks. To assess cumulative incidence, we analyzed data for 2231 COVID-19 cases that occurred in students and staff compared with the 86 576 persons in NYC diagnosed with COVID-19 during the same period; the overall incidence was lower for persons in public schools compared with the general community. Of 36 423 school-based close contacts, 191 (0.5%) subsequently tested positive for COVID-19; the likely index case was an adult for 78.0% of secondary cases. CONCLUSIONS: We found that in-person learning in NYC public schools was not associated with increased prevalence or incidence overall of COVID-19 infection compared with the general community.

Antimicrobial resistance control efforts in Africa: a survey of the role of Civil Society Organisations.

Background: Antimicrobial resistance (AMR) is a growing public health threat in Africa. AMR prevention and control requires coordination across multiple sectors of government and civil society partners. Objectives: To assess the current role, needs, and capacities of CSOs working in AMR in Africa. Methods: We conducted an online survey of 35 CSOs working in 37 countries across Africa. The survey asked about priorities for AMR, current AMR-specific activities, monitoring practices, training needs, and preferences for sharing information on AMR. Further data were gathered on the main roles of the organisations, the length of time engaged in and budget spent on AMR-related activities, and their involvement in the development and implementation of National Action Plans (NAPs). Results were assessed against The Africa Centres for Disease Control and Prevention (Africa CDC) Framework for Antimicrobial Resistance (2018-2023). Results: CSOs with AMR-related activities are working in all four areas of Africa CDC's Framework: improving surveillance, delaying emergence, limiting transmission, and mitigating harm from infections caused by AMR microorganisms. Engagement with the four objectives is mainly through advocacy, followed by accountability and service delivery. There were limited monitoring activities reported by CSOs, with only seven (20%) providing an example metric used to monitor their activities related to AMR, and 27 (80%) CSOs reporting having no AMR-related strategy. Half the CSOs reported engaging with the development and implementation of NAPs; however, only three CSOs are aligning their work with these national strategies. Conclusion: CSOs across Africa are supporting AMR prevention and control, however, there is potential for more engagement. Africa CDC and other government agencies should support the training of CSOs in strategies to control AMR. Tailored training programmes can build knowledge of AMR, capacity for monitoring processes, and facilitate further identification of CSOs' contribution to the AMR Framework and alignment with NAPs and regional strategies.

Development of the first edition of African treatment guidelines for common bacterial infections and syndromes.

Standard treatment guidelines (STGs) are an important tool for ensuring high quality clinical care and prudent antimicrobial use (AMU) and stewardship (AMS). In 2018, African Union (AU) member state representatives recognized the lack of STGs as a barrier to AMS at national and facility levels. Previous research reported that only 17 of 55 (31%) member states had STGs that provided disease- or pathogen-specific antimicrobial treatment recommendations, excluding those that covered only treatment of HIV, malaria, and tuberculosis). The Africa Centres for Disease Control and Prevention convened expert panels to develop first edition antibiotic treatment guidelines for priority infectious diseases and clinical syndromes for pediatric and adult patient populations in Africa. The purpose of the guidelines is to provide healthcare workers with treatment guidance by harmonising existing national STGs, filling gaps where existing STGs are not available, and serving as a model for future guidelines. Two expert panels of 28 total clinicians, pharmacists, and other relevant stakeholders from 14 AU member states representing each continental region convened to develop consensus treatment recommendations for select priority bacterial infections and clinical syndromes. In developing recommendations, the panels considered treatment recommendations from existing STGs, drug availability, clinical experience, and available antimicrobial resistance data. The guidelines underwent an external review process where clinical stakeholders who did not serve on either panel were invited to submit feedback prior to their publication. The guidelines provide empiric antibiotic therapy guidelines - including drug selection, route of administration, formulation, dosage, and therapy duration - and principles of stewardship for 28 bacterial infections or clinical syndromes. The first edition guidelines for the treatment of common infectious diseases and clinical syndromes in Africa aims to improve clinical treatment and antimicrobial stewardship and will serve as a template for future regional guidelines.

Healthcare-associated outbreaks of bacterial infections in Africa, 2009-2018: A review.

BACKGROUND: Healthcare-associated infections (HAIs) are a major global public health problem, increasing the transmission of drug-resistant infections. In Africa, the prevalence of HAIs among all hospital inpatients is estimated to be between 3% and 15%, but outbreaks are infrequently reported. Failure to detect and/or report outbreaks can increase the risk of ongoing infections and recurrent outbreaks. METHODS: A search of the PubMed, Web of Science, Cochrane Library, and other outbreak databases was performed to identify published literature on bacterial HAI outbreaks in Africa (January 2009 to December 2018). Details of the outbreak characteristics, hospital environment, and the control measures implemented were extracted. RESULTS: Twenty-two studies published over the 10-year period were identified. These reported 31 distinct outbreaks and a total of 31 causative pathogens, including Klebsiella pneumoniae (six outbreaks, 19%), Staphylococcus aureus (six outbreaks, 19%), and Enterococcus (five outbreaks, 16%). Most outbreaks were reported from university (n = 8, 26%) and tertiary hospitals (n = 11, 55%), from South Africa (n = 9, 41%) and Tunisia (n = 4, 18%). Interventions to control the outbreaks were described in 27 (90%) outbreaks, and all instituted or recommended enhancing hand hygiene and education. CONCLUSIONS: Few facilities in Africa reported HAI outbreaks over the 10-year period, suggesting substantial under-detection and under-reporting. The quality and timeliness of reporting require improvement to ensure changes in public health practice.

Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data

BACKGROUND: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. METHODS: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. FINDINGS:We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per µL (the median for the cohort) was 45% (95% CI 38­52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63­87), increasing to 89% (80­94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05­3·08) but not after 30 days (1·25, 0·84­2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16­8·84). INTERPRETATION:In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients

Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data.

BACKGROUND: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. METHODS: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. FINDINGS: We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per µL (the median for the cohort) was 45% (95% CI 38-52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63-87), increasing to 89% (80-94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05-3·08) but not after 30 days (1·25, 0·84-2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16-8·84). INTERPRETATION: In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients. FUNDING: This study was supported by Wellcome fellowships 109105Z/15/A and 105165/Z/14/A.

Public Health Management of Persons Under Investigation for Ebola Virus Disease in New York City, 2014-2016.

During 2014-2016, the largest outbreak of Ebola virus disease (EVD) in history occurred in West Africa. The New York City Department of Health and Mental Hygiene (DOHMH) worked with health care providers to prepare for persons under investigation (PUIs) for EVD in New York City. From July 1, 2014, through December 29, 2015, we classified as a PUI a person with EVD-compatible signs or symptoms and an epidemiologic risk factor within 21 days before illness onset. Of 112 persons who met PUI criteria, 74 (66%) sought medical care and 49 (44%) were hospitalized. The remaining 38 (34%) were isolated at home with daily contact by DOHMH staff members. Thirty-two (29%) PUIs received a diagnosis of malaria. Of 10 PUIs tested, 1 received a diagnosis of EVD. Home isolation minimized unnecessary hospitalization. This case study highlights the importance of developing competency among clinical and public health staff managing persons suspected to be infected with a high-consequence pathogen.