Summary Background: Genetic risk scores (GRS) for type 1 diabetes (T1D) have been developed primarily in European populations, limiting their generalisability across ancestries. Indians differ from Europeans in clinical characteristics of T1D and overall genetic architecture, yet systematic evaluation of T1D GRS performance in multi-regional Indian cohorts is lacking. Methods: The study included 597 T1D patients and 3347 non-diabetic controls from different regions in India. Genotyping, imputation, quality control analysis, and construction of the 67-SNPs T1D GRS were performed using standardised pipelines. Discriminative performance was assessed using Receiver Operative Curve-Area under Curve (ROC-AUC) analysis, and optimal thresholds were derived using Youden's index. HLA-DQ diplotype frequencies were compared, and association analysis was conducted using multivariable logistic regression. Findings: T1D GRS showed consistent discriminative performance across Indian cohorts [ROC-AUC=0.84 (range=0.78-0.87)], supporting its comprehensive use for T1D classification in India. Notably, its performance was lower in islet cell autoantibody (IA) negative compared with IA positive T1D patients (ROC-AUC, 0.75 vs 0.85) and in adult-onset than in childhood-onset patients (0.74 vs 0.84). We observed a lower frequency of protective HLA-DQ diplotypes and a strong association of HLA-DQ81 containing diplotypes in childhood-onset T1D. Application of an India-specific T1D GRS score improved the sensitivity than the European cut-off. Interpretation: T1D GRS is a valuable unified diagnostic tool in Indians, but its performance varies by islet cell autoantibody status and age at onset, likely reflecting population-specific HLA architecture. European-derived T1D GRS thresholds under-classify the genetic risk, highlighting the importance of ancestry-aware optimisation in Indians. Funding: CDRC grant CDRC202111026 and CSIR Intramural Grant P50. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was funded by Chellaram Diabetes and Research Centre (CDRC), Pune, India (CDRC grant CDRC202111026) and the Council of Scientific and Industrial Research (CSIR), Ministry of Science and Technology, Government of India, New Delhi, India (CSIR Intramural Grant P50). ### 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: The collection of clinical data and use of bio-banked samples for the biochemical, immunological, and genetic measurements was sanctioned by the Ethics committee of the respective collaborating institutes. CSIR-CCMB (IEC-92/2022), TDRC (IHEC-TDRC-HYD/1/2022), CDI (CDI/BR/2024/058), JSS (JSSMC/IEC/19052022/01NCT/2022-23), OSM (IEC-BHR/OMC/M.NO(07)/P-89). 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 Requests to data access should be submitted to the corresponding author Dr. Giriraj R. Chandak (chandakgrc.ccmb{at}csir.res.in).
Introduction: Hospital-acquired infections (HAI) are nosocomial infections that develop after 48 hours of admission, and surgical site infections (SSI) are a major and significant contributor, with high morbidity and mortality, catastrophic healthcare costs, prolonged hospital stays, and poor quality of life. This study aimed to determine the prevalence of nosocomial SSI and their susceptibility profiles at three teaching hospitals in Zambia. Methodology: This prospective cohort study was conducted at three tertiary hospitals in the Copperbelt Province of Zambia. Results: A total of 1 122 participants were included in the study. Of these, 468 were female and 654 were male. The prevalence of nosocomial SSI in the three teaching hospitals was 21%, representing 95 of the 478 participants. The five most common cultured organisms were Staphylococcus aureus (23%), Enterobacter agglomerans (14%), Pseudomonas aeruginosa (11%), Proteus mirabilis (10%), and Escherichia coli (9%). Most isolates were sensitive to meropenem (15%), chloramphenicol (15%), metronidazole (15%), and septrin (11%) and were resistant to ciprofloxacin (36%), azithromycin (13%), gentamycin (11%), and penicillin (10%). Conclusion: The prevalence of Nosocomial SSI was 21%. The cultured bacterial isolates were Staphylococcus aereus (23%), Enterobacter agglomerans (14%), Pseudomonas aeruginosa (11%), Proteus mirabilis (10%), and Escherichia coli (9%). Susceptibility results showed sensitivity to meropenem (15%), chloramphenicol (15%), metronidazole (15%), and septrin (11%), and resistance to ciprofloxacin (36%), azithromycin (13%), gentamycin (11%), and penicillin (10%). Our study recommends chloramphenicol or meropenem in combination with metronidazole as first- and second-line treatments, respectively, for nosocomial SSI at the three tertiary hospitals.
Asian hepatointestinal schistosomiasis due to Schistosoma japonicum is prevalent in the Philippines and in Indonesia, while it is close to elimination in China. The second Asian schistosome, S. mekongi, is found in Cambodia and Laos. The main pathology caused by both species is liver fibrosis, which can cause significant morbidity and mortality, mainly due to portal hypertension leading to bleeding from esophageal varices. Ultrasonography was introduced several decades ago as a safe, fast, non-invasive, and relatively inexpensive technique for assessing chronic schistosomiasis-related hepatic pathology in the clinical and field settings. A standardized ultrasound protocol had been established by experts at a WHO-chaired meeting in Cairo, Egypt, in 1990. The peculiarities of sonomorphologic abnormalities caused by S. japonicum and S. mekongi were not sufficiently covered in the Cairo protocol and not addressed at all in the subsequent WHO chaired meeting in Niamey 1996. At a follow-up WHO-chaired meeting in Phnom Pehnh, Cambodia, in 2002, an attempt was made to develop a protocol for Asian schistosomiasis, but a protocol resulting from this meeting has never been published. Although several studies investigated the use of ultrasonography to assess S. japonicum- and S. mekongi-related sonomorphological morbidity across endemic areas the lack of a standardized protocol hampered the characterization of sonomorphologic abnormalities with regard to progression, reversibility, prognosis, and correlation to morbidity. In addition, the comparison of data from different endemic areas and populations remained difficult. Therefore, a WHO-chiared expert meeting took place in Basel, Switzerland in September 2024 with the aim to establish a standardized ultrasound protocol for reporting the pathology caused by S. japonicum and S. mekongi. The proposed protocol is described in this article.
Background:Mosquito species belonging to the Anopheles coustani group have been implicated in driving residual malaria transmission in sub-Saharan Africa and are regarded as an established primary vector in Madagascar. The morphological identification of mosquitoes in this group is challenging due to cryptic features and their molecular confirmation is difficult due to a paucity of reference sequence data representing all members of the group. Conventional molecular barcoding with the cytochrome oxidase I (COI) gene and the internal transcribed spacer 2 (ITS2) region targets is limited in their discrimination and conclusive identification of members of species complexes. In contrast, complete mitochondrial genomes (mitogenomes) have demonstrated much improved power over barcodes to be useful in rectifying taxonomic discrepancies in Culicidae. Methods:We utilized a genome skimming approach via shallow shotgun sequencing on individual mosquito specimens to generate sequence reads for mitogenome assembly. Bayesian inferred phylogenies and molecular dating estimations were perfomed on the concatenated protein coding genes using the Bayesian Evolutionary Analysis by Sampling Trees 2 (BEAST 2) platform. Divergence estimates were calibrated on published calucations for Anopheles-Aedes. Results:This study generated 17 new complete mitogenomes which were comprable to reference An. coustani mitogenomes in the GenBank repository by having 13 protein coding, 22 transfer RNA and 2 ribosomal RNA genes, with an average length of 15,400 bp and AT content of 78.3%. Bayesian inference using the concatenated protein coding genes from the generated and publicly available mitogenomes yielded six clades: one for each of the four taxa targeted in this study, the GenBank references, and a currently unknown species. Divergence times estimated that the An. coustani group separated from the An. gambiae complex approximately 110 million years ago (MYA), and members within the complex diverged at times points ranging from~34 MYA to as recent as ~7 MYA. Conclusions:These findings demonstrate the value of mitochondrial genomes in differentiating cryptic taxa and help to confirm morphological identities of An. coustani s.s., An. paludis, An. zeimanni and An. tenebrosus. Divergence estimates with the An. coustani group are similar to those for well-studied anopheline vector groups. These analyses also highlight the likely prescence of other cryptic An. coustani group members circulating in Zambia.
BACKGROUND:Indoor residual spraying (IRS) is a malaria control strategy implemented before the rainy season. Nchelenge District, Zambia, is a holoendemic setting where IRS has been conducted since 2008 with little impact on malaria incidence or parasite prevalence. Pre-rainy season IRS may not reduce the post-rainy season peak abundance of the major vector Anopheles funestus. METHODS:A controlled, pretest-posttest, prospective cohort study assessed the impact of late-rainy season IRS on malaria prevalence, incidence, hazard, and vector abundance. A total of 382 individuals were enrolled across 4 household clusters, of which 2 were sprayed in April 2022 toward the end of the rainy season. Monthly household and individual surveys and indoor overnight vector collections were conducted through August 2022. Multivariate regression and time-to-event analyses estimated the impact of IRS on outcomes measured by rapid diagnostic tests, microscopy, and quantitative polymerase chain reaction. RESULTS:Among participants, 72% tested positive by rapid diagnostic test at least once, and incidence by microscopy was 3.4 infections per person-year. Residing in a household in a sprayed area was associated with a 52% reduction in infection hazard (hazards ratio, 0.48; 95% CI, .29-.78) but not with changes in incidence, prevalence, or vector abundance. The study-wide entomologic inoculation rate was 34 infectious bites per person per year. CONCLUSIONS:Monthly tracking of incidence and prevalence did not demonstrate meaningful changes in holoendemic transmission intensity. However, hazard of infection, which provides greater power for detecting changes in transmission, demonstrated that late-rainy season IRS reduced malaria risk.
