Riris Andono Ahmad

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.

Promoting good health research practice in low- and middle-income countries

Background Good clinical practice (GCP) guidelines have been the source of improvement in the quality of clinical trials; however, there are limitations to the application of GCP in the conduct of health research beyond industry-sponsored clinical trials. The UNICEF/UNDP/World Bank/WHO Special Program for Research and Training in Tropical Disease is promoting good practice in all health research involving human through the Good Health Research Practice (GHRP) training program initiative. Objective To report the results of piloting the GHRP training program and formulate further steps to harness GHRP for promoting good practices in all health research involving human, particularly in low- and middle-income countries (LMICs). Design The objective of this training is to impart knowledge and skills for the application of ethical and quality principles to the design, conduct, recording, and reporting of health research involving human participants based on the level of risk, to ensure a fit-for-purpose quality system. This has been formulated into five sequential modules to be delivered in a 4-day course. Four courses have been organized in the pilot phase (2014–2015). The courses have been evaluated and assessed based on course feedback (quantitative and qualitative data) collected during course implementation and qualitative email-based pre- and post-course evaluation. Results Participants were highly satisfied with the course content and its organization. The relevance and applicability of the course content resulted in positive feedback and an articulated willingness to adapt and disseminate the course. Action points to strengthen the training program have been identified, and showed the imminent need to develop a consensus with a broader range of key stakeholders on the final set of GHRP standards and means for implementation. Conclusions There is an urgent need to harness the momentum to promote high-quality and ethical health research in LMICs through scaling up GHRP training and further development of GHRP principles into international standards.Background Good clinical practice (GCP) guidelines have been the source of improvement in the quality of clinical trials; however, there are limitations to the application of GCP in the conduct of health research beyond industry-sponsored clinical trials. The UNICEF/UNDP/World Bank/WHO Special Program for Research and Training in Tropical Disease is promoting good practice in all health research involving human through the Good Health Research Practice (GHRP) training program initiative. Objective To report the results of piloting the GHRP training program and formulate further steps to harness GHRP for promoting good practices in all health research involving human, particularly in low- and middle-income countries (LMICs). Design The objective of this training is to impart knowledge and skills for the application of ethical and quality principles to the design, conduct, recording, and reporting of health research involving human participants based on the level of risk, to ensure a fit-for-purpose quality system. This has been formulated into five sequential modules to be delivered in a 4-day course. Four courses have been organized in the pilot phase (2014-2015). The courses have been evaluated and assessed based on course feedback (quantitative and qualitative data) collected during course implementation and qualitative email-based pre- and post-course evaluation. Results Participants were highly satisfied with the course content and its organization. The relevance and applicability of the course content resulted in positive feedback and an articulated willingness to adapt and disseminate the course. Action points to strengthen the training program have been identified, and showed the imminent need to develop a consensus with a broader range of key stakeholders on the final set of GHRP standards and means for implementation. Conclusions There is an urgent need to harness the momentum to promote high-quality and ethical health research in LMICs through scaling up GHRP training and further development of GHRP principles into international standards.

The AWED trial (Applying Wolbachia to Eliminate Dengue) to assess the efficacy of Wolbachia-infected mosquito deployments to reduce dengue incidence in Yogyakarta, Indonesia: study protocol for a cluster randomised controlled trial

BackgroundDengue and other arboviruses transmitted by Aedes aegypti mosquitoes, including Zika and chikungunya, present an increasing public health challenge in tropical regions. Current vector control strategies have failed to curb disease transmission, but continue to be employed despite the absence of robust evidence for their effectiveness or optimal implementation. The World Mosquito Program has developed a novel approach to arbovirus control using Ae. aegypti stably transfected with Wolbachia bacterium, with a significantly reduced ability to transmit dengue, Zika and chikungunya in laboratory experiments. Modelling predicts this will translate to local elimination of dengue in most epidemiological settings. This study protocol describes the first trial to measure the efficacy of Wolbachia in reducing dengue virus transmission in the field.Methods/designThe study is a parallel, two-arm, non-blinded cluster randomised controlled trial conducted in a single site in Yogyakarta, Indonesia. The aim is to determine whether large-scale deployment of Wolbachia-infected Ae. aegypti mosquitoes leads to a measurable reduction in dengue incidence in treated versus untreated areas. The primary endpoint is symptomatic, virologically confirmed dengue virus infection of any severity. The 26 km2 study area was subdivided into 24 contiguous clusters, allocated randomly 1:1 to receive Wolbachia deployments or no intervention. We use a novel epidemiological study design, the cluster-randomised test-negative design trial, in which dengue cases and arbovirus-negative controls are sampled concurrently from among febrile patients presenting to a network of primary care clinics, with case or control status classified retrospectively based on the results of laboratory diagnostic testing. Efficacy is estimated from the odds ratio of Wolbachia exposure distribution (probability of living in a Wolbachia-treated area) among virologically confirmed dengue cases compared to test-negative controls. A secondary per-protocol analysis allows for individual Wolbachia exposure levels to be assessed to account for movements outside the cluster and the heterogeneity in local Wolbachia prevalence among treated clusters.DiscussionThe findings from this study will provide the first experimental evidence for the efficacy of Wolbachia in reducing dengue incidence. Together with observational evidence that is accumulating from pragmatic deployments of Wolbachia in other field sites, this will provide valuable data to estimate the effectiveness of this novel approach to arbovirus control, inform future cost-effectiveness estimates, and guide plans for large-scale deployments in other endemic settings.Trial registrationClinicalTrials.gov, identifier: NCT03055585. Registered on 14 February 2017.

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

Abstract. 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.

Development of the Good Health Research Practice course: ensuring quality across all health research in humans

Quality and ethics need to be embedded into all areas of research with human participants. Good Clinical Practice (GCP) guidelines are international ethical and scientific quality standards for designing, conducting, recording and reporting trials involving human participants. Compliance with GCP is expected to provide public assurance that the rights, safety and wellbeing of participants are protected and that the clinical research data are credible. However, whilst GCP guidelines, particularly their principles, are recommended across all research types, it is difficult for non-clinical trial research to fit in with the exacting requirements of GCP. There is therefore a need for guidance that allows health researchers to adhere to the principles of GCP, which will improve the quality and ethical conduct of all research involving human participants. These concerns have led to the development of the Good Health Research Practice (GHRP) course. Its goal is to ensure that research is conducted to the highest possible standards, similar to the conduct of trials to GCP. The GHRP course provides training and guidance to ensure quality and ethical conduct across all health-related research. The GHRP course has been run so far on eight occasions. Feedback from delegates has been overwhelmingly positive, with most delegates stating that the course was useful in developing their research protocols and documents. Whilst most training in research starts with a guideline, GHRP has started with a course and the experience gained over running the courses will be used to write a standardised guideline for the conduct of health-related research outside the realm of clinical trials, so that researchers, funders and ethics committees do not try to fit non-trials into clinical trials standards.