Conversion or reversion of interferon gamma release assays for Mycobacterium tuberculosis infection: a systematic review and meta-analysis.

BACKGROUND: Interferon-gamma release assays (IGRA) are widely used for diagnosis of latent tuberculosis infection. However, with repeat testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation. METHODS: We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and subject characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors. RESULTS: The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% CI 6.1-8.5%) or 22.8% (20.1-25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (35.7-56.4%) or 19.6% (9.2-31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [0.1-3.5%]). IGRA results in the borderline positive or negative range were associated with increased risk of conversion or reversion (pooled OR: conversion, 4.15 [3.00-5.30]; reversion, 4.06 [3.07-5.06]). BCG vaccination was associated with decreased risk of conversion (0.70, 0.56-0.84), cigarette smoking with decreased risk of reversion (0.44, 0.06-0.82), and female sex with decreased risk of either conversion or reversion (conversion, 0.66 [0.58-0.75]; reversion, 0.46 [0.31-0.61]). CONCLUSIONS: IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis preventive treatment. Re-testing of people with indeterminate results is probably not indicated, since indeterminate results seldom revert to positive.

The Prevalence of HIV Infection in Minority Indigenous Populations of the South-East Asia and Western Pacific Regions: A Systematic Review and Meta-analysis.

A random effects meta-analysis was used to estimate the pooled prevalence of HIV infection within minority indigenous populations of the South-East Asia (SEAR) and Western Pacific Regions (WPR). Sub-group analyses were conducted, and the sources of heterogeneity explored through meta-regression. The majority of studies were undertaken in high HIV risk subpopulations. There was a paucity of data for many countries with data from China representing 70% of the comparative studies. Within minority indigenous populations the pooled prevalence of HIV infection was 13.7% (95% CI 8.9, 19) and 8.4% (95% CI 6.3, 10.7) among other populations. The prevalence differential between populations was significant in the WPR (adjusted odds ratio 1.1, 95% CI 1.0, 1.2). Across both regions, in contrast to other populations, minority indigenous did not experience any significant reduction in HIV prevalence over the years of data collection. There was large heterogeneity in the prevalence of HIV across studies.

Risk factors associated with unsuccessful tuberculosis treatment outcomes in Hunan Province, China.

OBJECTIVES: Globally, China has the third highest number of tuberculosis (TB) cases despite high rates (85.6%) of effective treatment coverage. Identifying risk factors associated with unsuccessful treatment outcomes is an important component of maximising the efficacy of TB control programmes. METHODS: Retrospective cohort study to evaluate the outcomes of 306,860 drug-susceptible TB patients who underwent treatment in Hunan Province, China between 2013 and 2018. Univariable and multivariable logistic regression models were used to identify factors associated with unsuccessful TB treatment outcomes. RESULTS: A successful treatment outcome was recorded for 98.6% of patients, defined as the sum of patients who were cured (36.2%) and completed treatment (62.4%). An unsuccessful treatment outcome was recorded for 1.8% of patients, defined as the sum of treatment failure (1.1%), deaths (0.5%) and lost to follow up (0.2%). The odds of an unsuccessful treatment outcome showed an increasing trend in more recent years of registration (2018 adjusted odds ratio (AOR): 1.43; 95% Confidence Interval (CI) 1.31, 1.57 relative to 2013). Other significant risk factors were male sex (AOR: 1.17; 95% CI 1.10, 1.25); increasing age (AOR:1.02 per year increase; 95% CI 1.02,1.02); being severely ill (AOR: 1.50; 95% CI 1.33, 1.70); having a history of TB treatment (AOR: 2.93; 95% CI 2.69, 3.20); not being under systematic management (AOR: 16.10 (14.49, 17.88) and treatment regimens that differed from full course management. CONCLUSIONS: The increasing likelihood of an unsuccessful treatment outcome over time necessitates the need for further research.

The impact of ethnic minority status on tuberculosis diagnosis and treatment delays in Hunan Province, China.

BACKGROUND: Tuberculosis (TB) continues to be a major public health challenge in China. Understanding TB management delays within the context of China's unique ethnic diversity may be of value in tackling the disease. This study sought to evaluate the impact of ethnic minority status on TB diagnosis and treatment delays. METHODS: This retrospective cohort study was conducted on patients diagnosed with TB in Hunan Province, China between 2013 and 2018. Diagnosis delay was defined as the time interval between the onset of symptoms and the date of diagnosis. Treatment delay was defined as the time interval between diagnosis and treatment commencement. Univariable and multivariable logistic regression models were used to identify factors associated with TB diagnosis and treatment delay, including ethnic minority status. Adjusted odds ratios (AOR) with 95% confidence intervals (CI) were calculated to assess the strength of association between the dependant and independent variables. RESULTS: A total of 318,792 TB patients were included in the study with a mean age of 51.7 years (SD 17.7). The majority of patients were male (72.6%) and Han ethnicity (90.6%). The odds of experiencing diagnosis delay (> 21 days) were significantly higher for Tujia (AOR: 1.46, 95% CI: 1.41, 1.51), Miao (AOR: 1.31, 95% CI: 1.26, 1.37), Dong (AOR: 1.97, 95% CI: 1.85, 2.11), Yao (AOR: 1.27, 95% CI: 1.17, 1.37), and Bai (AOR: 1.45, 95% CI: 1.22, 1.74) ethnic minorities compared to the Han majority. The odds of experiencing treatment delay (> 15 days) were significantly lower for five of the seven ethnic minority groups relative to the Han majority: Tujia (AOR 0.92, 95% CI 0.88, 0.96), Miao (AOR 0.74, 95% CI 0.70, 0.79), Dong (AOR 0.87, 95% CI 0.81, 0.95), Yao (AOR 0.20, 95% CI 0.17, 0.24) and 'other' (ethnic minorities that individually represented < 0.1% of the patient population) (AOR 0.70, 955 CI 0.51, 0.97). CONCLUSIONS: This study shows ethnic minority status to be a significant risk factor in diagnosis delay, but for it to reduce the odds of treatment delay. Further research is required to determine the underlying causes of diagnosis delay within ethnic minority populations.

Prevalence of tuberculosis infection among contacts of drug-resistant tuberculosis patients: A systematic review and meta-analysis.

INTRODUCTION: Contact investigations with drug-susceptible tuberculosis (DS-TB) patients have demonstrated a high prevalence of tuberculosis infection (TBI). However, the prevalence of TBI among individuals in close contact with drug-resistant tuberculosis (DR-TB) patients is poorly understood. This systematic review and meta-analysis aimed to determine the prevalence of TBI among household and non-household contacts of DR-TB patients. METHOD AND ANALYSIS: We searched five databases (Medline, Embase, Scopus, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL)) from inception to 2 June 2023. All studies that reported the prevalence of TBI among DR-TB contacts were included in the study. A random-effects meta-analysis was conducted to estimate the pooled prevalence of TBI with a 95% confidence interval (CI). Sub-group analyses were conducted using study characteristics as covariates. RESULTS: Thirty studies involving 7659 study participants from 19 countries were included. The pooled prevalence of TBI among DR-TB contacts was 36.52% (95% CI: 30.27-42.77). The sub-group analysis showed considerable heterogeneity in the estimates, with the highest prevalence reported in Southeast Asia (80.74%; 95% CI: 74.09-87.39), household contacts (38.60%; 95% CI: 30.07-47.14), lower-middle-income countries (LMICs) (54.72; 95% CI: 35.90, 73.55), children (43.27%; 95% CI: 25.50, 61.04), and studies conducted between 2004 and 2012 (45.10; 95% CI: 32.44, 57.76). CONCLUSION: The prevalence of TBI among DR-TB contacts was high, with substantial regional variations. Further research is needed to determine the drug susceptibility status of TBI in DR-TB contacts. PROTOCOL REGISTRATION: The protocol is registered in PROSPERO (CRD42023390339).

Ecological-level factors associated with tuberculosis incidence and mortality: A systematic review and meta-analysis.

Globally, tuberculosis (TB) is the leading infectious cause of morbidity and mortality, with the risk of infection affected by both individual and ecological-level factors. While systematic reviews on individual-level factors exist, there are currently limited studies examining ecological-level factors associated with TB incidence and mortality. This study was conducted to identify ecological factors associated with TB incidence and mortality. A systematic search for analytical studies reporting ecological factors associated with TB incidence or mortality was conducted across electronic databases such as PubMed, Embase, Scopus, and Web of Science, from each database's inception to October 30, 2023. A narrative synthesis of evidence on factors associated with TB incidence and mortality from all included studies, alongside random-effects meta-analysis where applicable, estimated the effects of each factor on TB incidence. A total of 52 articles were included in the analysis, and one study analysed two outcomes, giving 53 studies. Narrative synthesis revealed predominantly positive associations between TB incidence and factors such as temperature (10/18 studies), precipitation (4/6), nitrogen dioxide (6/9), poverty (4/4), immigrant population (3/4), urban population (3/8), and male population (2/4). Conversely, air pressure (3/5), sunshine duration (3/8), altitude (2/4), gross domestic product (4/9), wealth index (2/8), and TB treatment success rate (2/2) mostly showed negative associations. Particulate matter (1/1), social deprivation (1/1), and population density (1/1) were positively associated with TB mortality, while household income (2/2) exhibited a negative association. In the meta-analysis, higher relative humidity (%) (relative risk (RR) = 1.45, 95%CI:1.12, 1.77), greater rainfall (mm) (RR = 1.56, 95%CI: 1.11, 2.02), elevated sulphur dioxide (µg m-3) (RR = 1.04, 95% CI:1.01, 1.08), increased fine particulate matter concentration (PM2.5) (µg/ m3) (RR = 1.33, 95% CI: 1.18, 1.49), and higher population density (people/km2) (RR = 1.01,95%CI:1.01-1.02) were associated with increased TB incidence. Conversely, higher average wind speed (m/s) (RR = 0.89, 95%CI: 0.82,0.96) was associated with decreased TB incidence. TB incidence and mortality rates were significantly associated with various climatic, socioeconomic, and air quality-related factors. Intersectoral collaboration across health, environment, housing, social welfare and economic sectors is imperative for developing integrated approaches that address the risk factors associated with TB incidence and mortality.

Interventions to prevent post-tuberculosis sequelae: a systematic review and meta-analysis.

Background: Tuberculosis (TB) remains a global public health challenge, causing substantial mortality and morbidity. While TB treatment has made significant progress, it often leaves survivors with post-TB sequelae, resulting in long-term health issues. Current healthcare systems and guidelines lack comprehensive strategies to address post-TB sequelae, primarily due to insufficient evidence. This systematic review and meta-analysis aimed to identify effective interventions for preventing post-TB sequelae. Methods: A systematic search was conducted across four databases including PubMed, SCOPUS, Web of Science, and Cochrane Central Register of Controlled Trials from inception to September 22, 2023. Eligible studies reported interventions designed to prevent post-TB sequelae were included. A random effect meta-analysis was conducted where applicable, and heterogeneity between studies was evaluated visually using forest plots and quantitatively using an index of heterogeneity (I2). This study is registered with PROSPERO (CRD42023464392). Findings: From the 2525 unique records screened, 25 studies involving 10,592 participants were included. Different interventions were evaluated for different outcomes. However, only a few interventions were effective in preventing post-TB sequelae. Rehabilitation programs significantly improved lung function (Hedges's g = 0.21; 95% confidence interval (CI): 0.03, 0.39) and prevented neurological sequelae (relative risk (RR) = 0.10; 95% CI: 0.02, 0.42). Comprehensive interventions and cognitive-behavioural therapy significantly reduced the risk of mental health disorders among TB survivors (Hedges's g = -1.89; 95% CI: -3.77, -0.01). In contrast, interventions targeting post-TB liver sequelae, such as vitamin A and vitamin D supplementation and hepatoprotective agents, did not show significant reductions in sequelae (RR = 0.90; 95% CI: 0.52, 1.57). Moreover, adjunctive therapies did not show a significant effect in preventing post-TB neurological sequelae (RR = 0.62, 95% CI: 0.31, 1.24). Interpretation: Rehabilitation programs prevented post-TB lung, neurologic and mental health sequelae, while adjuvant therapies and other interventions require further investigation. Funding: Healy Medical Research Raine Foundation, Curtin School of Population Health and the Australian National Health and Medical Research Council.

Protocol for spatial prediction of soil transmitted helminth prevalence in the Western Pacific region using a meta-analytical approach.

BACKGROUND: Soil transmitted helminth (STH) infections are estimated to impact 24% of the world's population and are responsible for chronic and debilitating morbidity. Disadvantaged communities are among the worst affected and are further marginalized as infection prevalence fuels the poverty cycle. Ambitious targets have been set to eliminate STH infections, but accurate epidemiological data will be required to inform appropriate interventions. This paper details the protocol for an analysis that aims to produce spatial prediction mapping of STH prevalence in the Western Pacific Region (WPR). METHODS: The protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) guidelines. The study design will combine the principles of systematic review, meta-analysis, and geospatial analysis. Systematic searches will be undertaken in PubMed, Scopus, ProQuest, Embase, and Web of Science for studies undertaken post 2000, to identify surveys that enable the prevalence of human STH infection within the WPR to be calculated. Covariate data for multivariable analysis will be obtained from publicly accessible sources. Survey data will be geolocated, and STH prevalence and covariates will be linked to produce a spatially referenced dataset for analysis. Bayesian model-based geostatistics will be used to generate spatially continuous estimates of STH prevalence mapped to a resolution of 1 km2. A separate geospatial model will be constructed for each STH species. Predictions of prevalence will be made for unsampled locations and maps will be overlaid for each STH species to obtain co-endemicity maps. DISCUSSION: This protocol facilitates study replication and may be applied to other infectious diseases or alternate geographies. Results of the subsequent analysis will identify geographies with high STH prevalence's and can be used to inform resource allocation in combating this neglected tropical disease. TRIAL REGISTRATION: Open Science Framework: osf.io/qmxcj.

Comparative effectiveness of interventions for preventing tuberculosis: systematic review and network meta-analysis of interventional studies.

Background: Tuberculosis (TB) is the leading infectious cause of death globally. Several preventive measures are employed to prevent TB, yet there is a paucity of evidence on the effectiveness of these interventions. Therefore, this study aimed to identify the most effective interventions for reducing TB incidence. Methods: A systematic search was undertaken across five relevant databases including PubMed, SCOPUS, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to February 22, 2023. Bayesian network meta-analysis (NMA) was conducted to compare the effectiveness of preventive interventions including preventive therapy, nutritional intervention, targeted screening, and vaccination in reducing TB incidence. Subgroup analysis was conducted to investigate the effectiveness of TB preventive treatments. Findings: Overall 82 articles were included in the NMA. Preventive therapy (OR = 0.44, 95% CrI 0.36-0.52), BCG vaccination (OR = 0.62, 95% CrI 0.39-0.98) and TB candidate vaccines (OR = 0.67, 95% CrI 0.46-0.98) were more effective than placebo or no intervention. When all active interventions were considered, preventive therapy ranked as the best intervention. Of the preventive treatments, isoniazid (OR = 0.46, 95% CrI 0.35-0.55), isoniazid plus rifampicin (OR = 0.56, 95% CrI 0.32-0.97), isoniazid plus rifapentine (OR = 0.49, 95% CrI 0.29-0.83), isoniazid plus ethambutol (OR = 0.39, 95% CrI 0.15-0.99), isoniazid plus streptomycin (OR = 0.12, 95% CrI 0.02-0.55), rifampicin (OR = 0.41, 95% CrI 0.18-0.92), and rifampicin plus pyrazinamide (OR = 0.51, 95% CrI 0.29-0.87) surpassed placebo/none. Interpretation: Our study suggested that when all available preventive interventions are considered, preventive therapy is likely the most effective intervention. Within TB preventive treatments, isoniazid plus streptomycin is likely ranked at the top. This comparative study provides important information for policymakers and stakeholders, enabling them to make informed decisions on preventive strategies, whilst considering local resources and capacity constraints. Funding: Curtin University strategic scholarship and Australian National Health and Medical Research Council, through an Emerging Leadership Investigator grant.

The prevalence of tuberculosis and malaria in minority indigenous populations of South- East Asia and the Western Pacific Region: a systematic review and meta-analysis.

Infectious diseases have been shown to disproportionately affect indigenous populations. Tuberculosis (TB) and malaria continue to impose a significant burden on humanity and are among the infectious diseases targeted within the 2030 Agenda for Sustainable Development. A systematic review and meta-analyses were undertaken to evaluate the prevalence of TB and malaria infections within minority indigenous populations of the South-East Asia and Western Pacific Regions. The review was undertaken in accordance with The Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines following a published protocol. A random effects meta-analysis was used to calculate the pooled prevalence of TB and malaria. A meta-regression analysis was applied to quantify associations with study covariates and a sub-group analysis undertaken where studies provided comparative data between minority indigenous and other population groups. From the 3,275 unique publications identified, 24 on TB, and 39 on malaria were included in the final analysis. The pooled prevalence of TB was 2.3% (95% CI: 1.7, 2.9) and the pooled prevalence of malaria was 19.9% (95% CI: 15.9, 24.2). There was significant (p = 0.000) heterogeneity (I2) between studies. Significant difference was not observed in TB and malaria prevalence between minority indigenous and other population groups, although the odds ratio of malaria infection in minority indigenous populations was 1.15 (95% CI 0.99, 1.34: p-value 0.06) compared to other population groups. The review identified a paucity of data on TB and malaria in minority indigenous populations despite the significant prevalence and burden of these diseases within these regions.

The prevalence of soil transmitted helminth infections in minority indigenous populations of South-East Asia and the Western Pacific Region: A systematic review and meta-analysis.

INTRODUCTION: Soil transmitted helminth (STH) infections cause one of the most prevalent diseases in man. STHs disproportionately impact socio-economically disadvantaged communities including minority indigenous populations. This systematic review aimed to quantify the prevalence of STH infection within minority indigenous populations of the South-East Asia and Western Pacific Regions. METHODS: The systematic review was conducted in accordance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines following a published protocol. A random effects meta-analysis was used to estimate the pooled prevalence of STH infection, and meta-regression analysis was used to quantify associations with study characteristics. Where comparative data were available, sub-group analysis was conducted to evaluate the risk of STH infection in minority indigenous people relative to other population groups. The heterogeneity between studies was evaluated visually using Forest plots and was assessed quantitatively by the index of heterogeneity (I2) and Cochran Q-statistics. RESULTS: From 1,366 unique studies that were identified, 81 were included in the final analysis. The pooled prevalence of infection within minority indigenous populations was 61.4% (95% CI 50.8, 71.4) for overall STH infection; 32.3% (95% CI 25.7, 39.3) for Ascaris.lumbricoides; 43.6% (95% CI 32.6, 54.8) for Trichuris.trichiura; 19.9% (95% CI 15.7, 24.5) for hookworm and 6.3% (95% CI 3.2, 10.2) for Strongyloides.stercoralis. A significant increase in T. trichiura prevalence was observed over time. The stratified analysis showed that the prevalence of infection for STH overall and for each STH species were not significantly different in minority indigenous participants compared to other populations groups. CONCLUSION: The prevalence of STH infection is high within minority indigenous populations across countries at very different levels of socio-economic development. The increasing prevalence of T. trichiura calls for the implementation of more effective therapies and control strategies.

The prevalence of tuberculosis, malaria and soil-transmitted helminth infection in minority indigenous people of Southeast Asia and the Western Pacific: protocol for a systematic review and meta-analysis.

BACKGROUND: Infectious diseases such as tuberculosis (TB), malaria and soil-transmitted helminthiasis continue to impose a significant global health burden and socio-economic impact. Globally, minority indigenous people are disproportionately affected by poverty and are shown to experience a disparate burden of disease and poorer health outcomes than the comparative majority population. Despite these inequalities, countries rarely systematically compile epidemiological data disaggregated by ethnicity to enable the extent of the differential to be quantified. METHODS: The systematic review will be reported in accordance with The Preferred Reporting Items for Systematic Review and Meta- Analyses (PRISMA) guidelines. Systematic searches will be conducted in EMBASE, Medline, Scopus and Web of Science for studies reporting data which enable the prevalence of TB, malaria, and/or soil-transmitted helminth (STH) infections amongst minority indigenous populations within the Southeast Asia Region (SEAR) and Western Pacific Region (WPR) to be calculated. Where studies provide data on disease prevalence for both minority indigenous and other populations within the same study, a comparative analysis will be undertaken. In addition to a narrative synthesis, where sufficient data are available, a random-effects meta-analysis will be conducted to obtain a pooled estimate value for each disease/infection by country and mortality stratum. Heterogeneity between studies will be examined using the Cochran's Q test and quantitatively measured by the index of heterogeneity squared (I2) statistics. The methodological quality of the included studies will be assessed using a modified Newcastle-Ottawa Scale. DISCUSSION: This systematic review aims to analyse the available data on the prevalence of TB, malaria and STH infections within minority indigenous populations of the SEAR and WPR. REGISTRATION: Open Science Framework registration: osf.io/m6sqc.