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ObjectiveTo identify aetiologies of childhood community-acquired pneumonia (CAP) based on a comprehensive diagnostic approach.Design‘Partnerships for Enhanced Engagement in Research-Pneumonia in Paediatrics (PEER-PePPeS)’ study was an observational prospective cohort study conducted from July 2017 to September 2019.SettingGovernment referral teaching hospitals and satellite sites in three cities in Indonesia: Semarang, Yogyakarta and Tangerang.ParticipantsHospitalised children aged 2–59 months who met the criteria for pneumonia were eligible. Children were excluded if they had been hospitalised for >24 hours; had malignancy or history of malignancy; a history of long-term (>2 months) steroid therapy, or conditions that might interfere with compliance with study procedures.Main outcome(s) measure(s)Causative bacterial, viral or mixed pathogen(s) for pneumonia were determined using microbiological, molecular and serological tests from routinely collected specimens (blood, sputum and nasopharyngeal swabs). We applied a previously published algorithm (PEER-PePPeS rules) to determine the causative pathogen(s).Results188 subjects were enrolled. Based on our algorithm, 48 (25.5%) had a bacterial infection, 31 (16.5%) had a viral infection, 76 (40.4%) had mixed bacterial and viral infections, and 33 (17.6%) were unable to be classified. The five most common causative pathogens identified were Haemophilus influenzae non-type B (N=73, 38.8%), respiratory syncytial virus (RSV) (N=51, 27.1%), Klebsiella pneumoniae (N=43, 22.9%), Streptococcus pneumoniae (N=29, 15.4%) and Influenza virus (N=25, 13.3%). RSV and influenza virus diagnoses were highly associated with Indonesia’s rainy season (November–March). The PCR assays on induced sputum (IS) specimens captured most of the pathogens identified in this study.ConclusionsOur study found that H. influenzae non-type B and RSV were the most frequently identified pathogens causing hospitalised CAP among Indonesian children aged 2–59 months old. Our study also highlights the importance of PCR for diagnosis and by extension, appropriate use of antimicrobials.Trail registration numberNCT03366454

We describe the first 11 detected COVID-19 cases in Indonesia, resulting from a local transmission occurring in a club and a restaurant. The virus was detected until an average of 21.3 days (range: 11–25, SD: 4.1) after the onset of illness, and the partial N gene sequences (28,321–28,707 nucleotide position) had 100% similarity with the SARS-CoV-2 sequence from Wuhan. Two subjects were asymptomatic, and one subject has died.

BackgroundSince its emergence in China, SARS-CoV-2 has infected more than 240 million people worldwide, including in regions where dengue virus (DENV) is hyperendemic such as Latin America and Southeast Asia, including Indonesia. Diagnosis of COVID-19 in dengue endemic regions as well as DENV and SARS-CoV-2 co-infection can be challenging.Case PresentationWe describe a 68-year-old woman with diabetes mellitus type II who was admitted to the Tangerang District Hospital on 14 April 2020. She lived in a neighborhood where a few people were contracting dengue fever. She presented with five days of fever, malaise, anorexia, nausea, myalgia, and arthralgia. Hematology revealed anemia, thrombocytopenia, normal leukocyte count, increased neutrophil proportion, and decreased lymphocyte proportion and absolute lymphocytes. Her chest X-ray showed right pericardial infiltrates. Although dengue was clinically suspected, she was also tested for SARS-CoV-2 infection as she met screening criteria. After being confirmed SARS-CoV-2 positive by RT-PCR, she was treated with ceftriaxone, paracetamol, azithromycin, oseltamivir, and chloroquine. She was clinically improved four days later and discharged from the hospital on 25 April 2020 after SARS-CoV-2 RT-PCR was negative on two consecutive samples. Dengue was diagnosed retrospectively based on sero-conversion of dengue IgM and a very high dengue IgG index (ELISA, Focus Diagnostics®, Cypress, CA, USA), and sero-conversion of dengue IgM and positive IgG (Rapid test, PanBio ®Dengue duo cassette, Inverness Medical Innovations, QLD, AU), which was equivalent to high Hemagglutination Inhibition (HI) antibody titer (≥1280) found in secondary dengue infection.ConclusionThe overlapping clinical presentations of COVID-19 and dengue; limited diagnostic capacity of laboratories in resource constrained settings; and complexities of interpreting results make identification of COVID-19 in the dengue endemic setting challenging. Clinicians in endemic areas must be aware of diagnostic challenges and maintain a high index of suspicion for COVID-19 coinfection with DENV and other tropical pathogens.

The Coronavirus disease 2019 (COVID-19) pandemic has caused health, economic, and social challenges globally. Under these circumstances, effective vaccines play a critical role in saving lives, improving population health, and facilitating economic recovery. In Muslim-majority countries, Islamic jurisprudence, which places great importance on sanctity and safety of human life and protection of livelihoods, may influence vaccine uptake. Efforts to protect humans, such as vaccines, are highly encouraged in Islam. However, concerns about vaccine products’ Halal (permissible to consume by Islamic law) status and potential harm can inhibit acceptance. Fatwa councils agree that vaccines are necessary in the context of our current pandemic; receiving a COVID-19 vaccination is actually a form of compliance with Sharia law. Broader use of animal component free reagents during manufacturing may further increase acceptance among Muslims. We herein explain the interplay between Sharia (Islamic law) and scientific considerations in addressing the challenge of COVID-19 vaccine acceptance, particularly in Muslim populations.

Mutations in the hepatitis B virus (HBV) X region and truncation of the preS2 region are well‑known to affect the progression of liver disease. Recently, it has been observed that an increasing number of S region quasispecies variants are associated with disease progression. However, few studies have analysed quasispecies of the whole genome using high‑throughput sequencing methods. Using high‑throughput sequencing, whole‑genome variations in 12 Indonesian patients infected with HBV (eight with advanced liver disease and four with chronic hepatitis) were examined. Variations with cut‑off values of ≥1% of the total viral population were investigated. It was revealed that within the four open reading frames, quasispecies variations of the S and X regions were higher in advanced liver diseases compared with in chronic hepatitis (S region: 89.53 vs. 50.69%, P=0.047; X region: 76.95 vs. 35.88%, P=0.044). Notably, the mutation frequencies in the basal core promoter, B cell epitope, RT Box G, RNAseH and small S region were greater in advanced liver disease. The proportion of quasispecies variants increased for the majority of the mutations, with the exception for W196* in the small S gene, during disease progression. The present study demonstrated that quasispecies in the S and X regions of the HBV genome changed during disease progression and were associated with advanced liver disease development in Indonesian patients with HBV.

Background: Since its emergence in China, SARS-CoV-2 has infected more than 15.5 million people worldwide, including in regions where dengue virus (DENV) is hyperendemic such as Latin America and Southeast Asia, including Indonesia. Hence, anticipation for simultaneous infection by DENV and SARS-CoV-2 has been raised.Case presentation: We describe a 68-year-old woman with diabetes mellitus type II who was admitted to the Tangerang District Hospital on 14 April 2020. She lived in a neighborhood where a few people were contracting dengue fever. She presented with five days of fever, malaise, anorexia, nausea, myalgia, and arthralgia. Hematology results revealed anemia, thrombocytopenia, normal leukocyte count, increased neutrophil proportion, and decreased lymphocyte proportion and absolute lymphocyte. Her chest X-ray showed right pericardial infiltrates. Although dengue was clinically suspected, as she met COVID-19 screening criteria, she was also tested for SARS-CoV-2 infection. The patient was treated with ceftriaxone, paracetamol, azithromycin, oseltamivir, and chloroquine. She was clinically improved four days later and was discharged from the hospital on 25 April 2020 after SARS-CoV-2 rRT-PCR was negative on two consecutive samples. Dengue was diagnosed retrospectively based on sero-conversion of dengue IgM and a very high dengue IgG index (Focus Diagnostics®, ELISA), and sero-conversion of dengue IgM and positive IgG (PanBio ®Dengue duo cassette), which was equivalent to high hemagglutination inhibition antibody titer found in secondary dengue infection.Conclusion: The overlapping clinical presentations of COVID-19 and dengue; limited diagnostic capacity of laboratories in resource constrained settings; and complexities of interpreting results make identification of COVID-19 in the dengue endemic setting challenging. Clinicians in endemic areas must maintain a high index of suspicion for the possibility of COVID-19 coinfection with DENV and other tropical pathogens.

Background A large-scale Japanese study showed that low skeletal muscle index (SMI) and intramuscular fat (IMF) deposition are associated with hepatocellular carcinoma (HCC) survival. Here, we evaluated the effects of SMI and IMF on the survival of Indonesian HCC patients, whose characteristics differ from those of Japanese patients. Methods SMI and mean muscle attenuation (MA) were evaluated using computed tomography images of the third lumbar vertebra (L3) in a prospective cohort of 100 Indonesian HCC patients. Clinical, laboratory and body composition data were analysed using the Kaplan–Meier method and Cox regression model to investigate which factors are associated with prognosis. Results Of 100 patients, 31 were diagnosed with sarcopenia (L3 SMI value ≤36.2 cm2/m2 for men and ≤ 29.6 cm2/m2 for women), and 65 had IMF deposition (MA value ≤44.4 HU for men and ≤ 39.3 HU for women). These groups had shorter median survival than the reference groups (both P P = 0.016), IMF deposition (HR, 3.580; P P P P = 0.020), and male gender (HR: 3.211, P Conclusion Sarcopenia and IMF deposition showed superior value in combination with BCLC stage and JIS score for predicting the survival of Indonesian HCC patients. Increased awareness and strategies to prevent or reverse these factors might improve patient outcomes. (Electric word counts: 249).

Background A large-scale Japanese retrospective study showed that low skeletal muscle index (SMI) and intramuscular fat (IMF) deposition are associated with hepatocellular carcinoma (HCC) survival. Here, we evaluated the effects of SMI and IMF on the survival of Indonesian HCC patients, whose characteristics differ from those of Japanese patients.Methods SMI and mean muscle attenuation (MA) were evaluated using computed tomography images of the third lumbar vertebra (L3) in a prospective cohort of 100 Indonesian HCC patients. Clinical, laboratory and body composition data were analysed using the Kaplan–Meier method and Cox regression model to investigate which factors are associated with prognosis.Results Of 100 patients, 31 were diagnosed with sarcopenia (L3 SMI value ≤36.2 cm 2 /m 2 for men and ≤29.6 cm 2 /m 2 for women), and 65 had IMF deposition (MA value ≤44.4 HU for men and ≤39.3 HU for women). These groups had shorter median survival than the reference groups (both P

Background Severe acute respiratory infection (SARI) accounts for a large burden of illness in Indonesia. However, epidemiology of SARI in tertiary hospitals in Indonesia is unknown. This study sought to assess the burden, clinical characteristics, and etiologies of SARI and concordance of clinical diagnosis with confirmed etiology. Methods Data and samples were collected from subjects presenting with SARI as part of the acute febrile Illness requiring hospitalization study (AFIRE). In tertiary hospitals, clinical diagnosis was ascertained from chart review. Samples were analyzed to determine the “true” etiology of SARI at hospitals and Indonesia Research Partnership on Infectious Diseases (INA‐RESPOND) laboratory. Distribution and characteristics of SARI by true etiology and accuracy of clinical diagnosis were assessed. Results Four hundred and twenty of 1464 AFIRE subjects presented with SARI; etiology was identified in 242 (57.6%), including 121 (28.8%) viruses and bacteria associated with systemic infections, 70 (16.7%) respiratory bacteria and viruses other than influenza virus, and 51 (12.1%) influenza virus cases. None of these influenza patients were accurately diagnosed as having influenza during hospitalization. Conclusions Influenza was misdiagnosed among all patients presenting with SARI to Indonesian tertiary hospitals in the AFIRE study. Diagnostic approaches and empiric management should be guided by known epidemiology. Public health strategies to address the high burden of influenza should include broad implementation of SARI screening, vaccination programs, clinician education and awareness campaigns, improved diagnostic capacity, and support for effective point‐of‐care tests.

Background Body composition components (Sarcopenia and intramuscular fat [IMF] deposition) were proven as risk factors predicting poor survival among HCC patients in the Japanese population. Since HCC characteristics were peculiar in Indonesia: advanced-stage at presentation; early-age onset; and HBV endemicity; our objective was to demonstrate key determinants of HCC prognosis in Indonesia. Methods Skeletal muscle index (SMI) and mean muscle attenuation (MA) were measured from transverse Computed Tomography (CT) images at the third lumbar vertebra (L3) in a prospective cohort of 49 Indonesia patients with different stages of HCC. Images were analysed using SliceOmatic V5.0 (Tomovision, QC Canada), which enables specific tissue demarcation using Hounsfield unit (HU) thresholds. Clinical, laboratory and body composition assessments are comprehensively analysed using Kaplan-Meier procedure and Cox’s regression model to investigate critical features associated with prognosis. Results Patients with low MA (called intramuscular fat [IMF] deposition) had shorter median survival than non-IMF deposition (73 11.61 vs. 252 26.56 days, p=0.008) as also observed shorter in patients with alpha-fetoprotein (AFP) level ≥200 ng/ml than AFP Conclusions Muscle Attenuation and BCLC stage were significant independent predictors of survival in HCC Indonesian patients. External validation of these prognostic factors in larger cohorts of HCC patients is warranted.

Hepatitis B virus (HBV) polymerase gene is targeted by nucleos(t)ide analogues (NUC), but it is unclear how HBV quasispecies of whole genome changes during early period of NUC treatment. To understand the unknown region of drug sensitivity and treatment resistance, HBV quasispecies of whole genome during early period of NUC treatment was examined using ultra‑deep sequencing. Eleven patients with chronic HBV infection who received NUC treatment were enrolled in the current study. Viral DNA was extracted from serum samples before and early period of NUC treatment. Polymerase chain reaction analysis was subsequently performed on the DNA products. The viral quasispecies of the entire genome was analyzed by ultra‑deep sequencing. The regions and positions corresponding to the changes in the quasispecies were investigated before and early period of NUC treatment. The secondary structure changes were predicted by mutations/substitutions detected using Lasergene Protean v14.1 software. The frequency of quasispecies variants increased significantly in the polymerase domain from before to early period of NUC treatment (3.08±1.28 vs. 3.51±1.47%, P

Background Occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the serum and/or liver in HBsAg-negative individuals. OBI is associated with the risk of viral transmission, especially in developing countries, and with progressive liver disease and reactivation in immunosuppressive patients. The objective of this study was to evaluate the relation of OBI to HLA-DP single nucleotide polymorphisms (SNPs) encoding antigen-binding sites for the immune response to HBV infection. As HLA-DP variants affect the mRNA expression of HLA-DPA1 and HLA-DPB1 in the liver, we hypothesised that high levels of HLA-DPA1 and HLA-DPB1 expression favour OBI development. Methods The study enrolled 456 Indonesian healthy blood donors (HBsAg negative). OBI was defined as the presence of HBV-DNA in at least two of four open reading frames (ORFs) of the HBV genome detected by nested PCR. SNPs in HLA-DPA1 (rs3077) and HLA-DPB1 (rs3135021, rs9277535, and rs2281388) were genotyped using real-time Taqman® genotyping assays. Results Of 122 samples positive for anti-HBs and/or anti-HBc, 17 were determined as OBI. The minor allele in rs3077 was significantly correlated with OBI [odds ratio (OR) = 3.87, 95% confidence interval (CI) = 1.58–9.49, p = 0.0015]. The prevalence of the minor allele (T) was significantly higher in subjects with OBI than in those without (59% and 33%, respectively). The combination of haplotype markers (TGA for rs3077–rs3135021–rs9277535) was associated with increased risk of OBI (OR = 4.90, 95%CI = 1.12–21.52 p = 0.038). The prevalence of OBI was highest in the isolated anti-HBc group among the three seropositive categories: anti-HBs