Iterative evaluation of mobile computer-assisted digital chest x-ray screening for TB improves efficiency, yield, and outcomes in Nigeria.

Wellness on Wheels (WoW) is a model of mobile systematic tuberculosis (TB) screening of high-risk populations combining digital chest radiography with computer-aided automated detection (CAD) and chronic cough screening to identify presumptive TB clients in communities, health facilities, and prisons in Nigeria. The model evolves to address technical, political, and sustainability challenges. Screening methods were iteratively refined to balance TB yield and feasibility across heterogeneous populations. Performance metrics were compared over time. Screening volumes, risk mix, number needed to screen (NNS), number needed to test (NNT), sample loss, TB treatment initiation and outcomes. Efforts to mitigate losses along the diagnostic cascade were tracked. Persons with high CAD4TB score (≥80), who tested negative on a single spot GeneXpert were followed-up to assess TB status at six months. An experimental calibration method achieved a viable CAD threshold for testing. High risk groups and key stakeholders were engaged. Operations evolved in real time to fix problems. Incremental improvements in mean client volumes (128 to 140/day), target group inclusion (92% to 93%), on-site testing (84% to 86%), TB treatment initiation (87% to 91%), and TB treatment success (71% to 85%) were recorded. Attention to those as highest risk boosted efficiency (the NNT declined from 8.2 ± SD8.2 to 7.6 ± SD7.7). Clinical diagnosis was added after follow-up among those with ≥ 80 CAD scores and initially spot -sputum negative found 11 additional TB cases (6.3%) after 121 person-years of follow-up. Iterative adaptation in response to performance metrics foster feasible, acceptable, and efficient TB case-finding in Nigeria. High CAD scores can identify subclinical TB and those at risk of progression to bacteriologically-confirmed TB disease in the near term.

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.

Prevalence of drug-resistant tuberculosis in Zimbabwe: A health facility-based cross-sectional survey.

OBJECTIVE: To determine the prevalence of resistance to rifampicin alone; rifampicin and isoniazid, and second-line anti-TB drugs among sputum smear-positive tuberculosis patients in Zimbabwe. DESIGN: A health facility-based cross-sectional survey. RESULTS: In total, 1114 (87.6%) new and 158 (12.4%) retreatment TB patients were enrolled. MTB was confirmed by Xpert MTB/RIF among 1184 (93%) smear-positive sputum samples. There were 64 samples with Xpert MTB/RIF-determined rifampicin resistance. However, two were rifampicin susceptible on phenotypic drug susceptibility testing. The prevalence of RR-TB was [4.0% (95% CI, 2.9, 5.4%), n=42/1043) and 14.2% (95% CI, 8.9, 21.1%; n=20/141) among new and retreatment patients, respectively. The prevalence of MDR-TB was 2.0% (95% CI, 1.3, 3.1%) and 6.4% (95% CI, 2.4, 10.3%) among new and retreatment TB patients, respectively. Risk factors for RR-TB included prior TB treatment, self-reported HIV infection, travel outside Zimbabwe for ≥one month (univariate), and age <15 years. Having at least a secondary education was protective against RR-TB. CONCLUSION: The prevalence of MDR-TB in Zimbabwe has remained stable since the 1994 subnational survey. However, the prevalence of rifampicin mono-resistance was double that of MDR-TB.

Interferon-gamma release assays for tuberculosis screening of healthcare workers: a systematic review.

Healthcare workers (HCWs) are at increased risk of exposure to tuberculosis (TB). Traditionally, screening for latent TB infection (LTBI) is done using the tuberculin skin test (TST). Interferon-gamma release assays (IGRAs) are now increasingly being used for diagnosis of LTBI, but their role in HCW screening is unclear. A systematic review was conducted of all IGRA studies in HCWs to summarise their performance in cross-sectional and serial testing settings. By searching four electronic databases and other sources, all available studies using any one of the commercial IGRA assays in HCWs were retrieved and screened. 50 unique studies were identified which met the inclusion criteria including five from high TB incidence settings. Among 24 cross-sectional studies in low TB incidence settings, the pooled prevalence of positive IGRA using either test was significantly lower than for a positive TST. However, in high-incidence settings (n=2) there were no consistent differences in the prevalence of positive tests. IGRAs showed good correlation with occupational risk factors for TB exposure in low-incidence settings. Only 10 studies assessed use of IGRA for serial testing and all showed large variation in the rates of conversions and reversions, with no data suggesting that IGRAs are better at identifying the incidence of new TB infection than the TST. The use of IGRAs instead of TST for one-time screening may result in a lower prevalence of positive tests and fewer HCWs who require LTBI treatment, particularly in low TB incidence settings. However, the use of IGRAs for serial testing is complicated by lack of data on optimum cut-offs for serial testing and unclear interpretation and prognosis of conversions and reversions. Further longitudinal research will be required to inform guidelines on serial testing using IGRAs.

Effectiveness of isoniazid treatment for latent tuberculosis infection among human immunodeficiency virus (HIV)-infected and HIV-uninfected injection drug users in methadone programs.

Injection drug users (IDUs) were heavily affected by the tuberculosis (TB) resurgence in New York City in the 1990s. We assessed the effectiveness of screening for latent TB infection in methadone users and of selective treatment with isoniazid. Risk for future TB was classified as low or high on the basis of tuberculin, anergy, and HIV test results. The cohort of 2212 IDUs was followed up for a median of 4.2 years; 25 IDUs, of whom 20 (80%) were infected with human immunodeficiency virus (HIV), developed TB. In an adjusted Cox proportional hazards model of high-risk IDUs, the risk of TB was associated with HIV infection (HR 10.3; 95% CI, 3.4-31.3); receipt of <6 months of isoniazid therapy (HR 7.6; 95% CI, 1.02-57.1); a CD4+ T lymphocyte count of <200 cells/mm3 (HR 6.6; 95% CI, 1.7-25.9); and tuberculin positivity (HR 4.0; 95% CI, 1.6-10.2). Treatment with isoniazid was beneficial in HIV-infected, tuberculin-positive IDUs.

Tuberculin testing and risk of tuberculosis infection among New York City schoolchildren.

OBJECTIVES: To assess adherence to a 1996 health policy change, which discontinued mandatory tuberculin skin testing (TST) of new entrants to NYC primary schools and continued mandatory testing of new entrants to secondary schools. METHODS: The proportion tested before (1991-1995) and after (1996-1998) the change in health policy was determined. Factors associated with TST positivity and the cost of continued testing were assessed. RESULTS: A total of 76.6% of 551 636 new entrants to primary schools were tested in 1991-1995; slightly fewer, 71.1% of 339 958, were tested in 1996- 1998. Among new entrants to secondary schools, 31.0% of 106 463 were tested in 1991-1995 and 51.4% of 53 762 were tested in 1996-1998. The proportion who were TST-positive continued to decrease after 1996 to 1.2% among primary and 9.7% among secondary schoolchildren in 1998. Older age and birth outside the United States were associated with TST positivity. The estimated minimum cost of continued testing in primary schools was $123 152 per tuberculosis case prevented. CONCLUSION: An approach aimed at reducing testing of children at low risk for latent tuberculosis infection did not decrease testing of younger children. More important, older children who were more likely to be born in countries of high tuberculosis incidence were not tested. Additional efforts are needed to increase awareness among medical and school personnel to decrease testing among children who do not have risk factors for latent tuberculosis infection and to increase tuberculin testing of children who are entering school for the first time at the secondary level and do have risk factors for tuberculosis infection.