Tuberculosis active case finding in Cambodia: a pragmatic, cost-effectiveness comparison of three implementation models.

BACKGROUND: Globally, almost 40% of tuberculosis (TB) patients remain undiagnosed, and those that are diagnosed often experience prolonged delays before initiating correct treatment, leading to ongoing transmission. While there is a push for active case finding (ACF) to improve early detection and treatment of TB, there is extremely limited evidence about the relative cost-effectiveness of different ACF implementation models. Cambodia presents a unique opportunity for addressing this gap in evidence as ACF has been implemented using different models, but no comparisons have been conducted. The objective of our study is to contribute to knowledge and methodology on comparing cost-effectiveness of alternative ACF implementation models from the health service perspective, using programmatic data, in order to inform national policy and practice. METHODS: We retrospectively compared three distinct ACF implementation models - door to door symptom screening in urban slums, checking contacts of TB patients, and door to door symptom screening focusing on rural populations aged above 55 - in terms of the number of new bacteriologically-positive pulmonary TB cases diagnosed and the cost of implementation assuming activities are conducted by the national TB program of Cambodia. We calculated the cost per additional case detected using the alternative ACF models. RESULTS: Our analysis, which is the first of its kind for TB, revealed that the ACF model based on door to door screening in poor urban areas of Phnom Penh was the most cost-effective (249 USD per case detected, 737 cases diagnosed), followed by the model based on testing contacts of TB patients (308 USD per case detected, 807 cases diagnosed), and symptomatic screening of older rural populations (316 USD per case detected, 397 cases diagnosed). CONCLUSIONS: Our study provides new evidence on the relative effectiveness and economics of three implementation models for enhanced TB case finding, in line with calls for data from 'routine conditions' to be included in disease control program strategic planning. Such cost-effectiveness comparisons are essential to inform resource allocation decisions of national policy makers in resource constraint settings. We applied a novel, pragmatic methodological approach, which was designed to provide results that are directly relevant to policy makers, costing the interventions from Cambodia's national TB program's perspective and using case finding data from implementation activities, rather than experimental settings

Evaluation of the 2007 WHO guideline to improve the diagnosis of tuberculosis in ambulatory HIV-positive adults.

BACKGROUND: In 2007 WHO issued a guideline to improve the diagnosis of smear-negative and extrapulmonary tuberculosis (EPTB) in HIV-positive patients. This guideline relies heavily on the acceptance of HIV-testing and availability of chest X-rays. METHODS AND FINDINGS: Cohort study of TB suspects in four tuberculosis (TB) clinics in Phnom Penh, Cambodia. We assessed the operational performance of the guideline, the incremental yield of investigations, and the diagnostic accuracy for smear-negative tuberculosis in HIV-positive patients using culture positivity as reference standard. 1,147 (68.9%) of 1,665 TB suspects presented with unknown HIV status, 1,124 (98.0%) agreed to be tested, 79 (7.0%) were HIV-positive. Compliance with the guideline for chest X-rays and sputum culture requests was 97.1% and 98.3% respectively. Only 35 of 79 HIV-positive patients (44.3%) with a chest X-ray suggestive of TB started TB treatment within 10 days. 105 of 442 HIV-positive TB suspects started TB treatment (56.2% smear-negative pulmonary TB (PTB), 28.6% smear-positive PTB, 15.2% EPTB). The median time to TB treatment initiation was 5 days (IQR: 2-13 days), ranging from 2 days (IQR: 1-11.5 days) for EPTB, over 2.5 days (IQR: 1-4 days) for smear-positive PTB to 9 days (IQR: 3-17 days) for smear-negative PTB. Among the 34 smear-negative TB patients with a confirmed diagnosis, the incremental yield of chest X-ray, clinical suspicion or abdominal ultrasound, and culture was 41.2%, 17.6% and 41.2% respectively. The sensitivity and specificity of the algorithm to diagnose smear-negative TB in HIV-positive TB suspects was 58.8% (95%CI: 42.2%-73.6%) and 79.4% (95%CI: 74.8%-82.4%) respectively. CONCLUSIONS: Pending point-of-care rapid diagnostic tests for TB disease, diagnostic algorithms are needed. The diagnostic accuracy of the 2007 WHO guideline to diagnose smear-negative TB is acceptable. There is, however, reluctance to comply with the guideline in terms of immediate treatment initiation

Effect of community active case-finding strategies for detection of tuberculosis in Cambodia: study protocol for a pragmatic cluster randomized controlled trial.

BACKGROUND: Cambodia has made notable progress in the fight against tuberculosis (TB). However, these gains are impeded by a significant proportion of undiagnosed cases. To effectively reach people with TB, active case-finding (ACF) strategies have been adopted by countries affected by the epidemic, including Cambodia, alongside passive case finding (PCF). Despite increased efforts to improve case detection, approximately 40% of TB cases in Cambodia remained undiagnosed in 2018. In Cambodia, several community-based TB ACF modalities have been implemented, but their effectiveness has yet to be systematically assessed. METHODS: This pragmatic cluster randomized controlled trial will be conducted between December 2019 and June 2021. We will randomize eight operational districts (clusters) in seven provinces (Kampong Cham, Kampong Thom, Prey Veng, Thbong Khmum, Kampong Chhnang, Kandal, and Kampong Speu) to either the control group (PCF) or the intervention groups (ACF using a seed-and-recruit model, ACF targeting household and neighborhood contacts, and ACF targeting persons aged ≥ 55 years using mobile screening units). The primary endpoints will be TB case notification rates, additionality, and cumulative yield of TB cases. The secondary endpoints include treatment outcomes, the number needed to screen to find one TB case, and cost-effectiveness outcome measures. We will analyze the primary and secondary endpoints by intention to treat. We will compare cluster and individual-level characteristics using Student's t test and hierarchical or mixed-effect models to estimate the ratio of these means. The incremental cost-effectiveness ratio per disability-adjusted life year averted will also be considered as a benchmark to determine whether the interventions are cost-effective. DISCUSSION: This study will build an evidence base to inform future scale-up, implementation, and sustainability of ACF strategies in Cambodia and other similar settings. Implementation of this study will also complement TB control strategies in Cambodia by conducting ACF in operational districts without active interventions to find TB cases currently. Those who are ill and might have TB will be promptly screened, diagnosed, and linked to care. Early diagnosis and treatment initiation will also benefit their community by interrupting transmission and prevent further infections. The experience gained from this project will inform future attempts in conducting pragmatic trials in low-resource settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04094350. Registered on 18 September 2019

Spatial and temporal projections of the prevalence of active tuberculosis in Cambodia.

INTRODUCTION: Cambodia is among the 30 highest burden of tuberculosis (TB) countries. Active TB prevalence has been estimated using nationally representative multistage sampling that represents urban, rural and remote parts of the country, but the prevalence in non-sampled communes remains unknown. This study uses geospatial Bayesian statistics to estimate point prevalence across Cambodia, and demographic modelling that accounts for secular trends in fertility, mortality, urbanisation and prevalence rates to project the future burden of active TB. METHODS: A Bayesian hierarchical model was developed for the 2011 National Tuberculosis Prevalence survey to estimate the differential effect of age, sex and geographic stratum on active TB prevalence; these estimates were then married with high-resolution geographic information system layers to project prevalence across Cambodia. Future TB projections under alternative scenarios were then derived by interfacing these estimates with an individual-based demographic model. RESULTS: Strong differences in risk by age and sex, together with geographically varying population structures, yielded the first estimated prevalence map at a 1 km scale. The projected number of active TB cases within the catchment area of each existing government healthcare facility was derived, together with projections to the year 2030 under three scenarios: no future improvement, c ontinual r eduction and GDP projection. CONCLUSION: Synthesis of health and geographic data allows likely disease rates to be mapped at a high resolution to facilitate resource planning, while demographic modelling allows scenarios to be projected, demonstrating the need for the acceleration of control efforts to achieve a substantive impact on the future burden of TB in Cambodia

Resistance and renewal: health sector reform and Cambodia’s national tuberculosis programme

Following the destruction of Cambodia’s health infrastructure during the Khmer Rouge period (1975–1979) and the subsequent decade of United Nations sanctions, international development assistance has focused on reconstructing the country’s health system. The recognition of Cambodia’s heavy burden of tuberculosis (TB) and the lapse of TB control strategies during the transition to democracy prompted the national tuberculosis programme’s relaunch in the mid-1990s as WHO-backed health sector reforms were introduced. This paper examines the conflicts that arose between health reforms and TB control programmes due to their different operating paradigms. It also discusses how these tensions were resolved during introduction of the DOTS strategy for TB treatment

Increased Case Notification through Active Case Finding of Tuberculosis among Household and Neighbourhood Contacts in Cambodia.

BACKGROUND:Globally, there has been growing evidence that suggests the effectiveness of active case finding (ACF) for tuberculosis (TB) in high-risk populations. However, the evidence is still insufficient as to whether ACF increases case notification beyond what is reported in the routine passive case finding (PCF). In Cambodia, National TB Control Programme has conducted nationwide ACF with Xpert MTB/RIF that retrospectively targeted household and neighbourhood contacts alongside routine PCF. This study aims to investigate the impact of ACF on case notifications during and after the intervention period. METHODS:Using a quasi-experimental cluster randomized design with intervention and control arms, we compared TB case notification during the one-year intervention period with historical baseline cases and trend-adjusted expected cases, and estimated additional cases notified during the intervention period (separately for Year 1 and Year 2 implementation). The proportion of change in case notification was compared between intervention and control districts for Year 1. The quarterly case notification data from all intervention districts were consolidated, aligning different implementation quarters, and separately analysed to explore the additionality. The effect of the intervention on the subsequent case notification during the post-intervention period was also assessed. RESULTS:In Year 1, as compared to expected cases, 1467 cases of all forms (18.5%) and 330 bacteriologically-confirmed cases (9.6%) were additionally notified in intervention districts, whereas case notification in control districts decreased by 2.4% and 2.3%, respectively. In Year 2, 2737 cases of all forms (44.3%) and 793 bacteriologically-confirmed cases (38%) were additionally notified as compared to expected cases. The proportions of increase in case notifications from baseline cases and expected cases to intervention period cases were consistently higher in intervention group than in control group. The consolidated quarterly data showed sharp rises in all forms and bacteriologically-confirmed cases notified during the intervention quarter, with 64.6% and 68.4% increases (compared to baseline cases), and 46% and 52.9% increases (compared to expected cases), respectively. A cumulative reduction of case notification for five quarters after ACF reached more than -200% of additional cases. CONCLUSIONS:The Cambodia's ACF with Xpert MTB/RIF that retrospectively targeted household and neighbourhood contacts resulted in the substantial increase in case notification during the intervention period and reduced subsequent case notification during the post-intervention period. The applicability of retrospective contact investigation in other high-burden settings should be explored

Results from a roving, active case finding initiative to improve tuberculosis detection among older people in rural cambodia using the Xpert MTB/RIF assay and chest X-ray

Background: Cambodia has one of the highest tuberculosis (TB) prevalence rates in the world. People aged 55 years and over account for an estimated 50% of the country's TB burden, yet this group has a low notification rate owing to specific barriers in accessing health services. One-off active case finding (ACF) days with mobile GeneXpert and X-ray systems were organized at 75 government health facilities in four operational districts. Symptomatic community members with an abnormal chest X-ray were tested using the Xpert MTB/RIF assay. People with TB were then treated at health facilities after screening services moved onto the next site. Methods: De-identified project data were analysed to produce descriptive statistics about the people tested on Xpert and those diagnosed with TB. A linear regression was fit through the 12 quarters of National TB Program (NTP) TB case notification data immediately prior to ACF. The regression was used to calculate trend-expected notifications during and after the ACF quarters. Notifications from the ACF quarters were then compared to actual notifications from the previous year and to the trend-expected notifications during the ACF quarter by age group and type of TB. Finally, NTP TB treatment outcomes for the patients started on treatment during the ACF quarter were compared to those from a year prior. Results: 2068 individuals submitted sputum for Xpert MTB/RIF testing, resulting in the identification of 319 (15.4%) bacteriologically-positive TB patients and an additional 574 people who were clinically diagnosed with TB. In the ACF quarters, new bacteriologically-positive notifications increased +119.2% for all ages and +262.7% for people aged 55 and over compared with trend-expected notifications. Treatment initiation figures remained above trend-expected notifications for three full quarters after ACF. The treatment success rate across all operational districts was significantly higher for patients detected in the ACF quarters (88.8% vs 94.5%, p = 0.012). Conclusion: A series of roving, one-off ACF days at government health facilities were able to increase TB diagnosis, treatment initiation and treatment outcomes in a key population with high TB prevalence. Targeted ACF interventions such as this could be used to reduce a backlog of untreated, prevalent TB. Keywords: Tuberculosis, Active case finding, Elderly, Chest X-ray, Xpert, GeneXper

Summary of quarter-adjusted case notification and additional cases.

<p>Summary of quarter-adjusted case notification and additional cases.</p