Improved limit of detection for zoonotic Plasmodium knowlesi and P. cynomolgi surveillance using reverse transcription for total nucleic acid preserved samples or dried blood spots.

Background: Zoonotic P. knowlesi and P. cynomolgi symptomatic and asymptomatic infections occur across endemic areas of Southeast Asia. Most infections are low-parasitemia, with an unknown proportion below routine microscopy detection thresholds. Molecular surveillance tools optimizing the limit of detection (LOD) would allow more accurate estimates of zoonotic malaria prevalence. Methods: An established ultra-sensitive Plasmodium genus quantitative-PCR (qPCR) assay targeting the 18S rRNA gene underwent LOD evaluation with and without reverse transcription (RT) for P. knowlesi, P. cynomolgi and P. vivax using total nucleic acid preserved (DNA/RNA Shield™) isolates and archived dried blood spots (DBS). LODs for selected P. knowlesi-specific assays, and reference P. vivax- and P. cynomolgi-specific assays were determined with RT. Assay specificities were assessed using clinical malaria samples and malaria-negative controls. Results: The use of reverse transcription improved Plasmodium species detection by up to 10,000-fold (Plasmodium genus), 2759-fold (P. knowlesi), 1000-fold (P. vivax) and 10-fold (P. cynomolgi). The median LOD with RT for the Kamau et al. Plasmodium genus RT-qPCR assay was ≤0.0002 parasites/µL for P. knowlesi and 0.002 parasites/µL for both P. cynomolgi and P. vivax. The LODs with RT for P. knowlesi-specific PCRs were: Imwong et al. 18S rRNA (0.0007 parasites/µL); Divis et al. real-time 18S rRNA (0.0002 parasites/µL); Lubis et al. hemi-nested SICAvar (1.1 parasites/µL) and Lee et al. nested 18S rRNA (11 parasites/µL). The LOD for P. vivax- and P. cynomolgi-specific assays with RT were 0.02 and 0.20 parasites/µL respectively. For DBS P. knowlesi samples the median LOD for the Plasmodium genus qPCR with RT was 0.08, and without RT was 19.89 parasites/uL (249-fold change); no LOD improvement was demonstrated in DBS archived beyond 6 years. The Plasmodium genus and P. knowlesi-assays were 100% specific for Plasmodium species and P. knowlesi detection, respectively, from 190 clinical infections and 48 healthy controls. Reference P. vivax-specific primers demonstrated known cross-reactivity with P. cynomolgi. Conclusion: Our findings support the use of an 18S rRNA Plasmodium genus qPCR and species-specific nested PCR protocol with RT for highly-sensitive surveillance of zoonotic and human Plasmodium species infections.

Characteristics and clinical outcomes of patients with pre-delta, delta and omicron SARS-CoV-2 infection in Indonesia (2020-2023): a multicentre prospective cohort study.

Background: Limited data exist from southeast Asia on the impact of SARS-CoV-2 variants and inactivated vaccines on disease severity and death among patients hospitalised with COVID-19. Methods: A multicentre hospital-based prospective cohort was enrolled from September 2020 through January 2023, spanning pre-delta, delta, and omicron periods. The participant hospitals were conveniently sampled based on existing collaborations, site willingness and available study resources, and included six urban and two rural general hospitals from East Nusa Tenggara, Jakarta, and North Sumatra provinces. Factors associated with severe disease and day-28 mortality were examined using logistic and Cox regression. Findings: Among 822 participants, the age-adjusted percentage of severe disease was 26.8% (95% CI 22.7-30.9) for pre-delta, 50.1% (44.0-56.2) for delta, and 15.2% (9.7-20.7) for omicron. The odds of severe disease were 64% (18-84%) lower for omicron than delta (p < 0.001). One or more vaccine doses reduced the odds of severe disease by 89% (65-97%) for delta and 98% (91-100%) for omicron. Age-adjusted mortality was 11.9% (8.8-15.0) for pre-delta, 24.4% (18.8-29.9) for delta and 9.6% (5.2-14.0) for omicron. The day-28 cumulative incidence of death was lower for omicron (9.2% [5.6-13.9%]) than delta (28.6% [22.0-35.5%]) (p < 0.001). Severe disease on admission was the predominant prognostic factor for death (aHR34.0 [16.6-69.9] vs mild-or-moderate; p < 0.001). After controlling for disease severity on admission as an intermediate, the risk of death was 48% (32-60%) lower for omicron than delta (p < 0.001); and 51% (38-61%; p < 0.001) lower for vaccinated participants than unvaccinated participants overall, and 56% (37-69%; p < 0.001) for omicron, 46% (-5 to 73%; p = 0.070) for pre-delta (not estimable for delta). Interpretation: Infections by omicron variant resulted in less severe and fatal outcomes than delta in hospitalised patients in Indonesia. However, older, and unvaccinated individuals remained at greater risk of adverse outcomes. Funding: University of Oxford and Wellcome Trust.

Impact of the COVID-19 pandemic on tuberculosis control in Indonesia: a nationwide longitudinal analysis of programme data.

BACKGROUND: The impact of the COVID-19 pandemic on tuberculosis control in high-burden countries has not been adequately assessed. We aimed to estimate the impact of the COVID-19 pandemic on the national tuberculosis programme in Indonesia, in association with indicators of human development and health-system capacity across all 514 districts in 34 provinces. METHODS: We did a nationwide longitudinal analysis to compare tuberculosis case notification, treatment coverage, and mortality rates in Indonesia before (2016-19) and during (2020-21) the COVID-19 pandemic. The following outcomes were assessed: the district-level quarterly reported tuberculosis case notification rate (number of all reported tuberculosis cases per 100 000 population), treatment coverage (proportion of tuberculosis patients who started treatment), and all-cause mortality rate in patients with tuberculosis (number of reported deaths per 100 000 population). District-level data on COVID-19 incidence and deaths, health-system capacity, and human development and sociodemographics were also analysed. Multilevel linear spline regression was done to assess quarterly time trends for the three outcomes. FINDINGS: During the COVID-19 pandemic, the tuberculosis case notification rate declined by 26% (case notification rate ratio 0·74, 95% CI 0·72-0·77) and treatment coverage declined by 11% (treatment coverage ratio 0·89, 95% CI 0·88-0·90), but there was no significant increase in all-cause mortality (all-cause mortality rate ratio 0·97, 95% CI 0·91-1·04) compared with the pre-pandemic period. In the second year of the pandemic, we observed a partial recovery of the case notification rate from Q1 to Q4 of 2021, a persistent decrease in treatment coverage, and a decrease in the all-cause mortality rate from Q2 of 2020 to Q4 of 2021. The multivariable analysis showed that the reduction in the tuberculosis case notification rate was associated with a higher COVID-19 incidence rate (adjusted odds ratio 3·1, 95% CI 1·1-8·6, for the highest compared with the lowest group) and fewer GeneXpert machines for tuberculosis diagnosis (3·1, 1·0-9·4, for the lowest compared with the highest group) per 100 000 population. The reduction in tuberculosis treatment coverage was associated with higher COVID-19 incidence (adjusted odds ratio 11·7, 95% CI 1·5-93·4, for the highest compared with the lowest group), fewer primary health centres (10·6, 4·1-28·0, for the lowest compared with the middle-high group), and a very low number of doctors (0·3, 0·1-0·9, for the low-middle compared with the lowest group) per 100 000 population. No factors were shown to be significantly associated with all-cause mortality. INTERPRETATION: The COVID-19 pandemic adversely and unevenly affected the national tuberculosis programme across Indonesia, with the greatest impacts observed in districts with the lowest health-system capacity. These disruptions could lead to an escalation in tuberculosis transmission in the coming years, warranting the need for intensified efforts to control tuberculosis and strengthen local health systems. FUNDING: Wellcome Africa Asia Programme Vietnam. TRANSLATION: For the Bahasa translation of the abstract see Supplementary Materials section.

Clinical characteristics and factors associated with COVID-19-related mortality and hospital admission during the first two epidemic waves in 5 rural provinces in Indonesia: A retrospective cohort study.

BACKGROUND: Data on coronavirus disease 2019 (COVID-19) clinical characteristics and severity from resource-limited settings are limited. This study examined clinical characteristics and factors associated with COVID-19 mortality and hospitalisation in rural settings of Indonesia, from 1 January to 31 July, 2021. METHODS: This retrospective cohort included individuals diagnosed with COVID-19 based on polymerase chain reaction or rapid antigen diagnostic test, from five rural provinces in Indonesia. We extracted demographic and clinical data, including hospitalisation and mortality from a new piloted COVID-19 information system named Sistem Informasi Surveilans Epidemiologi (SISUGI). We used mixed-effect logistic regression to examine factors associated with COVID-19-related mortality and hospitalisation. RESULTS: Of 6,583 confirmed cases, 205 (3.1%) died and 1,727 (26.2%) were hospitalised. The median age was 37 years (Interquartile range 26-51), with 825 (12.6%) under 20 years, and 3,371 (51.2%) females. Most cases were symptomatic (4,533; 68.9%); 319 (4.9%) had a clinical diagnosis of pneumonia and 945 (14.3%) presented with at least one pre-existing comorbidity. Age-specific mortality rates were 0.9% (2/215) for 0-4 years; 0% (0/112) for 5-9 years; 0% (1/498) for 10-19 years; 0.8% (11/1,385) for 20-29 years; 0.9% (12/1,382) for 30-39 years; 2.1% (23/1,095) for 40-49 years; 5.4% (57/1,064) for 50-59 years; 10.8% (62/576) for 60-69 years; 15.9% (37/232) for ≥70 years. Older age, pre-existing diabetes, chronic kidney disease, liver diseases, malignancy, and pneumonia were associated with higher risk of mortality and hospitalisation. Pre-existing hypertension, cardiac diseases, COPD, and immunocompromised condition were associated with risk of hospitalisation but not with mortality. There was no association between province-level density of healthcare workers with mortality and hospitalisation. CONCLUSION: The risk of COVID-19-related mortality and hospitalisation was associated with higher age, pre-existing chronic comorbidities, and clinical pneumonia. The findings highlight the need for prioritising enhanced context-specific public health action to reduce mortality and hospitalisation risk among older and comorbid rural populations.

Geographical variations and district-level factors associated with COVID-19 mortality in Indonesia: a nationwide ecological study.

BACKGROUND: Ensuring health equity, especially for vulnerable populations in less developed settings with poor health system is essential for the current and future global health threats. This study examined geographical variations of COVID-19 mortality and its association with population health characteristics, health care capacity in responding pandemic, and socio-economic characteristics across 514 districts in Indonesia. METHODS: This nationwide ecological study included aggregated data of COVID-19 cases and deaths from all 514 districts in Indonesia, recorded in the National COVID-19 Task Force database, during the first two years of the epidemic, from 1 March 2020 to 27 February 2022. The dependent variable was district-level COVID-19 mortality rate per 100,000 populations. The independent variables include district-level COVID-19 incidence rate, population health, health care capacity, and socio-demographics data from government official sources. We used multivariable ordinal logistic regression to examine factors associated with higher mortality rate. RESULTS: Of total 5,539,333 reported COVID-19 cases, 148,034 (2.7%) died, and 5,391,299 (97.4%) were recovered. The district-level mortality rate ranged from 0 to 284 deaths per 100,000 populations. The top five districts with the highest mortality rate were Balikpapan (284 deaths per 100,000 populations), Semarang (263), Madiun (254), Magelang (250), and Yogyakarta (247). A higher COVID-19 incidence (coefficient 1.64, 95% CI 1.22 to 1.75), a higher proportion of ≥ 60 years old population (coefficient 0.26, 95% CI 0.06 to 0.46), a higher prevalence of diabetes mellitus (coefficient 0.60, 95% CI 0.37 to 0.84), a lower prevalence of obesity (coefficient -0.32, 95% CI -0.56 to -0.08), a lower number of nurses per population (coefficient -0.27, 95% CI -0.50 to -0.04), a higher number of midwives per population (coefficient 0.32, 95% CI 0.13 to 0.50), and a higher expenditure (coefficient 0.34, 95% CI 0.10 to 0.57) was associated with a higher COVID-19 mortality rate. CONCLUSION: COVID-19 mortality rate in Indonesia was highly heterogeneous and associated with higher COVID-19 incidence, different prevalence of pre-existing comorbidity, healthcare capacity in responding the pandemic, and socio-economic characteristics. This study revealed the need of controlling both COVID-19 and those known comorbidities, health capacity strengthening, and better resource allocation to ensure optimal health outcomes for vulnerable population.

Antibody Responses and Reactogenicity of a Heterologous, Full-Dose Messenger RNA-1273 Booster in Heavily SARS-CoV-2-Exposed CoronaVac-Vaccinated Health-Care Workers in Indonesia: A Real-World Observational Study.

Real-world data on heterologous boosting with messenger RNA (mRNA)-1273 (Moderna) after inactivated COVID-19 vaccination are limited. We report mRNA-1273 boosting in heavily SARS-CoV-2-exposed Indonesian health-care workers who received a two-dose CoronaVac 6 months prior. Between August and November 2021, we measured SARS-CoV-2 spike-specific IgG binding antibody (Bab) titers in all 304 participants, and neutralizing antibody titers in a random subset of 71 participants, on stored paired serum samples taken before and 28 days after a full-dose (100-µg) mRNA-1273 booster. At the time of the mRNA-1273 boost, 107 participants (35.2%) were not previously infected (naive vaccinated), 42 (13.8%) were infected before CoronaVac (infected vaccinated), and 155 (51.0%) were infected after CoronaVac (mostly during the Delta wave; vaccinated infected). At time of the mRNA-1273 boost, neutralizing antibodies could still be detected in 83% of participants (59 of 71) overall, 60% of naive-vaccinated participants (15 of 25), 95.7% of vaccinated-infected participants (22 of 23), and 95.7% of infected vaccinated participants (22 of 23). After the mRNA-1273 boost, 100% of participants (71 of 71) had neutralizing antibody activity, with increases in median Bab and neutralizing antibody serum titers of 9.3- and 27.0-fold overall, 89.1- and 2,803.4-fold in naive-vaccinated participants, 15.9- and 19.9-fold in infected-vaccinated participants, and 2.2- and 18.4-fold in vaccinated-infected participants. In the multivariable analysis, Bab titers after the mRNA-1273 boost were greatest in individuals who had a previous virus breakthrough post-CoronaVac, and when a longer time period (> 4 months) had elapsed since the most recent prior "spike antigen exposure" (either second CoronaVac or virus breakthrough). Overall, adverse reactions were mild and short-lived. In conclusion, a full-dose mRNA-1273 booster after CoronaVac was well tolerated and immunogenic after 28 days, including in those with very low antibody levels.

A framework for evaluating health system surveillance sensitivity to support public health decision-making for malaria elimination: a case study from Indonesia.

BACKGROUND: The effectiveness of a surveillance system to detect infections in the population is paramount when confirming elimination. Estimating the sensitivity of a surveillance system requires identifying key steps in the care-seeking cascade, from initial infection to confirmed diagnosis, and quantifying the probability of appropriate action at each stage. Using malaria as an example, a framework was developed to estimate the sensitivity of key components of the malaria surveillance cascade. METHODS: Parameters to quantify the sensitivity of the surveillance system were derived from monthly malaria case data over a period of 36 months and semi-quantitative surveys in 46 health facilities on Java Island, Indonesia. Parameters were informed by the collected empirical data and estimated by modelling the flow of an infected individual through the system using a Bayesian framework. A model-driven health system survey was designed to collect empirical data to inform parameter estimates in the surveillance cascade. RESULTS: Heterogeneity across health facilities was observed in the estimated probability of care-seeking (range = 0.01-0.21, mean ± sd = 0.09 ± 0.05) and testing for malaria (range = 0.00-1.00, mean ± sd = 0.16 ± 0.29). Care-seeking was higher at facilities regularly providing antimalarial drugs (Odds Ratio [OR] = 2.98, 95% Credible Intervals [CI]: 1.54-3.16). Predictably, the availability of functioning microscopy equipment was associated with increased odds of being tested for malaria (OR = 7.33, 95% CI = 20.61). CONCLUSIONS: The methods for estimating facility-level malaria surveillance sensitivity presented here can help provide a benchmark for what constitutes a strong system. The proposed approach also enables programs to identify components of the health system that can be improved to strengthen surveillance and support public-health decision-making.

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.

Quantifying spatial heterogeneity of malaria in the endemic Papua region of Indonesia: Analysis of epidemiological surveillance data.

Background: As control efforts progress towards elimination, malaria is likely to become more spatially concentrated in few local areas. The purpose of this study was to quantify and characterise spatial heterogeneity in malaria transmission-intensity across highly endemic Indonesian Papua. Methods: We analysed individual-level malaria surveillance data for nearly half a million cases (2019-2020) reported in the Papua and West Papua provinces and adapted the Gini index approach to quantify spatial heterogeneity at the district and health-unit levels. In this context, high Gini index implies disproportionately distributed malaria cases across the region. We showed malaria incidence trends and the spatial and temporal distribution of sociodemographic characteristics and aetiological parasites among cases. Findings: While Papua province accounted for the majority of malaria cases reported in the region and had seen a rise in transmission since 2015, West Papua province had maintained a comparatively low incidence. We observed that Gini index estimates were high, particularly when the lower spatial scale of health units was evaluated. The Gini index appears to be inversely associated to annual parasite-incidence, as well as the proportions of vivax malaria, male sex, and adults. Interpretation: This study suggests that areas with varying levels of transmission-intensities exhibited distinct characteristics. Malaria was distributed in a markedly disproportionate manner throughout the region, emphasising the need for spatially targeted interventions. Periodic quantification and characterisation of risk heterogeneity at various spatial levels using routine malaria surveillance data may aid in tracking progress towards elimination and guiding evidence-informed prioritisation of resource allocation. Funding: The study was funded by the Australian Government Department of Foreign Affairs and Trade Indo-Pacific Centre for Health Security through the Strengthening Preparedness in the Asia-Pacific Region through Knowledge (SPARK) project.

Mortality among healthcare workers in Indonesia during 18 months of COVID-19.

The impact of SARS-CoV-2 infections upon Indonesian health care workers (HCWs) is unknown due to the lack of systematic collection and analysis of mortality data specific to HCWs in this setting. This report details the results of a systematic compilation, abstraction and analysis of HCW fatalities in Indonesia during the first 18 months of COVID-19. HCW who passed away between March 2020 and July 2021 were identified using Pusara Digital, a community-based digital cemetery database dedicated to HCW. We calculated the mortality rates and death risk ratio of HCWs versus the general population. The analysis indicates that at least 1,545 HCWs died during the study period. Death rates among males and females HCWs were nearly equivalent (51% vs. 49%). The majority were physicians and specialists (535, 35%), nurses (428, 28%), and midwives (359, 23%). Most deaths occurred between the ages of 40 to 59 years old, with the median age being 50 years (IQR: 39-59). At least 322 deaths (21%) occurred with pre-existing conditions, including 45 pregnant women. During the first 18 months of COVID-19 in Indonesia, we estimated a minimum HCW mortality rate of 1.707 deaths per 1,000 HCWs. The provincial rates of HCW mortality ranged from 0.136 (West Sulawesi) to 5.32 HCW deaths per 1,000 HCWs (East Java). The HCW mortality rate was significantly higher than that of the general population (RR = 4.92, 95% CI 4.67-5.17). The COVID-19 pandemic in Indonesia resulted in the loss of many hundreds of HCWs, the majority of whom were senior healthcare workers. The HCW mortality rate is five times that of the general population. A national systematic surveillance of occupational mortality is urgently needed in this setting.

Epidemiology of the zoonotic malaria Plasmodium knowlesi in changing landscapes.

Within the past two decades, incidence of human cases of the zoonotic malaria Plasmodium knowlesi has increased markedly. P. knowlesi is now the most common cause of human malaria in Malaysia and threatens to undermine malaria control programmes across Southeast Asia. The emergence of zoonotic malaria corresponds to a period of rapid deforestation within this region. These environmental changes impact the distribution and behaviour of the simian hosts, mosquito vector species and human populations, creating new opportunities for P. knowlesi transmission. Here, we review how landscape changes can drive zoonotic disease emergence, examine the extent and causes of these changes across Southeast and identify how these mechanisms may be impacting P. knowlesi dynamics. We review the current spatial epidemiology of reported P. knowlesi infections in people and assess how these demographic and environmental changes may lead to changes in transmission patterns. Finally, we identify opportunities to improve P. knowlesi surveillance and develop targeted ecological interventions within these landscapes.

Sub-national disparities in accessing anti-malarial drug treatment in eastern Indonesia.

BACKGROUND: Poor access to health care providers was among the contributing factors to less prompt and ineffective malaria treatment. This limitation could cause severe diseases in remote areas. This study examined the sub-national disparities and predictors in accessing anti-malarial drug treatment among adults in Eastern Indonesia. METHODS: The study analyzed a subset of the 2018 National Basic Health Survey conducted in all 34 provinces in Indonesia. We extracted socio-demographic data of 4655 adult respondents diagnosed with malaria in the past 12 months in five provinces in Eastern Indonesia. The association between socio-demographic factors and the access to anti-malarial drug treatment was assessed using logistic regression. RESULTS: Over 20% of respondents diagnosed with malaria within last 12 months admitted that they did not receive anti-malarial drug treatment (range 12-29.9%). The proportion of untreated cases was 12.0% in East Nusa Tenggara, 29.9% in Maluku, 23.1% in North Maluku, 12.7% in West Papua, and 15.6% in Papua. The likelihood of receiving anti-malarial drug treatment was statistically lower in Maluku (adjusted OR = 0.258; 95% CI 0.161-0.143) and North Maluku (adjusted OR = 0.473; 95% CI 0.266-0.840) than those in Eastern Nusa Tenggara (reference). Urban respondents were less likely to receive malaria treatment than rural (adjusted OR = 0.545; 95% CI 0.431-0.689). CONCLUSIONS: This study found that there were sub-national disparities in accessing anti-malarial drug treatment in Eastern Indonesia, with a high proportion of untreated malaria cases across the areas. Findings from this study could be used as baseline information to improve access to anti-malarial drug treatment and better target malaria intervention in Eastern Indonesia.

Using syndromic measures of mortality to capture the dynamics of COVID-19 in Java, Indonesia, in the context of vaccination rollout.

BACKGROUND: As in many countries, quantifying COVID-19 spread in Indonesia remains challenging due to testing limitations. In Java, non-pharmaceutical interventions (NPIs) were implemented throughout 2020. However, as a vaccination campaign launches, cases and deaths are rising across the island. METHODS: We used modelling to explore the extent to which data on burials in Jakarta using strict COVID-19 protocols (C19P) provide additional insight into the transmissibility of the disease, epidemic trajectory, and the impact of NPIs. We assess how implementation of NPIs in early 2021 will shape the epidemic during the period of likely vaccine rollout. RESULTS: C19P burial data in Jakarta suggest a death toll approximately 3.3 times higher than reported. Transmission estimates using these data suggest earlier, larger, and more sustained impact of NPIs. Measures to reduce sub-national spread, particularly during Ramadan, substantially mitigated spread to more vulnerable rural areas. Given current trajectory, daily cases and deaths are likely to increase in most regions as the vaccine is rolled out. Transmission may peak in early 2021 in Jakarta if current levels of control are maintained. However, relaxation of control measures is likely to lead to a subsequent resurgence in the absence of an effective vaccination campaign. CONCLUSIONS: Syndromic measures of mortality provide a more complete picture of COVID-19 severity upon which to base decision-making. The high potential impact of the vaccine in Java is attributable to reductions in transmission to date and dependent on these being maintained. Increases in control in the relatively short-term will likely yield large, synergistic increases in vaccine impact.

A participatory approach to address within-country cross-border malaria: the case of Menoreh Hills in Java, Indonesia.

BACKGROUND: Malaria remains a significant public health issue in Indonesia. Most of the endemic areas are in the eastern parts of Indonesia, but there are a few remaining foci of persistent endemic malaria in Java, particularly in Menoreh Hills, a region bordering three districts of two provinces on this island. Despite a commitment to build a partnership to eliminate cross-border malaria, there is a lack of understanding of how this partnership might be translated into an implementable strategic plan. The study aims to provide evidence of how a participatory approach was used to strengthen the cross-border collaboration and stakeholders' capacity to develop a joint strategic, operational, and costing plan for cross-border malaria elimination. METHODS: A participatory action research was conducted from January to August 2017, involving participants from the village, district, provincial, and national levels. This study was conducted in seven phases, including document review, focus group discussions (FGDs), planning and costing workshops, and a dissemination meeting. A total of 44 participants from primary health centres (PHC) and 27 representatives of affected villages in three districts, 16 participants from the district and provincial malaria programmes and planning bureaus, and 11 participants from the national level were involved in the processes. Data on priority issues, costing, programme coverage, and administration were collected. Thematic coding and feedback were used for analysis. RESULTS: Problems identified by stakeholders included low community awareness and participation in malaria prevention, high mobility across three districts, lack of financial and human resources, lack of inter-district coordination, and poor implementation of migration surveillance. Cross-border strategies identified to address malaria were improving cross-border migration surveillance, strengthening the network, governance, and advocacy of malaria control implementation across borders, and developing the malaria information system. A working group composed of the three districts' representatives authorized to decide on cross-border issues will be created. CONCLUSIONS: The participatory approach was applicable in cross-border malaria planning for within-country settings and useful in enhancing stakeholders' capacities as implementers. While done in a participatory way, the joint plan crafted was a non-binding agreement; stakeholders should advocate to ensure adequate funds are poured into mobilizing the programme.

Clinical characteristics and mortality associated with COVID-19 in Jakarta, Indonesia: A hospital-based retrospective cohort study.

BACKGROUND: Data on COVID-19-related mortality and associated factors from low-resource settings are scarce. This study examined clinical characteristics and factors associated with in-hospital mortality of COVID-19 patients in Jakarta, Indonesia, from March 2 to July 31, 2020. METHODS: This retrospective cohort included all hospitalised patients with PCR-confirmed COVID-19 in 55 hospitals. We extracted demographic and clinical data, including hospital outcomes (discharge or death). We used logistic regression to examine factors associated with mortality. FINDINGS: Of 4265 patients with a definitive outcome by July 31, 3768 (88%) were discharged and 497 (12%) died. The median age was 46 years (IQR 32-57), 5% were children, and 31% had >1 comorbidity. Age-specific mortalities were 11% (7/61) for <5 years; 4% (1/23) for 5-9; 2% (3/133) for 10-19; 2% (8/638) for 20-29; 3% (26/755) for 30-39; 7% (61/819) for 40-49; 17% (155/941) for 50-59; 22% (132/611) for 60-69; and 34% (96/284) for ≥70. Risk of death was associated with higher age, male sex; pre-existing hypertension, diabetes, or chronic kidney disease; clinical diagnosis of pneumonia; multiple (>3) symptoms; immediate ICU admission, or intubation. Across all ages, risk of death was higher for patients with >1 comorbidity compared to those without; notably the risk was six-fold increased among patients <50 years (adjusted odds ratio 5.87, 95%CI 3.28-10.52; 27% vs 3% mortality). INTERPRETATION: Overall in-hospital mortality was lower than reported in high-income countries, probably due to younger age distribution and fewer comorbidities. Deaths occurred across all ages, with >10% mortality among children <5 years and adults >50 years.

Climate change and health in Southeast Asia - defining research priorities and the role of the Wellcome Trust Africa Asia Programmes.

This article summarises a recent virtual meeting organised by the Oxford University Clinical Research Unit in Vietnam on the topic of climate change and health, bringing local partners, faculty and external collaborators together from across the Wellcome and Oxford networks. Attendees included invited local and global climate scientists, clinicians, modelers, epidemiologists and community engagement practitioners, with a view to setting priorities, identifying synergies and fostering collaborations to help define the regional climate and health research agenda. In this summary paper, we outline the major themes and topics that were identified and what will be needed to take forward this research for the next decade. We aim to take a broad, collaborative approach to including climate science in our current portfolio where it touches on infectious diseases now, and more broadly in our future research directions. We will focus on strengthening our research portfolio on climate-sensitive diseases, and supplement this with high quality data obtained from internal studies and external collaborations, obtained by multiple methods, ranging from traditional epidemiology to innovative technology and artificial intelligence and community-led research. Through timely agenda setting and involvement of local stakeholders, we aim to help support and shape research into global heating and health in the region.

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.

Analysis of serological data to investigate heterogeneity of malaria transmission: a community-based cross-sectional study in an area conducting elimination in Indonesia.

BACKGROUND: Analysis of anti-malarial antibody responses has the potential to improve characterization of the variation in exposure to infection in low transmission settings, where conventional measures, such as entomological estimates and parasitaemia point prevalence become less sensitive and expensive to measure. This study evaluates the use of sero-epidemiological analysis to investigate heterogeneity of transmission in area conducting elimination in Indonesia. METHODS: Filter paper bloodspots and epidemiological data were collected through a community-based cross-sectional study conducted in two sub-districts in Sabang municipality, Aceh province, Indonesia in 2013. Antibody responses to merozoite surface protein 1 (MSP-119) and apical membrane antigen 1 (AMA-1) for Plasmodium falciparum and Plasmodium vivax were measured using indirect enzyme-linked immunosorbent assay (ELISA). Seroconversion rates (SCR) were estimated by fitting a simple reversible catalytic model to seroprevalence data for each antibody. Spatial analysis was performed using a Normal model (SaTScan v.9.4.2) to identify the clustering of higher values of household antibody responses. Multiple logistic regression was used to investigate factors associated with exposure. RESULTS: 1624 samples were collected from 605 households. Seroprevalence to any P. falciparum antigen was higher than to any P. vivax antigen, 6.9% (95% CI 5.8-8.2) vs 2.0% (95% CI 1.4-2.8). SCR estimates suggest that there was a significant change in P. falciparum transmission with no exposure seen in children under 5 years old. Plasmodium falciparum SCR in over 5 years old was 0.008 (95% CI 0.003-0.017) and 0.012 (95% CI 0.005-0.030) in Sukakarya and Sukajaya sub-districts, respectively. Clusters of exposure were detected for both P. falciparum and P. vivax, most of them in Sukajaya sub-district. Higher age, P. vivax seropositivity and use of long-lasting insecticide-treated bed net (LLIN) were associated with higher P. falciparum exposure. CONCLUSION: Analysis of community-based serological data helps describe the level of transmission, heterogeneity and factors associated with malaria transmission in Sabang. This approach could be an important additional tool for malaria monitoring and surveillance in low transmission settings in Indonesia.

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.