Social determinants of low uptake of childhood vaccination in high-risk squatter settlements in Karachi, Pakistan - A step towards addressing vaccine inequity in urban slums.

Background: Routine vaccination has remained historically low in major urban pockets of Pakistan, and now lags behind rural vaccination rates. Grossly insufficient publicly funded primary healthcare infrastructure, heterogeneous mix of providers and multi-ethnicity of populations pose challenges in the delivery of essential health services. This paper ascertains factors associated with uptake of routine childhood vaccination, using Pentavalent-3 vaccine, as a proxy indicator for completion of age-appropriate vaccines in urban slums of Karachi, at high risk of Polio and vaccine preventable disease outbreaks. Methods: Data was drawn from baseline assessment of an urban immunization delivery pilot project in urban slums of Karachi, Pakistan. The study sample comprised of 2,097 households with children aged 4-12 months, sampled through a cross-sectional cluster survey, applying a structured questionnaire. Multivariable logistic regression was used to determine the association between Penta-3 vaccination, as the outcome variable, and predictor variables including socio-demographic characteristics and healthcare access factors. Results: The findings showed that the likelihood of being immunized with Penta-3 was higher for non-Pashtun ethnicity [adjusted odds ratio (aOR) 1.69; 95% CI 1.33-2.14], children of educated mothers, secondary or higher [aOR 2.95, 95% CI 2.34-3.71], and those whose fathers were formally employed (aOR 1.53; 95% CI 1.19-1.97). No association was seen by gender of child [aOR 0.89; 95% CI 0.73-1.08], and place of new born delivery [aOR 1.01; 95% CI 0.83-1.24]. Conclusion: Pockets of critically low under-vaccinations within the urban slums of Karachi are associated with Pashtun ethnicity, distance to the vaccination centre, lack of mothers' education and lack of stable family income as in the case of unemployed and daily wage-earning fathers. Recognition of these factors is required in designing contextually appropriate strategies to address vaccine inequity in urban settings.

A spatial analysis of TB cases and abnormal X-rays detected through active case-finding in Karachi, Pakistan.

Tuberculosis (TB) is the leading cause of avoidable deaths from an infectious disease globally and a large of number of people who develop TB each year remain undiagnosed. Active case-finding has been recommended by the World Health Organization to bridge the case-detection gap for TB in high burden countries. However, concerns remain regarding their yield and cost-effectiveness. Data from mobile chest X-ray (CXR) supported active case-finding community camps conducted in Karachi, Pakistan from July 2018 to March 2020 was retrospectively analyzed. Frequency analysis was carried out at the camp-level and outcomes of interest for the spatial analyses were mycobacterium TB positivity (MTB+) and X-ray abnormality rates. The Global Moran's I statistic was used to test for spatial autocorrelation for MTB+ and abnormal X-rays within Union Councils (UCs) in Karachi. A total of 1161 (78.1%) camps yielded no MTB+ cases, 246 (16.5%) camps yielded 1 MTB+, 52 (3.5%) camps yielded 2 MTB+ and 27 (1.8%) yielded 3 or more MTB+. A total of 79 (5.3%) camps accounted for 193 (44.0%) of MTB+ cases detected. Statistically significant clustering for MTB positivity (Global Moran's I: 0.09) and abnormal chest X-rays (Global Moran's I: 0.36) rates was identified within UCs in Karachi. Clustering of UCs with high MTB positivity were identified in Karachi West district. Statistically significant spatial variation was identified in yield of bacteriologically positive TB cases and in abnormal CXR through active case-finding in Karachi. Cost-effectiveness of active case-finding programs can be improved by identifying and focusing interventions in hotspots and avoiding locations with no known TB cases reported through routine surveillance.

Gender-based differences in community-wide screening for pulmonary tuberculosis in Karachi, Pakistan: an observational study of 311 732 individuals undergoing screening.

We describe gender-based differences in a community-wide TB screening programme in Karachi, Pakistan, in which 311 732 individuals were screened in mobile camps using symptom questionnaires and van-mounted digital chest X-ray, between 1 January 2018 and 31 December 2019. Only 22.4% (69 869) of camp attendees were women. Female attendees were less likely to have sputum collected and tested (31.5% (95% CI 30.4% to 32.7%) vs 38.5% (95% CI 37.6% to 39.1%)) or to initiate TB treatment (75.9% (95% CI 68.1% to 82.6%) vs 82.8% (95% CI 78.9% to 86.2%)), when indicated. Among the participants, the age-standardised prevalence of active TB was higher among women (prevalence ratio 1.4, 95% CI 1.1 to 1.7). These findings underscore the importance of integrating gender into the design and monitoring of TB screening programmes to ensure that women and men benefit equally from this important intervention.

Barriers to Access of Healthcare Services for Rural Women-Applying Gender Lens on TB in a Rural District of Sindh, Pakistan.

BACKGROUND: Women in the rural districts of Pakistan face numerous barriers to healthcare, rendering gender-responsive health programming important, including for the disease of tuberculosis (TB). This study was conducted to assess the general understanding of TB and for women's access to healthcare, as a first step towards implementation of a gender responsive TB program in Tando Allahyar, a rural district of Pakistan. METHODS: A total of 36 participants were interviewed for the study. The focus group discussion guide comprised of questions on: (1) family/household dynamics, (2) community norms, (3) healthcare systems, (4) women's access to healthcare, (5) TB Awareness, and (6) women's access to TB Care. RESULTS: Limited autonomy in household financial decision-making, disapproval of unassisted travel, long travel time, lack of prioritization of spending on women's health and inadequate presence of female health providers, were identified as barriers to access healthcare for women, which is even higher in younger women. Facilitators to access of TB care included a reported lack of TB-related stigma, moderate knowledge about TB disease, and broad understanding of tuberculosis as a curable disease. Other suggested facilitators include health facilities closer to the villages and the availability of higher quality services. CONCLUSION: Significant barriers are faced by women in accessing TB care in rural districts of Pakistan. Program implementers in high burden countries should shift towards improved gender-responsive TB programming.

Exploring willingness to pay for health insurance and preferences for a benefits package from the perspective of women from low-income households of Karachi, Pakistan.

BACKGROUND: Achieving universal health coverage (UHC) and reduction in out of pocket (OOP) expenditures on health, is a critical target of the Sustainable Development Goals (SDG). In low-middle income countries, micro-health insurance (MHI) schemes have emerged as a useful financing tool for laying grounds for Universal Health Coverage. The aim of this study was to provide evidence for designing a feasible health insurance scheme targeted at urban poor, by exploring preferences for an insurance benefits package and co-payments among women from low-income households in Karachi, Pakistan. METHODS: This was a descriptive cross-sectional study, conducted using household surveys between July-August 2015. A total of 167 female beneficiaries of Benazir Income Support Programme (BISP), a large-scale cash transfer scheme targeted at low-income households, were recruited in Karachi through a mix of convenience and snowball sampling. Hypothetical insurance benefits packages for a prospective health insurance scheme were formulated to capture respondents' preferences for health insurance benefits package and co-payments. All data was analyzed using Stata (version 13). RESULTS: Respondents reporting expenditure on OPD and hospitalization in the last 2 weeks were 93.4 and 11.9% respectively. The highest median expenditure was incurred on medicines. Out of the proposed benefits package, a majority (53%) of the study participants opted for the comprehensive benefits package that provided coverage for emergency care, hospitalization, OPD consultation, diagnostic tests and transportation. For the co-payment plan, 38.9% participants preferred no co-payments that is 100% insurance coverage of medicines followed by hospitalization (25.9%). Nearly half of the respondents (49.4%) chose outpatient consultation for 50% co-payment. A majority of the participants (65.3%) agreed to 100% co-payment for the transportation cost. CONCLUSION: Health insurance schemes can be introduced in urban areas, against collection of micro-payments, to prevent low-income households from facing financial catastrophe. A comprehensive benefits package covering emergency care, hospitalization, OPD consultation, diagnostic tests and transportation, is the most preferred among low-income beneficiaries.

Engagement of private healthcare providers for case finding of tuberculosis and diabetes mellitus in Pakistan.

BACKGROUND: The rising co-epidemic of tuberculosis (TB) and diabetes mellitus (DM) is a challenge for constrained health systems in low and middle-income countries. Diabetes is a known risk factor for tuberculosis and associated with poor tuberculosis treatment outcomes, while tuberculosis is associated with worsening glycemic control. We investigated the performance of bi-directional TB and DM case finding approaches through a private-sector engagement model in Karachi, Pakistan. METHODS: Between July 2016 and July 2018, private health care providers were engaged to generate referrals for bi-directional TB and DM screening at private diagnostic and treatment centers in Karachi, Pakistan. Individuals diagnosed with TB underwent glycated hemoglobin (HbA1c) testing at the time of anti-tuberculous treatment initiation and at three -month follow up stage. All individuals with a history of diabetes or random blood sugar of greater than 200 mg/dl were screened for TB using a chest X-ray and Xpert MTB/RIF. RESULTS: A total of 6312 persons with tuberculosis were tested on HbA1c at treatment initiation, of whom 1516 (24%) were newly diagnosed with DM. About one third of those with HbA1c in the diabetic range (≥ 6.5%) at baseline were found to have a normal HbA1c (< 5.7%) result at 3-month follow-up. A total of 3824 individuals with DM, of whom 2396 (63%) were known cases and 1428 (37%) were newly identified with random blood sugar > 200 mg/dl, underwent chest x-ray and Xpert MTB/RIF testing, with 321 (13.4%) known and 54 (3.8%) new diabetics respectively identified with tuberculosis. CONCLUSION: This study demonstrates a high yield of TB and DM through bidirectional screening and the feasibility of engagement of private sector in finding missing cases of tuberculosis and diabetes. Given the high prevalence of undiagnosed DM in individuals with TB tuberculosis patients, there is a need to scale-up DM screening within TB programmes. Increased awareness of the high risk of TB among individuals with DM is needed among private health providers and screening for TB among diabetics should be strongly considered.

Evaluation of computer aided detection of tuberculosis on chest radiography among people with diabetes in Karachi Pakistan.

Pakistan ranks fifth among high tuberculosis (TB) burden countries and also has seventh highest burden for diabetes mellitus (DM). DM increases the risk of developing TB and contributes to adverse TB treatment outcomes hence screening and integrated management for both diseases in high burden countries is suggested. Computer-Aided Detection for TB (CAD4TB) can potentially be used as triage tool in low resource settings to pre-screen individuals for Xpert MTB/RIF testing. The aim of this study was to evaluate the diagnostic accuracy and performance of CAD4TB software in people with diabetes (PWD) enrolled in a TB screening program in Karachi, Pakistan. A total of 694 individuals with a diagnosis of DM (of whom 31.1% were newly diagnosed) were screened with CAD4TB and simultaneously provided sputum for Xpert MTB/RIF testing. Of the 74 (10.7%) participants who had bacteriologically positive (MTB+) results on Xpert testing, 54 (73%) had a CAD4TB score >70; and 155 (25%) participants who tested MTB-negative had scores >70. The area under the receiver operator curve was 0.78 (95% CI: 0.77-0.80). Our study findings indicate that CAD4TB offers good diagnostic accuracy as a triage test for TB screening among PWD using Xpert MTB/RIF as the reference standard.

Computer aided detection of tuberculosis on chest radiographs: An evaluation of the CAD4TB v6 system.

There is a growing interest in the automated analysis of chest X-Ray (CXR) as a sensitive and inexpensive means of screening susceptible populations for pulmonary tuberculosis. In this work we evaluate the latest version of CAD4TB, a commercial software platform designed for this purpose. Version 6 of CAD4TB was released in 2018 and is here tested on a fully independent dataset of 5565 CXR images with GeneXpert (Xpert) sputum test results available (854 Xpert positive subjects). A subset of 500 subjects (50% Xpert positive) was reviewed and annotated by 5 expert observers independently to obtain a radiological reference standard. The latest version of CAD4TB is found to outperform all previous versions in terms of area under receiver operating curve (ROC) with respect to both Xpert and radiological reference standards. Improvements with respect to Xpert are most apparent at high sensitivity levels with a specificity of 76% obtained at a fixed 90% sensitivity. When compared with the radiological reference standard, CAD4TB v6 also outperformed previous versions by a considerable margin and achieved 98% specificity at the 90% sensitivity setting. No substantial difference was found between the performance of CAD4TB v6 and any of the various expert observers against the Xpert reference standard. A cost and efficiency analysis on this dataset demonstrates that in a standard clinical situation, operating at 90% sensitivity, users of CAD4TB v6 can process 132 subjects per day at an average cost per screen of $5.95 per subject, while users of version 3 process only 85 subjects per day at a cost of $8.38 per subject. At all tested operating points version 6 is shown to be more efficient and cost effective than any other version.

Evaluation of the diagnostic accuracy of Computer-Aided Detection of tuberculosis on Chest radiography among private sector patients in Pakistan.

The introduction of digital CXR with automated computer-aided interpretation, has given impetus to the role of CXR in TB screening, particularly in low resource, high-burden settings. The aim of this study was to evaluate the diagnostic accuracy of CAD4TB as a screening tool, implemented in the private sector in Karachi, Pakistan. This study analyzed retrospective data from CAD4TB and Xpert MTB/RIF testing carried out at two private TB treatment and diagnostic centers in Karachi. Sensitivity, specificity, potential Xperts saved, were computed and the receiver operator characteristic curves were constructed for four different models of CAD4TB. A total of 6,845 individuals with presumptive TB were enrolled in the study, 15.2% of which had MTB + ve result on Xpert. A high sensitivity (range 65.8-97.3%) and NPV (range 93.1-98.4%) were recorded for CAD4TB. The Area under the ROC curve (AUC) for CAD4TB was 0.79. CAD4TB with patient demographics (age and gender) gave an AUC of 0.83. CAD4TB offered high diagnostic accuracy. In low resource settings, CAD4TB, as a triage tool could minimize use of Xpert. Using CAD4TB in combination with age and gender data enhanced the performance of the software. Variations in demographic information generate different individual risk probabilities for the same CAD4TB scores.

Emergence of fluoroquinolone resistance among drug resistant tuberculosis patients at a tertiary care facility in Karachi, Pakistan.

BACKGROUND: Pakistan is classified as one of the high multi-drug resistant tuberculosis (MDR-TB) burden countries. A poorly regulated private sector, over-prescription of antibiotics and self-medication has led to augmented rates of drug-resistance in the country. Pakistan's first national anti-tuberculosis drug resistance survey identified high prevalence of fluoroquinolone resistance among MDR-TB patients. Further institutional evidence of fluoroquinolone drug-resistance can support re-evaluation of treatment regimens as well as invigorate efforts to control antibiotic resistance in the country. FINDINGS: In this study, data for drug-susceptibility testing (DST) was retrospectively analyzed for a total of 133 patients receiving MDR-TB treatment at the Chest Department of Jinnah Postgraduate Medical Center, Karachi, Pakistan. Frequency analyses for resistance patterns was carried out and association of fluoroquinolone (ofloxacin) resistance with demographics and past TB treatment category were assessed. Within first-line drugs, resistance to isoniazid was detected in 97.7% of cases, followed by rifampicin (96.9%), pyrazinamide (86.4%), ethambutol (69.2%) and streptomycin (64.6%). Within second-line drugs, ofloxacin resistance was detected in 34.6% of cases. Resistance to ethionamide and amikacin was 2.3% and 1.6%, respectively. Combined resistance of oflaxacin and isoniazid was detected in 33.9% of cases. Age, gender and past TB treatment category were not significantly associated with resistance to ofloxacin. CONCLUSION: Fluoroquinolone resistance was observed in an alarmingly high proportion of MDR-TB cases. Our results suggest caution in their use for empirical management of MDR-TB cases and recommended treatment regimens for MDR-TB may require re-evaluation. Greater engagement of private providers and stringent pharmacy regulations are urgently required.

The role of micro health insurance in providing financial risk protection in developing countries--a systematic review.

BACKGROUND: Out of pocket payments are the predominant method of financing healthcare in many developing countries, which can result in impoverishment and financial catastrophe for those affected. In 2010, WHO estimated that approximately 100 million people are pushed below the poverty line each year by payments for healthcare. Micro health insurance (MHI) has been used in some countries as means of risk pooling and reducing out of pocket health expenditure. A systematic review was conducted to assess the extent to which MHI has contributed to providing financial risk protection to low-income households in developing countries, and suggest how the findings can be applied in the Pakistani setting. METHODS: We conducted a systematic search for published literature using the search terms "Community based health insurance AND developing countries", "Micro health insurance AND developing countries", "Mutual health insurance AND developing countries", "mutual OR micro OR community based health insurance" "Health insurance AND impact AND poor" "Health insurance AND financial protection" and "mutual health organizations" on three databases, Pubmed, Google Scholar and Science Direct (Elsevier). Only those records that were published in the last ten years, in English language with their full texts available free of cost, were considered for inclusion in this review. Hand searching was carried out on the reference lists of the retrieved articles and webpages of international organizations like World Bank, World Health Organization and International Labour Organization. RESULTS: Twenty-three articles were eligible for inclusion in this systematic review (14 from Asia and 9 from Africa). Our analysis shows that MHI, in the majority of cases, has been found to contribute to the financial protection of its beneficiaries, by reducing out of pocket health expenditure, catastrophic health expenditure, total health expenditure, household borrowings and poverty. MHI also had a positive safeguarding effect on household savings, assets and consumption patterns. CONCLUSION: Our review suggests that MHI, targeted at the low-income households and tailored to suit the cultural and geographical structures in the various areas of Pakistan, may contribute towards providing protection to the households from catastrophe and impoverishment resulting from health expenditures. This paper emphasizes the need for further research to fill the knowledge gap that exists about the impact of MHI, using robust study designs and impact indicators.