Sequence of COVID-19 Vaccination and COVID-19 Infection and Their Association With the Development of Active Tuberculosis: A Case-Control Study.

Introduction Information regarding the cross-risk of coronavirus disease 2019 (COVID-19) and tuberculosis (TB) is still sparse. This study aimed to identify the patterns of sequence of COVID-19 vaccination and COVID-19 infection and to explore the association between COVID-19 vaccination, COVID-19 infection, and the development of active TB. Methods It was a case-control study conducted in RSUD Dr. Iskak Hospital, Tulungagung, between October 2022 and April 2023. Active cases of TB patients were compared with non-TB controls in the same hospital, with the same age and sex. Their pattern of sequence of COVID-19 vaccination and infection was investigated. Logistic regression was used to assess the association between these key variables. Results Of 296 case-control sets, 64.2% were female. The mean ± standard deviation of age was 46 ± 15.6 years. 5.7% of the cases and 6.4% of the controls had a history of COVID-19 infection, whereas 58.8% and 68.4% had been vaccinated (mostly after infection). The adjusted odds ratio (95% confidence interval) of COVID-19 infection on risk to the development of active TB was 1.45 (0.58, 3.65). Those of COVID-19 vaccination of one to four doses were 0.42 (0.17, 1), 0.98 (0.58, 1.66), 0.48 (0.25, 0.93), and 0.09 (0.01, 0.81), respectively. Conclusion It was found that there were five patterns of sequence of COVID-19 infection and COVID-19 vaccination, with the most frequent being having COVID-19 infection before COVID-19 vaccination. Our data did not support the association between COVID-19 infection and the subsequent development of active TB. On the other hand, COVID-19 vaccination has been demonstrated to increase some protection against the development of active TB.

Cross-Risk Between Tuberculosis and COVID-19 in East Java Province, Indonesia: An Analysis of Tuberculosis and COVID-19 Surveillance Registry Period 2020-2022.

INTRODUCTION: Tuberculosis (TB) and COVID-19 are highly transmissible diseases and pose a serious risk to public health. Unfortunately, information on cross-risk between the two diseases was still sparse. Our main objective was to estimate the excess risk among TB patients in getting COVID-19 infection and vice versa. METHODS: The study design was a series of analyses of existing data from TB and COVID-19 registries in East Java Province, Indonesia. The study period was from January 2020 to June 2022. Case-by-case data for this study were obtained from the registration systems for TB and COVID-19 in separate databases. In comparing risk across different groups, adjusting for differences in risk factors that influence the outcome was essential. We overcame this problem by employing a standardized morbidity ratio. RESULTS: Among 92,424 newly diagnosed TB patients, 1,326 were subsequently infected with COVID-19 during the study period, compared with 1,679 expected. The standardized morbidity ratio (95% confidence interval) was 72.61% (60.19%, 85.03%). Among 635,946 newly diagnosed COVID-19-infected patients, 987 subsequently got active TB during the study period against 1,679 expected. The standardized morbidity ratio (95% confidence interval) was 55.33% (49.24%, 61.42%). CONCLUSION: There was no evidence of excess risk in either direction, the excess risk among TB patients in getting COVID-19 infection and vice versa.

Negligible Impact of Mass Screening and Treatment on Mesoendemic Malaria Transmission at West Timor in Eastern Indonesia: A Cluster-Randomized Trial.

Background: Mass screening and treatment (MST) aims to reduce malaria risk in communities by identifying and treating infected persons without regard to illness. Methods: A cluster-randomized trial evaluated malaria incidence with and without MST. Clusters were randomized to 3, 2, or no MST interventions: MST3, 6 clusters (156 households/670 individuals); MST2, 5 clusters (89 households/423 individuals); and MST0, 5 clusters (174 households/777 individuals). All clusters completed the study with 14 residents withdrawing. In a cohort of 324 schoolchildren (MST3, n = 124; MST2, n = 57; MST0, n = 143) negative by microscopy at enrollment, we evaluated the incidence density of malaria during 3 months of MST and 3 months following. The MST intervention involved community-wide expert malaria microscopic screening and standard therapy with dihydroartemisinin-piperaquine and primaquine for glucose-6 phosphate dehydrogenase-normal subjects. All blood examinations included polymerase chain reaction assays, which did not guide on-site treatment. Results: The risk ratios for incidence density of microscopically patent malaria in MST3 or MST2 relative to that in MST0 clusters were 1.00 (95% confidence interval [CI], .53-1.91) and 1.22 (95% CI, .42-3.55), respectively. Similar results were obtained with molecular analysis and species-specific (P. falciparum and P. vivax) infections. Microscopically subpatent, untreated infections accounted for 72% of those infected. Conclusions: Two or 3 rounds of MST within 3 months did not impact the force of anopheline mosquito-borne infection in these communities. The high rate of untreated microscopically subpatent infections likely explains the observed poor impact. Clinical Trials Registration: NCT01878357.

Therapeutic Response to Dihydroartemisinin-Piperaquine for P. falciparum and P. vivax Nine Years after Its Introduction in Southern Papua, Indonesia.

Dihydroartemisinin-piperaquine (DHP) has been the first-line treatment of uncomplicated malaria due to both Plasmodium falciparum and Plasmodium vivax infections in Papua, Indonesia, since March 2006. The efficacy of DHP was reassessed to determine whether there had been any decline following almost a decade of its extensive use. An open-label drug efficacy study of DHP for uncomplicated P. falciparum and P. vivax malaria was carried out between March 2015 and April 2016 in Timika, Papua, Indonesia. Patients with uncomplicated malaria were administered supervised DHP tablets once daily for 3 days. Clinical and laboratory data were collected daily until parasite clearance and then weekly for 6 weeks. Molecular analysis was undertaken for all patients with recurrent parasitemia. A total of 129 study patients were enrolled in the study. At day 42, the polymerase chain reaction-adjusted efficacy was 97.7% (95% confidence intervals [CI]: 87.4-99.9) in the 61 patients with P. falciparum malaria, and 98.2% [95% CI: 90.3-100] in the 56 patients with P. vivax malaria. By day 2, 98% (56/57) of patients with P. falciparum and 96.9% (63/65) of those with P. vivax had cleared their peripheral parasitemia; none of the patients were still parasitaemic on day 3. Molecular analysis of P. falciparum parasites showed that none (0/61) had K13 mutations associated previously with artemisinin resistance or increased copy number of plasmepsin 2-3 (0/61). In the absence of artemisinin resistance, DHP has retained high efficacy for the treatment of uncomplicated malaria despite extensive drug pressure over a 9-year period.

Quality Tuberculosis Care in Indonesia: Using Patient Pathway Analysis to Optimize Public-Private Collaboration.

Background: Tuberculosis (TB) is the fourth leading cause of death in Indonesia. In 2015, the World Health Organization estimated that nearly two-thirds of the TB patients in Indonesia had not been notified, and the status of their care remained unknown. As such, Indonesia is home to nearly 20% of the world's "missing" TB patients. Understanding where patients go for care may enable strategic planning of services to better reach them. Methods: A patient pathway analysis (PPA) was conducted to assess the alignment between patient care seeking and the availability of TB diagnostic and treatment services at the national and subnational level in Indonesia. Results: The PPA results revealed that only 20% of patients encountered diagnostic capacity at the location where they first sought care. Most initial care seeking occurred in the private sector and case notification lagged behind diagnostic confirmation in the public sector. Conclusions: The PPA results emphasize the role that the private sector plays in TB patient care seeking and suggested a need for differentiated approaches, by province, to respond to variances in care-seeking patterns and the capacities of public and private providers.

Epidemiology of Plasmodium vivax in Indonesia.

Endemic malaria occurs across much of the vast Indonesian archipelago. All five species of Plasmodium known to naturally infect humans occur here, along with 20 species of Anopheles mosquitoes confirmed as carriers of malaria. Two species of plasmodia cause the overwhelming majority and virtually equal shares of malaria infections in Indonesia: Plasmodium falciparum and Plasmodium vivax The challenge posed by P. vivax is especially steep in Indonesia because chloroquine-resistant strains predominate, along with Chesson-like strains that relapse quickly and multiple times at short intervals in almost all patients. Indonesia's hugely diverse human population carries many variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency, most of them exhibiting severely impaired enzyme activity. Therefore, the patients most likely to benefit from primaquine therapy by preventing aggressive relapse, may also be most likely to suffer harm without G6PD deficiency screening. Indonesia faces the challenge of controlling and eventually eliminating malaria across > 13,500 islands stretching > 5,000 km and an enormous diversity of ecological, ethnographic, and socioeconomic settings, and extensive human migrations. This article describes the occurrence of P. vivax in Indonesia and the obstacles faced in eliminating its transmission.

Targeting populations at higher risk for malaria: a survey of national malaria elimination programmes in the Asia Pacific.

BACKGROUND: Significant progress has been made in reducing the malaria burden in the Asia Pacific region, which is aggressively pursuing a 2030 regional elimination goal. Moving from malaria control to elimination requires National Malaria Control Programmes (NMCPs) to target interventions at populations at higher risk, who are often not reached by health services, highly mobile and difficult to test, treat, and track with routine measures, and if undiagnosed, can maintain parasite reservoirs and contribute to ongoing transmission. METHODS: A qualitative, free-text questionnaire was developed and disseminated among 17 of the 18 partner countries of the Asia Pacific Malaria Elimination Network (APMEN). RESULTS: All 14 countries that responded to the survey identified key populations at higher risk of malaria in their respective countries. Thirteen countries engage in the dissemination of malaria-related Information, Education, and Communication (IEC) materials. Eight countries engage in diagnostic screening, including of mobile and migrant workers, military staff, and/or overseas workers. Ten countries reported distributing or recommending the use of long-lasting insecticide-treated nets (LLINs) among populations at higher risk with fewer countries engaging in other prevention measures such as indoor residual spraying (IRS) (two countries), spatial repellents (four countries), chemoprophylaxis (five countries), and mass drug administration (MDA) (three countries). Though not specifically tailored to populations at higher risk, 11 countries reported using mass blood surveys as a surveillance tool and ten countries map case data. Most NMCPs lack a monitoring and evaluation structure. CONCLUSION: Countries in the Asia Pacific have identified populations at higher risk and targeted interventions to these groups but there is limited information on the effectiveness of these interventions. Platforms like APMEN offer the opportunity for the sharing of protocols and lessons learned related to finding, targeting and successfully clearing malaria from populations at higher risk. The sharing of programme data across borders may further strengthen national and regional efforts to eliminate malaria. This exchange of real-life experience is invaluable to NMCPs when scarce scientific evidence on the topic exists to aid decision-making and can further support NMCPs to develop strategies that will deliver a malaria-free Asia Pacific by 2030.

Behaviour and molecular identification of Anopheles malaria vectors in Jayapura district, Papua province, Indonesia.

BACKGROUND: Members of the Anopheles punctulatus group dominate Papua, Indonesia and Papua New Guinea (PNG), with a geographic range that extends south through Vanuatu. An. farauti and An. punctulatus are the presumed major vectors in this region. Although this group of species has been extensively studied in PNG and the southern archipelagoes within their range, their distribution, ecology and vector behaviours have not been well characterized in eastern Indonesia. METHODS: Mosquitoes were collected in five villages in Jayapura province, Papua, Indonesia using human-landing collections, animal-baited tents and backpack aspirators. Mosquitoes were morphologically typed and then molecularly distinguished based on ribosomal ITS2 sequences and tested for Plasmodium falciparum and P. vivax infection using circumsporozoite ELISA and PCR. RESULTS: The presence and vector status of An. farauti 4 in Papua, Indonesia is confirmed here for the first time. The data indicate that this species is entering houses at a rate that increases its potential to come into contact with humans and act as a major malaria vector. An. farauti 4 was also abundant outdoors and biting humans during early evening hours. Other species collected in this area include An. farauti 1, An. hinesorum, An. koliensis, An. punctulatus, and An. tessellatus. Proboscis morphology was highly variable within each species, lending support to the notion that this characteristic is not a reliable indicator to distinguish species within the An. punctulatus group. CONCLUSIONS: The vector composition in Papua, Indonesia is consistent with certain northern areas of PNG, but the behaviours of anophelines sampled in this region, such as early and indoor human biting of An. farauti 4, may enable them to act as major vectors of malaria. Presumed major vectors An. farauti and An. punctulatus were not abundant among these samples. Morphological identification of anophelines in this sample was often inaccurate, highlighting the importance of using molecular analysis in conjunction with morphological investigations to update keys and training tools.

Low and Declining Risk for Malaria in Visitors to Indonesia: A Review of Local Indonesian and European Travelers' Data and a Suggestion for New Prophylactic Guidelines.

INTRODUCTION: The world's malaria map is constantly changing and with it the risk for travelers to contract malaria. While some efforts to appreciate the malaria situation for indigenous populations in Indonesia have been made recently, there is only sparse data in the literature on the risk for travelers to Indonesia. METHODS: Data were collected from the Indonesian Ministry of Health (MoH), the World Health Organization (WHO), the Indonesian official statistics website Badan Pusat Statistik (BPS), and from the different European national surveillance bodies. Finally, a comparison between recent official guidelines for prevention of malaria in travelers from Germany, the United States, the UK, and from WHO was done. RESULTS: Data from Denmark, Germany, Sweden and Switzerland show a steady decline of imported cases of malaria from Indonesia from 1997 to 2013, with a leveling off during the last few years. In our study material, the Plasmodium falciparum incidence 2009 to 2013 was 0.35 cases per 100,000 visits and the Plasmodium vivax incidence 1.3 cases per 100,000 visits, with a 95% confidence interval of 0.1-0.9 and 0.7-2.2, respectively. Indonesian data also show a decline of malaria cases-the Annual Parasite Index (API) for all species of malaria has decreased from 4.68 cases per 1,000 inhabitants in 1990 to 1.38 cases per 1,000 inhabitants in 2013. CONCLUSION: Based on these data updated recommendations for malaria prophylaxis in travelers to Indonesia are suggested.

Active case detection for malaria elimination: a survey among Asia Pacific countries.

BACKGROUND: Moving from malaria control to elimination requires national malaria control programmes to implement strategies to detect both symptomatic and asymptomatic cases in the community. In order to do this, malaria elimination programmes follow up malaria cases reported by health facilities to carry out case investigations that will determine the origin of the infection, whether it has been imported or is due to local malaria transmission. If necessary, the malaria programme will also carry out active surveillance to find additional malaria cases in the locality to prevent further transmission. To understand current practices and share information on malaria elimination strategies, a survey specifically addressing country policies on case investigation and reactive case detection was carried out among fourteen countries of the Asia Pacific Malaria Elimination Network (APMEN). METHODS: A questionnaire was distributed to the malaria control programme managers amongst 14 countries in the Asia Pacific who have national or sub-national malaria elimination goals. RESULTS: Results indicate that there are a wide variety of case investigation and active case detection activities employed by the 13 countries that responded to the survey. All respondents report conducting case investigation as part of surveillance activities. More than half of these countries conduct investigations for each case. Over half aim to accomplish the investigation within one to two days of a case report. Programmes collect a broad array of demographic data during investigation procedures and definitions for imported cases are varied across respondents. Some countries report intra-national (from a different province or district) importation while others report only international importation (from a different country). Reactive case detection in respondent countries is defined as screening households within a pre-determined radius in order to identify other locally acquired infections, whether symptomatic or asymptomatic. Respondents report that reactive case detection can be triggered in different ways, in some cases with only a single case report and in others if a defined threshold of multiple cases occurs. The spatial range of screening conducted varies from a certain number of households to an entire administrative unit (e g, village). Some countries target symptomatic people whereas others target all people in order to detect asymptomatic infections. The majority of respondent programmes collect a range of information from those screened for malaria, similar to the range of information collected during case investigation. CONCLUSION: Case investigation and reactive case detection are implemented in the malaria elimination programmes in the Asia Pacific, however practices vary widely from country to country. There is little evidence available to support countries in deciding which methods to maintain, change or adopt for improved effectiveness and efficiency. The development and use of common evaluation metrics for these activities will allow malaria programmes to assess performance and results of resource-intensive surveillance measures and may benefit other countries that are considering implementing these activities.

The distribution and bionomics of anopheles malaria vector mosquitoes in Indonesia.

Malaria remains one of the greatest human health burdens in Indonesia. Although Indonesia has a long and renowned history in the early research and discoveries of malaria and subsequently in the successful use of environmental control methods to combat the vector, much remains unknown about many of these mosquito species. There are also significant gaps in the existing knowledge on the transmission epidemiology of malaria, most notably in the highly malarious eastern half of the archipelago. These compound the difficulty of developing targeted and effective control measures. The sheer complexity and number of malaria vectors in the country are daunting. The difficult task of summarizing the available information for each species and/or species complex is compounded by the patchiness of the data: while relatively plentiful in one area or region, it can also be completely lacking in others. Compared to many other countries in the Oriental and Australasian biogeographical regions, only scant information on vector bionomics and response to chemical measures is available in Indonesia. That information is often either decades old, geographically patchy or completely lacking. Additionally, a large number of information sources are published in Dutch or Indonesian language and therefore less accessible. This review aims to present an updated overview of the known distribution and bionomics of the 20 confirmed malaria vector species or species complexes regarded as either primary or secondary (incidental) malaria vectors within Indonesia. This chapter is not an exhaustive review of each of these species. No attempt is made to specifically discuss or resolve the taxonomic record of listed species in this document, while recognizing the ever evolving revisions in the systematics of species groups and complexes. A review of past and current status of insecticide susceptibility of eight vector species of malaria is also provided.

New treatment policy of malaria as a part of malaria control program in Indonesia.

Malaria control program is one of the oldest program in the Ministry of Health (MoH) Republic of Indonesia. Started with effort to eradicate malaria in 1959 through Malaria Eradication Command well known as KOPEM (Komando Pembasmian Malaria) then it evolves to Malaria Control Program, Roll Back Malaria Program, and the current Malaria Elimination Program. In terms of diagnostic and treatment, the policy has formulated by strictly follow evidence-based principles as well as technical guided from World Health Organization (WHO). In 2004, based on numerous researches conducted in Indonesia the use of chloroquine was stopped and artemisinin-based combination therapy (ACT) was then initiated. For severe cases the use of intravenous (iv) Artesunate for cases treated in hospitals and intramuscular (im) Arthemeter for cases treated in the primary care setting were also introduced. ACT, Artesunate iv, and Artemether im, all are provided nationwide through the procurement system. For radical treatment, the recommendation in Indonesia is to add primaquine (PQ) to ACT for Plasmodium vivax and Plasmodium ovale infections to prevent relapses and for Plasmodium Falciparum infection to kill the gametocytes. These recommendations put hope to reduce malaria mortality to zero and eventually with other interventions will eliminate malaria from the country by 2030. The dissemination of this information is important for the policy to apply in practice across the country.

Sustainable scaling up of good quality health worker education for tuberculosis control in Indonesia: a case study.

BACKGROUND: In 2000, an external review mission of the National Tuberculosis Control Programme of Indonesia identified suboptimal results of TB control activities. This led to a prioritization on human resource capacity building representing a major shift in the approach following the recommendations of the external review team. CASE DESCRIPTION: The National Tuberculosis Control Programme (NTP) used a systematic process to develop and implement two strategic action plans focussing on competence development based on specific job descriptions. The approach was a change from only focussing on training, to a broader, long term approach to human resource development for comprehensive TB control. A structured plan for capacity building, including standardized competency based training modules and curricula, was developed in the first phase. This was supported by an organisational system comprised of a training focal point, master trainers, and regional training centres in which nationwide training of supervisors was implemented. Training was expanded to the health service delivery level in the second phase, as well as broadened in the scope of activities beyond training to also include other aspects of human resource development. DISCUSSION AND EVALUATION: The result was improved technical and managerial capacity of health workers for TB control at all levels. The impact on case detection and treatment outcome was spectacular, with major improvements in quality of all aspects of service delivery. CONCLUSION: The strategic decision by the NTP in 2000 to put the highest priority on capacity building has resulted in impressive progress towards TB control targets, a progress that despite many challenges has been sustained.