In resource-constrained community settings, identifying which febrile children require referral remains a major unmet need. Current World Health Organization (WHO) danger signs have limited accuracy, resulting in missed severe illness and unnecessary referrals. Here we developed and validated clinical prediction models to support referral decisions using data from 3,405 children aged 1-59 months presenting with community-acquired acute febrile illnesses to seven hospitals across Bangladesh, Cambodia, Indonesia, Laos and Vietnam. Cambodian data were held out for external validation. The model using simple clinical parameters (sensitivity 74.7% (95% confidence interval (CI): 59.4-88.1); specificity 99.1% (95% CI: 97.7-99.7)) outperformed WHO criteria (sensitivity 55.5% (95% CI: 39.4-72.7); specificity 82.6% (95% CI: 77.1-87.6)) for identification of children at risk of severe disease (death or organ support within 2 days). Including either pulse oximetry or the host biomarker soluble TREM1 (sTREM1) increased sensitivity to 88.9% (95% CI: 76.7-97.8; pulse oximetry) and 89.2% (95% CI: 76.9-97.5; sTREM1), respectively. The pulse oximetry-based model achieved these gains with a threefold reduction in referral rates. These approaches appear cost-effective (pulse oximetry incremental cost effectiveness ratio (ICER) = $26.28; sTREM1 ICER = $196.46) and could improve triage for febrile illness in low-resource settings by enabling more accurate referral decisions. They warrant evaluation in community-based trials.

Central Java Province, Indonesia, has successfully reduced malaria incidence from 1.08 per 1,000 population in 2018 to 0.03 per 1,000 population in 2024, and similarly decreased newly found chronic limphatic filariasis cases from 23 cases in 2018 to 3 cases in 2024, through effective vector control programs. However, dengue incidence remains unstable, with incidence rate (IR) fluctuating between 6.27 and 33.9 annually during the same period. Competent staff, specifically public health entomologists, are essential for successful vector control implementation, yet their numbers in health offices remain insufficient. This qualitative implementation study assessed workforce capacity related to vector control through semi-structured interviews with 29 participants across thirteen institutions. Thematic analysis revealed two key findings: (1) the critical need to increase the availability of public health entomologists to strengthen vector control, and (2) the importance of continuous training to enhance staff capacity at regional levels. The findings underscore urgent actions to meet Ministry of Health staffing standards and advocate for prioritizing investment in workforce development to accelerate elimination of vector-borne diseases.

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus and was officially declared a pandemic by the World Health Organization (WHO) in 2020. Clinical manifestations in children are more heterogeneous than in adults, and several factors may influence the disease severity. Platelet count (PC), mean platelet volume (MPV), and mean platelet volume to platelet ratio (MPR) are simple and widely available inflammation markers used as predictors in pediatric patients with sepsis and other critical illnesses. This study aimed to determine the performance of PC, MPV, and MPR as biomarkers predicting severity in pediatric patients with COVID-19. A retrospective cohort study was conducted, involving COVID-19 pediatric patients admitted to Dr. Sardjito from January 2020 to December 2022. Samples were selected using a total sampling approach, applying defined inclusion and exclusion criteria. Data analysis included both bivariate and multivariate analyses, using logistic and linear regression. The associations between variables were expressed as odds ratios (OR) with 95

To estimate the risk projection of temperature on pediatric asthma severity and hospitalization under four Shared Socioeconomic Pathways (SSPs) possible future climate scenarios using the Intergovernmental Panel on Climate Change (IPCC) model. A retrospective study was conducted involving 102,160 pediatric asthma patients from the Taipei Medical University Clinical Research Database (TMUCRD). We utilized global climate model (GCM) outputs to project future temperature for each subject from optimistic (SSP126) to pessimistic (SSP585) projections. A multinomial logistic regression was used to examine the odds ratio of pediatric asthma severity and hospitalization. A 1 °C increase in 1-year, 5-year, and 10-year average temperatures was associated with 1.004-fold (95

BACKGROUND:This study describes the seroconversion and serodynamics of IgG antibodies against the RBD of SARS-CoV-2 in the general population of Sleman District, Yogyakarta Special Province. We aim to identify possible factors that correlate with the seroconversion and serodynamics of IgG antibodies against the RBD of SARS-CoV-2. METHODS:We performed a longitudinal study of the population at Health and Demographic Surveillance System (HDSS) Sleman, Yogyakarta, Indonesia. Study subjects were recruited between April and December 2021 using convenience sampling and were followed up 2 times, i.e. 4-5 and 8-9 weeks. The inclusion criteria for subjects were age ≥ 18 years, absence of flu-like symptoms, and negative COVID-19 by using GeNose C19® screening. A community-based survey on demographics, comorbidities and smoking habits were documented at baseline, while a history of vaccination, COVID-19-related symptoms, mobility, and preventive measures, weight and height as well as a venous blood draw, were collected at each visit. The anti-RBD-SARS-CoV-2 IgG antibody concentration from blood plasma was measured using chemiluminescent microplate immunoassay (CMIA). Descriptive analysis was performed based on IgG seropositivity by using chi-squared test or Fisher's exact test, as appropriate. Logistic regression was subsequently performed to identify factors that were correlated with IgG seropositivity. Further, a grouping of subjects based on IgG seropositivity was done to analyze factors that might correlate with seroconversion and serodynamics of anti-RBD-SARS-CoV-2 IgG antibody. A P value ≤ 0.05 was considered to indicate a significant difference. RESULTS:Three hundred eighty-five (385) participants were analyzed. At baseline, 307 out of 385 (79.7%) subjects were seropositive for the IgG antibody against the RBD of SARS-CoV-2. Descriptive analysis showed that sex, marital status, smoking habits, obesity, vaccination status, and preventive measures were different between the IgG anti-RBD-SARS-CoV-2 seropositive and negative individuals (p≤ 0.05). Further analysis showed that, vaccination was the factor most strongly correlated with seropositivity [OR = 20.58; 95% CI 10.82, 39.15]. Based on the correlation, we separated subjects into 4 groups. Group 1 (seronegative-unvaccinated individuals; 50 subjects); Group 2 (seronegative-vaccinated individuals; 27 subjects); Group 3 (seropositive-unvaccinated individuals; 25 subjects); and Group 4 (seropositive-vaccinated individuals; 282 subjects). During monitoring, 27/49 (55.10%), 5/25 (20%), 9/22 (40.91%), and 27/257 (10.51%) of subjects in Group 1, 2, 3, and 4 respectively, received 1 or 2 doses of COVID19 vaccine. When comparing seroconversion at baseline and monitoring 2, positive IgG seroconversion was observed in Group 1 (from 0/51 (0%) to 23/49 (46.94%)) and Group 2 (from 0/27 (0%) to 10/25 (40%)), but negative seroconversion was observed in Group 4 (from 282/0 (100%) to 248/257 (96.50%)); while, all subjects in Group 3 remained seropositive at the end of monitoring. This evidence suggested for hybrid immunity, on which infection and vaccine simultaneously contributes to anti-RBD-SARS-CoV-2 IgG seroconversion. CONCLUSIONS:A high seroprevalence of the IgG antibody against RBD-SARS-CoV-2 in the Sleman population was found to correlate with COVID-19 vaccination and as infection occurred, thus enhancing hybrid immunity. We also identified nonresponder and rapid antibody decaying individuals, that call for targeted vaccinations in addition to annual universal boosting.

Background Severe dengue is a serious manifestation of dengue infection and one of the causes of death in children. Recognizing the prognostic factors for death in severe dengue, based on the 2009 WHO guidelines, can help provide appropriate management to reduce the death rate. Objective To determine the prognostic factors for mortality in pediatric patients with severe dengue admitted to Dr. Sardjito General Hospital, Yogyakarta. Methods We retrospectively collected data on children with severe dengue from January 2017 to December 2022 at Dr. Sardjito Hospital. Bivariate and multivariate analyses were performed to determine the prognostic factors that significantly impacted the outcome of death. Results There were 120 eligible patients with severe dengue during the study period; 17 subjects (14.2 %) died and 103 subjects (85.8 %) survived. Multivariate analysis showed that mechanical ventilation (RR 8.97, 95 % CI 1.31-103.21, p 0.025), fluid overload >10 % (RR 7.56, 95 % CI 1.15-49.72, p-value = 0.035), and vasoactive-inotropic score (VIS) >= 13.75 (RR 13.56, 95 % CI 1.78-103.21 p-value = 0.012) were the prognostic factors for mortality in pediatric patients with severe dengue. Conclusion Mechanical ventilation, excess fluid and the need for multiple vasoactive drugs are the prognostic factors for mortality in severe dengue in children.

The introgression of w Mel Wolbachia into Aedes aegypti populations is being used for the biocontrol of arboviruses such as dengue and chikungunya in 14 countries to date. A w Mel infection in Ae. aegypti both reduces the transmission of viruses by the mosquito and causes a reproductive manipulation that aids w Mel introgression into naive populations. However, a critical concern is whether w Mel could evolve over time, potentially diminishing these desired phenotypes. Here, we investigated the stability of the w Mel genome in Ae. aegypti released for biocontrol in Colombia, Indonesia, and Vietnam. We sequenced the w Mel genome at the start of releases and up to six years after w Mel introgression into each population. Our study identifies very few genomic changes, suggesting the w Mel genome is not rapidly evolving despite its release into three geographically different field sites and subsequent exposure to novel environments. These results align with previous w Mel sequencing studies from Australia and provide strong evidence for the long-term genomic stability of w Mel, reinforcing its potential as a reliable biocontrol tool against Ae. aegypti -transmitted arboviruses. ### Competing Interest Statement The authors have declared no competing interest.

The introgression ofwMelWolbachiaintoAedes aegyptipopulations is being used for the biocontrol of arboviruses such as dengue and chikungunya in 14 countries to date. AwMel infection inAe. aegyptiboth reduces the transmission of viruses by the mosquito and causes a reproductive manipulation that aidswMel introgression into naive populations. However, a critical concern is whetherwMel could evolve over time, potentially diminishing these desired phenotypes. Here, we investigated the stability of thewMel genome inAe. aegyptireleased for biocontrol in Colombia, Indonesia, and Vietnam. We sequenced thewMel genome at the start of releases and up to six years afterwMel introgression into each population. Our study identifies very few genomic changes, suggesting thewMel genome is not rapidly evolving despite its release into three geographically different field sites and subsequent exposure to novel environments. These results align with previouswMel sequencing studies from Australia and provide strong evidence for the long-term genomic stability ofwMel, reinforcing its potential as a reliable biocontrol tool againstAe. aegypti-transmitted arboviruses.

BACKGROUND:The objective of this study was to examine the associations of blood inflammatory phenotypes with acute pediatric asthma exacerbations during different seasons and the COVID-19 pandemic. METHODS:A retrospective study was conducted involving 32,160 pediatric asthma patients from January 2008 to December 2021. Asthma blood inflammatory phenotypes were categorized based on low (L) and high (H) eosinophils (E) and neutrophils (N) (LBE/HBE: ≥ 0.25 × 109/L and LBN/HBN: ≥ 5 × 109/L, respectively) and logistic regression was used to examine the odds ratio (OR) of outcome variables. RESULTS:A 109/L increase of neutrophils and eosinophils was associated with a 1.015-fold (95% CI: 1.009-1.021) and a 1.057-fold increase in the OR (95% CI: 1.026-1.088) for asthma exacerbations of hospitalized pediatric asthma patients. An increase in HBE/LBN phenotype was associated with a respective 1.232-fold (95% CI: 1.081-1.404) and 1.248-fold (95% CI: 1.101-1.414) increase in the OR for asthma exacerbations of hospitalized pediatric asthma patients before the COVID-19 pandemic in the winter and autumn seasons. However, an increase of LBE/LBN phenotype was associated with a respective 0.873-fold (95% CI: 0.769-0.991), 0.872-fold (95% CI: 0.771-0.986), and 0.813-fold (95% CI: 0.709-0.932) decrease in the OR for asthma exacerbations in the winter, spring and summer seasons. CONCLUSIONS:HBE/LBN phenotype had a higher risk of asthma exacerbations among hospitalized pediatric asthma patients in the winter and autumn, while LBE/LBN phenotype had a lower risk in the winter, spring, and summer. IMPACT:Blood eosinophils and neutrophils have been indicated to have a potential influence on pediatric asthma development and severity. HBE/LBN phenotype was associated with increased asthma exacerbations among hospitalized pediatric asthma patients during winter and autumn. Eosinophil and neutrophil predominance exhibited a higher influence on pediatric asthma exacerbations.

Background:The objective of this study was to examine the effects of extreme temperatures on the gene signature and pathways of airway epithelial cells in mice and asthma patients. Methods:We investigated the effects of temperature exposure at normal (22°C), and extreme low (10°C), high (40°C) and temperature fluctuation (40°C for 2 h followed by 10°C for next 2 h) in B6.Sftpc-CreER T2 ;Ai14(RCL-tdT)-D mice and pediatric and adult patient's airway epithelial exposed to extreme temperatures. Results:We observed that Mmp8, Sftpb, Cxcl15 and Cd14 were significantly upregulated in airway epithelial cells in mice model. Cma1, Kit, Fdx1, Elf1a, Cdkn2aipnl, Htatsf1, Mfsd13a, Gtf2h5, Tiam2, and Trmt10c were significantly upregulated in 40°C exposure in airway epithelial cells. Sftpc, Gpr171, Sic34a2, Cox14, Lamp3, Luc7l, Nxnl, Tmub2, Tob1, and Cd3e genes were significantly upregulated in 10°C exposure group. Pediatric asthma subjects in the extreme high temperature group consistently showed decreased Wfdc21, Cib3, and Sftpc, at the same time increased Tiam2 and Cma1 expression, while in the extreme low temperature group exhibited consistently higher expression of Sftpc and Nxnl, at the same time decreased Wfdc21, Cib3, Cma1, and Dld expression. Notably, the mice in the extreme temperature fluctuation group showed decreased Wfdc21, Cib3, Gpr171, and Cttnbp2 expression, while increased Hbb-bs expression. Adult asthma subjects in the extreme temperature fluctuation group showed consistently decreased Wfdc21, Cib3, Gpr171, and Cttnbp2 expression, while increased Tiam2 and Cma1 expression. We observed that the mild, moderate, and severe asthma subject in the extreme low temperature group showed increased Tob1, Mub2, Sic34a2, Sftpc, Nxnl, Luc71, Lamp3, Gpr171, Cox14, and Cd3e expression, while in the severe asthma subjects showed increased expression in all temperature exposure group. Conclusion:Our study highlights the effects of extreme temperatures on the gene signature of the airway epithelium in both mice and asthma patients. These findings suggest that extreme temperatures modulate gene expression in the airway epithelium, potentially serving as clinical indicators or biomarkers in response to climate change.

Background:: Dengue is a systemic, viral, mosquito-borne infection that continues to be a major public health issue in endemic regions in tropical and subtropical climates. Accurate tests for rapid diagnosis in point-of-care settings are important to reduce the fatality rates of severe dengue. We evaluated the diagnostic accuracy of the Standard M10 DENV 1-4 system (SD Biosensor, Gyeonggi, Korea), which is a cartridge-based, automated system that integrates nucleic acid extraction, reverse transcription-PCR (RT-PCR) amplification, and detection of dengue virus (DENV) serotypes. Methods:: This was a retrospective diagnostic evaluation study. The index test, Standard M10 DENV 1-4, was evaluated using 320 dengue-positive and 279 dengue-negative archived samples. The reference tests were a combination of Centers for Disease Control and Prevention (CDC) DENV 1-4 real-time RT-PCR, dengue NS1 antigen and IgM antibody detection, and DENV whole-genome sequencing. Results:: The overall sensitivity and specificity of Standard M10 DENV 1-4 were 94% and 100%, respectively. By serotype, the highest sensitivity was 100% for DENV-1, and the lowest was 82% for DENV-4. The overall between the CDC RT-PCR dengue serotyping method and the Standard M10 DENV 1-4 was 95%. Standard M10 DENV 1-4 RT-PCR had comparable sensitivity and specificity to CDC DENV RT-PCR. Conclusions:: Based on its commensurate performance to an established RT-PCR method combined with additional benefits of convenient storage and transport, easy use, and rapid processing, the Standard M10 DENV 1-4 system has potential for DENV detection and serotyping in point-of-care settings.

BACKGROUND:Prognostic tools for febrile illnesses are urgently required in resource-constrained community contexts. Circulating immune and endothelial activation markers stratify risk in common childhood infections. We aimed to assess their use in children with febrile illness presenting from rural communities across Asia. METHODS:Spot Sepsis was a prospective cohort study across seven hospitals in Bangladesh, Cambodia, Indonesia, Laos, and Viet Nam that serve as a first point of contact with the formal health-care system for rural populations. Children were eligible if aged 1-59 months and presenting with a community-acquired acute febrile illness that had lasted no more than 14 days. Clinical parameters were recorded and biomarker concentrations measured at presentation. The primary outcome measure was severe febrile illness (death or receipt of organ support) within 2 days of enrolment. Weighted area under the receiver operating characteristic curves (AUC) were used to compare prognostic accuracy of endothelial activation markers (ANG-1, ANG-2, and soluble FLT-1), immune activation markers (CHI3L1, CRP, IP-10, IL-1ra, IL-6, IL-8, IL-10, PCT, soluble TNF-R1, soluble TREM1 [sTREM1], and soluble uPAR), WHO danger signs, the Liverpool quick Sequential Organ Failure Assessment (LqSOFA) score, and the systemic inflammatory response syndrome (SIRS) score. Prognostic accuracy of combining WHO danger signs and the best performing biomarker was analysed in a weighted logistic regression model. Weighted measures of classification were used to compare prognostic accuracies of WHO danger signs and the best performing biomarker and to determine the number of children needed to test (NNT) to identify one additional child who would progress to severe febrile illness. The study was prospectively registered on ClinicalTrials.gov, NCT04285021. FINDINGS:3423 participants were recruited between March 5, 2020, and Nov 4, 2022, 18 (0·5%) of whom were lost to follow-up. 133 (3·9%) of 3405 participants developed severe febrile illness (22 deaths, 111 received organ support; weighted prevalence 0·34% [95% CI 0·28-0·41]). sTREM1 showed the highest prognostic accuracy to identify patients who would progress to severe febrile illness (AUC 0·86 [95% CI 0·82-0·90]), outperforming WHO danger signs (0·75 [0·71-0·80]; p<0·0001), LqSOFA (0·74 [0·69-0·78]; p<0·0001), and SIRS (0·63 [0·58-0·68]; p<0·0001). Combining WHO danger signs with sTREM1 (0·88 [95% CI 0·85-0·91]) did not improve accuracy in identifying progression to severe febrile illness over sTREM1 alone (p=0·24). Sensitivity for identifying progression to severe febrile illness was greater for sTREM1 (0·80 [95% CI 0·73-0·85]) than for WHO danger signs (0·72 [0·66-0·79]; NNT=3000), whereas specificities were comparable (0·81 [0·78-0·83] for sTREM1 vs 0·79 [0·76-0·82] for WHO danger signs). Discrimination of immune and endothelial activation markers was best for children who progressed to meet the outcome more than 48 h after enrolment (sTREM1: AUC 0·94 [95% CI 0·89-0·98]). INTERPRETATION:sTREM1 showed the best prognostic accuracy to discriminate children who would progress to severe febrile illness. In resource-constrained community settings, an sTREM1-based triage strategy might enhance early recognition of risk of poor outcomes in children presenting with febrile illness. FUNDING:Médecins Sans Frontières, Spain, and Wellcome. TRANSLATIONS:For the Arabic and French translations of the abstract see Supplementary Materials section.

In resource-constrained community settings, distinguishing which febrile children require referral is a major unmet need. Current WHO danger signs lack accuracy, resulting in missed severe illness and unnecessary referrals. We developed and validated simple clinical prediction models using data from 3,405 children aged 1-59 months presenting with community-acquired acute febrile illnesses to seven hospitals across Bangladesh, Cambodia, Indonesia, Laos, and Viet Nam. Cambodian data were held-out for external validation. All models outperformed WHO criteria to predict progression to severe febrile illness (death or organ support) within two days (sensitivity = 0.56, 95% CI = 0.42-0.69; specificity = 0.83, 95% CI = 0.78-0.87). Incorporating pulse oximetry or the host biomarker sTREM1 further enhanced sensitivity (0.89, 95% CI = 0.79-0.97) vs. clinical features alone (0.75, 95% CI = 0.62-0.86). The pulse oximetry-based model achieved these gains while improving specificity, concomitantly reducing referral rates three-fold. These approaches appear cost-effective and could transform referral practices for febrile children in resource-constrained community settings. They warrant evaluation in randomised controlled trials. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement The study was co-funded by Medecins Sans Frontieres, Spain (MSF) and Wellcome. MSF maintained a sponsor-investigator role for the study. Wellcome had no role in study design, data collection, data analysis, data interpretation, writing of the report, or decision to submit for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Medecins Sans Frontieres Ethical Review Board; Oxford Tropical Medicine Research Committee; International Centre for Diarrhoeal Disease Research; Angkor Hospital for Children Research Committee; National Ethics Committee for Health Research, Cambodia; Medical and Health Research Ethics Committee, Indonesia; National Ethics Committee for Health Research, Lao PDR; University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam; Ethics Committee for Biomedical Research, Viet Nam I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes De-identified, individual participant data from this study will be available to researchers whose proposed purpose of use is approved by the data access committees at MSF and MORU. Enquiries or requests for data can be sent to data.sharing{at}london.msf.org and datasharing{at}tropmedres.ac. Researchers interested in accessing biobanked samples should contact the corresponding author, who will coordinate with the Spot Sepsis Sample Use Committee.

During the COVID-19 pandemic, vaccine technology and development advanced substantially in high-income countries, but this progress was not followed by the equitable knowledge transfer and accessibility and uptake of vaccines, particularly among low-and middle-income countries (LMICs). The Asia-Pacific Vaccine Research Network is a collaborative platform that aims to address common challenges faced by Asia-Pacific LMICs in undertaking vaccine research and barriers to evidence-based immunisation policy and practice. A network workshop was held in 2023 that aimed to identify critical challenges and opportunities to advance vaccine research to inform immunisation policy in LMICs in the Asia-Pacific. We found common themes to be challenges and opportunities in vaccine research capacity and infrastructure, workforce availability, financing and regulatory issues. To help to address some of these common challenges across the region, the Asia-Pacific Vaccine Research Network aims to facilitate the upskilling of vaccine research capability and knowledge exchange by bringing together experts and stakeholders from diverse backgrounds and through collaboration.

BackgroundDengue has emerged as a significant public health issue in Nepal since 2006, necessitating innovative approaches to disseminating timely information and promoting preventive behaviour. Our study focuses on developing and pretesting a mobile health app called NepaDengue, assessing its acceptance and factors influencing its implementation.MethodsA concurrent triangulation mixed-method design was used, and an intervention was conducted among 228 university students using the mobile application. Acceptability was assessed using the technology acceptance model (TAM) based on user experiences over 1 week. Focus group discussions among students and female community health volunteers and key informant interviews among key dengue stakeholders were conducted to explore facilitators and barriers. Descriptive statistics were calculated, and a thematic analysis was conducted.ResultsThe high acceptability mean rating scores reported based on the TAM construct indicate that the application is perceived as useful and easy to use and exhibits good functioning and gestural design. The use of the NepaDengue application for dengue prevention and control activities has been perceived as acceptable by users and stakeholders. However, specific barriers were identified, including concerns about sustained usability, illiteracy and limited access to the internet and smartphones. We suggested promoting the application, fostering government ownership and encouraging collaboration to enhance its reach and effective implementation.ConclusionsThe NepaDengue application has been perceived as a promising tool for dengue prevention and control in Nepal. Further piloting and implementation of the app in the community setting is recommended.

During the Covid-19 pandemic, the resurgence of SARS-CoV-2 was due to the development of novel variants of concern (VOC). Thus, genomic surveillance is essential to monitor continuing evolution of SARS-CoV-2 and to track the emergence of novel variants. In this study, we performed phylogenetic, mutation, and selection pressure analyses of the Spike, nsp12, nsp3, and nsp5 genes of SARS-CoV-2 isolates circulating in Yogyakarta and Central Java provinces, Indonesia from May 2021 to February 2022. Various bioinformatics tools were employed to investigate the evolutionary dynamics of distinct SARS-CoV-2 isolates. During the study period, 213 and 139 isolates of Omicron and Delta variants were identified, respectively. Particularly in the Spike gene, mutations were significantly more abundant in Omicron than in Delta variants. Consistently, in all of four genes studied, the substitution rates of Omicron were higher than that of Delta variants, especially in the Spike and nsp12 genes. In addition, selective pressure analysis revealed several sites that were positively selected in particular genes, implying that these sites were functionally essential for virus evolution. In conclusion, our study demonstrated a distinct evolutionary pattern of SARS-CoV-2 variants circulating in Yogyakarta and Central Java provinces, Indonesia.

Release of Aedes aegypti mosquitoes infected with Wolbachia pipientis (wMel strain) is a biocontrol approach against Ae. aegypti-transmitted arboviruses. The Applying Wolbachia to Eliminate Dengue (AWED) cluster-randomised trial was conducted in Yogyakarta, Indonesia in 2018-2020 and provided pivotal evidence for the efficacy of wMel-Ae. aegypti mosquito population replacement in significantly reducing the incidence of virologically-confirmed dengue (VCD) across all four dengue virus (DENV) serotypes. Here, we sequenced the DENV genomes from 318 dengue cases detected in the AWED trial, with the aim of characterising DENV genetic diversity, measuring genotype-specific intervention effects, and inferring DENV transmission dynamics in wMel-treated and untreated areas of Yogyakarta. Phylogenomic analysis of all DENV sequences revealed the co-circulation of five endemic DENV genotypes: DENV-1 genotype I (12.5%) and IV (4.7%), DENV-2 Cosmopolitan (47%), DENV-3 genotype I (8.5%), and DENV-4 genotype II (25.7%), and one recently imported genotype, DENV-4 genotype I (1.6%). The diversity of genotypes detected among AWED trial participants enabled estimation of the genotype-specific protective efficacies of wMel, which were similar (+/- 10%) to the point estimates of the respective serotype-specific efficacies reported previously. This indicates that wMel afforded protection to all of the six genotypes detected in Yogyakarta. We show that within this substantial overall viral diversity, there was a strong spatial and temporal structure to the DENV genomic relationships, consistent with highly focal DENV transmission around the home in wMel-untreated areas and a near-total disruption of transmission by wMel. These findings can inform long-term monitoring of DENV transmission dynamics in Wolbachia-treated areas including Yogyakarta.

BackgroundPost streptococcal acute glomerulonephritis (PSAGN) patients have favorable prognosis, in which most patients showed full recovery in terms of kidney function. However, there is a slight chance ranging from 3–6% that PSAGN patients develop chronic kidney diseasewhich may progress into end stage kidney disease in later life. It is important to identify the factors that can predict the development of chronic glomerulonephritis following PSAGN. Therefore, early intervention can be performed to halt the progression of chronic kidney disease. This study aimed to determine the predictive factors of chronic glomerulonephritis in pediatric patients with PSAGN.MethodsThis study was an analytical observational study with retrospective cohort design. The accessible population was children within the age of 2–18 years old who were admitted with PSAGN between January 2015 and December 2020 in Dr. Sardjito General Hospital Yogyakarta. All anonymized patient data were evaluated for demographic variables, clinical features, laboratory profiles and outcome. Multivariate analysis was performed with multivariate logistic regression method.ResultsA total of 124 patients with PSAGN were obtained from medical record data. There were 65 patients (52.4%) with chronic glomerulonephritis. Bivariate analysis was performed on assumed predictive factors with the results indicating massive proteinuria with hypoalbuminemia (OR = 1.670, 95%CI:1.199–2.326; p = 0.003), oliguria (OR 1.517, 95%CI:1.101–2.089; p = 0.028) and macroscopic hematuria (OR 1.647, 95%CI:1.061-2.555; p=0.013) were significantly higher in the PSAGN group with chronic glomerulonephritis compared to those without. Results of the multivariate logistic regression analysis showed massive proteinuria with hypoalbuminemia (OR = 2.896, 95%CI:1.177–7.123, p = 0.021) and macroscopic hematuria (OR = 2.457, 95%CI:1.018-5.933, p = 0.046) would highly predict chronic glomerulonephritis in subjects with PSAGN.ConclusionWe concluded that massive proteinuria with hypoalbuminemia and macroscopic hematuria are the predictive factors which highly predict chronic glomerulonephritis in PSAGN.