Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue.

BACKGROUND: Aedes aegypti mosquitoes infected with the wMel strain of Wolbachia pipientis are less susceptible than wild-type A. aegypti to dengue virus infection. METHODS: We conducted a cluster-randomized trial involving releases of wMel-infected A. aegypti mosquitoes for the control of dengue in Yogyakarta, Indonesia. We randomly assigned 12 geographic clusters to receive deployments of wMel-infected A. aegypti (intervention clusters) and 12 clusters to receive no deployments (control clusters). All clusters practiced local mosquito-control measures as usual. A test-negative design was used to assess the efficacy of the intervention. Patients with acute undifferentiated fever who presented to local primary care clinics and were 3 to 45 years of age were recruited. Laboratory testing was used to identify participants who had virologically confirmed dengue (VCD) and those who were test-negative controls. The primary end point was symptomatic VCD of any severity caused by any dengue virus serotype. RESULTS: After successful introgression of wMel into the intervention clusters, 8144 participants were enrolled; 3721 lived in intervention clusters, and 4423 lived in control clusters. In the intention-to-treat analysis, VCD occurred in 67 of 2905 participants (2.3%) in the intervention clusters and in 318 of 3401 (9.4%) in the control clusters (aggregate odds ratio for VCD, 0.23; 95% confidence interval [CI], 0.15 to 0.35; P = 0.004). The protective efficacy of the intervention was 77.1% (95% CI, 65.3 to 84.9) and was similar against the four dengue virus serotypes. The incidence of hospitalization for VCD was lower among participants who lived in intervention clusters (13 of 2905 participants [0.4%]) than among those who lived in control clusters (102 of 3401 [3.0%]) (protective efficacy, 86.2%; 95% CI, 66.2 to 94.3). CONCLUSIONS: Introgression of wMel into A. aegypti populations was effective in reducing the incidence of symptomatic dengue and resulted in fewer hospitalizations for dengue among the participants. (Funded by the Tahija Foundation and others; AWED ClinicalTrials.gov number, NCT03055585; Indonesia Registry number, INA-A7OB6TW.).

HIV-related stigma and discrimination among health care workers during early program decentralization in rural district Gunungkidul, Indonesia: a cross-sectional study.

BACKGROUND: Expanding HIV services by decentralizing provision to primary care raises a possible concern of HIV-related stigma and discrimination (SAD) from health care workers (HCWs) as new service points gain experience in HIV care delivery during early implementation. We surveyed indicators and examined the correlates of HIV-related SAD among HCWs in a decentralizing district of rural Gunungkidul, Indonesia. METHODS: We conducted a cross-sectional survey on a random stratified sample of 234 HCWs in 14 public health facilities (one district hospital, 13 primary health centers [PHC]) during the second year of decentralization roll-out in the district. We computed the prevalence of SAD indicators and used multivariable logistic regression to identify the correlates of these SAD indicators. RESULTS: The prevalence of SAD among HCWs was similarly high between hospital and PHC HCWs for fear of HIV transmission (~71%) and perceived negative image of PHIV (~75%). Hospital HCWs exhibited somewhat lower avoidance of service duties (52.6% vs. 63.7%; p = 0.088) with weak evidence of a difference and significantly higher levels of discriminatory practice (96.1% vs. 85.6%; p = 0.009) than those working in PHCs. Recent interactions with PLHIV and receipt of training lowered the odds of fear of HIV transmission (p <0.021). However, the odds of avoiding care duties increased with receipt of training (p =0.003) and decreased for hospital HCWs (p = 0.030). HIV knowledge lowered the odds of discriminatory practice (p = 0.002), but hospital facility and nurse/midwife cadres were associated with increased odds of discriminatory practices (p <0.021). No significant correlate was found for perceived negative image of PLHIV. CONCLUSION: HIV-related SAD among HCWs can be prevalent during early decentralization, highlighting the need for timely or preparatory interventions with a focus on building the capacity of hospital and non-physician workforce for positive patient-provider interactions when delivering HIV care.

Using health facility-based serological surveillance to predict receptive areas at risk of malaria outbreaks in elimination areas.

BACKGROUND: In order to improve malaria burden estimates in low transmission settings, more sensitive tools and efficient sampling strategies are required. This study evaluated the use of serological measures from repeated health facility-based cross-sectional surveys to investigate Plasmodium falciparum and Plasmodium vivax transmission dynamics in an area nearing elimination in Indonesia. METHODS: Quarterly surveys were conducted in eight public health facilities in Kulon Progo District, Indonesia, from May 2017 to April 2018. Demographic data were collected from all clinic patients and their companions, with household coordinates collected using participatory mapping methods. In addition to standard microscopy tests, bead-based serological assays were performed on finger-prick bloodspot samples from 9453 people. Seroconversion rates (SCR, i.e. the proportion of people in the population who are expected to seroconvert per year) were estimated by fitting a simple reversible catalytic model to seroprevalence data. Mixed effects logistic regression was used to examine factors associated with malaria exposure, and spatial analysis was performed to identify areas with clustering of high antibody responses. RESULTS: Parasite prevalence by microscopy was extremely low (0.06% (95% confidence interval 0.03-0.14, n = 6) and 0 for P. vivax and P. falciparum, respectively). However, spatial analysis of P. vivax antibody responses identified high-risk areas that were subsequently the site of a P. vivax outbreak in August 2017 (62 cases detected through passive and reactive detection systems). These areas overlapped with P. falciparum high-risk areas and were detected in each survey. General low transmission was confirmed by the SCR estimated from a pool of the four surveys in people aged 15 years old and under (0.020 (95% confidence interval 0.017-0.024) and 0.005 (95% confidence interval 0.003-0.008) for P. vivax and P. falciparum, respectively). The SCR estimates in those over 15 years old were 0.066 (95% confidence interval 0.041-0.105) and 0.032 (95% confidence interval 0.015-0.069) for P. vivax and P. falciparum, respectively. CONCLUSIONS: These findings demonstrate the potential use of health facility-based serological surveillance to better identify and target areas still receptive to malaria in an elimination setting. Further implementation research is needed to enable integration of these methods with existing surveillance systems.

Use of mobile technology-based participatory mapping approaches to geolocate health facility attendees for disease surveillance in low resource settings.

BACKGROUND: Identifying fine-scale spatial patterns of disease is essential for effective disease control and elimination programmes. In low resource areas without formal addresses, novel strategies are needed to locate residences of individuals attending health facilities in order to efficiently map disease patterns. We aimed to assess the use of Android tablet-based applications containing high resolution maps to geolocate individual residences, whilst comparing the functionality, usability and cost of three software packages designed to collect spatial information. RESULTS: Using Open Data Kit GeoODK, we designed and piloted an electronic questionnaire for rolling cross sectional surveys of health facility attendees as part of a malaria elimination campaign in two predominantly rural sites in the Rizal, Palawan, the Philippines and Kulon Progo Regency, Yogyakarta, Indonesia. The majority of health workers were able to use the tablets effectively, including locating participant households on electronic maps. For all households sampled (n = 603), health facility workers were able to retrospectively find the participant household using the Global Positioning System (GPS) coordinates and data collected by tablet computers. Median distance between actual house locations and points collected on the tablet was 116 m (IQR 42-368) in Rizal and 493 m (IQR 258-886) in Kulon Progo Regency. Accuracy varied between health facilities and decreased in less populated areas with fewer prominent landmarks. CONCLUSIONS: Results demonstrate the utility of this approach to develop real-time high-resolution maps of disease in resource-poor environments. This method provides an attractive approach for quickly obtaining spatial information on individuals presenting at health facilities in resource poor areas where formal addresses are unavailable and internet connectivity is limited. Further research is needed on how to integrate these with other health data management systems and implement in a wider operational context.

Pandemic inequity in a megacity: a multilevel analysis of individual, community and healthcare vulnerability risks for COVID-19 mortality in Jakarta, Indonesia.

INTRODUCTION: Worldwide, the 33 recognised megacities comprise approximately 7% of the global population, yet account for 20% COVID-19 deaths. The specific inequities and other factors within megacities that affect vulnerability to COVID-19 mortality remain poorly defined. We assessed individual, community-level and healthcare factors associated with COVID-19-related mortality in a megacity of Jakarta, Indonesia, during two epidemic waves spanning 2 March 2020 to 31 August 2021. METHODS: This retrospective cohort included residents of Jakarta, Indonesia, with PCR-confirmed COVID-19. We extracted demographic, clinical, outcome (recovered or died), vaccine coverage data and disease prevalence from Jakarta Health Office surveillance records, and collected subdistrict level sociodemographics data from various official sources. We used multilevel logistic regression to examine individual, community and subdistrict-level healthcare factors and their associations with COVID-19 mortality. RESULTS: Of 705 503 cases with a definitive outcome by 31 August 2021, 694 706 (98.5%) recovered and 10 797 (1.5%) died. The median age was 36 years (IQR 24-50), 13.2% (93 459) were <18 years and 51.6% were female. The subdistrict level accounted for 1.5% of variance in mortality (p<0.0001). Mortality ranged from 0.9 to 1.8% by subdistrict. Individual-level factors associated with death were older age, male sex, comorbidities and age <5 years during the first wave (adjusted OR (aOR)) 1.56, 95% CI 1.04 to 2.35; reference: age 20-29 years). Community-level factors associated with death were poverty (aOR for the poorer quarter 1.35, 95% CI 1.17 to 1.55; reference: wealthiest quarter) and high population density (aOR for the highest density 1.34, 95% CI 1.14 to 2.58; reference: the lowest). Healthcare factor associated with death was low vaccine coverage (aOR for the lowest coverage 1.25, 95% CI 1.13 to 1.38; reference: the highest). CONCLUSION: In addition to individual risk factors, living in areas with high poverty and density, and low healthcare performance further increase the vulnerability of communities to COVID-19-associated death in urban low-resource settings.

Patient delay determinants for patients with suspected tuberculosis in Yogyakarta province, Indonesia.

OBJECTIVES: Indonesia has a high incidence of tuberculosis (TB), despite the successful introduction of the directly observed treatment short-course strategy (DOTS strategy). DOTS depends on passive case finding. It is therefore important to identify determinants of patient delay and reasons for visiting a DOTS healthcare provider when seeking care. The aim of this study was to assess these determinants in TB suspects (coughing for at least 2 weeks). METHODS: Cross-sectional data were gathered with a structured questionnaire in which psychosocial determinants were based on an extended version of the theory of planned behaviour (TPB). The study was conducted in five governmental lung clinics of Yogyakarta province. In total, 194 TB suspects that registered at the lung clinics were interviewed. RESULTS: The median patient delay was 14 days (range 0-145). Ordinal regression analyses showed that visiting a private healthcare provider when first seeking health care, reporting travel distance/travel time as reason for choosing a certain healthcare provider when first seeking health care, discussing the symptoms with family and a reported short travel time, but no factors of TPB, were significantly associated with a shorter patient delay. An important factor negatively associated with visiting a DOTS clinic was the reported travel time. CONCLUSION: Accessibility of the healthcare provider was the main determinant of patient delay, but the role of psychosocial factors cannot be fully excluded. Urban and suburban areas have relatively good access to (private) health care, hence the short delay. Thus, future studies should be focussed on extending the DOTS strategy to the private sector.

How to optimize tuberculosis case finding: explorations for Indonesia with a health system model.

BACKGROUND: A mathematical model was designed to explore the impact of three strategies for better tuberculosis case finding. Strategies included: (1) reducing the number of tuberculosis patients who do not seek care; (2) reducing diagnostic delay; and (3) engaging non-DOTS providers in the referral of tuberculosis suspects to DOTS services in the Indonesian health system context. The impact of these strategies on tuberculosis mortality and treatment outcome was estimated using a mathematical model of the Indonesian health system. METHODS: The model consists of multiple compartments representing logical movement of a respiratory symptomatic (tuberculosis suspect) through the health system, including patient- and health system delays. Main outputs of the model are tuberculosis death rate and treatment outcome (i.e. full or partial cure). We quantified the model parameters for the Jogjakarta province context, using a two round Delphi survey with five Indonesian tuberculosis experts. RESULTS: The model validation shows that four critical model outputs (average duration of symptom onset to treatment, detection rate, cure rate, and death rate) were reasonably close to existing available data, erring towards more optimistic outcomes than are actually reported. The model predicted that an intervention to reduce the proportion of tuberculosis patients who never seek care would have the biggest impact on tuberculosis death prevention, while an intervention resulting in more referrals of tuberculosis suspects to DOTS facilities would yield higher cure rates. This finding is similar for situations where the alternative sector is a more important health resource, such as in most other parts of Indonesia. CONCLUSION: We used mathematical modeling to explore the impact of Indonesian health system interventions on tuberculosis treatment outcome and deaths. Because detailed data were not available regarding the current Indonesian population, we relied on expert opinion to quantify the parameters. The fact that the model output showed similar results to epidemiological data suggests that the experts had an accurate understanding of this subject, thereby reassuring the quality of our predictions. The model highlighted the potential effectiveness of active case finding of tuberculosis patients with limited access to DOTS facilities in the developing country setting.

Baseline Characterization of Dengue Epidemiology in Yogyakarta City, Indonesia, before a Randomized Controlled Trial of Wolbachia for Arboviral Disease Control.

Dengue is endemic in Indonesia. Here, we describe the epidemiology of dengue in the city of Yogyakarta, Central Java, as a prelude to implementation of a cluster-randomized trial of Wolbachia for the biocontrol of arboviral transmission. Surveillance records from 2006 to 2016 demonstrate seasonal oscillations of dengue incidence with varying magnitude. Two lines of evidence demonstrate a high force of infection; the hospitalized case burden of patients diagnosed with dengue hemorrhagic fever or dengue shock syndrome over the last decade consisted predominantly of children/adolescents, and a serosurvey of 314 healthy children aged 1-10 years found 68% possessed dengue virus-neutralizing antibodies. Finally, a mobility survey indicated children aged 1-10 years, and particularly 1-5 year-olds, spent most of their daytime hours at home. These findings inform the design of clinical trials to measure the impact of novel vector control methods such as Wolbachia introgression into Aedes aegypti mosquitoes, by providing baseline data on disease incidence and identifying subpopulations for recruitment into prospective studies of dengue virus infection and disease. The mobility survey findings indicate that in cluster trials of interventions applied at the community level, young children can reasonably be expected to spend most of their exposure time, in epidemiological terms, within the treatment arm to which they were randomized.

Care-seeking behaviour among individuals with TB symptoms in Jogjakarta Province, Indonesia: a community-based study.

BACKGROUND: Care-seeking behaviour of individuals with TB symptoms is a critical factor in early detection and treatment. Thorough understanding of determinants of the care-seeking process helps TB programme managers to improve TB case finding. The aim of this study was to assess determinants of care-seeking behaviour among patients with suspected TB at the population level. METHODS: A cross-sectional survey was conducted among adults with cough for >2 weeks. Data on sociodemographics, onset of TB symptoms, TB knowledge, health facility visited and duration of each visit were collected. RESULTS: Of the 746 respondents interviewed, approximately 10% had not yet sought care. Of those who sought care, less than one-half presented directly to medical healthcare providers. Being female and having multiple symptoms were associated with care-seeking action. The duration of patient delay (i.e. time between onset of symptoms and visiting a health provider) was relatively short, which may be due to the availability of an extended network of healthcare providers in Jogjakarta Province. Being male, a student or self-employed were associated with longer delay in presentation. CONCLUSIONS: Patient delay was relatively short. Efforts need to be focused on encouraging individuals with suspected TB to seek appropriate services through health education and quality improvement of health providers.

The incremental cost-effectiveness of engaging private practitioners to refer tuberculosis suspects to DOTS services in Jogjakarta, Indonesia.

We aimed to evaluate the incremental cost-effectiveness of engaging private practitioners (PPs) to refer tuberculosis (TB) suspects to public health centers in Jogjakarta, Indonesia. Effectiveness was assessed for TB suspects notified between May 2004 and April 2005. Private practitioners referred 1,064 TB suspects, of which 57.5% failed to reach a health center. The smear-positive rate among patients reaching a health center was 61.8%. Two hundred eighty (280) out of a total of 1,306 (21.4%) new smear-positive cases were enrolled through the PPs strategy. The incremental cost-effectiveness ratio per smear-positive case successfully treated for the PPs strategy was US$351.66 (95% CI 322.84-601.33). On the basis of an acceptability curve using the National TB control program's willingness-to-pay threshold (US$448.61), we estimate the probability that the PPs strategy is cost-effective at 66.8%. The strategy of engaging PPs was incrementally cost-effective, although under specific conditions, most importantly a well-functioning public directly observed treatment, short-course (DOTS) program.

Voluntary counselling and testing uptake and HIV prevalence among tuberculosis patients in Jogjakarta, Indonesia.

We aimed to establish HIV prevalence and uptake of unlinked anonymous testing and voluntary counselling and testing (VCT) among tuberculosis (TB) patients in Jogjakarta, Indonesia. We introduced unlinked anonymous HIV testing for TB patients attending directly observed treatment, short-course services between April and December 2006. Patients were additionally offered VCT services. Of 1269 TB patients who were offered unlinked anonymous testing, 989 (77.9%; 95% CI 75.6-80.1%) accepted. HIV prevalence was 1.9% (95% CI 1.6-2.2%). HIV infections were less frequently diagnosed among TB patients who attended a public health centre [odds ratio (OR) 0.15; 95% CI 0.03-0.70] rather than public hospital. They were more frequent in TB patients with a university education background (OR 5.16; 95% CI 1.01-26.63) or a history of HIV testing (OR 57.87; 95% CI 9.42-355.62). Of the 989 patients who accepted unlinked anonymous testing, only 133 (13.4%; 95% CI 11.5-15.7%) expressed interest in VCT. Of these, 52 (39.1%; 95% CI 31.2-47.6%) attended VCT, but interest was higher among students and those offered VCT by public health centres. The HIV prevalence in Jogjakarta is higher than expected and needs to be monitored cautiously. Unlinked anonymous HIV testing is well accepted and can be implemented with modest additional efforts.