Tobacco smoking clusters in households affected by tuberculosis in an individual participant data meta-analysis of national tuberculosis prevalence surveys: Time for household-wide interventions?

Tuberculosis (TB) and non-communicable diseases (NCD) share predisposing risk factors. TB-associated NCD might cluster within households affected with TB requiring shared prevention and care strategies. We conducted an individual participant data meta-analysis of national TB prevalence surveys to determine whether NCD cluster in members of households with TB. We identified eligible surveys that reported at least one NCD or NCD risk factor through the archive maintained by the World Health Organization and searching in Medline and Embase from 1 January 2000 to 10 August 2021, which was updated on 23 March 2023. We compared the prevalence of NCD and their risk factors between people who do not have TB living in households with at least one person with TB (members of households with TB), and members of households without TB. We included 16 surveys (n = 740,815) from Asia and Africa. In a multivariable model adjusted for age and gender, the odds of smoking was higher among members of households with TB (adjusted odds ratio (aOR) 1.23; 95% CI: 1.11-1.38), compared with members of households without TB. The analysis did not find a significant difference in the prevalence of alcohol drinking, diabetes, hypertension, or BMI between members of households with and without TB. Studies evaluating household-wide interventions for smoking to reduce its dual impact on TB and NCD may be warranted. Systematically screening for NCD using objective diagnostic methods is needed to understand the actual burden of NCD and inform comprehensive interventions.

Adherence trajectory as an on-treatment risk indicator among drug-resistant TB patients in the Philippines.

INTRODUCTION: High levels of treatment adherence are critical for achieving optimal treatment outcomes among patients with tuberculosis (TB), especially for drug-resistant TB (DR TB). Current tools for identifying high-risk non-adherence are insufficient. Here, we apply trajectory analysis to characterize adherence behavior early in DR TB treatment and assess whether these patterns predict treatment outcomes. METHODS: We conducted a retrospective analysis of Philippines DR TB patients treated between 2013 and 2016. To identify unique patterns of adherence, we performed group-based trajectory modelling on adherence to the first 12 weeks of treatment. We estimated the association of adherence trajectory group with six-month and final treatment outcomes using univariable and multivariable logistic regression. We also estimated and compared the predictive accuracy of adherence trajectory group and a binary adherence threshold for treatment outcomes. RESULTS: Of 596 patients, 302 (50.7%) had multidrug resistant TB, 11 (1.8%) extremely drug-resistant (XDR) TB, and 283 (47.5%) pre-XDR TB. We identified three distinct adherence trajectories during the first 12 weeks of treatment: a high adherence group (n = 483), a moderate adherence group (n = 93) and a low adherence group (n = 20). Similar patterns were identified at 4 and 8 weeks. Being in the 12-week moderate or low adherence group was associated with unfavorable six-month (adjusted OR [aOR] 3.42, 95% CI 1.90-6.12) and final (aOR 2.71, 95% 1.73-4.30) treatment outcomes. Adherence trajectory group performed similarly to a binary threshold classification for the prediction of final treatment outcomes (65.9% vs. 65.4% correctly classified), but was more accurate for prediction of six-month treatment outcomes (79.4% vs. 60.0% correctly classified). CONCLUSIONS: Adherence patterns are strongly predictive of DR TB treatment outcomes. Trajectory-based analyses represent an exciting avenue of research into TB patient adherence behavior seeking to inform interventions which rapidly identify and support patients with high-risk adherence patterns.

Expansion of social protection is necessary towards zero catastrophic costs due to TB: The first national TB patient cost survey in the Philippines.

BACKGROUND: Tuberculosis (TB) is a disease associated with poverty. Moreover, a significant proportion of TB patients face a substantial financial burden before and during TB care. One of the top targets in the End TB strategy was to achieve zero catastrophic costs due to TB by 2020. To assess patient costs related to TB care and the proportion of TB-affected households that faced catastrophic costs, the Philippines National TB Programme (NTP) conducted a national TB patient cost survey in 2016-2017. METHODS: A cross-sectional survey of 1,912 TB patients taking treatment in health facilities engaged with the NTP. The sample consists of 786 drug-sensitive TB (DS-TB) patients in urban facilities, 806 DS-TB patients in rural facilities, and 320 drug-resistant TB (DR-TB) patients. Catastrophic cost due to TB is defined as total costs, consisting of direct medical and non-medical costs and indirect costs net of social assistance, exceeding 20% of annual household income. RESULTS: The overall mean total cost including pre- and post-diagnostic costs was US$601. The mean total cost was five times higher among DR-TB patients than DS-TB patients. Direct non-medical costs and income loss accounted for 42.7% and 40.4% of the total cost of TB, respectively. More than 40% of households had to rely on dissaving, taking loans, or selling their assets to cope with the costs. Overall, 42.4% (95% confidence interval (95% CI): 40.2-44.6) of TB-affected households faced catastrophic costs due to TB, and it was significantly higher among DR-TB patients (89.7%, 95%CI: 86.3-93.0). A TB enabler package, which 70% of DR-TB patients received, reduced catastrophic costs by 13.1 percentage points (89.7% to 76.6%) among DR-TB patients, but only by 0.4 percentage points (42.4% to 42.0%), overall. CONCLUSIONS: TB patients in the Philippines face a substantial financial burden due to TB despite free TB services provided by the National TB Programme. The TB enabler package mitigated catastrophic costs to some extent, but only for DR-TB patients. Enhancing the current social and welfare support through multisectoral collaboration is urgently required to achieve zero catastrophic costs due to TB.

Behavioural barriers and perceived trade-offs to care-seeking for tuberculosis in the Philippines.

Effective tuberculosis (TB) treatment has existed for more than 50 years, but TB remains a leading cause of death worldwide and in the Philippines, in part because symptomatic individuals delay or avoid seeking care. Through qualitative interviews in Pampanga, Philippines, we investigated barriers to care-seeking using a behavioural science lens. We found barriers to TB care-seeking to be shaped by: (1) ambiguous symptoms; (2) association of TB risk with lifestyle and habits; (3) expectations of stigma, discrimination, and isolation; (4) short-term costs and long-term financial burden of TB; and (5) visibility of care in public sector facilities. Findings suggest that these barriers are deeply intertwined and that, typically, it is a combination of barriers that holds back a particular symptomatic individual from seeking care, as the barriers influence implicit trade-offs related to health, social, and financial consequences of having TB or another serious illness and of seeking care or not seeking care. The findings suggest avenues for more effectively reaching those with symptoms and their family members to encourage care-seeking by elevating the perceived benefits and putting perceived costs in proper perspective.

Cost-effectiveness of bedaquiline, pretomanid and linezolid for treatment of extensively drug-resistant tuberculosis in South Africa, Georgia and the Philippines.

OBJECTIVES: Patients with highly resistant tuberculosis have few treatment options. Bedaquiline, pretomanid and linezolid regimen (BPaL) is a new regimen shown to have favourable outcomes after six months. We present an economic evaluation of introducing BPaL against the extensively drug-resistant tuberculosis (XDR-TB) standard of care in three epidemiological settings. DESIGN: Cost-effectiveness analysis using Markov cohort model. SETTING: South Africa, Georgia and the Philippines. PARTICIPANTS: XDR-TB and multidrug-resistant tuberculosis (MDR-TB) failure and treatment intolerant patients. INTERVENTIONS: BPaL regimen. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) Incremental cost per disability-adjusted life years averted by using BPaL against standard of care at the Global Drug Facility list price. (2) The potential maximum price at which the BPaL regimen could become cost neutral. RESULTS: BPaL for XDR-TB is likely to be cost saving in all study settings when pretomanid is priced at the Global Drug Facility list price. The magnitude of these savings depends on the prevalence of XDR-TB in the country and can amount, over 5 years, to approximately US$ 3 million in South Africa, US$ 200 000 and US$ 60 000 in Georgia and the Philippines, respectively. In South Africa, related future costs of antiretroviral treatment (ART) due to survival of more patients following treatment with BPaL reduced the magnitude of expected savings to approximately US$ 1 million. Overall, when BPaL is introduced to a wider population, including MDR-TB treatment failure and treatment intolerant, we observe increased savings and clinical benefits. The potential threshold price at which the probability of the introduction of BPaL becoming cost neutral begins to increase is higher in Georgia and the Philippines (US$ 3650 and US$ 3800, respectively) compared with South Africa (US$ 500) including ART costs. CONCLUSIONS: Our results estimate that BPaL can be a cost-saving addition to the local TB programmes in varied programmatic settings.

Impact of shelter-in-place orders on TB case notifications and mortality in the Philippines during the COVID-19 pandemic.

BACKGROUND: Policies implemented to slow transmission of COVID-19 are expected to have disrupted delivery of routine health services, including tuberculosis (TB) care. METHODS: We analyzed daily counts of drug-susceptible (DS)-TB case notifications from all health facilities affiliated with the Philippines National TB Program (NTP) before and after implementation of community quarantine (January 1-December 31, 2020). Using an interrupted time series design, we assessed the immediate and sustained effects of community quarantine on TB case reporting. Using 2019 WHO estimates of national TB incidence, treatment, and mortality rates for the Philippines, we modeled excess mortality from TB, assuming a national decline in TB case reporting were extended for 12 months, followed by a return to pre-community quarantine trends. RESULTS: The analysis included 192,918 DS-TB case notifications from 2,986 facilities located in 113 provinces and highly urbanized cities across 17 regions and covered 49 observations days before and 174 days after community quarantine implementation. We found an significant drop and steeper decline in daily TB case notifications after the implementation of community quarantine, resulting in 44.6% (95% CI 38.3-50.1) fewer daily TB case notifications 60 days after implementation of community quarantine. During 2020, DS-TB case notifications never returned to pre-quarantine levels. Assuming a 12-month disruption of TB case reporting, we estimate there will be 56.3% increase in TB-related deaths in the Philippines. CONCLUSION: Modified delivery of TB prevention and care should be prioritized alongside efforts to combat COVID-19.

High TB burden and low notification rates in the Philippines: The 2016 national TB prevalence survey.

SETTING: The 3rd national tuberculosis (TB) survey in the Philippines in 2007 reported a significant decline in the prevalence of TB. Since then, more significant investments for TB control have been made, yet TB burden estimates from routine surveillance data remain relatively stable. OBJECTIVE: To estimate the prevalence of bacteriologically confirmed pulmonary TB in the Philippines amongst individuals aged ≥15 years in 2016. DESIGN: In March-December 2016, we conducted a population-based survey with stratified, multi-stage cluster sampling of residents in 106 clusters aged ≥15 years. Survey participants were screened for TB by symptom-based interview and digital chest X-ray. Those with cough ≥2 weeks and/or haemoptysis and/or chest X-ray suggestive of TB were requested to submit 2 sputum specimens for Xpert MTB/RIF, direct sputum smear microscopy using LED fluorescent microscopy, and mycobacterial solid culture (Ogawa method). Bacteriologically confirmed pulmonary TB was defined as MTB culture positive and/or Xpert positive. RESULTS: There were 46,689 individuals interviewed, and 41,444 (88.8%) consented to a chest X-ray. There were 18,597 (39.8%) eligible for sputum examination and 16,242 (87.3%) submitted at least one specimen. Out of 16,058 sputum-eligible participants, 183 (1.1%) were smear-positive. There were 466 bacteriologically confirmed TB cases: 238 (51.1%) Xpert positive, 69 (14.8%) culture positive, and 159 (34.1%) positive by both Xpert and culture. The estimated TB prevalence per 100,000 population aged ≥15 years was 434 (95% CI: 350-518) for smear-positive TB, and 1,159 (95% CI: 1,016-1,301) for bacteriologically confirmed TB. CONCLUSION: This nationally representative survey found that the TB burden in the Philippines in 2016 was higher than estimated from routine TB surveillance data. There was no evidence of a decline in smear and culture positive TB from the 2007 survey despite significant investments in TB control. New strategies for case-finding and patient-centered care must be intensified and expanded.

Patterns and predictors of co-morbidities in Tuberculosis: A cross-sectional study in the Philippines.

Diabetes and undernutrition are common risk factors for TB, associated with poor treatment outcomes and exacerbated by TB. We aimed to assess non-communicable multimorbidity (co-occurrence of two or more medical conditions) in Filipino TB outpatients, focusing on malnutrition and diabetes. In a cross-sectional study, 637 adults (70% male) from clinics in urban Metro Manila (N = 338) and rural Negros Occidental (N = 299) were enrolled. Diabetes was defined as HbA1c of ≥6.5% and/or current diabetes medication. Study-specific HIV screening was conducted. The prevalence of diabetes was 9.2% (54/589, 95%CI: 7.0-11.8%) with 52% newly diagnosed. Moderate/severe undernutrition (body mass index (BMI) <17 kg/2) was 20.5% (130/634, 95%CI: 17.4-23.9%). Forty percent of participants had at least one co-morbidity (diabetes, moderate/severe undernutrition or moderate/severe anaemia (haemoglobin <11 g/dL)). HIV infection (24.4%, 74/303) was not associated with other co-morbidities (but high refusal in rural clinics). Central obesity assessed by waist-to-hip ratio was more strongly associated with diabetes (Adjusted Odds Ratio (AOR) = 6.16, 95%CI: 3.15-12.0) than BMI. Undernutrition was less common in men (AOR = 0.44, 95%CI: 0.28-0.70), and associated with previous history of TB (AOR = 1.97, 95%CI: 1.28-3.04) and recent reduced food intake. The prevalence of multimorbidity was high demonstrating a significant unmet need. HIV was not a risk factor for increased non-communicable multimorbidity.

Use of GeneXpert and the role of an expert panel in improving clinical diagnosis of smear-negative tuberculosis cases.

SETTING: A high proportion of notified tuberculosis cases in the Philippines are clinically diagnosed (63%) as opposed to bacteriologically confirmed. Better understanding of this phenomenon is required to improve tuberculosis control. OBJECTIVES: To determine the percentage of smear negative presumptive tuberculosis patients that would be diagnosed by GeneXpert; compare clinical characteristics of patients diagnosed as tuberculosis cases; and review the impact that the current single government physician and a reconstituted Tuberculosis Diagnostic committee (expert panel) may have on tuberculosis over-diagnosis. DESIGN: This a cross-sectional study of 152 patients 15-85 years old with two negative Direct Sputum Smear Microscopy results, with abnormal chest X-ray who underwent GeneXpert testing and review by an expert panel. RESULTS: Thirty-two percent (48/152) of the sample were Xpert positive and 93% (97/104) of GeneXpert negatives were clinically diagnosed by a single physician. Typical symptoms and X-ray findings were higher in bacteriologically confirmed tuberculosis. When compared to the GeneXpert results the Expert panel's sensitivity for active tuberculosis was high (97.5%, 39/40), specificity was low (40.2%, 35/87). CONCLUSION: Using the GeneXpert would increase the level of bacteriologically confirmed tuberculosis substantially among presumptive tuberculosis. An expert panel will greatly reduce over-diagnosis usually seen when a decision is made by a single physician.

Bringing state-of-the-art diagnostics to vulnerable populations: The use of a mobile screening unit in active case finding for tuberculosis in Palawan, the Philippines.

BACKGROUND: Globally, case detection of tuberculosis (TB) has stabilized in recent years. Active case finding (ACF) has regained an increased attention as a complementary strategy to fill the case detection gap. In the Philippines, the DetecTB project implemented an innovative ACF strategy that offered a one-stop diagnostic service with a mobile unit equipped with enhanced diagnostic tools including chest X-ray (CXR) and Xpert®MTB/RIF (Xpert). The project targeted the rural poor, the urban poor, prison inmates, indigenous population and high school students. METHODS: This is a retrospective review of TB screening data from 25,103 individuals. A descriptive analysis was carried out to compare screening and treatment outcomes across target populations. Univariate and multivariate analyses were performed to identify predictors of TB for each population. The composition of bacteriologically-confirmed cases by smear and symptom status was further investigated. RESULTS: The highest yield with lowest number needed to screen (NNS) was found in prison (6.2%, NNS: 16), followed by indigenous population (2.9%, NNS: 34), the rural poor (2.2%, NNS: 45), the urban poor (2.1%, NNS: 48), and high school (0.2%, NNS: 495). The treatment success rate for all populations was high with 89.5% in rifampicin-susceptible patients and 83.3% in rifampicin-resistant patients. A relatively higher loss to follow-up rate was observed in indigenous population (7.5%) and the rural poor (6.4%). Only cough more than two weeks showed a significant association with TB diagnosis in all target populations (Adjusted Odds Ratio ranging from 1.71 to 6.73) while other symptoms and demographic factors varied in their strength of association. The urban poor had the highest proportion of smear-positive patients with cough more than two weeks (72.0%). The proportion of smear-negative (Xpert-positive) patients without cough more than two weeks was the highest in indigenous population (39.3%), followed by prison inmates (27.7%), and the rural poor (22.8%). CONCLUSIONS: The innovative ACF strategy using mobile unit yielded a substantial number of TB patients and achieved successful treatment outcomes. TB screening in prison, indigenous population, and urban and rural poor communities was found to be effective. The combined use of CXR and Xpert largely contributed to increased case detection.

Factors Associated with Loss to Follow-up during Treatment for Multidrug-Resistant Tuberculosis, the Philippines, 2012-2014.

To identify factors associated with loss to follow-up during treatment for multidrug-resistant (MDR) tuberculosis (TB) in the Philippines, we conducted a case-control study of adult patients who began receiving treatment for rifampin-resistant TB during July 1-December 31, 2012. Among 91 case-patients (those lost to follow-up) and 182 control-patients (those who adhered to treatment), independent factors associated with loss to follow-up included patients' higher self-rating of the severity of vomiting as an adverse drug reaction and alcohol abuse. Protective factors included receiving any type of assistance from the TB program, better TB knowledge, and higher levels of trust in and support from physicians and nurses. These results provide insights for designing interventions aimed at reducing patient loss to follow-up during treatment for MDR TB.

Restarting the tuberculosis programme post-Haiyan.

PROBLEM: Typhoon Haiyan damaged or destroyed health infrastructure, equipment and services essential to the Philippine National Tuberculosis Programme (NTP), and it had to be re-established in the affected areas in Regions 6, 7 and 8. Continuing treatment and restoring diagnostic capacity were also challenging. CONTEXT: The Philippines has one of the highest tuberculosis (TB) burdens in the world. At the time of Typhoon Haiyan, there were an estimated 26 ,00 TB cases on treatment at directly observed treatment, short-course (DOTS) centres and 356 multidrug-resistant TB cases registered at programmatic management of drug-resistant TB (PMDT) sites. As TB was not included in the Philippines early-warning post-disaster surveillance system, tracking TB patients was difficult after Haiyan. ACTIONS AND OUTCOMES: Immediately following Haiyan, each aspect of the NTP was assessed to determine the extent of damage. TB patients were traced and services restored. We created maps showing the location of temporary TB diagnostic and treatment services, which hastened referrals. We provided new laboratory equipment, training and rapid testing capabilities in the affected regions. All TB services in the affected areas (473 DOTS, 490 TB microscopy and six PMDT facilities) were restored just two months after Haiyan. LESSONS LEARNT: Key lessons learnt from the NTP experience following Tyhoon Haiyan were: (1) the importance of having an electronic TB registry (database); (2) the need to include TB in the post-disaster surveillance system; (3) clear guidelines for TB control in disasters; and (4) the importance of coordination with all partners.

The tuberculosis profile of the Philippines, 2003-2011: advancing DOTS and beyond.

The Philippines is one of the highest tuberculosis (TB) burden countries in the world with nationwide coverage of directly observed treatment, short-course (DOTS) achieved in 2003. This study reports on the National TB Control Programme (NTP) surveillance data for the period 2003 to 2011. During this period, the number of TB symptomatics examined increased by 82% with 94% completing the required three diagnostic sputum microscopy examinations. Of the 1,379,390 cases diagnosed and given TB treatment, 98.9% were pulmonary TB cases. Of these, 54.9% were new smear-positive cases, 39.3% new smear-negative cases and 4.7% were cases previously treated. From 2008 to 2011, 50,030 TB cases were reported by non-NTP providers. Annual treatment success rates were over 85% with an average of 90%; the annual cure rates had an eight-year average of 82.1%. These surveillance data represent NTP priorities - the large proportion of smear-positive cases reflected the country's priority to treat highly infectious cases to cut the chain of transmission. The performance trend suggests that the Philippines is likely to achieve Millennium Development Goals and Stop TB targets before 2015.