Pengaruh Diabetes Melitus terhadap Gambaran Klinis dan Keberhasilan Pengobatan Tuberkulosis di Tujuh RSU Kelas A dan B di Jawa dan Bali

Diabetes mellitus (DM) may complicate tuberculosis (TB) treatment and control. The National Institute of Health Research and Development in collaboration with seven referral public hospitals in Java and Bali established a disease registry system for tuberculosis (TB) and diabetes mellitus (DM). Medical records containing data of ≥15 years old patients, diagnosed with TB (ICD-10 code A15-A19) in 2014, with or without DM (ICD-10 code E10-E14) were recorded into case report form (CRF). From January 1st 2014 to January 12th 2016, the registry recorded 1975 TB cases, 15% of cases were TB-DM. 73.6% TB-DM were ≥45 years old and 70,8% TB-non DM were <45 years old. Previously treated TB cases were higher than naïve in TB-DM (OR 2.588; 95%CI 2.0-3.4). In TB-DM, predominant symptoms were cough >2 weeks (76.4%), weight loss (72.6%), loss of appetite (65.9%), and night sweats (65.2%). In TB-non DM, predominant symptoms were weight loss (59.4%), loss of appetite (57.8%), cough >2 weeks (57.6%), and fever (56.9%). Higher chest X-rays abnormality in TB-DM (OR 7.249; 95%CI 3.2-16.5) and higher positive AFB smears (OR 2.568; 95%CI 1.8-3.8). TB treatment failure (death, defaulted, failure, or transferred out) were three times higher in TB-DM (aOR 3.042; 95%CI 1.7-5.4). TB-DM Registry showed negative effects of DM on clinical condition and the treatment success of TB. Abstrak Diabetes melitus (DM) menyulitkan pengobatan dan kontrol tuberkulosis (TB). Badan Penelitian dan Pengembangan Kesehatan bersama tujuh rumah sakit (RS) umum kelas A dan B di Pulau Jawa dan Bali mengembangkan Sistem Registri Penyakit TB-DM. Data pasien berusia ≥15 tahun, didiagnosis TB (kode A15-A19 ICD-10) mulai tahun 2014, dengan atau tanpa DM (kode E10-E14 ICD-10) diabstraksi ke dalam case report form (CRF). Mulai 1 Januari 2014 – 2 Januari 2016, terdapat 1975 kasus TB, 15% adalah TB dengan DM. 73,6% pasien TB-DM berusia ≥45 tahun dan 70,8% TB-non DM berusia <45 tahun. Pada kasus TB-DM, kasus TB sebelumnya pernah diobati lebih tinggi dibanding TB naïve (OR 2,588; KI95% 2,0-3,4). Pada TB-DM, gejala terbanyak adalah batuk lebih dari dua minggu, penurunan berat badan, penurunan nafsu makan, dan berkeringat di malam hari, berturut-turut sebanyak 76,4%; 72,6%; 65,9%; dan 65,2%. Pada TB-non DM, gejala dominan adalah penurunan berat badan, penurunan nafsu makan, batuk lebih dari dua minggu, dan demam, berturut-turut sebanyak 59,4%; 57,8%; 57,6%; dan 56,9%. Foto toraks abnormal lebih banyak pada TB-DM (OR 7,249; KI95% 3,2-16,5), demikian juga dengan BTA positif (OR 2,568; KI95% 1,8-3,8). Kegagalan pengobatan TB (meninggal, putus berobat, gagal pengobatan, atau pindah) tiga kali lebih besar pada TD-DM dibanding TB-non DM (aOR 3.042; KI95%1.7-5.4). Registri TB-DM menunjukkan efek negatif DM terhadap gambaran klinis dan keberhasilan pengobatan TB

Treatment-seeking behaviour and associated costs for malaria in Papua, Indonesia.

BACKGROUND: Malaria remains a significant public health issue in Eastern Indonesia, where multidrug resistant Plasmodium falciparum and Plasmodium vivax are highly prevalent. The objective of this study was to describe treatment-seeking behaviour and household costs prior to a change to a unified treatment policy of dihydroartemisinin-piperaquine in Mimika district, Papua province in 2006. METHODS: In 2005 a randomized cross-sectional household survey was conducted to collect data on demographics, socio-economic status (SES), treatment-seeking, case management, and household costs. Information on the cost of illness was also collected from patients exiting health facilities, in order to compare the cost of episodes diagnosed as P. vivax compared with those diagnosed as P. falciparum. RESULTS: 825 households were included in the survey. Of the 764 individuals who sought treatment for fever outside the home in the last month, 46% (349/764) went to a public health facility. Of the 894 reported visits to healthcare providers, 48% (433) resulted in a blood test, of which 78% (337) were reportedly positive. Only 10% (17/177) of individuals who reported testing positive for P. falciparum or mixed infection received the first-line treatment of chloroquine with SP, and 38% (61/159) of those with a diagnosis of P. vivax reportedly received the first-line treatment of chloroquine and primaquine. Overall, public facilities were more likely to prescribe the correct prevailing first-line drug combinations than private providers (OR = 3.77 [95% CI 2.31-6.14], p < 0.001). The mean cost to the household of an episode of P. vivax was similar to the cost of P. falciparum [US$44.50 (SD: 46.23) vs US$48.58 (SD: 64.65)]. CONCLUSIONS: Private providers were a popular source of treatment for malaria, but adherence to the national guidelines was low and the economic burden of malaria for both P. falciparum and P. vivax infections was substantial. Engagement with the private sector is needed to ensure that patients have access to affordable good quality, effective diagnostics and anti-malarials for both P. falciparum and P. vivax

Malaria morbidity in Papua Indonesia, an area with multidrug resistant Plasmodium vivax and Plasmodium falciparum

BACKGROUND: Multidrug resistance has emerged to both Plasmodium vivax and Plasmodium falciparum and yet the comparative epidemiology of these infections is poorly defined. METHODS: All laboratory-confirmed episodes of malaria in Timika, Papua, Indonesia, presenting to community primary care clinics and an inpatient facility were reviewed over a two-year period. In addition information was gathered from a house-to-house survey to quantify the prevalence of malaria and treatment-seeking behaviour of people with fever. RESULTS: Between January 2004 and December 2005, 99,158 laboratory-confirmed episodes of malaria were reported, of which 58% (57,938) were attributable to P. falciparum and 37% (36,471) to P. vivax. Malaria was most likely to be attributable to pure P. vivax in children under one year of age (55% 2,684/4,889). In the household survey, the prevalence of asexual parasitaemia was 7.5% (290/3,890) for P. falciparum and 6.4% (248/3,890) for P. vivax. The prevalence of P. falciparum infection peaked in young adults aged 15-25 years (9.8% 69/707), compared to P. vivax infection which peaked in children aged 1 to 4 years (9.5% 61/642). Overall 35% (1,813/5,255) of people questioned reported a febrile episode in the preceding month. Of the 60% of people who were estimated to have had malaria, only 39% would have been detected by the surveillance network. The overall incidence of malaria was therefore estimated as 876 per 1,000 per year (Range: 711-906). CONCLUSION: In this region of multidrug-resistant P. vivax and P. falciparum, both species are associated with substantial morbidity, but with significant differences in the age-related risk of infection

RePORT International: Advancing Tuberculosis Biomarker Research Through Global Collaboration

Progress in tuberculosis clinical research is hampered by a lack of reliable biomarkers that predict progression from latent to active tuberculosis, and subsequent cure, relapse, or failure. Regional Prospective Observational Research in Tuberculosis (RePORT) International represents a consortium of regional cohorts (RePORT India, RePORT Brazil, and RePORT Indonesia) that are linked through the implementation of a Common Protocol for data and specimen collection, and are poised to address this critical research need. Each RePORT network is designed to support local, in-country tuberculosis-specific data and specimen biorepositories, and associated research. Taken together, the expected results include greater global clinical research capacity in high-burden settings, and increased local access to quality data and specimens for members of each network and their domestic and international collaborators. Additional networks are expected to be added, helping to spur tuberculosis treatment and prevention research around the world

Multidrug-Resistant Plasmodium vivax Associated with Severe and Fatal Malaria: A Prospective Study in Papua, Indonesia

Ric Price and colleagues present data from southern Papua, Indonesia, suggesting that malaria resulting from infection withPlasmodium vivax is associated with substantial morbidity and mortality

Performance of Xpert MTB/RIF and sputum microscopy compared to sputum culture for diagnosis of tuberculosis in seven hospitals in Indonesia

IntroductionTuberculosis (TB) is a major public health concern in Indonesia, where the incidence was 301 cases per 100,000 inhabitants in 2020 and the prevalence of multi-drug resistant (MDR) TB is increasing. Diagnostic testing approaches vary across Indonesia due to resource limitations. Acid-fast bacilli (AFB) smear is widely used, though Xpert MTB/RIF has been the preferred assay for detecting TB and rifampicin resistance since 2012 due to higher sensitivity and ability to rapidly identify rifampicin resistance. However, &lt;1,000 Xpert instruments were available in Indonesia as of 2020 and the Xpert supply chain has suffered interruptions.MethodsWe compared the performance of Xpert MTB/RIF and AFB smear to facilitate optimization of TB case identification. We analyzed baseline data from a cohort study of adults with pulmonary TB conducted at seven hospitals across Indonesia. We evaluated sensitivity and specificity of AFB smear and Xpert MTB/RIF using Mycobacterium tuberculosis (Mtb) culture as the gold standard, factors associated with assay results, and consistency of Xpert MTB/RIF with drug susceptibility test (DST) in detecting rifampicin resistance.ResultsSensitivity of AFB smear was significantly lower than Xpert MTB/RIF (86.2 vs. 97.4%, p-value &lt;0.001), but specificity was significantly better (86.7 vs. 73.3%, p-value &lt;0.001). Performance varied by hospital. Positivity rate for AFB smear and Mtb culture was higher in subjects with pulmonary cavities and in morning sputum samples. Consistency of Xpert MTB/RIF with DST was lower in those with rifampicin- sensitive TB by DST.DiscussionAdditional evaluation using sputa from primary and secondary Indonesian health centers will increase the generalizability of the assessment of AFB smear and Xpert MTB/RIF performance, and better inform health policy.Clinical trial registration[https://clinicaltrials.gov/], identifier [NCT027 58236]

Validation of a Liquid Chromatography/Tandem Mass Spectrometry Assay for the Quantification of Plasma Dihydroartemisinin

Background: Insufficient plasma level of dihydroartemisinin (DHA) can select resistance and will further hinder malaria elimination program. We investigated clinical applicability of a validated liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay to quantify plasma concentration of DHA in healthy subjects from a single oral administration of fixed dose combination of Dihydroartemisinin-Piperaquine.Materials and Methods: Micro-elution solid-phase extraction in a 96-well plate format was used to prepare the samples. DHA separation happened in Acquity UPLCTM BEH C18 column (50 × 2.1 mm, 1.7 µm). Mobile phase was a mixture of acetonitrile-ammonium acetate 10 mM pH 3.5 (50:50, v/v) at 0.3 mL/minute flow rate. Waters Acquity UPLC™ H-Class system coupled with triple quadruple mass spectrometry in positive electrospray ionization mode was used for detection. The internal standard was a stable isotope labelled DHA.Results: Calibration curve was linear with a correlation coefficient >0.995 over a concentration range of 1–1,000 ng/mL. Bias and variation for accuracy and precision were in the range of 15% (20% at the lower limit of quantification). Using 5 µL sample, lower limit of quantification was 1 ng. Matrix effect was less than 15%. The method was successfully applied to investigate the pharmacokinetics of DHA from five healthy subjects, although carry over and the role of anticoagulants were not tested.Conclusion: The LC-MS/MS assay for the quantification of plasma DHA was validated for selectivity, linearity, lower limit of quantitation, accuracy, precision, matrix effect and stability. Although clinical applicability was demonstrated, this method was to be improved to address the not-tested validation parameters.Keywords: dihydroartemisinin, liquid chromatography/tandem mass spectrometry assay (LC-MS/MS), malaria, Indonesia

Poor Tuberculosis Treatment Outcomes Associated with Older Age, Previous Treatment, HIV and Drug Resistance at Seven Hospitals in Indonesia

Abstract Indonesia is a high burden country for tuberculosis (TB), multidrug-resistant (MDR) TB, and TB-HIV. We aimed to determine factors associated with poor TB treatment outcomes. A hospital-based TB Registry at seven referral hospitals in Java and Bali included data from patients aged ≥15 years who were diagnosed with TB from 1 January 2014 - 31 December 2015. The factors were assessed by logistic regression. From 2,051 TB patients, 1,180 (57.5%) were male and median age was 38 years (IQR 27-50 years), 452 (22%) had previous TB treatment history, 1,447 (70.6%) had pulmonary TB, 216 (10.5%) TB-HIV, 296 (14.4%) TB-DM and 248 (12.1%) were resistant to ≥1 anti-TB drug. Treatment outcome was unknown for 135 (6.6%) subjects and 1,137 (55.4%) who were still on treatment. Among the 779 with available outcome, 358 (46%) were treatment success, 248 (31.8%) transferred out, 112 (14.4%) defaulted, 46 (5.9%) died and 15 (1.9%) failed. After controlling other factors, poor TB treatment was associated with age ≥38 years (p=0.003; aOR 1.58; 95% CI 1.2-2.1), previous history of TB treatment (p&lt;0.001; aOR 2.55; 95% CI 1.5-4.2) and resistance to ≥1 anti-TB drug (p&lt;0.001; aOR 11.66; 95% CI 3.8-36.1). Mortality was associated with previous history of TB treatment (p=0.003; aOR 3.87; 95% CI 1.7-9.6), TB-HIV (p=0.001; aOR 10.43; 95% CI 4.2-26.1), and resistance to ≥1 anti-TB drug (p=0.001; aOR 9.48; 95% CI 2.6-34.0). Treatment in TB patients with older age, history of previous TB treatment, HIV, and drug resistance should be closely monitored. Keywords: Indonesia, tuberculosis, treatment outcome Abstrak Indonesia adalah negara dengan beban tinggi untuk tuberkulosis (TB), TB resisten obat (MDR) dan TB-HIV. Analisis ini bertujuan untuk menentukan faktor yang terkait dengan luaran pengobatan TB yang buruk. Registri TB berbasis rumah sakit di tujuh rumah sakit rujukan di Jawa dan Bali mencakup data dari pasien berusia ≥15 tahun yang didiagnosis TB dari 1 Januari 2014 - 31 Desember 2015. Faktor-faktor tersebut dinilai dengan regresi logistik. Dari 2.051 pasien TB, 1.180 (57,5%) laki-laki dan median usia 38 tahun (IQR 27-50 tahun), 452 (22%) memiliki riwayat pengobatan TB sebelumnya, 1.447 (70,6%) memiliki TB paru, 216 (10,5%) TB-HIV, 296 (14,4%) TB-DM dan 248 (12,1%) resisten terhadap ≥1 obat anti-TB. Luaran pengobatan TB tidak diketahui untuk 135 (6,6%) subjek dan 1.137 (55,4%) yang masih dalam pengobatan. Di antara 779 dengan luaran pengobatan diketahui, 358 (46%) pengobatan berhasil, 248 (31,8%) pindah, 112 (14,4%) putus pengobatan, 46 (5,9%) meninggal dan 15 (1,9%) gagal. Setelah dikontrol terhadap faktor lain, luaran pengobatan TB yang buruk dikaitkan dengan usia ≥38 tahun (p = 0,003; aOR 1,58; 95% CI 1,2-2,1), riwayat pengobatan TB sebelumnya (p &lt;0,001; aOR 2,55; 95% CI 1,5-4,2) dan resistansi terhadap ≥1 obat anti-TB (p &lt;0,001; aOR 11,66; 95% CI 3,8-36,1). Kematian dikaitkan dengan riwayat pengobatan TB sebelumnya (p = 0,003; aOR 3,87; 95% CI 1,7-9,6), TB-HIV (p = 0,001; aOR 10,43; 95% CI 4,2-26,1), dan resistansi terhadap ≥1 anti -TB obat (p = 0,001; aOR 9,48; 95% CI 2,6-34,0). Pengobatan pada pasien TB dengan usia yang lebih tua, riwayat pengobatan TB sebelumnya, HIV dan resistansi obat harus dipantau secara ketat. Kata kunci: Indonesia, tuberkulosis, luaran pengobata

A Review of Hantavirus Research in Indonesia: Prevalence in Humans and Rodents, and the Discovery of Serang Virus

Dengue and other common tropical infectious diseases of similar clinical presentation are endemic in Indonesia, which may lead to an underestimation of the prevalence of hantavirus (HTV) infection in the country. To better understand the current burden of HTV infection, this study aimed to both identify acute HTV infection among hospitalized patients with fever and to determine the overall seroprevalence of HTV. These results were further considered within the context of previously reported HTV infection in humans and animals in Indonesia by conducting a review of published literature. As part of an observational cohort study of acute febrile illness, this sub-study retrospectively analyzed blood specimens obtained during admission, during the 2&ndash;4-week convalescent period, and three months after admission. Convalescent specimens from patients with clinical signs and symptoms of HTV infection were first screened for HTV IgG. When positive, convalescent specimens and paired acute specimens were screened for HTV IgM, and paired acute specimens were tested for HTV by Reverse Transcription Polymerase Chain Reaction (RT-PCR). A literature review of HTV in Indonesia was conducted on manuscripts manually reviewed for relevance after identification from a search using the terms &ldquo;hantavirus/Seoul virus&rdquo; and &ldquo;Indonesia&rdquo;. From patients at eight hospitals in seven provincial capitals, HTV IgG seroprevalence was 11.6% (38/327), with the highest being in Denpasar (16.3%, 7/43) and the lowest being in Yogyakarta (3.4%, 1/31). Anti-HTV IgG was most prevalent in adults (13.5%, 33/244) and males (15.6%, 29/186). Acute HTV infections were identified in two subjects, both of whom had Seoul virus. In Indonesia, HTVs have been studied in humans and animals since 1984. Over the past 35 years, the reported seroprevalences in rodents ranged from 0% to 34%, and in humans from 0% to 13%. Fourteen acute infections have been reported, including one in a tourist returning to Germany, but only two have been confirmed by RT-PCR. Almost all rodent and human surveillance results demonstrated serological and molecular evidence of Seoul virus infection. However, in Semarang, anti-Puumala virus IgM has been detected in humans and Puumala RNA in one rodent. In Serang, a new virus named Serang virus was identified due to its differences from Seoul virus. In Maumere, HTV and Leptospira spp. were identified simultaneously in rodents. The burden of HTV infection in Indonesia is underestimated, and additional studies are needed to understand the true prevalence. Seroprevalence data reported here, previous observations of HTV co-infections in rodents, and the prevalence of rodent-borne bacterial infections in Indonesia suggest that the population may be routinely encountering HTVs. While Seoul virus appears to be the most prevalent HTV in the country, further studies are needed to understand which HTVs are circulating