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, <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 <0.001), but specificity was significantly better (86.7 vs. 73.3%, p-value <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]

Virus-Virus Saluran Pernapasan yang Paling Banyak Ditemukan pada Anak Balita Pasien SARI (Severe Acute Respiratory Infections)

In children, 50% respiratory infection was caused by viruses. This research was aimed to identify type of viruses causing respiratory infection among SARI patients under five years old in several regions in Indonesia.Study design of this reserach was prospective study using survey and laboratory analysis. Data was being collected from SARI surveillance. There were 215 throat specimens from 350 children under five years old patients. Specimens were collected from March 2008 to December 2008. To detect viruses in the respiratory tract, this research used Multiplex Bead Array Assay technique.Among 215 specimens tested, 91 specimens (40.12%) were positive respiratory viruses. In children under 1 year old, Coxsakie and Enterovirus (8.72%) were two viruses that mostly detected. In children aged 2 to 3 years old, the virus that mostly found was Respiratory Syncytial virus. And in children aged 4 to 5 years old, Entero and Rhinovirus were mostly found (14.29%). Based on the distribution of respiratory viruses in hospital, there were two peaks shown in the graphs. Firstly, Entero and Rhinovirus were high in Kupang and DKI Jakarta. Secondly, Respiratory Syncytial virus was found high in Kupang, Semarang, and DKI Jakarta.Respiratory Syncytial, Coxsakie, Enterovirus, and Entero Rhinovirus were mostly identified in SARI Patients under five years old.Key word: respiratory viruses, SARI, children under five years AbstrakPada anak-anak lima puluh persen penyebab infeksi saluran pernapasan adalah virus. Tujuan dari penelitian ini adalah unutk mengetahui jenis virus-virus pernapasan pada pasien balita rawat inap penderita SARI (Severe Acute Respiratory Infectiouns) di beberapa daerah di Indonesia. Desain penelitian prospektif dengan jenis studi survey dan studi laboratorium. Data berasal dari spesimen tersimpan surveilans SARI. Jumlah spesimen 215 usap tenggorok dari total 350 pasien balita. Spesimen dikumpulkan dari bulan Maret 2008-Desember 2008. Untuk mendeteksi virus-virus pada saluran pernapasan digunakan teknologi Multiplex Bead Array Assay. Diantara 215 spesimen, 91 spesimen (40,12 %) positif virus pernapasan. Pada anak dibawah 1 tahun, virus yang paling banyak ditemui adalah virus Coxsakie dan Entero Virus (8,72 %). Sedangkan pada anak usia 2-3 tahun virus yang paling banyak ditemukan adalah virus Respiratory Syncytial (17,24 %) dan pada anak usia 4-5 tahun virus yang paling banyak ditemukan adalah virus Entero dan Rhinovirus (14,29 %). Berdasarkan distribusi virus pernapasan di rumah sakit terlihat 2 puncak grafik yang menunjukkan tingginya virus Entero dan Rhino di Daerah Kupang dan DKI. Puncak grafik kedua yang menunjukkan tingginya virus Respiratory Syncytial di Daerah Kupang, Semarang dan DKI. Virus Respiratory Syncytial, Coxsakie dan entero virus serta Entero-Rhinovirus paling banyak ditemukan pada pasien balita SARI.Kata kunci: virus pernapasan, SARI, anak balit

Proportion of influenza cases in severe acute respiratory illness in Indonesia during 2008-2009

Aim: To access the proportion of Influenza which caused SARI casesMethods: From April 2008 until March 2009, 549 samples of nasal and throat swabs were collected from SARI patients from eight hospitals in eight provinces in Indonesia. The samples were analyzed for Influenza by real-time RT-PCR method using several specific primers for influenza A (A/H1N1, A/H3N2 and A/H5N1) and Influenza B. The sequence of these primers was provided by CDC, Atlanta.Results: We found 516 (94%) of the specimens testing results were not infl uenza A or B viruses. There was 21 (4%) cases caused by influenza A and 12 (2%) caused by influenza B. From the influenza A cases, one case of SARI was caused by A/H1N1, two cases were A/H5N1, 17 cases were A/H3N2 and one case was unsubtypeable Influenza A.Conclusion: The majority of SARI cases were not caused by influenza viruses. From this surveillance the most common influenza  A related to SARI is A/H3N2. Facts of the avian influenza virus A/H5N1 cases have been found in Indonesia and the spread of novel virus influenza A/H1N1 in 2009 raised our concern about the importance of SARI surveillance. (Med J Indones 2010; 19:264-7)Keywords: influenza, severe acute respiratory illness</p

MOESM1 of Case report: Weil’s disease with multiple organ failure in a child living in dengue endemic area

Additional file 1. Dataset for the case report

Chikungunya in Indonesia: Epidemiology and diagnostic challenges.

BACKGROUND:Chikungunya virus (CHIKV) is often overlooked as an etiology of fever in tropical and sub-tropical regions. Lack of diagnostic testing capacity in these areas combined with co-circulation of clinically similar pathogens such as dengue virus (DENV), hinders CHIKV diagnosis. To better address CHIKV in Indonesia, an improved understanding of epidemiology, clinical presentation, and diagnostic approaches is needed. METHODOLOGY/PRINCIPAL FINDINGS:Acutely hospitalized febrile patients ≥1-year-old were enrolled in a multi-site observational cohort study conducted in Indonesia from 2013 to 2016. Demographic and clinical data were collected at enrollment; blood specimens were collected at enrollment, once during days 14 to 28, and three months after enrollment. Plasma samples negative for DENV by serology and/or molecular assays were screened for evidence of acute CHIKV infection (ACI) by serology and molecular assays. To address the co-infection of DENV and CHIKV, DENV cases were selected randomly to be screened for evidence of ACI. ACI was confirmed in 40/1,089 (3.7%) screened subjects, all of whom were DENV negative. All 40 cases initially received other diagnoses, most commonly dengue fever, typhoid fever, and leptospirosis. ACI was found at five of the seven study cities, though evidence of prior CHIKV exposure was observed in 25.2% to 45.9% of subjects across sites. All subjects were assessed during hospitalization as mildly or moderately ill, consistent with the Asian genotype of CHIKV. Subjects with ACI had clinical presentations that overlapped with other common syndromes, atypical manifestations of disease, or persistent or false-positive IgM against Salmonella Typhi. Two of the 40 cases were possibly secondary ACI. CONCLUSIONS/SIGNIFICANCE:CHIKV remains an underdiagnosed acute febrile illness in Indonesia. Public health measures should support development of CHIKV diagnostic capacity. Improved access to point-of-care diagnostic tests and clinical training on presentations of ACI will facilitate appropriate case management such as avoiding unneccessary treatments or antibiotics, early response to control mosquito population and eventually reducing disease transmission

Correction: An observational prospective cohort study of the epidemiology of hospitalized patients with acute febrile illness in Indonesia.

[This corrects the article DOI: 10.1371/journal.pntd.0007927.]

An observational prospective cohort study of the epidemiology of hospitalized patients with acute febrile illness in Indonesia.

BackgroundThe epidemiology of acute febrile illness, a common cause of hospitalization in Indonesia, has not been systematically studied.Methodology/principal findingsThis prospective observational study enrolled febrile patients (temperature ≥38°C) aged ≥1 year from July 2013 until June 2016 at eight government referral teaching hospitals in seven provincial capitals in Indonesia. Patients were managed according to the hospital standard-of-care (SOC), and blood samples were drawn for molecular and serological assays. Clinical data, laboratory results, and specimens for additional tests were collected at enrollment, days 14-28, and at three months. Regular follow-up visits were then scheduled for every three months either until symptoms resolved or until one year. In total, this study included 1,486 adult and pediatric patients presenting with multi-organ (768, 51.7%), gastrointestinal (497, 33.0%), respiratory (114, 7.7%), constitutional (62, 4.2%), skin and soft-tissue (24, 1.6%), central nervous system (17, 1.1%), or genitourinary (4, 0.3%) manifestations. Microbiological diagnoses were found in 1,003/1,486 (67.5%) participants, of which 351/1,003 (35.0%) were not diagnosed during hospitalization using SOC diagnostic tests. Missed diagnoses included all cases caused by Rickettsia spp., chikungunya, influenza, and Seoul virus. The most common etiologic agents identified were dengue virus (467, 46.6%), Salmonella spp. (103, 10.3%), and Rickettsia spp. (103, 10.3%). The overall mortality was 89 (5.9%).Conclusions/significanceFebrile illness in Indonesia has various microbiologic etiologies and substantial overall mortality. Diagnostic limitations and lack of epidemiologic data resulted in potentially treatable, and at times fatal, diseases being missed

The characteristics of bacteremia among patients with acute febrile illness requiring hospitalization in Indonesia

Blood culturing remains the "gold standard"for bloodstream infection (BSI) diagnosis, but the method is inaccessible to many developing countries due to high costs and insufficient resources. To better understand the utility of blood cultures among patients in Indonesia, a country where blood cultures are not routinely performed, we evaluated data from a previous cohort study that included blood cultures for all participants. An acute febrile illness study was conducted from July 2013 to June 2016 at eight major hospitals in seven provincial capitals in Indonesia. All participants presented with a fever, and two-sided aerobic blood cultures were performed within 48 hours of hospital admission. Positive cultures were further assessed for antimicrobial resistance (AMR) patterns. Specimens from participants with negative culture results were screened by advanced molecular and serological methods for evidence of causal pathogens. Blood cultures were performed for 1,459 of 1,464 participants, and the 70.6 (1,030) participants that were negative by dengue NS1 antigen test were included in further analysis. Bacteremia was observed in 8.9 (92) participants, with the most frequent pathogens being Salmonella enterica serovar Typhi (41) and Paratyphi A (10), Escherichia coli (14), and Staphylococcus aureus (10). Two S. Paratyphi A cases had evidence of AMR, and several E. coli cases were multidrug resistant (42.9, 6/14) or monoresistant (14.3, 2/14). Culture contamination was observed in 3.6 (37) cases. Molecular and serological assays identified etiological agents in participants having negative cultures, with 23.1 to 90 of cases being missed by blood cultures. Blood cultures are a valuable diagnostic tool for hospitalized patients presenting with fever. In Indonesia, pre-screening patients for the most common viral infections, such as dengue, influenza, and chikungunya viruses, would maximize the benefit to the patient while also conserving resources. Blood cultures should also be supplemented with advanced laboratory tests when available. © 2022 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication