Transmission modeling to infer tuberculosis incidence prevalence and mortality in settings with generalized HIV epidemics.

Tuberculosis (TB) killed more people globally than any other single pathogen over the past decade. Where surveillance is weak, estimating TB burden estimates uses modeling. In many African countries, increases in HIV prevalence and antiretroviral therapy have driven dynamic TB epidemics, complicating estimation of burden, trends, and potential intervention impact. We therefore develop a novel age-structured TB transmission model incorporating evolving demographic, HIV and antiretroviral therapy effects, and calibrate to TB prevalence and notification data from 12 African countries. We use Bayesian methods to include uncertainty for all TB model parameters, and estimate age-specific annual risks of TB infection, finding up to 16.0%/year in adults, and the proportion of TB incidence from recent (re)infection, finding a mean across countries of 34%. Rapid reduction of the unacceptably high burden of TB in high HIV prevalence settings will require interventions addressing progression as well as transmission.

Xpert Ultra stool testing to diagnose tuberculosis in children in Ethiopia and Indonesia: a model-based cost-effectiveness analysis.

OBJECTIVES: The WHO currently recommends stool testing using GeneXpert MTB/Rif (Xpert) for the diagnosis of paediatric tuberculosis (TB). The simple one-step (SOS) stool method enables processing for Xpert testing at the primary healthcare (PHC) level. We modelled the impact and cost-effectiveness of implementing the SOS stool method at PHC for the diagnosis of paediatric TB in Ethiopia and Indonesia, compared with the standard of care. SETTING: All children (age <15 years) presenting with presumptive TB at primary healthcare or hospital level in Ethiopia and Indonesia. PRIMARY OUTCOME: Cost-effectiveness estimated as incremental costs compared with incremental disability-adjusted life-years (DALYs) saved. METHODS: Decision tree modelling was used to represent pathways of patient care and referral. We based model parameters on ongoing studies and surveillance, systematic literature review, and expert opinion. We estimated costs using data available publicly and obtained through in-country expert consultations. Health outcomes were based on modelled mortality and discounted life-years lost. RESULTS: The intervention increased the sensitivity of TB diagnosis by 19-25% in both countries leading to a 14-20% relative reduction in mortality. Under the intervention, fewer children seeking care at PHC were referred (or self-referred) to higher levels of care; the number of children initiating anti-TB treatment (ATT) increased by 18-25%; and more children (85%) initiated ATT at PHC level. Costs increased under the intervention compared with a base case using smear microscopy in the standard of care resulting in incremental cost-effectiveness ratios of US$132 and US$94 per DALY averted in Ethiopia and Indonesia, respectively. At a cost-effectiveness threshold of 0.5×gross domestic product per capita, the projected probability of the intervention being cost-effective in Ethiopia and Indonesia was 87% and 96%, respectively. The intervention remained cost-effective under sensitivity analyses. CONCLUSIONS: The addition of the SOS stool method to national algorithms for diagnosing TB in children is likely to be cost-effective in both Ethiopia and Indonesia.

TB Hackathon: Development and Comparison of Five Models to Predict Subnational Tuberculosis Prevalence in Pakistan.

Pakistan's national tuberculosis control programme (NTP) is among the many programmes worldwide that value the importance of subnational tuberculosis (TB) burden estimates to support disease control efforts, but do not have reliable estimates. A hackathon was thus organised to solicit the development and comparison of several models for small area estimation of TB. The TB hackathon was launched in April 2019. Participating teams were requested to produce district-level estimates of bacteriologically positive TB prevalence among adults (over 15 years of age) for 2018. The NTP provided case-based data from their 2010-2011 TB prevalence survey, along with data relating to TB screening, testing and treatment for the period between 2010-2011 and 2018. Five teams submitted district-level TB prevalence estimates, methodological details and programming code. Although the geographical distribution of TB prevalence varied considerably across models, we identified several districts with consistently low notification-to-prevalence ratios. The hackathon highlighted the challenges of generating granular spatiotemporal TB prevalence forecasts based on a cross-sectional prevalence survey data and other data sources. Nevertheless, it provided a range of approaches to subnational disease modelling. The NTP's use and plans for these outputs shows that, limitations notwithstanding, they can be valuable for programme planning.

Seroprevalence of SARS-CoV-2 antibody among individuals aged above 15 years and residing in congregate settings in Dire Dawa city administration, Ethiopia.

BACKGROUND: Determining the extent of seropositivity of SARS-CoV-2 antibody has the potential to guide prevention and control efforts. We aimed to determine the seroprevalence of SARS-CoV-2 antibody among individuals aged above15 years and residing in the congregate settings of Dire Dawa city administration, Ethiopia. METHOD: We analyzed COVID-19 seroprevalence data on 684 individuals from a community based cross-sectional survey conducted among individuals aged above 15 years and residing in congregate settings in Dire Dawa from June 15 to July 30, 2020. Data were collected using interview and blood sample collection. Participants were asked about demographic characteristics, COVID-19 symptoms, and their practice of preventive measures. Seroprevalence was determined using SARS-CoV-2 IgG test. Bivariate and multivariate multilevel mixed effects logistic regression model was fitted and statistical significance was set at p value < 0.05. RESULT: The estimated SARS-CoV-2 seroprevalence was 3.2% (95 % CI 2.0-4.8) in the study region with no differences by age and sex but considerable differences were observed by self-reported practice of COVID-19 preventive measures. The cluster effect is not significant (P = 0.396) which has suggested no evidence of heterogeneity in SARS-CoV-2 seroprevalence among the clusters. The odds of SARS-CoV-2 antibody seroprevalence were higher for individuals who were employed and work by moving from home to work area (AOR; 9.73 95% CI 2.51, 37.68), reported of not wearing facemasks when leaving home (AOR; 6.4 95% CI 2.30, 17.66) and did not practice physical distancing measures (AOR; 10 95% CI 3.01, 33.20) compared to their counterparts, respectively. Our estimated seroprevalence of SARS-CoV-2 among participants who reported not to have practiced social distancing measures was 12.8 (95% CI, 7.0, 19) and 1.5 (95% CI, 0.5, 2.5) among those who reported of practicing them. More than 80% of study participants reported of implementing infection prevention measures (face masks and physical distancing recommendations). CONCLUSION: The detected SARS-CoV-2 seroprevalence among the study participants was low at the time of the survey indicating higher proportion of population yet to be infected. COVID-19 preventive measures were associated with reduced seroprevalence and should be promoted to avoid transmission to the uninfected majority.

Geospatial clustering and modelling provide policy guidance to distribute funding for active TB case finding in Ethiopia.

Tuberculosis (TB) exhibits considerable spatial heterogeneity, occurring in clusters that may act as hubs of community transmission. We evaluated the impact of an intervention targeting spatial TB hotspots in a rural region of Ethiopia. To evaluate the impact of targeted active case finding (ACF), we used a spatially structured mathematical model that has previously been described. From model equilibrium, we simulated the impact of a hotspot-targeted strategy (HTS) on TB incidence ten years from intervention commencement and the associated cost-effectiveness. HTS was also compared with an untargeted strategy (UTS). We used logistic cost-coverage analysis to estimate cost-effectiveness of interventions. At a community screening coverage level of 95 % in a hotspot region, which corresponds to screening 20 % of the total population, HTS would reduce overall TB incidence by 52 % compared with baseline. For UTS to achieve an equivalent effect, it would be necessary to screen more than 80 % of the total population. Compared to the existing passive case detection strategy, the HTS at a CDR of 75 percent in hotspot regions is expected to avert 1,023 new TB cases over ten years saving USD 170 per averted case. Similarly, at the same CDR, the UTS will detect 1316 cases over the same period saving USD 3 per averted TB case. The incremental-cost effectiveness-ratio (ICER) of UTS compared with HTS is USD 582 per averted case corresponding to 293 more TB cases averted at an additional cost of USD 170,700. Where regional TB program spending was capped at current levels, maximum gains in incidence reduction were seen when the regional budget was shared between hotspots and non-hotspot regions in the ratio of 40% : 60%. Our analysis suggests that a spatially targeted strategy is efficient and cost-saving, with the potential for significant reduction in overall TB burden.

Assortative social mixing and sex disparities in tuberculosis burden.

Globally, men have higher tuberculosis (TB) burden but the mechanisms underlying this sex disparity are not fully understood. Recent surveys of social mixing patterns have established moderate preferential within-sex mixing in many settings. This assortative mixing could amplify differences from other causes. We explored the impact of assortative mixing and factors differentially affecting disease progression and detection using a sex-stratified deterministic TB transmission model. We explored the influence of assortativity at disease-free and endemic equilibria, finding stronger effects during invasion and on increasing male:female prevalence (M:F) ratios than overall prevalence. Variance-based sensitivity analysis of endemic equilibria identified differential progression as the most important driver of M:F ratio uncertainty. We fitted our model to prevalence and notification data in exemplar settings within a fully Bayesian framework. For our high M:F setting, random mixing reduced equilibrium M:F ratios by 12% (95% CrI 0-30%). Equalizing male case detection there led to a 20% (95% CrI 11-31%) reduction in M:F ratio over 10 years-insufficient to eliminate sex disparities. However, this potentially achievable improvement was associated with a meaningful 8% (95% CrI 4-14%) reduction in total TB prevalence over this time frame.

Barriers to Maternal and Child Health Care Service Uptake in Assosa Zone, Benishangul Gumuz Region, Ethiopia: A Qualitative Study.

BACKGROUND: Ethiopia has reduced maternal mortality from 871 to 412 per 100,000 live births between 2000 and 2016. In 2019, under-5 mortality rates in Ethiopia were 55 deaths per 1,000 live births. Benishangul Gumuz was the second-largest region in the under-5 mortality rate (98/1,000 live births) in the country. Maternal and child health care service uptake is an important indicator of health outcomes. This study is aimed at exploring major barriers to maternal and child health care uptake in Assosa Zone. METHODS: This study was conducted in the Bambasi, Menge, and Sherkole districts of the Assosa Zone from July 17 to August 31/2019. The study explored the life experience of study participants about MCH services. The sampling technique was purposive, and data collection methods were focus group discussions, key informant interviews, and in-depth interviews. Data were analyzed thematically. RESULT: The main barriers to child health care services were financial problems, lack of knowledge, preference of traditional medicines for a sick child, women having no time to care for their sick child, poor roads. poor health facility readiness, the poor economy of families, lack of ambulance, cultural and traditional beliefs, providers being male, and unprofessional behaviors which were the major barriers hindering the uptake of maternal health service utilization. CONCLUSION: Poor health facility readiness, indirect costs, inaccessibility to health facilities, and cultural and traditional practices were among the major barriers to service uptake identified by this research in the study area.

Methods used in the spatial analysis of tuberculosis epidemiology: a systematic review.

BACKGROUND: Tuberculosis (TB) transmission often occurs within a household or community, leading to heterogeneous spatial patterns. However, apparent spatial clustering of TB could reflect ongoing transmission or co-location of risk factors and can vary considerably depending on the type of data available, the analysis methods employed and the dynamics of the underlying population. Thus, we aimed to review methodological approaches used in the spatial analysis of TB burden. METHODS: We conducted a systematic literature search of spatial studies of TB published in English using Medline, Embase, PsycInfo, Scopus and Web of Science databases with no date restriction from inception to 15 February 2017. The protocol for this systematic review was prospectively registered with PROSPERO ( CRD42016036655 ). RESULTS: We identified 168 eligible studies with spatial methods used to describe the spatial distribution (n = 154), spatial clusters (n = 73), predictors of spatial patterns (n = 64), the role of congregate settings (n = 3) and the household (n = 2) on TB transmission. Molecular techniques combined with geospatial methods were used by 25 studies to compare the role of transmission to reactivation as a driver of TB spatial distribution, finding that geospatial hotspots are not necessarily areas of recent transmission. Almost all studies used notification data for spatial analysis (161 of 168), although none accounted for undetected cases. The most common data visualisation technique was notification rate mapping, and the use of smoothing techniques was uncommon. Spatial clusters were identified using a range of methods, with the most commonly employed being Kulldorff's spatial scan statistic followed by local Moran's I and Getis and Ord's local Gi(d) tests. In the 11 papers that compared two such methods using a single dataset, the clustering patterns identified were often inconsistent. Classical regression models that did not account for spatial dependence were commonly used to predict spatial TB risk. In all included studies, TB showed a heterogeneous spatial pattern at each geographic resolution level examined. CONCLUSIONS: A range of spatial analysis methodologies has been employed in divergent contexts, with all studies demonstrating significant heterogeneity in spatial TB distribution. Future studies are needed to define the optimal method for each context and should account for unreported cases when using notification data where possible. Future studies combining genotypic and geospatial techniques with epidemiologically linked cases have the potential to provide further insights and improve TB control.

Mental health disorders, social stressors, and health-related quality of life in patients with multidrug-resistant tuberculosis: A systematic review and meta-analysis.

BACKGROUND: Mental health disorders, social stress, and poor health-related quality of life are commonly reported among people with tuberculosis (TB). We conducted a systematic review and meta-analysis to quantify mental health disorders, social stressors, and health-related quality of life in patients with multidrug-resistant tuberculosis (MDR-TB). METHODS: We searched PubMed, SCOPUS, ProQuest, Web of Science, and PsycINFO databases for studies that reported data on mental health disorders, social stressors, and health-related quality of life among MDR-TB patients. Hand-searching the reference lists of included studies was also performed. Studies were selected according to pre-defined selection criteria and data were extracted by two authors. Pooled prevalence and weighted mean difference estimates were performed using random-effects meta-analysis. Heterogeneity was explored using meta-regression, and subgroup analyses were performed. RESULTS: We included a total of 40 studies that were conducted in 20 countries. Depression, anxiety, and psychosis were the most common mental health disorders reported in the studies. The overall pooled prevalence was 25% (95% confidence interval (CI): 14, 39) for depression, 24% (95% CI: 2, 57) for anxiety, and 10% (95% CI: 7, 14) for psychosis. There was substantial heterogeneity in the estimates. The stratified analysis showed that the prevalence of psychosis was 4% (95% CI: 0, 22) before MDR-TB treatment commencement, and 9% (95% CI: 5, 13) after MDR-TB treatment commencement. The most common social stressors reported were stigma, discrimination, isolation, and a lack of social support. Health-related quality of life was significantly lower among MDR-TB patients when compared to drug-susceptible TB patients (Q = 9.88, p = 0.01, I2 = 80%). CONCLUSIONS: This review found that mental health and social functioning are compromised in a significant proportion of MDR-TB patients, a finding confirmed by the poor health-related quality of life reported. Thus, there is a substantial need for integrating mental health services, social protection and social support into the clinical and programmatic management of MDR-TB.

Sequelae of multidrug-resistant tuberculosis: protocol for a systematic review and meta-analysis.

INTRODUCTION: The sequelae of multidrug-resistant tuberculosis (MDR-TB) are poorly understood and inconsistently reported. We will aim to assess the existing evidence for the clinical, psychological, social and economic sequelae of MDR-TB and to assess the health-related quality of life in patients with MDR-TB. METHODS AND ANALYSIS: We will perform a systematic review and meta-analysis of published studies reporting sequelae of MDR-TB. We will search PubMed, SCOPUS, ProQuest, Web of Science and PsychINFO databases up to 5 September 2017. MDR-TB sequelae will include any clinical, psychological, social and economic effects as well as health-related quality of life that occur after MDR-TB treatment or illness. Two researchers will screen the titles and abstracts of all citations identified in our search, extract data, and assess the scientific quality using standardised formats. Providing there is appropriate comparability in the studies, we will use a random-effects meta-analysis model to produce pooled estimates of MDR-TB sequelae from the included studies. We will stratify the analyses based on treatment regimen, comorbidities (such as HIV status and diabetes mellitus), previous TB treatment history and study setting. ETHICS AND DISSEMINATION: As this study will be based on published data, ethical approval is not required. The final report will be disseminated through publication in a peer-reviewed scientific journal and will also be presented at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42017073182.