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.

BackgroundDiagnosing scrub typhus clinically is difficult, hence laboratory tests play a very important role in diagnosis. As performing sophisticated laboratory tests in resource-limited settings is not feasible, accurate point-of-care testing (POCT) for scrub typhus diagnosis would be invaluable for patient diagnosis and management. Here we summarise the existing evidence on the accuracy of scrub typhus POCTs to inform clinical practitioners in resource-limited settings of their diagnostic value.Methodology/principal findingsStudies on POCTs which can be feasibly deployed in primary health care or outpatient settings were included. Thirty-one studies were identified through PubMed and manual searches of reference lists. The quality of the studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). About half (n = 14/31) of the included studies were of moderate quality. Meta-analysis showed the pooled sensitivity and specificity of commercially available immunochromatographic tests (ICTs) were 66.0% (95% CI 0.37–0.86) and 92.0% (95% CI 0.83–0.97), respectively. There was a significant and high degree of heterogeneity between the studies (I2 value = 97.48%, 95% CI 96.71–98.24 for sensitivity and I2 value = 98.17%, 95% CI 97.67–98.67 for specificity). Significant heterogeneity was observed for total number of samples between studies (p = 0.01), study design (whether using case-control design or not, p = 0.01), blinding during index test interpretation (p = 0.02), and QUADAS-2 score (p = 0.01).Conclusions/significanceThere was significant heterogeneity between the scrub typhus POCT diagnostic accuracy studies examined. Overall, the commercially available scrub typhus ICTs demonstrated better performance when ‘ruling in’ the diagnosis. There is a need for standardised methods and reporting of diagnostic accuracy to decrease between-study heterogeneity and increase comparability among study results, as well as development of an affordable and accurate antigen-based POCT to tackle the inherent weaknesses associated with serological testing.

Background Scrub typhus is a neglected tropical disease that causes acute febrile illness. Diagnosis is made based upon serology, or detection of the causative agent– Orientia tsutsugamushi– using PCR or in vitro isolation. The enzyme-linked immunosorbent assay (ELISA) is an objective and reproducible means of detecting IgM or IgG antibodies. However, lack of standardization in ELISA methodology, as well as in the choice of reference test with which the ELISA is compared, calls into question the validity of cut-offs used in diagnostic accuracy studies and observational studies. Methodology/Principal findings A PubMed search and manual screening of reference lists identified 46 studies that used ELISA antibody cut-offs to diagnose scrub typhus patients, 22 of which were diagnostic accuracy studies. Overall, 22 studies (47.8%) provided little to no explanation as to how the ELISA cut-off was derived, and 7 studies (15.2%) did not even state the cut-off used. Variation was seen locally in reference standards used, in terms of both the diagnostic test and cut-off titer. Furthermore, with the exception of studies using ELISAs manufactured by InBios, there was no standardization of the selection of antigenic strains. As a result, no consensus was found for determining a cut-off, ELISA methodology, or for a single value diagnostic cut-off. Conclusions/Significance We have concluded that there is a lack of consensus in the determination of a cut-off. We recommend interpreting the results from these studies with caution. Further studies will need to be performed at each geographic location to determine region-specific cut-offs, taking into consideration background antibody levels to discriminate true disease from healthy individuals.

BackgroundThe global prevalence of diabetes mellitus is increasing alarmingly. However, the quality of vital medicines and medical products used to treat and monitor diabetes remains uncertain but of potential great public health significance. Here, we review the available evidence on the quality of antidiabetic medicines and supplies for self-monitoring of blood glucose (SMBG) and discuss their potential impact for the patients and society.MethodsSearches were conducted in PubMed, Embase, Google Scholar, Google and relevant websites in English and French. The Medicine Quality Assessment Reporting Guideline (MEDQUARG) was used to assess the quality of medicine quality surveys.Results52 publications on the quality of antidiabetic medicines, including 5 medicine quality prevalence surveys and 20 equivalence studies, were analysed. The prevalence surveys and equivalence studies included 674 samples of which 73 (10.8%) were of poor quality. The median (Q1–Q3) concordance with MEDQUARG items was 30.8% (19.2%–42.3%). No prevalence surveys on SMBG supplies’ quality were found, but 29 publications, including falsified products and incorrect results due to strip degradation or contamination, were identified.ConclusionThere is little accessible evidence on the quality of antidiabetic medicines and SMBG supplies. Surveys were poorly designed and reported, making data aggregation and interpretation problematic. Despite these caveats, these results suggest that there are important issues with the quality of medical products for diabetes that need focused monitoring. There is an urgent need to achieve consensus protocols for designing, conducting and reporting medical product quality surveys.PROSPERO registration numberCRD42016039841.

BackgroundData 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.MethodsThis 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 Cox regression to examine factors associated with mortality.FindingsOf 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 at least one 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; pre-existing hypertension, cardiac disease, chronic kidney disease or liver disease; clinical diagnosis of pneumonia; multiple (>3) symptoms; and shorter time from symptom onset to admission. Patients <50 years with >1 comorbidity had a nearly six-fold higher risk of death than those without (adjusted hazard ratio 5·50, 95% CI 2·72-11·13; 27% vs 3% mortality).InterpretationOverall mortality was lower than reported in high-income countries, probably due to younger age distribution and fewer comorbidities. However, deaths occurred across all ages, with >10% mortality among children <5 years and adults >50 years.

Background Scrub typhus is an acute febrile illness caused by intracellular bacteria from the genus Orientia. It is estimated that one billion people are at risk, with one million cases annually mainly affecting rural areas in Asia-Oceania. Relative to its burden, scrub typhus is understudied, and treatment recommendations vary with poor evidence base. These knowledge gaps could be addressed by establishing an individual participant-level data (IPD) platform, which would enable pooled, more detailed and statistically powered analyses to be conducted. This study aims to assess the characteristics of scrub typhus treatment studies and explore the feasibility and potential value of developing a scrub typhus IPD platform to address unanswered research questions. Methodology/principal findings We conducted a systematic literature review looking for prospective scrub typhus clinical treatment studies published from 1998 to 2020. Six electronic databases (Ovid Embase, Ovid Medline, Ovid Global Health, Cochrane Library, Scopus, Global Index Medicus), ClinicalTrials.gov, and WHO ICTRP were searched. We extracted data on study design, treatment tested, patient characteristics, diagnostic methods, geographical location, outcome measures, and statistical methodology. Among 3,100 articles screened, 127 were included in the analysis. 12,079 participants from 12 countries were enrolled in the identified studies. ELISA, PCR, and eschar presence were the most commonly used diagnostic methods. Doxycycline, azithromycin, and chloramphenicol were the most commonly administered antibiotics. Mortality, complications, adverse events, and clinical response were assessed in most studies. There was substantial heterogeneity in the diagnostic methods used, treatment administered (including dosing and duration), and outcome assessed across studies. There were few interventional studies and limited data collected on specific groups such as children and pregnant women. Conclusions/significance There were a limited number of interventional trials, highlighting that scrub typhus remains a neglected disease. The heterogeneous nature of the available data reflects the absence of consensus in treatment and research methodologies and poses a significant barrier to aggregating information across available published data without access to the underlying IPD. There is likely to be a substantial amount of data available to address knowledge gaps. Therefore, there is value for an IPD platform that will facilitate pooling and harmonisation of currently scattered data and enable in-depth investigation of priority research questions that can, ultimately, inform clinical practice and improve health outcomes for scrub typhus patients.

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Background Scrub typhus is a potentially fatal acute febrile illness caused by bacteria in the genus Orientia. Though cases have been documented, a comprehensive body of evidence has not previously been compiled to give an overview of scrub typhus in Indonesia. This study aimed to address this key knowledge gap by mapping and ranking geographic areas based on existing data on the presence or absence of the pathogen in humans, vectors, and host animals. Methodology/Principal Findings We performed searches on local and international electronic databases, websites, libraries, and collections including Embase, Medline, and Scopus to gather relevant evidence (including grey literature). After extracting data on the presence and absence of the pathogen and its vectors, we ranked the evidence based on the certainty for the presence of human infection risk. The country was divided into subnational units, and each were assigned a score based on the evidence available for that unit. We presented this in an evidence map. Orientia tsutsugamushi presence has been identified on all the main islands (Sumatra, Java, Borneo, Celebes, Papua). About two thirds of the data points were collected before 1946. South Sumatra and Biak had the strongest evidence for sustaining infectious vectors. There was only one laboratory confirmed case in a human identified but 2,780 probable cases were documented. The most common vector was Leptotrombidium deliense. Conclusions/Significance Our review highlights the concerning lack of data on scrub typhus in Indonesia, the fourth most populous country in the world. The presence of seropositive samples, infected vectors and rodents confirm O. tsutsugamushi is widespread in Indonesia and likely to be causing significant morbidity and mortality. There is an urgent need to increase surveillance to better understand the burden of the disease across the archipelago and to inform national empirical fever treatment guidelines.