EPIDEMIOLOGY OF TUBERCULOSIS IN INTERNATIONALLY DISPLACED CHILDREN RESETTLING IN HARRIS COUNTY

Background More than 300,000 refugees arrived in the United States (U.S.) from 2010-2015, and Texas accepts the 2nd highest number of refugees. Texas also accepts large numbers of asylees, parolees, and special immigrant visa holders. Additionally, a large proportion of trafficked persons in the U.S. live in or pass through Texas. Foreign-born children are disproportionately affected by tuberculosis (TB) and account for two-thirds of U.S. childhood TB cases. Children are at greater risk for progression from TB infection to disease and experience greater morbidity and mortality from TB disease. This makes screening for and treatment of TB infection in children from high-prevalence areas an important public health intervention. Since 2007, children 2-14 years old emigrating from high-prevalence countries (TB incidence \u3e20 cases /100,000 persons) have been tested for TB infection. Children ≥15 years old are additionally screened with a chest radiograph. The Centers for Disease Control and Prevention (CDC) recommends treatment of children with TB infection, as treatment reduces the risk of life threatening disease and prevents future transmission. There are few studies describing the epidemiology of TB in internationally displaced children relocating to the U.S.; there have been no studies centered on Texas. We describe the secular trends and comparative epidemiology of positive TSTs and IGRAs in children of different immigration statuses cared for through the Houston-area public health program. Methods This was a retrospective cross-sectional study of children \u3c18 years-old evaluated by the Harris County Public Health Refugee Health Screening Program between January 1st, 2010 and December 31st, 2015 with the following immigration statuses: refugee, asylee, parolee, special immigrant visa holder, or victim of human trafficking. We analyzed factors associated with TB test positivity, infection and disease for children with these immigration statuses. Data are from the U.S. Committee for Refugees and Immigrants (USCRI), the Harris County Public Health Refugee Health Screening Program, and the Texas Children\u27s Hospital TB clinic. Chi-square test or Fisher’s exact test were used for dichotomous variables, one-way ANOVAs for univariate analyses, and Wilcoxon rank sum or Kruskal-Wallis for continuous variables. Multivariate logistic regression was performed to further analyze factors associated with TB test positivity. To assess secular trends in usage and positivity, monthly totals were analyzed using linear regression and the Wilcoxon Sign Rank test. A p-value \u3c0.05 was considered significant. Children \u3c 5 years were typically tested using tuberculin skin test (TSTs) and older children typically using interferon-gamma release assays (IGRAs). The primary outcome was a positive test of TB infection (TST and/or IGRA). Children who were TST+/IGRA- with no known contacts, a normal chest radiograph and no signs or symptoms consistent with TB disease were typically considered uninfected. However, there were some children who met these criteria who were considered to have TB infection and were treated as such –this typically occurred earlier in the study period, and was most commonly due to young age (\u3c 2 years old) or some variability in provider practice. Results The program evaluated 5,990 children, of whom 5870 (98%) were tested, predominantly (64%) with an IGRA alone. During the study period, IGRA use increased (p\u3c0.001), though percentages of positive test results (IGRA or TST) did not decline significantly (p=0.10). Overall, 364 (6.2%) children had at least one positive test of infection: 143/1,842 (7.8%) tested with TST alone, 129/3,730 (63.6%) tested with IGRA alone, and 92/298 (30.9%) had at least one positive test result for those tested with both TST and IGRA. Among the 364 children with any positive test of infection, 4 (1.1%) were diagnosed with TB disease, 325 (89.3%) were diagnosed with TB infection, and 35 (9.6%) were considered uninfected. Three factors were significantly associated with a positive TST or IGRA result: region of origin, younger age group, and HIV infection. All children were more likely to have a positive TST compared to IGRA (OR 2.92, 95% CI: 2.37-3.59). Discordant test results were common (20%) and most often were TST+/IGRA- (95.0%). 35/57 (61.4%) of children who were TST+/IGRA- were considered uninfected and did not receive therapy for TB infection; none developed TB disease. The 22/57 (38.6%) TST+/IGRA- children who were treated for TB infection, were treated as such typically due to young age (\u3c 2 years old) or variability in provider practice. Conclusions Positive TST results were twice as common as positive IGRA results and discordant TST/IGRA results were common. Positive TST results in BCG-immunized children frequently represent cross-reactivity and false positivity. Use of IGRAs as opposed to TSTs in BCG-immunized children would reduce false positive tests and allow for TB infection therapy to be targeted to those who would most benefit. These findings support 2018 changes in U.S. immigration guidelines that mandate IGRA use for recently immigrated children above 2 years of age

The age-specific burden and household and school-based predictors of child and adolescent tuberculosis infection in rural Uganda.

BackgroundThe age-specific epidemiology of child and adolescent tuberculosis (TB) is poorly understood, especially in rural areas of East Africa. We sought to characterize the age-specific prevalence and predictors of TB infection among children and adolescents living in rural Uganda, and to explore the contribution of household TB exposure on TB infection.MethodsFrom 2015-2016 we placed and read 3,121 tuberculin skin tests (TST) in children (5-11 years old) and adolescents (12-19 years old) participating in a nested household survey in 9 rural Eastern Ugandan communities. TB infection was defined as a positive TST (induration ≥10mm or ≥5mm if living with HIV). Age-specific prevalence was estimated using inverse probability weighting to adjust for incomplete measurement. Generalized estimating equations were used to assess the association between TB infection and multi-level predictors.ResultsThe adjusted prevalence of TB infection was 8.5% (95%CI: 6.9-10.4) in children and 16.7% (95% CI:14.0-19.7) in adolescents. Nine percent of children and adolescents with a prevalent TB infection had a household TB contact. Among children, having a household TB contact was strongly associated with TB infection (aOR 5.5, 95% CI: 1.7-16.9), but the strength of this association declined among adolescents and did not meet significance (aOR 2.3, 95% CI: 0.8-7.0). The population attributable faction of TB infection due to a household TB contact was 8% for children and 4% among adolescents. Mobile children and adolescents who travel outside of their community for school had a 1.7 (95% CI 1.0-2.9) fold higher odds of TB infection than those who attended school in the community.ConclusionChildren and adolescents in this area of rural eastern Uganda suffer a significant burden of TB. The majority of TB infections are not explained by a known household TB contact. Our findings underscore the need for community-based TB prevention interventions, especially among mobile youth

Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa.

The WHO recommends integrating interventions to address the devastating TB/HIV co-epidemics in South Africa, yet integration has been poorly implemented and TB/HIV control efforts need strengthening. Identifying infected individuals is particularly difficult in rural settings. We used mathematical modeling to predict the impact of community-based, integrated TB/HIV case finding and additional control strategies on South Africa's TB/HIV epidemics. We developed a model incorporating TB and HIV transmission to evaluate the effectiveness of integrating TB and HIV interventions in rural South Africa over 10 years. We modeled the impact of a novel screening program that integrates case finding for TB and HIV in the community, comparing it to status quo and recommended TB/HIV control strategies, including GeneXpert, MDR-TB treatment decentralization, improved first-line TB treatment cure rate, isoniazid preventive therapy, and expanded ART. Combining recommended interventions averted 27% of expected TB cases (95% CI 18-40%) 18% HIV (95% CI 13-24%), 60% MDR-TB (95% CI 34-83%), 69% XDR-TB (95% CI 34-90%), and 16% TB/HIV deaths (95% CI 12-29). Supplementing these interventions with annual community-based TB/HIV case finding averted a further 17% of TB cases (44% total; 95% CI 31-56%), 5% HIV (23% total; 95% CI 17-29%), 8% MDR-TB (68% total; 95% CI 40-88%), 4% XDR-TB (73% total; 95% CI 38-91%), and 8% TB/HIV deaths (24% total; 95% CI 16-39%). In addition to increasing screening frequency, we found that improving TB symptom questionnaire sensitivity, second-line TB treatment delays, default before initiating TB treatment or ART, and second-line TB drug efficacy were significantly associated with even greater reductions in TB and HIV cases. TB/HIV epidemics in South Africa were most effectively curtailed by simultaneously implementing interventions that integrated community-based TB/HIV control strategies and targeted drug-resistant TB. Strengthening existing TB and HIV treatment programs is needed to further reduce disease incidence

Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy

Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis

Using Search Queries to Understand Health Information Needs in Africa

The lack of comprehensive, high-quality health data in developing nations creates a roadblock for combating the impacts of disease. One key challenge is understanding the health information needs of people in these nations. Without understanding people's everyday needs, concerns, and misconceptions, health organizations and policymakers lack the ability to effectively target education and programming efforts. In this paper, we propose a bottom-up approach that uses search data from individuals to uncover and gain insight into health information needs in Africa. We analyze Bing searches related to HIV/AIDS, malaria, and tuberculosis from all 54 African nations. For each disease, we automatically derive a set of common search themes or topics, revealing a wide-spread interest in various types of information, including disease symptoms, drugs, concerns about breastfeeding, as well as stigma, beliefs in natural cures, and other topics that may be hard to uncover through traditional surveys. We expose the different patterns that emerge in health information needs by demographic groups (age and sex) and country. We also uncover discrepancies in the quality of content returned by search engines to users by topic. Combined, our results suggest that search data can help illuminate health information needs in Africa and inform discussions on health policy and targeted education efforts both on- and offline.Comment: Extended version of an ICWSM 2019 pape

Drug-Resistant Tuberculosis--Current Dilemmas, Unanswered Questions, Challenges and Priority Needs

Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis–specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR tuberculosis are discussed

MODELLING THE HEALTH SECTOR POLICY REFORMS FOR NIGERIA:A PHASED PROJECT STUDY

Good health is a crucial part of well-being but spending on health can be justified on economic grounds. The goal of reducing poverty provides a different but equally powerful case for health investments. However, if policymakers are to accelerate the substantial health gains of recent decades, especially for the poor in African countries such as Nigeria, the agenda for reform is clear. Therefore, the thrust of this project is to formulate a model-based viable health policy reforms framework that will guarantee the attainment of the United Nations millennium development goals(as well as the capacity to live longer, healthier and more productive lives).Health, Aids, Malaria, SARS, MORTALITY, MATERNAL HEALTH, PUBLICHEALTH, DNA, CLINICAL SERVICES, POVERTY, MODELLING, DEVELOPMENT, NIGERIA, MDG, POLICY

How can mathematical models advance tuberculosis control in high HIV prevalence settings?

Existing approaches to tuberculosis (TB) control have been no more than partially successful in areas with high human immunodeficiency virus (HIV) prevalence. In the context of increasingly constrained resources, mathematical modelling can augment understanding and support policy for implementing those strategies that are most likely to bring public health and economic benefits. In this paper, we present an overview of past and recent contributions of TB modelling in this key area, and suggest a way forward through a modelling research agenda that supports a more effective response to the TB-HIV epidemic, based on expert discussions at a meeting convened by the TB Modelling and Analysis Consortium. The research agenda identified high-priority areas for future modelling efforts, including 1) the difficult diagnosis and high mortality of TB-HIV; 2) the high risk of disease progression; 3) TB health systems in high HIV prevalence settings; 4) uncertainty in the natural progression of TB-HIV; and 5) combined interventions for TB-HIV. Efficient and rapid progress towards completion of this modelling agenda will require co-ordination between the modelling community and key stakeholders, including advocates, health policy makers, donors and national or regional finance officials. A continuing dialogue will ensure that new results are effectively communicated and new policy-relevant questions are addressed swiftly