Etiological spectrum and diagnostic challenges of short-duration fever in West Bengal (India). A cross-sectional tertiary care study.

INTRODUCTION: The scarcity of epidemiological data on acute febrile illnesses from South Asia impairs evidence-based clinical decision-making. Our study aimed to explore the etiological spectrum of short-duration fever in patients admitted to a tertiary care hospital in West Bengal, India. METHODS: We conducted a cross-sectional study from May 2021 to April 2022 involving 150 adult patients presenting with a fever lasting less than two weeks at Burdwan Medical College and Hospital (West Bengal, India). We performed comprehensive clinical assessments, including microbiological, serological, and other specific investigations, to identify the causes of the fever. RESULTS: The demographic profile predominantly included individuals aged 21-40 years, with a male-to-female ratio of 1.9:1; 60.7% of participants were from rural areas. The primary etiological agents identified were scrub typhus (25.3%), dengue (15.3%), and enteric fever (13.3%). Notably, 80% of patients presented with non-localizing symptoms, while 14.7% had respiratory symptoms. Blood cultures pinpointed Salmonella typhi and Staphylococcus aureus in a minority of cases (3.3%); malaria, primarily Plasmodium vivax, was diagnosed in 12% of the cases. CONCLUSION: Our findings highlight the complexity of diagnosing short-duration fevers, dominated by a wide range of etiological agents, with a notable prevalence of scrub typhus. These results underscore the urgent need for enhanced diagnostic facilities, including the availability of scrub typhus testing at primary healthcare centers. We recommend empirical doxycycline therapy for suspected cases and emphasize the need for further research to develop management guidelines for acute febrile illnesses. This study also highlights the importance of raising both community and clinician awareness to prevent irrational antibiotic use.

Correlation of Vascular Changes in Skin Tissue of Diabetic Patients with Glycosylated Hb and duration of Disease.

Skin is the largest organ and outer covering of human body. It plays a great role in our visible appearance. Humans are more conscious about skin disease because it has a cosmetic priority. The cases that fulfil the selection criteria will be enrolled as study samples with a view to see correlation with glycosylated Hb, vascular changes and duration of DM. This cross-sectional study was performed in the Department of Skin and VD and the Department of Pathology of BIRDEM, Dhaka, Bangladesh from March 2017 to February 2019. Study population was all diabetic patients with skin diseases attending dermatology department of BIRDEM hospital. Among them 90 patients were selected who will do skin biopsy with diabetes mellitus. Skin biopsy tissue and blood sample were taken as materials to determine the type of skin lesion in patients with satisfactory and unsatisfactory glycaemic control; the relationship of diabetic skin lesions with duration of diabetes; and assessing the cutaneous or dermal capillary vascular changes was in Diabetes Mellitus and its correlation with HbA1c level and duration of Diabetes Mellitus. Among 90 cases age ranged from 31 to 85 years with mean age of the patients 55.06 ± 12.10 years. Maximum patients were in age group 41-50 years (32.2%). Skin disorders in Diabetes mellitus are more common in female in this study. Almost three fourth of the patients glycemic status was unsatisfactory. Satisfactory glycemic patients were 17 cases (18.9%) and unsatisfactory glycemic patients were 73 cases (81.1%). Mean HbA1c shows unsatisfactory glycemic status among 90 cases in this study. Mean HbA1c is more unsatisfactory in female patients in this study. Most common group of lesion was 37.7 % belong to miscellaneous group followed by skin diseases with strong to weak association with DM. There were no significant differences in different types of skin lesions between satisfactory and unsatisfactory blood glucose patients. Majority of the cases (37.8%) occurred after 10 years of diagnosis of DM. Mean duration of DM was highest among the patients with skin reaction to diabetic treatment (10.04±6.19). There is marked variation in thickness of dermal capillary basement membrane with duration of diabetes. There was a significant inverse correlation between perivascular infiltration and capillary basement membrane thickness.

Mutations in the stromal antigen 3 (STAG3) gene cause male infertility due to meiotic arrest.

STUDY QUESTION: Are sequence variants in the stromal antigen 3 (STAG3) gene a cause for non-obstructive azoospermia (NOA) in infertile human males? SUMMARY ANSWER: Sequence variants affecting protein function of STAG3 cause male infertility due to meiotic arrest. WHAT IS KNOWN ALREADY: In both women and men, STAG3 encodes for a meiosis-specific protein that is crucial for the functionality of meiotic cohesin complexes. Sequence variants in STAG3 have been reported to cause meiotic arrest in male and female mice and premature ovarian failure in human females, but not in infertile human males so far. STUDY DESIGN, SIZE, DURATION: The full coding region of STAG3 was sequenced directly in a cohort of 28 men with NOA due to meiotic arrest. In addition, a larger group of 275 infertile men that underwent whole-exome sequencing (WES) was screened for potential STAG3 sequence variants. Furthermore, meiotic spreads, immunohistochemistry, WES and population sampling probability (PSAP) have been conducted in the index case. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included 28 infertile but otherwise healthy human males who underwent Sanger sequencing of the full coding region of STAG3. Additionally, WES data of 275 infertile human males with different infertility phenotypes have been screened for relevant STAG3 variants. All participants underwent karyotype analysis and azoospermia factor (AZF) screening in advance. In the index patient, segregation analysis, WES data, PSAP, lab parameters, testis histology and nuclear spreads have been added to suplort the findings. MAIN RESULTS AND THE ROLE OF CHANCE: Two compound-heterozygous variants in STAG3 (c.[1262T>G];[1312C>T], p.[(Leu421Arg)];[(Arg438Ter)]) have been found to cause male infertility due to complete bilateral meiotic arrest in an otherwise healthy human male. Compound heterozygosity was confirmed by Sanger sequencing of the parents and the patient's brother. Other variants which may affect spermatogenesis have been ruled out through analysis of the patient's WES data and application of the PSAP pipeline. As expected from Stag3 knockout-mice meiotic spreads, germ cells did not develop further than zygotene and showed drastic chromosome aberrations. No rare variants in STAG3 were found in the 275 infertile males with other phenotypes. Our results indicate that STAG3 variants that negatively affect its protein function are a rare cause of NOA (<1% of cases). LIMITATIONS, REASONS FOR CAUTION: We identified only one patient with compound-heterozygous variants in STAG3 causing NOA due to meiotic arrest. Future studies should evaluate STAG3 variants in larger cohorts to support this finding. WIDER IMPLICATIONS OF THE FINDINGS: Identification of STAG3 sequence variants in infertile human males should improve genetic counselling as well as diagnostics and treatment. Especially before testicular sperm extraction (TESE) for ICSI, STAG3 variants should be ruled out to prevent unnecessary interventions with frustrating outcomes for both patients and clinicians. STUDY FUNDING/COMPETING INTEREST(S): This work was carried out within the frame of the German Research Foundation (DFG) Clinical Research Unit 'Male Germ Cells: from Genes to Function' (CRU326). Work in the laboratory of R.J. is supported by a grant of the European Union H2020 program GermAge. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Detection of New Delhi metallo-beta-lactamase and extended-spectrum beta-lactamase genes in Escherichia coli isolated from mastitic milk samples.

In this study, eight Escherichia coli isolates were obtained from milk samples of dairy cattle suffering from clinical/subclinical mastitis. Isolates were characterized for antimicrobial resistance traits and virulence genes. Results revealed that one isolate was harbouring New Delhi metallo-beta-lactamase gene (blaNDM ). Cloning and sequencing of the PCR amplicon confirmed the identity of the gene (GenBank accession no. KC769583) having 100% homology with blaNDM-5 (GenBank accession no. JN104597.1), and this isolate was susceptible to colistin, chloramphenicol and tetracycline only. Moreover, another isolate carried extended-spectrum beta-lactamase (ESBL) gene - blaCTX-M , and all isolates possessed blaTEM gene. Of the eight isolates, only one isolate was positive for shiga toxin gene (stx2), and none were harbouring stx1 gene. Occurrence of New Delhi metallo-beta-lactamase (blaNDM ) in one E. coli isolate and ESBL genes in other isolates poses a potential threat to human health following possible entry and spread through food chain.

Chronic toxicity of arsenic in goats: clinicobiochemical changes, pathomorphology and tissue residues.

Chronic inorganic arsenic toxicity was induced in goats by oral administration of one-fifth of the acute lethal dose 50 (ALD(50)) of sodium arsenite (25mgkg(-1) body weight) packed in gelatin capsules and given daily for 12 weeks. Clinical signs of toxicity developed from 3 week post-exposure, consisting of gastrointestinal disturbances and renal insufficiency with 100% mortality in all animals. There were significant (p<0.01) decreases in total serum protein and the albumin: globulin ratio, and increases in blood glucose and various enzymatic activities of treated animals. Toxicity also induced severe pathomorphological changes, indicative of haemorrhagic and degenerative and/or necrotic lesions in most organs. In addition, proliferative pneumonia in lungs, hyperplastic goitre in thyroid and chronic proliferative lesions in skin were observed. Liver contained the largest residues of arsenic, followed by intestine, kidneys, thyroid, abomasum, spleen, skin, lungs and lowest in brain. The intensity of pathomorphological changes was proportional to the accumulated amount of arsenic in tissues/organs.

Amphotericin versus sodium stibogluconate in first-line treatment of Indian kala-azar.

Patients do not always respond to treatment of visceral leishmaniasis with pentavalent antimony, and the drug has toxic effects. Amphotericin B might be useful as an alternative first-line treatment for the disease. We compared the efficacy of amphotericin and sodium stibogluconate in a prospective randomised trial in 80 uncomplicated and parasitologically confirmed cases of Indian kala-azar. None of the patients had received an antileishmanial agent before. Sodium stibogluconate was given at 20 mg/kg in two divided doses daily for 40 days, and amphotericin in fourteen doses of 0.5 mg/kg infused in 5% dextrose on alternate days. All 40 patients randomised to amphotericin were cured; of the 40 patients assigned to sodium stibogluconate, 28 (70%) showed initial cure and 25 (62.5%) showed definitive cure (p < 0.001). With amphotericin, there was quicker abatement of fever and more complete spleen regression with no serious adverse effects. Amphotericin is effective in the first-line treatment of Indian kala-azar and superior to antimony therapy.

Amphotericin versus pentamidine in antimony-unresponsive kala-azar.

We compared the efficacy of amphotericin B and pentamidine isethionate in a prospective randomised trial in 120 uncomplicated and parasitologically confirmed cases of antimony-unresponsive kala-azar. Doses were twenty intramuscular injections of pentamidine 4 mg/kg on alternate days or fourteen definitive doses of amphotericin 0.5 mg/kg infused in 5% dextrose on alternate days. 48 (80%) patients given pentamidine showed initial cure and 46 (77%) showed definitive cure compared with 60 (100%) and 59 (98%) cases, respectively, on amphotericin (p < 0.001). Amphotericin also brought about quicker abatement of fever and more complete spleen regression.