Effect of multicomponent interventions on tuberculosis notification in mining and pastoralist districts of Oromia region in Ethiopia: a longitudinal quasi-experimental study.

OBJECTIVE: To demonstrate the impact of interventions on tuberculosis (TB) case detection in mining and pastoralist districts in southeastern Ethiopia over a 10-year period. DESIGN: Longitudinal quasi-experimental study. SETTING: Health centres and hospitals in six mining districts implemented interventions and seven nearby districts functioned as controls. PARTICIPANTS: Data from the national District Health Information System (DHIS-2) were used for this study; therefore, people did not participate in this study. INTERVENTIONS: Directed at training, active case finding and improving treatment outcomes. PRIMARY AND SECONDARY OUTCOME MEASURES: Primarily, trends in TB case notification and percentage of bacteriologically confirmed TB-as collected by DHIS-2-between pre-intervention (2012-2015) and post-intervention (2016-2021) were analysed. Secondarily, post-intervention was split into early post-intervention (2016-2018) and late post-intervention (2019-2021) to also study the long-term effects of the intervention. RESULTS: For all forms of TB, case notification significantly increased between pre-intervention and early post-intervention (incidence rate ratio (IRR): 1.21, 95% CI: 1.13, 1.31; p<0.001) and significantly decreased between pre-intervention/early post-intervention and late post-intervention (IRR: 0.82, 95% CI: 0.76, 0.89; p<0.001 and IRR: 0.67, 95% CI: 0.62, 0.73; p<0.001). For bacteriologically confirmed cases, we found a significant decrease between pre-intervention/early post-intervention and late post-intervention (IRR: 0.88, 95% CI: 0.81, 0.97; p<0.001 and IRR: 0.81, 95% CI: 0.74, 0.89; p<0.001). The percentage of bacteriologically confirmed cases was significantly lower in the intervention districts during pre-intervention (B: -14.24 percentage points, 95% CI: -19.27, -9.21) and early post-intervention (B: -7.78, 95% CI: -15.46, -0.010; p=0.047). From early post-intervention to late post-intervention, we found a significant increase (B: 9.12, 95% CI: 0.92 to 17.33; p=0.032). CONCLUSIONS: The decrease in TB notifications in intervention districts during late post-intervention is possibly due to a decline in actual TB burden as a result of the interventions. The unabated increase in case notification in control districts may be due to continued TB transmission in the community.

The contribution of private health facilities to the urban tuberculosis program of Afghanistan.

SETTING: Although the prevalence of tuberculosis (TB) is generally higher in urban areas than in rural areas, coordination between the private and public sectors for TB control is weak. OBJECTIVE: To share experience from an urban DOTS program in five cities of Afghanistan. DESIGN: An urban DOTS project was designed in 2009 in Kabul, Afghanistan, and later expanded to Kandahar, Jalalabad, Herat, Mazari-i-Sharif, and Paul-i-Khomri cities. RESULTS: In total, 57 public health facilities and 49 private facilities provided DOTS services in the five cities from 2015 to 2018. A total of 28,542 (10.6%) adults (aged ≥15) screened were diagnosed with TB (all forms). The private sector contributed 5,618 (19.7%) of those. Positivity rates among presumptive TB cases in public facilities were 18.9%, 12.5%, 14.4%, and 4.8% in 2015, 2016, 2017, and 2018, respectively. In private facilities, positivity rates were 25.8%, 39.5%, and 27.4% in 2016, 2017, and 2018, respectively. CONCLUSION: The private sector's contribution to case detection was very high and the TB positivity rate among people screened in the private sector was high, which could be due to more selective screening rather than all health facility visitors done by public health facilities.

Coronavirus Disease 2019 Diagnosis in Low- and Middle-Income Countries: The Big New Bully Disrupting TB and HIV Diagnostic Services.

Coronavirus disease 2019 (COVID-19) undermines control of other infectious diseases. Diagnostics are critical in health care. This opinion paper explores approaches for leveraging diagnostics for COVID-19 while retaining diagnostics for other infectious diseases, including tuberculosis (TB) and HIV. The authors reflect on experiences with GeneXpert technology for TB detection and opportunities for integration with other diseases. They also reflect on benefits and risks of integration. Placement of diagnostics in laboratory networks is largely nonintegrated and designated for specific diseases. Restricting the use of diagnostics leaves gaps in detection of TB, HIV, malaria, and COVID-19. Integrated laboratory systems can lead to more efficient testing while increasing access to critical diagnostics. However, the authors have observed that HIV diagnosis within the TB diagnostic network displaced TB diagnosis. Subsequently, COVID-19 disrupted both TB and HIV diagnosis. The World Health Organization recommended rapid molecular diagnostic networks for infectious diseases and there is a need for more investment to achieve diagnostic capacity for TB, HIV, COVID-19, and other emerging infectious diseases. Integrated laboratory systems require mapping laboratory networks, assessing needs for each infectious disease, and identifying resources. Otherwise, diagnostic capacity for one infectious disease may displace another. Further, not all aspects of optimal diagnostic networks fit all infectious diseases, but many efficiencies can be gained where integration is possible.

Quantifying geographic heterogeneity in TB incidence and the potential impact of geographically targeted interventions in South and North City Corporations of Dhaka, Bangladesh: a model-based study.

In rapidly growing and high-burden urban centres, identifying tuberculosis (TB) transmission hotspots and understanding the potential impact of interventions can inform future control and prevention strategies. Using data on local demography, TB reports and patient reporting patterns in Dhaka South City Corporation (DSCC) and Dhaka North City Corporation (DNCC), Bangladesh, between 2010 and 2017, we developed maps of TB reporting rates across wards in DSCC and DNCC and identified wards with high rates of reported TB (i.e. 'hotspots') in DSCC and DNCC. We developed ward-level transmission models and estimated the potential epidemiological impact of three TB interventions: active case finding (ACF), mass preventive therapy (PT) and a combination of ACF and PT, implemented either citywide or targeted to high-incidence hotspots. There was substantial geographic heterogeneity in the estimated TB incidence in both DSCC and DNCC: incidence in the highest-incidence wards was over ten times higher than in the lowest-incidence wards in each city corporation. ACF, PT and combined ACF plus PT delivered to 10% of the population reduced TB incidence by a projected 7%-9%, 13%-15% and 19%-23% over five years, respectively. Targeting TB hotspots increased the projected reduction in TB incidence achieved by each intervention 1.4- to 1.8-fold. The geographical pattern of TB notifications suggests high levels of ongoing TB transmission in DSCC and DNCC, with substantial heterogeneity at the ward level. Interventions that reduce transmission are likely to be highly effective and incorporating notification data at the local level can further improve intervention efficiency.

Active household contact screening for tuberculosis and provision of isoniazid preventive therapy to under-five children in Afghanistan.

OBJECTIVES: This observational study analyzed the performance of the National TB Control Program (NTP) in Afghanistan in household contact screening from 2011 to 2018 and its use as an entry point for isoniazid preventive therapy (IPT), as well as the IPT completion rates for children under age five. METHODS: From 2011 to 2018, the Afghanistan NTP released guidelines for passive and active contact screening of bacteriologically confirmed TB cases. Health workers were trained in contact screening. Presumptive TB cases gave sputum for AFB smear microscopy; other diagnostics were used if patients could not produce sputum. Children under five (excluding those with active TB) were treated for latent TB infection. We calculated the yield and the number needed to screen and number needed to test to find a case of TB, as well as the rates of IPT initiation and completion. RESULTS: From 2011 to 2018, 142,797 bacteriologically confirmed TB cases were diagnosed in Afghanistan. The number of household members eligible for screening was estimated to be 856,782, of whom 586,292 (81%) were screened for TB and 117,643 (20.1%) were found to be presumptive TB cases. Among the cases screened, 10,896 TB cases (all forms) were diagnosed (1.85%, 95% CI 1.82-1.89), 54.4% in females. The number needed to screen to diagnose a single case of TB (all forms) was 53.8; the number needed to test was 10.7. Out of all children under five, 101,084 (85.9%) were initiated on IPT, and 69,273 (68.5%) completed treatment. CONCLUSIONS: Program performance in contact screening in Afghanistan is high, at 81%, and the yield of TB is also high-close to 10 times higher than the national TB incidence rate. IPT initiation and completion rates are also high as compared to those of many other countries but need further improvement, especially for completion.

Factors Determining Treatment Success in Children with Drug-Sensitive Tuberculosis in Ethiopia: A Three-Year Retrospective Analysis.

This study in the Amhara and Oromia regions of Ethiopia assessed the outcomes of tuberculosis (TB) treatment among children younger than 15 years. Retrospective data were collected on treatment outcomes and their determinants for children with TB for the cohorts of 2012-2014 enrolled in 40 hospitals and 137 health centers. Chi-square tests, t-tests, and logistic regression were used for the analysis. Of 2,557 children registered, 1,218 (47.6%) had clinically diagnosed pulmonary TB, 1,100 (43%) had extrapulmonary TB, and 277 (8.9%) had bacteriologically confirmed TB. Among all cases, 2,503 (97.9%) were newly diagnosed and 178 (7%) were HIV positive. Two-thirds of the children received directly observed treatment (DOT) in health centers and the remaining one-third, in hospitals. The treatment success rate (TSR) was 92.2%, and the death rate was 2.8%. The childhood TSR was high compared with those reported in focal studies in Ethiopia, but no national TSR report for children exists for comparison. Multivariate analysis showed that being older-5-9 years (adjusted odds ratio [AOR], 95% CI: 2.53, 1.30-4.94) and 10-14 years (AOR, 95% CI: 2.71, 1.40-5.26)-enrolled in DOT in a health center (AOR, 95% CI: 2.51, 1.82-3.48), and HIV negative (AOR, 95% CI: 1.77, 1.07-2.93) were predictors of treatment success, whereas underdosing during the intensive phase of treatment (AOR, 95% CI: 0.54, 0.36-0.82) was negatively correlated with treatment success. We recommend more research to determine if intensive monitoring of children with TB, dosage adjustment of anti-TB drugs based on weight changes, and training of health workers on dosage adjustment might improve treatment outcomes.

High urban tuberculosis case notification rates can be misleading: evidence from an urban setting in Ethiopia.

BACKGROUND: Tuberculosis (TB) is a major public health problem. Its magnitude the required interventions are affected by changes in socioeconomic condition and urbanization. Ethiopia is among the thirty high burden countries with increasing effort to end TB. We aimed to describe the case notification rate (CNR) for urban tuberculosis (TB) and estimate the percentage of TB patients who are not from the catchment population. METHODS: This cross-sectional study used data from TB registers from 2014/15 to 2017/18. We calculated the CNR and treatment success rate for the study area. RESULTS: Of 2892 TB cases registered, 2432 (84%) were from Adama City, while 460 (16%) were from other sites. The total TB CNR (including TB cases from Adama and other sites) was between 153 and 218 per 100,000 population. However, the adjusted TB CNR (excluding cases outside Adama City) was lower, between 135 and 179 per 100,000. Of 1737 TB cases registered, 1652 (95%) were successfully treated. About 16% of TB cases notified contributing to CNR of 32 per 100,000 population is contributed by TB cases coming from outside of Adama city. The CNR of 32 per 100,000 population (ranging from 18 to 46 per 100,000) for Adama City was from the patients that came from the surrounding rural areas who sought care in the town. CONCLUSION: Although the TB CNR in Adama City was higher than the national CNR, about one-fifth of TB cases came from other sites-which led to overestimating the urban CNR and underestimating the CNR of neighboring areas. TB programs should disaggregate urban TB case notification data by place of residence to accurately identify the proportion of missed cases.

Improvement in tuberculosis infection control practice via technical support in two regions of Ethiopia.

BACKGROUND: Globally recommended measures for comprehensive tuberculosis (TB) infection control (IC) are inadequately practiced in most health care facilities in Ethiopia. The aim of this study was to assess the extent of implementation of TB IC measures before and after introducing a comprehensive technical support package in two regions of Ethiopia. METHODS: We used a quasi-experimental design, whereby a baseline assessment of TB IC practices in 719 health care facilities was conducted between August and October 2013. Based on the assessment findings, we supported implementation of a comprehensive package of interventions. Monitoring was done on a quarterly basis, and one-year follow-up data were collected on September 30, 2014. We used the Student's t-test and chi-squared tests, respectively, to examine differences before and after the interventions and to test for inter-regional and inter-facility associations. RESULTS: At baseline, most of the health facilities (69%) were reported to have separate TB clinics. In 55.2% of the facilities, it was also reported that window opening was practiced. Nevertheless, triaging was practiced in only 19.3% of the facilities. Availability of an IC committee and IC plan was observed in 29.11 and 4.65% of facilities, respectively. Health care workers were nearly three times as likely to develop active TB as the general population. After 12 months of implementation, availability of a separate TB room, TB IC committee, triage, and TB IC plan had increased, respectively, by 18, 32, 44, and 51% (p < 0.001). CONCLUSIONS: After 1 year of intervention, the TB IC practices of the health facilities have significantly improved. However, availability of separate TB rooms and existence of TB IC committees remain suboptimal. The burden of TB among health care workers is higher than in the general population. TB IC measures must be strengthened to reduce TB transmission among health workers.

Comparison of the yield of tuberculosis among contacts of multidrug-resistant and drug-sensitive tuberculosis patients in Ethiopia using GeneXpert as a primary diagnostic test.

OBJECTIVES: This study compared the yield of tuberculosis (TB) among contacts of multidrug-resistant tuberculosis (MDR-TB) index cases with that in drug-sensitive TB (DS-TB) index cases in a program setting. METHODS: A comparative cross-sectional study was conducted among contacts of sputum smear-positive new DS-TB index cases and MDR-TB index cases. After contacts were screened, GeneXpert was used for the diagnosis of TB. RESULTS: The study included 111 MDR-TB and 119 DS-TB index cases. A total of 340 and 393 contacts of MDR-TB and DS-TB index cases, respectively, were traced, of whom 331 among MDR-TB contacts and 353 among DS-TB contacts were screened. There were 20 (6%) presumptive TB cases for MDR-TB contacts and 41 (11%) for DS-TB contacts. The prevalence of TB among MDR-TB contacts was 2.7% and among DS-TB contacts was 4.0%. The majority of the MDR-TB contacts diagnosed with TB had MDR-TB; the reverse was true for DS-TB. CONCLUSIONS: The yield of TB among contacts of MDR-TB and DS-TB patients using GeneXpert was high as compared to the population-level prevalence. The likelihood of diagnosing rifampicin-resistant TB among contacts of MDR-TB index cases was higher in comparison with contacts of DS-TB index cases. The use of GeneXpert in DS-TB contact investigation has the added advantage of diagnosing rifampicin-resistant TB cases when compared to the use of the nationally recommended acid-fast bacillus (AFB) microscopy for DS-TB contact investigation.

Vitamin D deficiency among smear positive pulmonary tuberculosis patients and their tuberculosis negative household contacts in Northwest Ethiopia: a case-control study.

BACKGROUND: Vitamin D is a fat-soluble vitamin that increases the immunity against tuberculosis (TB), decreases the re-activation of latent TB and reduces the severity of active TB disease. Epidemiological studies on the prevalence of vitamin D deficiency, and its association with TB showed inconsistent results in different countries. This study was aimed to determine the prevalence of vitamin D deficiency and its association with TB in Northwest Ethiopia. METHODS: A case-control study was conducted among smear positive pulmonary tuberculosis patients and their household contacts without symptoms suggestive of TB. Study participants were recruited at 11 TB diagnostic health facilities in North and South Gondar zones of Amhara region between May 2013 and April 2015. The spot-morning-spot sputum samples and 5 ml blood sample were collected prior to commencing TB treatment for the diagnosis of TB and serum vitamin D assay, respectively. The diagnosis of TB was performed using smear microscopy and GeneXpert. Serum vitamin D level was analyzed using VIDAS 25 OH Vitamin D Total testing kits (Biomerieux, Marcy I'Etoile, France) on mini VIDAS automated immunoassay platform. Vitamin D status was interpreted as deficient (<20 ng/ml), insufficient (20-29 ng/ml), sufficient (30-100 ng/ml) and potential toxicity (>100 ng/ml). RESULTS: Of the total study participants, 134 (46.2%) were vitamin D deficient, and only 56 (19.3%) had sufficient vitamin D level. A total of 59 (61.5%) TB patients and 75 (38.7%) non TB controls were vitamin D deficient. Results of multivariate logistic regression analyses showed a significantly higher vitamin D deficiency among tuberculosis cases (p < 0.001), females (p = 0.002), and urban residents (p < 0.001) than their respective comparison groups. Moreover, age groups of 35-44 (p = 0.001), 45-54 (p = 0.003) and ≥55 (p = 0.001) years had significantly higher vitamin D deficiency compared with age group <15 years. CONCLUSIONS: Vitamin D deficiency is highly prevalent among TB patients and non TB controls in Ethiopia where there is year round abundant sunshine. Study participants with tuberculosis, females, older age groups, and urban residents had significantly higher prevalence of vitamin D deficiency. These findings warrant further studies to investigate the role of vitamin D supplementation in the prevention and treatment of tuberculosis in high TB burden countries like Ethiopia.

Decentralization of Acid Fast Bacilli (AFB) External Quality Assurance Using Blind Rechecking for Sputum Smear Microscopy in Ethiopia.

INTRODUCTION: Ethiopia achieved a rapid expansion of TB microscopic centers for acid fast bacilli (AFB). However, external quality assurance (EQA) services were, until recently, limited to few regional and sub-regional laboratories. In this paper, we describe the decentralization experience and the result of EQA using random blinded rechecking. MATERIALS AND METHODS: The routine EQA quarterly report was compiled and analyzed. A positive result by the microscopic center while the EQA center reported negative result is categorized as false positive (FP). A negative result by the microscopic center while the EQA center reported positive is considered false negative (FN). The reading of EQA centers was considered a gold standard to compute the sensitivity, specificity, positive predictive (PPV) and negative predictive values (NPV) of the readings of microscopic centers. RESULTS: We decentralized sputum smear AFB EQA from 4 Regional Laboratories (RRLs) to 82 EQA centers and enrolled 956 health facilities in EQA schemes. Enrollment of HFs in EQA was gradual because it required training and mentoring laboratory professionals, institutionalizing internal QA measures, equipping all HFs to perform diagnosis, and establishing more EQA centers. From 2012 to 2014 (Phase I), the FP rate declined from 0.6% to 0.2% and FN fell from as high as 7.6% to 1.6% in supported health facilities (HFs). In HFs that joined in Phase II, FN rates ranged from 5.6 to 7.3%. The proportion of HFs without errors has increased from 77.9% to 90.5% in Phase I HFs and from 82.9% to 86.9% in Phase II HFs. Overall sensitivity and specificity were 95.0% and 99.7%, respectively. PPV and NPV were 93.3% and 99.7%, respectively. CONCLUSION: Decentralizing blinded rechecking of sputum smear microscopy is feasible in low-income settings. While a comprehensive laboratory improvement strategy enhanced the quality of microscopy, laboratory professionals' capacity in slide reading and smear quality requires continued support.

Multidrug-resistant Mycobacterium tuberculosis in HIV-infected persons, Peru.

During 1999 to 2000, we identified HIV-infected persons with new episodes of tuberculosis (TB) at 10 hospitals in Lima, Peru, and a random sample of other Lima residents with TB. Multidrug-resistant (MDR)-TB was documented in 35 (43%) of 81 HIV-positive patients and 38 (3.9%) of 965 patients who were HIV-negative or of unknown HIV status (p<0.001). HIV-positive patients with MDR-TB were concentrated at three hospitals that treat the greatest numbers of HIV-infected persons with TB. Of patients with TB, those with HIV infection differed from those without known HIV infection in having more frequent prior exposure to clinical services and more frequent previous TB therapy or prophylaxis. However, MDR-TB in HIV-infected patients was not associated with previous TB therapy or prophylaxis. MDR-TB is an ongoing problem in HIV-infected persons receiving care in public hospitals in Lima and Callao; they represent sentinel cases for a potentially larger epidemic of nosocomial MDR-TB.

Increasing transparency in partnerships for health--introducing the Green Light Committee.

Public-private partnerships have become central to efforts to combat infectious diseases. The characteristics of specific partnerships, their governance structures, and their ability to effectively address the issues for which they are developed are being clarified as experience is gained. In an attempt to promote access to and rational use of second-line anti-tuberculosis (TB) drugs for the treatment of multidrug-resistant TB, a unique partnership known as the Green Light Committee (GLC) was established by the World Health Organization. This partnership relies on five categories of actors to achieve its goal: academic institutions, civil society organizations, bilateral donors, governments of resource-limited countries, and a specialized United Nations agency. While the for-profit private sector is involved in terms of supplying concessionally priced drugs it is excluded from decision-making. The effectiveness of the partnership emerges from its review process, flexibility to modify its modus operandi to overcome obstacles, independence from the commercial sector, and its ability to link access, rational use, technical assistance, and policy development. The GLC mechanism may be useful in the development of other partnerships needed in the rational allocation of resources and tools for combating additional infectious diseases.

Feasibility and cost-effectiveness of standardised second-line drug treatment for chronic tuberculosis patients: a national cohort study in Peru.

BACKGROUND: There are no data on the feasibility and cost-effectiveness of using second-line drugs to treat patients with chronic tuberculosis, many of whom are infected with multidrug resistant (MDR) strains of Mycobacterium tuberculosis, in low or middle-income countries. METHODS: A national programme to treat chronic tuberculosis patients with a directly observed standardised 18-month daily regimen, consisting of kanamycin (3 months only), ciprofloxacin, ethionamide, pyrazinamide, and ethambutol, was established in Peru in 1997. Compliance and treatment outcomes were analysed for the cohort started on treatment between October, 1997, and March, 1999. Total and average costs were assessed. Cost-effectiveness was estimated as the cost per DALY gained. FINDINGS: 466 patients were enrolled; 344 were tested for drug susceptibility and 298 (87%) had MDR tuberculosis. 225 patients (48%) were cured, 57 (12%) died, 131 (28%) did not respond to treatment, and 53 (11%) defaulted. Of the 413 (89%) patients who complied with treatment, 225 (55%) were cured. Among MDR patients, resistance to five or more drugs was significantly associated with an unfavourable outcome (death, non-response to treatment, or default; odds ratio 3.37, 95% CI 1.32-8.60; p=0.01). The programme cost US $0.6 million per year, 8% of the National Tuberculosis Programme budget, and US $2381 per patient for those who completed treatment. The mean cost per DALY gained was $211 ($165 at drug prices projected for 2002). INTERPRETATION: Treating chronic tuberculosis patients with high levels of MDR with second-line drugs can be feasible and cost-effective in middle-income countries, provided a strong tuberculosis control programme is in place.