Should all pregnant women take calcium supplements in Nepal? GRADE evidence to policy assessment

Background The WHO recommends oral calcium supplementation (1.5–2.0 g) in pregnant women to reduce the risk of pre-eclampsia living in areas with low dietary calcium intake. Although maternal mortality is high in Nepal and eclampsia causes at least 20% of maternal deaths, implementing WHO recommendations would be a major undertaking. Objective This review aimed to assess whether the current evidence supports the blanket supplementation of calcium to prevent pre-eclampsia among pregnant women in Nepal. Methods We used a structured approach to appraise the evidence for calcium supplementation in Nepal. We identified what may influence the impact of calcium supplementation in Nepal and conducted a situation analysis in the country covering maternal mortality, pre-eclampsia occurrence, and existing government policy provisions for supplementation. We also consulted with experts and government officials to explore their perspectives and experience on supplementation. We then used AMSTAR (A MeaSurement Tool to Assess Systematic Reviews) to appraise the Cochrane Systematic Review of calcium supplementation. Finally, we used these data in a GRADE (Grading of Recommendations Assessment, Development and Evaluation)–Evidence to Decision framework to reach a policy recommendation. Results Our assessment of the Cochrane Review showed that the recommendation made by the WHO is based on weak evidence and trial findings that are not consistent between studies. The Cochrane Review found low certainty of the evidence for benefit (reduction in pre-eclampsia and maternal mortality). Conversely, there is a high certainty of the evidence of undesirable effects (HELLP [haemolysis, elevated liver enzymes and low platelets] syndrome) although this is uncommon. The likely absolute reduction in maternal deaths projected to Nepal was estimated to be low, while the implementation costs were high. Stakeholders also raised several concerns regarding feasibility, acceptability, appropriate dosing, and risk communication. Conclusions This review concludes that the blanket supplementation of calcium cannot be recommended in Nepal. A better approach may be to identify high-risk pregnant women and manage their antenatal visits and delivery to prevent mortality from pre-eclampsia

Is routine Vitamin A supplementation still justified for children in Nepal? Trial synthesis findings applied to Nepal national mortality estimates

Background The World Health Organization has recommended Vitamin A supplementation for children in low- and middle-income countries for many years to reduce child mortality. Nepal still practices routine Vitamin A supplementation. We examined the potential current impact of these programs using national data in Nepal combined with an update of the mortality effect estimate from a meta-analysis of randomized controlled trials. Methods We used the 2017 Cochrane review as a template for an updated meta-analysis. We conducted fresh searches, re-applied the inclusion criteria, re-extracted the data for mortality and constructed a summary of findings table using GRADE. We applied the best estimate of the effect obtained from the trials to the national statistics of the country to estimate the impact of supplementation on under-five mortality in Nepal. Results The effect estimates from well-concealed trials gave a 9% reduction in mortality (Risk Ratio: 0.91, 95% CI 0.85 to 0.97, 6 trials; 1,046,829 participants; low certainty evidence). The funnel plot suggested publication bias, and a meta-analysis of trials published since 2000 gave a smaller effect estimate (Risk Ratio: 0.96, 95% CI 0.89 to 1.03, 2 trials, 1,007,587 participants), with the DEVTA trial contributing 55.1 per cent to this estimate. Applying the estimate from well-concealed trials to Nepal’s under-five mortality rate, there may be a reduction in mortality, and this is small from 28 to 25 per 1000 live births; 3 fewer deaths (95% CI 1 to 4 fewer) for every 1000 children supplemented. Conclusions Vitamin A supplementation may only result in a quantitatively unimportant reduction in child mortality. Stopping blanket supplementation seems reasonable given these data

Barriers to Treatment Compliance of Directly Observed Treatment Shortcourse among Pulmunary Tuberculosis Patients.

Treatment compliance is an important aspect for tuberculosis prevention and control. Poor compliance to treatment can lead to the development of drug-resistant tuberculosis. The aim of this study was to explore the factors affecting treatment compliance for tuberculosis patients. Facility based unmatched case control study was done among the forty non-compliance and eighty compliance pulmonary tuberculosis patients registered at selected directly observed treatment short-course centers of six districts. Data were collected using in-depth interview guideline with the tuberculosis focal person and Focus Group Discussion with tuberculosis patients. A total of 120 respondents, 40 cases and 80 controls were enrolled in the study. About 72.5% of the cases and 56.2% of the controls were male. Five significant independent risk factors for non-compliance to TB treatment were identified. The qualitative session confirmed geographical barriers, inaccessibility to health facility, economic barriers, difficulty in convincing people, knowledge about Directly observed treatment shortcourse program, longer medication period, migration and stigma as a major barrier for treatment compliance. Wider ranges of barriers are prevalent in context of tuberculosis treatment pathway and outcome. Knowledge of the tuberculosis patients and attitude of the family plays a vital role in treatment compliance. Directly observed treatment shortcourse playing tremendous role to ensure treatment adherence has been identified as major barrier to adherence as well. Enablers of adherence need to be emphasized to address the barriers

The role of active case finding in reducing patient incurred catastrophic costs for tuberculosis in Nepal

Background: The World Health Organization (WHO) End TB Strategy has established a milestone to reduce the number of tuberculosis (TB)- affected households facing catastrophic costs to zero by 2020. The role of active case finding (ACF) in reducing patient costs has not been determined globally. This study therefore aimed to compare costs incurred by TB patients diagnosed through ACF and passive case finding (PCF), and to determine the prevalence and intensity of patient-incurred catastrophic costs in Nepal. Methods: The study was conducted in two districts of Nepal: Bardiya and Pyuthan (Province No. 5) between June and August 2018. One hundred patients were included in this study in a 1:1 ratio (PCF: ACF, 25 consecutive ACF and 25 consecutive PCF patients in each district). The WHO TB patient costing tool was applied to collect information from patients or a member of their family regarding indirect and direct medical and non-medical costs. Catastrophic costs were calculated based on the proportion of patients with total costs exceeding 20% of their annual household income. The intensity of catastrophic costs was calculated using the positive overshoot method. The chi-square and Wilcoxon-Mann-Whitney tests were used to compare proportions and costs. Meanwhile, the Mantel Haenszel test was performed to assess the association between catastrophic costs and type of diagnosis. Results: Ninety-nine patients were interviewed (50 ACF and 49 PCF). Patients diagnosed through ACF incurred lower costs during the pre-treatment period (direct medical: USD 14 vs USD 32, P = 0.001; direct non-medical: USD 3 vs USD 10, P = 0.004; indirect, time loss: USD 4 vs USD 13, P < 0.001). The cost of the pre-treatment and intensive phases combined was also lower for direct medical (USD 15 vs USD 34, P = 0.002) and non-medical (USD 30 vs USD 54, P = 0.022) costs among ACF patients. The prevalence of catastrophic direct costs was lower for ACF patients for all thresholds. A lower intensity of catastrophic costs was also documented for ACF patients, although the difference was not statistically significant. Conclusions: ACF can reduce patient-incurred costs substantially, contributing to the End TB Strategy target. Other synergistic policies, such as social protection, will also need to be implemented to reduce catastrophic costs to zero among TB-affected households. Keywords: Tuberculosis, Case finding, Cost, Catastrophic cost, Patient-incurred cost, NepalStop TB Partnership/UNOPS – TB REACH project (grant number: 5–31); European Union, Horizon 2020 – IMPACT TB project (grant number: 733174)

Protocol for the Addressing the Social Determinants and Consequences of Tuberculosis in Nepal (ASCOT) pilot trial.

The World Health Organization's End TB (tuberculosis) Strategy advocates social and economic support for TB-affected households but evidence from low-income settings is scarce. We will evaluate the feasibility and acceptability of a locally-appropriate socioeconomic support intervention for TB-affected households in Nepal. We will conduct a pilot randomised-controlled trial with mixed-methods process evaluation in four TB-endemic, impoverished districts of Nepal: Pyuthan, Chitwan, Mahottari, and Morang. We will recruit 128 people with TB notified to the Nepal National TB Program (NTP) and 40 multisectoral stakeholders including NTP staff, civil-society members, policy-makers, and ASCOT (Addressing the Social Determinants and Consequences of Tuberculosis) team members. People with TB will be randomised 1:1:1:1 to four study arms (n=32 each): control; social support; economic support; and combined social and economic (socioeconomic) support. Social support will be TB education and peer-led mutual-support TB Clubs providing TB education and stigma-reduction counselling. Economic support will be monthly unconditional cash transfers during TB treatment with expectations (not conditions) of meeting NTP goals. At 0, 2, and 6 months following TB treatment initiation, participants will be asked to complete a survey detailing the social determinants and consequences of TB and their feedback on ASCOT. Complementary process evaluation will use focus group discussions (FGD), key informant interviews (KII), and a workshop with multi-sectoral stakeholders to consider the challenges to ASCOT's implementation and scale-up. A sample of ~100 people with TB is recommended to estimate TB-related costs. Information power is estimated to be reached with approximately 25 FGD and 15 KII participants.  The ASCOT pilot trial will both generate robust evidence on a locally-appropriate, socioeconomic support intervention for TB-affected households in Nepal and inform a large-scale future ASCOT trial, which will evaluate the intervention's impact on catastrophic costs mitigation and TB outcomes. The trial is registered with the ISRCTN ( ISRCTN17025974). [Abstract copyright: Copyright: © 2022 Rai B et al.

Barriers and facilitators to accessing tuberculosis care in Nepal : a qualitative study to inform the design of a socioeconomic support intervention

OBJECTIVE: Psychosocial and economic (socioeconomic) barriers, including poverty, stigma and catastrophic costs, impede access to tuberculosis (TB) services in low-income countries. We aimed to characterise the socioeconomic barriers and facilitators of accessing TB services in Nepal to inform the design of a locally appropriate socioeconomic support intervention for TB-affected households. DESIGN: From August 2018 to July 2019, we conducted an exploratory qualitative study consisting of semistructured focus group discussions (FGDs) with purposively selected multisectoral stakeholders. The data were managed in NVivo V.12, coded by consensus and analysed thematically. SETTING: The study was conducted in four districts, Makwanpur, Chitwan, Dhanusha and Mahottari, which have a high prevalence of poverty and TB. PARTICIPANTS: Seven FGDs were conducted with 54 in-country stakeholders, grouped by stakeholders, including people with TB (n=21), community stakeholders (n=13) and multidisciplinary TB healthcare professionals (n=20) from the National TB Programme. RESULTS: The perceived socioeconomic barriers to accessing TB services were: inadequate TB knowledge and advocacy; high food and transportation costs; income loss and stigma. The perceived facilitators to accessing TB care and services were: enhanced championing and awareness-raising about TB and TB services; social protection including health insurance; cash, vouchers and/or nutritional allowance to cover food and travel costs; and psychosocial support and counselling integrated with existing adherence counselling from the National TB Programme. CONCLUSION: These results suggest that support interventions that integrate TB education, psychosocial counselling and expand on existing cash transfer schemes would be locally appropriate and could address the socioeconomic barriers to accessing and engaging with TB services faced by TB-affected households in Nepal. The findings have been used to inform the design of a socioeconomic support intervention for TB-affected households. The acceptability, feasibility and impact of this intervention on TB-related costs, stigma and TB treatment outcomes, is now being evaluated in a pilot implementation study in Nepal

The role of active case finding in reducing patient incurred catastrophic costs for tuberculosis in Nepal

Stop TB Partnership/UNOPS – TB REACH project (grant number: 5–31); European Union, Horizon 2020 – IMPACT TB project (grant number: 733174).Background The World Health Organization (WHO) End TB Strategy has established a milestone to reduce the number of tuberculosis (TB)- affected households facing catastrophic costs to zero by 2020. The role of active case finding (ACF) in reducing patient costs has not been determined globally. This study therefore aimed to compare costs incurred by TB patients diagnosed through ACF and passive case finding (PCF), and to determine the prevalence and intensity of patient-incurred catastrophic costs in Nepal. Methods The study was conducted in two districts of Nepal: Bardiya and Pyuthan (Province No. 5) between June and August 2018. One hundred patients were included in this study in a 1:1 ratio (PCF: ACF, 25 consecutive ACF and 25 consecutive PCF patients in each district). The WHO TB patient costing tool was applied to collect information from patients or a member of their family regarding indirect and direct medical and non-medical costs. Catastrophic costs were calculated based on the proportion of patients with total costs exceeding 20% of their annual household income. The intensity of catastrophic costs was calculated using the positive overshoot method. The chi-square and Wilcoxon-Mann-Whitney tests were used to compare proportions and costs. Meanwhile, the Mantel Haenszel test was performed to assess the association between catastrophic costs and type of diagnosis. Results Ninety-nine patients were interviewed (50 ACF and 49 PCF). Patients diagnosed through ACF incurred lower costs during the pre-treatment period (direct medical: USD 14 vs USD 32, P = 0.001; direct non-medical: USD 3 vs USD 10, P = 0.004; indirect, time loss: USD 4 vs USD 13, P <  0.001). The cost of the pre-treatment and intensive phases combined was also lower for direct medical (USD 15 vs USD 34, P = 0.002) and non-medical (USD 30 vs USD 54, P = 0.022) costs among ACF patients. The prevalence of catastrophic direct costs was lower for ACF patients for all thresholds. A lower intensity of catastrophic costs was also documented for ACF patients, although the difference was not statistically significant. Conclusions ACF can reduce patient-incurred costs substantially, contributing to the End TB Strategy target. Other synergistic policies, such as social protection, will also need to be implemented to reduce catastrophic costs to zero among TB-affected households.Publisher PDFPeer reviewe

How to reduce household costs for people with tuberculosis : a longitudinal costing survey in Nepal

The aim of this study was to compare costs and socio-economic impact of tuberculosis (TB) for patients diagnosed through active (ACF) and passive case finding (PCF) in Nepal. A longitudinal costing survey was conducted in four districts of Nepal from April 2018 to October 2019. Costs were collected using the WHO TB Patient Costs Survey at three time points: intensive phase of treatment, continuation phase of treatment and at treatment completion. Direct and indirect costs and socio-economic impact (poverty headcount, employment status and coping strategies) were evaluated throughout the treatment. Prevalence of catastrophic costs was estimated using the WHO threshold. Logistic regression and generalized estimating equation were used to evaluate risk of incurring high costs, catastrophic costs and socio-economic impact of TB over time. A total of 111 ACF and 110 PCF patients were included. ACF patients were more likely to have no education (75% vs 57%, P = 0.006) and informal employment (42% vs 24%, P = 0.005) Compared with the PCF group, ACF patients incurred lower costs during the pretreatment period (mean total cost: US$55 vs US$87, P < 0.001) and during the pretreatment plus treatment periods (mean total direct costs: US$72 vs US$101, P < 0.001). Socio-economic impact was severe for both groups throughout the whole treatment, with 32% of households incurring catastrophic costs. Catastrophic costs were associated with ‘no education’ status [odds ratio = 2.53(95% confidence interval = 1.16–5.50)]. There is a severe and sustained socio-economic impact of TB on affected households in Nepal. The community-based ACF approach mitigated costs and reached the most vulnerable patients. Alongside ACF, social protection policies must be extended to achieve the zero catastrophic costs milestone of the End TB strategy

Active Case Finding for Tuberculosis in Nepal

Background: Tuberculosis is one of the leading causes of death in globally and especially in LMICs. Despite being a preventable, curable disease, a person dies of TB every 20 seconds and every 2 minutes child dies because of tuberculosis. The Covid-19 pandemic had a devastating impact on access to TB diagnosis and treatment and the burden of TB disease. 10.6 million people fell ill with TB in 2021. Of these, approximately 6.4 million people with TB were ‘missing’: i.e. not diagnosed and notified through national TB programmes. The first national TB Prevalence survey for Nepal revealed that the burden of TB in Nepal is 1.6 times higher than WHO previously estimated. This showed that there are about 40,000 TB cases ‘missing’ every year in Nepal. This case detection gap reflects the substantial barriers to access TB diagnosis and care, particularly in rural Nepal. It is vital that Nepal closes the case detection gap to achieve the commitments to the END TB strategy and accelerate progress towards TB elimination. Active Case Finding is an essential component, of a comprehensive strategy to find, diagnosis and treat missing cases, but stronger evidence is required for national TB programmes to build evidence informed and cost-effective ACF strategies integrated with, and complementary to, existing passive case finding services. Aims: The thesis aimed to strengthen evidence to inform policy on effective ACF strategies appropriate to be implemented by the Nepali National TB programme embedded within the Nepali health system. Two major themes were explored (1) yields and additionality achieved using different ACF models (2) the potential impact of ACF on prevalence and intensity of catastrophic costs for TB patients in Nepal. Methods: The studies reported in this thesis were conducted within two major Birat Nepal Medical Trust (BNMT) community based TB active case finding implementation projects: the TB REACH wave 5 and IMPACT TB projects. The TB REACH project was implemented in 8 districts in the mid west and far west region. The IMPACT TB project was implemented in 4 districts of the central region of Nepal. Within both projects, the yield and additionality of active case finding using either the advanced molecular diagnostic GeneXpert test or smear microscopy for TB diagnosis was compared. Three case finding strategies were employed: social contact tracing, TB camps in hard-to-reach areas and screening at hospital OPD visits (TB REACH only). A network of community health workers identified individuals for screening, through interviewing index TB patients or consultation with health service providers. After verbal screening, symptomatic individuals were tested using either smear microscopy or GeneXpert tests. Case notification and additionality (crude and adjusted) was compared with control districts using TB REACH recommended methodology for analysis. The second theme of the thesis explored patient incurred costs for TB and the potential role of ACF in reducing prevalence and intensity of catastrophic costs. Patient Cost data were collected using an adapted, translated and validated version of the WHO TB patient costing tool. For the TB REACH project, a cross sectional (single interview timepoint) survey wasconducted during the intensive phase of treatment. During the IMPACT TB study, the costing tool was adapted to a longitudinal design and additional interviews conducted during the continuation phase and at treatment completion. Socio-economic impacts were also evaluated throughout the treatment to understand changes in socioeconomic impacts and household recovery during treatment. Results: The yield study from TB REACH project (chapter 3) showed that the project identified 1,092 TB cases. The highest yield was obtained from OPD screening at hospitals (n=566/1092; 52%). The proportion of positive test using GeneXpert (n=859/15637; 5.5%) was significantly higher than from smear microscopy testing (n=120/6309; 2%). The project achieved 29% additionality in case notifications in the GeneXpert intervention districts. Similarly, the IMPACT TB yield study (chapter 4) showed that the project identified 1,133 TB positive cases during community-based TB ACF implementation. The positive rate of tested individuals during active case finding using GeneXpert and microscopy was (n=764/17114; 4.5%) and (n=437/13285; 3.3%), respectively. Social contact tracing for TB using GeneXpert testing yielded an additional 22% to district level TB notifications in Nepal. The TB REACH cross sectional patient costing study (chapter 5) revealed that the prevalence of direct catastrophic costs was lower for ACF patients when compared with PCF patients (13% vs 33%, p = 0.029). Furthermore, patients over 60 were particularly vulnerable to catastrophic costs when diagnosed passively rather than actively. The IMPACT TB longitudinal costing study (chapter 6) revealed that the socio-economic impact was severe for both groups (ACF and PCF) throughout the whole treatment, with 32% of households incurring catastrophic costs. ACF was associated with significantly lower patient costs during the pre-treatment period (mean total pretreatment costs of 56 USD and 87 USD for ACF and PCF groups, respectively. P<0.001). Three quarters of patients experienced extreme poverty in the intensive phase of treatment. ACF reached more vulnerable patient groups, with those diagnosed more likely to have no formal education, work in the informal sector or be from the lowest socioeconomic groups. Incurment of costs over the catastrophic costs threshold was also associated with ‘no education’ status, reflecting the severest financial impact of TB on the most vulnerable population groups. Conclusions: Community based ACF is an important strategy to both close the case detection gap, improve equity of access to TB services and reduce patient incurred direct and catastrophic costs. Substantial additionality in TB case notifications was demonstrated through OPD screening and social-contact tracing strategies. GeneXpert based ACF was a more effective strategy with higher yields than smear microscopy based ACF. Although TB camps had a relatively low yield, this strategy reaches remote populations and is an important component of comprehensive TB case finding strategy in the context of Nepal. Early detection and treatment of TB can subsequently prevent suffering, death and further transmission of TB and substantially contribute to achieve the WHO End TB strategy targets by 2035. The community based ACF approach mitigated costs and reached the most vulnerable patients. Socio-economic consequences are severe and sustained on TB affected households in Nepal and therefore social protection policies have to be implemented to achieve the zero catastrophic costs milestone of the End TB strategy. This thesis provided significant evidence to inform both national and global TB ACF policy, and translation of policy to effective action. ACF should be scaled up nationwide, integrated within the existing health services applying comprehensive access to GeneXpert testing. It is vital that Nepal closes the case detection gap for TB to accelerate progress towards the END TB strategy goals. ACF scale-up has significant potential to contribute to the reduction of TB and to the elimination of catastrophic costs for TB patients in Nepal