Concurrent adult pulmonary tuberculosis prevalence survey using digital radiography and Xpert MTB/RIF Ultra and child interferon-gamma release assay Mycobacterium tuberculosis infection survey in Karachi, Pakistan: a study protocol.

Assessment of the effectiveness of tuberculosis control strategies requires the periodic measurement of M. tuberculosis transmission in populations, which is notoriously difficult. One well-established method is to measure the prevalence of infectious pulmonary tuberculosis in the population which is then repeated at a second time point after a period of 'intervention', such as scale up of the Search-Treat-Prevent strategy of the Zero TB Cities initiative, allowing for a 'before and after' comparison.  Protocol: The concurrent adult pulmonary tuberculosis prevalence survey (using digital radiography and Xpert MTB/RIF Ultra) and child M. tuberculosis infection survey (using QuantiFERON-TB® Gold Plus) will primarily provide a baseline measure of the burden of adult infectious tuberculosis in Karachi and assess whether a large-scale interferon gamma release assay survey in children aged 2 to 4 years is feasible. The target population for the prevalence survey is comprised of a stratified random sample of all adults aged 15 years and above and all children aged 2 to 4 years resident in four districts in Karachi. The survey procedures and analyses to estimate pulmonary tuberculosis prevalence are based on the World Health Organization methodology for tuberculosis prevalence surveys. Ethics and dissemination: The study protocol has been approved by the Interactive Research Development / The Indus Hospital Research Centre Research Ethics Committee in Karachi, Pakistan and the London School of Hygiene & Tropical Medicine Research Ethics Committee. Due to non-representative sampling in this setting, where a large proportion of the population are illiterate and are reluctant to provide fingerprints due to concerns about personal security, verbal informed consent will be obtained from each eligible participant or guardian. Results will be submitted to international peer-reviewed journals, presented at international conferences and shared with participating communities and with the Provincial and National TB programme

Newborn outcomes by place of birth.

Pakistan has among the highest rates of maternal, perinatal, and neonatal mortality globally. Many of these deaths are potentially preventable with low-cost, scalable interventions delivered through community-based health worker programs to the most remote communities. We conducted a cross-sectional survey of 10,264 households during the baseline phase of a cluster randomized controlled trial (cRCT) in Gilgit-Baltistan, Pakistan from June–August 2021. The survey was conducted through a stratified, two-stage sampling design with the objective of estimating the neonatal mortality rate (NMR) within the study catchment area, and informing implementation of the cRCT. Study outcomes were self-reported and included neonatal death, stillbirth, health facility delivery, maternal death, postpartum hemorrhage (PPH), and Lady Health Worker (LHW) coverage. Summary statistics (proportions and rates) were weighted according to the sampling design, and mixed-effects Poisson regression was conducted to explore the relationship between LHW coverage and maternal/newborn outcomes. We identified 7,600 women who gave birth in the past five years, among whom 13% reported experiencing PPH. The maternal mortality ratio was 225 maternal deaths per 100,000 live births (95% confidence interval [CI] 137–369). Among 12,376 total births, the stillbirth rate was 41.4 per 1,000 births (95% CI 36.8–46.7) and the perinatal mortality rate was 53.0 per 1,000 births (95% CI 47.6–59.0). Among 11,863 live births, NMR was 16.2 per 1,000 live births (95% CI 13.6–19.3) and 65% were delivered at a health facility. LHW home visits were associated with declines in PPH (risk ratio [RR] 0.89 per each additional visit, 95% CI 0.83–0.96) and late neonatal mortality (RR 0.80, 95% CI 0.67–0.97). Intracluster correlation coefficients were also estimated to inform the planning of future trials. The high rates of maternal, perinatal, and neonatal death in Gilgit-Baltistan continue to fall behind targets of the 2030 Sustainable Development Goals.</div

Five-year reproductive, delivery, and newborn outcomes at baseline.

Five-year reproductive, delivery, and newborn outcomes at baseline.</p

Associations between maternal, delivery, and newborn outcomes with village-level frequency of Lady Health Worker home visits.

Each line represents the unadjusted risk ratio between prenatal or postnatal LHW visits and the outcome of interest, from an unadjusted mixed effects Poisson regression. Clustering at the Union Council and village levels were accounted for using Stata’s svyset command, while within-household clusters was accounted for by including household ID as a random effect in the regression. We assessed for non-linearity by including quadratic terms for the number of LHW visits–interaction terms were removed if not significant using a Wald test. Solid lines indicate a p-value <0.05, while dashed lines indicate p≥0.05.</p

Non-parametric (Spearman) correlations between study indicators.

Non-parametric (Spearman) correlations between study indicators.</p

Inclusivity checklist.

PLOS inclusivity in global research checklist. (DOCX)</p

Intracluster correlation coefficients (ICC) and coefficients of variation (k).

Intracluster correlation coefficients (ICC) and coefficients of variation (k).</p

Study sampling design and flowchart of households included in baseline survey.

Trained data collectors then visited households to administer the study questionnaire; one representative per household was asked to participate and self-report all elements of the questionnaire. The questionnaire was administered primarily in Urdu; however, at least one member of each data collection team was proficient in the local language of each village visited, and translated the study questions as needed into Balti (spoken in Baltistan), Brushiski (spoken in Nagar), or Shina (spoken in Astore). Participants were asked about: a) household reproductive history, including the number of women who gave birth, the number who experienced PPH, and the number of live births and stillbirths delivered; b) live birth history, including the time and place of birth and any neonatal deaths; c) LHW household coverage, including the number of total visits, visits for prenatal care, and visits for postnatal care; and d) household experiences with COVID-19, which will be reported elsewhere. Respondents were asked to report reproductive and live birth outcomes in the past five years, and LHW household coverage in the past 12 months. Finally, quality control officers recontacted approximately 18% of households to verify accuracy of the data collection.</p