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Broadly neutralizing antibodies (bnAbs) develop in a subset of HIV-1 infected individuals over 2–3 years of infection. Infected infants develop plasma bnAbs frequently and as early as 1-year post-infection suggesting factors governing bnAb induction in infants are distinct from adults. Understanding viral characteristics in infected infants with early bnAb responses will provide key information about antigenic triggers driving B cell maturation pathways towards induction of bnAbs. Herein, we evaluate the presence of plasma bnAbs in a cohort of 51 HIV-1 clade-C infected infants and identify viral factors associated with early bnAb responses. Plasma bnAbs targeting V2-apex on the env are predominant in infant elite and broad neutralizers. Circulating viral variants in infant elite neutralizers are susceptible to V2-apex bnAbs. In infant elite neutralizers, multivariant infection is associated with plasma bnAbs targeting diverse autologous viruses. Our data provides information supportive of polyvalent vaccination approaches capable of inducing V2-apex bnAbs against HIV-1. Some infants develop broadly neutralizing antibodies (bnAbs) to HIV in a shorter time frame than adults, but the reasons aren’t well understood. Here, the authors study a cohort of 51 HIV-1 clade C perinatally infected infants of Indian origin and find that multivariant infection is associated with bnAbs in elite neutralizers.

Pneumococcal carriage studies are important for vaccine introduction and treatment strategies. Pneumococcal carriage rates estimated in this cohort study among children in a rural community of northern India. Between August 2012 and August 2014, trained nurses made weekly home visits to screen enrolled children aged <10 years for acute upper or lower respiratory infections (AURI/ALRI) in Ballabgarh, Haryana. Nasal swab from infants aged <1year and throat swab from children aged ≥1 year were collected. All specimens were cultured for pneumococci; isolates were serotyped and subjected to antimicrobial susceptibility testing. During the study period, 4348 nasal/throat swabs collected from children with clinical features of ARI (836 ALRI, 2492 AURI) and from 1020 asymptomatic children. Overall pneumococcal carriage was 5.1%, the highest carriage rate among children <1 year of age (22.6%). The detection rates were higher among children with ARI (5.6%; 95% CI: 4.8–6.4) than asymptomatic children (3.3%; 95% CI: 2.3–4.6). Among 220 pneumococcal isolates, 42 diverse serotypes were identified, with 6B/C (8.6%), 19A (7.2%), 19F (6.8%), 23F (6.4%), 35A/B/C (6.4%), 15B (5%), 14 (4.5%) and 11A/C/D (3.2%) accounting for 50%. Forty-five percent of the serotypes identified are included in the current formulation of 13-valent pneumococcal conjugate vaccine. Ninety-six percent of isolates were resistant to co-trimoxazole, 9% were resistant to erythromycin, and 10% had intermediate resistance to penicillin with minimum inhibitory concentration ranges (0.125 to 1.5 μg/ml). Pneumococcal detection was relatively low among children in our study community but demonstrated a diverse range of serotypes and half of these serotypes would be covered by the current formulation of 13-valent pneumococcal vaccine.

The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse. This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15-60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture. A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups. The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion. CTRI/2021/02/030977 (ICMR, Clinical trial registry-India).

We conducted a multicenter surveillance study to identify changes in antimicrobial susceptibility patterns of Salmonella Typhi and S. Paratyphi in India since the COVID-19 pandemic began. We collected S. Typhi and S. Paratyphi isolates from blood or bone marrow culture-confirmed enteric fever cases at eight sites in seven cities across India between 2021 and 2024. We tested the antibiotic susceptibility of 1150 S. Typhi isolates and 265 S. Paratyphi isolates via disc diffusion and determined their minimum inhibitory concentrations (MICs) of ceftriaxone and azithromycin via broth dilution. We identified 18 S. Typhi isolates from Ahmedabad that were resistant to ceftriaxone, indicating a larger emergence of third-generation cephalosporin-resistant S. Typhi in Western India with a novel plasmid profile. Furthermore, we observed yearly increases in the mean, median and 90th percentile of azithromycin MICs for S. Typhi and S. Paratyphi isolates throughout India between 2021 and 2023. Finally, we found that only 0.70% of S. Typhi isolates and 1.13% of S. Paratyphi isolates exhibited susceptibility to ciprofloxacin. Our results indicate the necessity for a shift from ciprofloxacin in the treatment of enteric fever, and the importance of implementing long-term monitoring of resistance to alternative antibiotics such as azithromycin and ceftriaxone.

The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse. This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15-60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture. A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups. The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion.

Enteric fever is an invasive infection predominantly caused by Salmonella enterica serovars Typhi and Paratyphi A. The pathogens have evolved from other nontyphoidal salmonellaeto become invasive and host restricted. Emergence of antimicrobial resistance in typhoidal salmonellae in some countries is a major therapeutic concern as the travelers returning from endemic countries carry resistant strains to non endemic areas. In order to understand the epidemiology and to design disease control strategies molecular typing of the pathogen is very important. We performed Multilocus Sequence Typing (MLST) of 251 S. Typhi and 18 S. Paratyphi strains isolated from enteric fever patients from seven centers across India during 2010-2013to determine the population structure and prevalence of MLST sequence types in India. MLST analysis revealed the presence of five sequence types (STs) of typhoidal salmonellae in India namely ST1, ST2 and ST3 for S. Typhi and ST85 and ST129 for S. Paratyphi A.S. Typhi strains showed monophyletic lineage and clustered in to 3 Sequence Types-ST1, ST2 and ST3 and S. Paratyphi A isolates segregated in two sequence types ST85 and ST129 respectively. No association was found between antimicrobial susceptibility and sequence types. This study found ST1 as the most prevalent sequence type of S. Typhi in India followed by ST2, which is in concordance with previous studies and MLST database. In addition a rare sequence type ST3 has been found which is reported for the first time from the Indian subcontinent. Amongst S. Paratyphi A, the most common sequence type is ST129 as also reported from other parts of world. This distribution and prevalence suggest the common spread of the sequence types across the globe and these findings can help in understanding the disease distribution.

BACKGROUND: Nowadays, the use of Internet with e-learning resources anytime and anywhere leads to interaction possibilities among teachers and students from different parts of the world. It is becoming increasingly pertinent that we exploit the Internet technologies to achieve the most benefits in the education. MATERIALS AND METHODS: This study compares the difference between traditional classroom and e-learning in the educational environment. Medical undergraduate students of our institution were enrolled to compare between the online versus traditional method of teaching through questionnaire. RESULTS: Forty percent of students found the online lecture material difficult to understand. 42.6% of respondents found it difficult to clear the doubts in online teaching; 64.4% of the participants believed that they have learned more in a face-to-face learning. CONCLUSION: In this study, we concluded that online mode offers flexibility on timing and delivery. Students can even download the content, notes, and assignment. Despite all the advantages offered, there is a general consensus that no technology can replace face-to-face teaching in real because in this, there will be visual as well as verbal discussion. Looking at the uncertainty of the current scenario, it is difficult to predict how long online classes will have to continue. Hence, it is of paramount importance that we assess the effectiveness of online classes and consequently take measures to ensure proper delivery of content to students, especially in a skilled field like medicine, so we concluded that face-to-face learning is of utmost importance in medical institutions.

Background Indiscriminate and widespread use of antibiotics has resulted in emergence of many antibiotic-resistant organisms. Antibiotic administration during pregnancy is mostly avoided, unless there is compelling medical condition. We hypothesized that the uropathogens isolated from pregnant women would be more susceptible to antibiotics compared to those isolated from nonpregnant women, thus will be helpful in formulating separate empiric guideline for pregnant women based on the resistance pattern. Methods This was a prospective cross-sectional study conducted over a period of 2 years in which females with the clinical diagnosis of either cystitis or asymptomatic bacteriuria during pregnancy were included from the community settings. Uropathogen species and their antimicrobial resistance pattern were compared between the pregnant and nonpregnant groups. After accounting for centre-to-centre variation and adjusting for age and socio-economic status, the adjusted odds ratio for antibiotic resistance was calculated and compared between pregnant and nonpregnant women using logistic regression analysis. Results A total of 1758 women (pregnant: 43.3%; nonpregnant: 56.6%) were screened in the study over a period of 2 years, out of which 9.3% (163/1758) were having significant bacteriuria. Escherichia coli and Klebsiella pneumoniae were the two commonest uropathogen in both the groups; their prevalence being 83.6% in pregnant women and 85.2% in nonpregnant women, respectively. Resistance against ampicillin, cefixime, cefoxitin, ceftazidime, ceftriaxone and amoxicillin-clavulanic acid were found significantly lower in the pregnant women compared to nonpregnant. After adjusting the age and socio-economic status accounting for centre-to-centre variation, the odds of resistance for cefixime, amoxicillin-clavulanic acid and co-trimoxazole were found lower and statistically significant among the pregnant women group. Conclusions The antimicrobial resistance was significantly higher among the community-dwelling nonpregnant women compared to pregnant women in case of few antibiotics. The study highlighted the need of building local antibiogram that could help to initiate the empirical treatment and thus prevent emergence of antimicrobial resistance.

IntroductionUniversal coverage of vaccines alone cannot be relied upon to protect at-risk populations in lower- and middle-income countries against the impact of the coronavirus disease 2019 (COVID-19) pandemic and newer variants. Live vaccines, including Bacillus Calmette–Guérin (BCG), are being studied for their effectiveness in reducing the incidence and severity of COVID-19 infection.MethodsIn this multi-centre quadruple-blind, parallel assignment randomised control trial, 495 high-risk group adults (aged 18–60 years) were randomised into BCG and placebo arms and followed up for 9 months from the date of vaccination. The primary outcome was the difference in the incidence of COVID-19 infection at the end of 9 months. Secondary outcomes included the difference in the incidence of severe COVID-19 infections, hospitalisation rates, intensive care unit stay, oxygen requirement and mortality at the end of 9 months. The primary analysis was done on an intention-to-treat basis, while safety analysis was done per protocol.ResultsThere was no significant difference in the incidence rates of cartridge-based nucleic acid amplification test (CB-NAAT) positive COVID-19 infection [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.54–2.14] in the two groups, but the BCG arm showed a statistically significant decrease in clinically diagnosed (symptomatic) probable COVID-19 infections (OR 0.38, 95% CI 0.20–0.72). Compared with the BCG arm, significantly more patients developed severe COVID-19 pneumonia (CB-NAAT positive) and required hospitalisation and oxygen in the placebo arm (six versus none; p = 0.03). One patient belonging to the placebo arm required intensive care unit (ICU) stay and died. BCG had a protective efficacy of 62% (95% CI 28–80%) for likely symptomatic COVID-19 infection.ConclusionsBCG is protective in reducing the incidence of acute respiratory illness (probable symptomatic COVID-19 infection) and severity of the disease, including hospitalisation, in patients belonging to the high-risk group of COVID-19 infection, and the antibody response persists for quite a long time. A multi-centre study with a larger sample size will help to confirm the findings in this study.Clinical Trials RegistryClinical Trials Registry India (CTRI/2020/07/026668).Plain Language SummaryThe Bacillus Calmette–Guérin (BCG) vaccine has been studied previously in several settings, including reducing childhood mortalities due to viral infections and induction of trained immunity and reducing upper respiratory tract infections and pneumonia in older adults. This multi-centre trial has tried to evaluate the efficacy of BCG revaccination in reducing the incidence and severity of COVID-19 infections in adults between 18 and 60 years of age belonging to the high-risk group owing to the presence of comorbidities including diabetes, chronic kidney disease, chronic liver disease and chronic lung diseases. A single dose of BCG vaccine produced significantly high titres of BCG antibodies lasting for six months. While there was no significant reduction in the incidence of COVID-19 infection, there was an 8.4% reduction in the incidence of symptomatic COVID-19 disease at the end of 9 months of follow-up. In addition, there were significantly fewer severe COVID-19 infections requiring hospital stay and oxygen support. However, the overall numbers of severe COVID-19 infections were low. Thus, the study shows that BCG can protect against symptomatic and severe COVID-19 disease. However, it might not reduce the incidence of new infections. The study results are significant for low- and middle-income countries without adequate coverage of primary doses of COVID-19 vaccination, let alone the booster doses. Future studies should evaluate the BCG vaccine’s efficacy as a booster compared with routine COVID-19 vaccine boosters.

Introduction: Multidrug-resistant Acinetobacter baumannii is galloping, posing threat to tackle, and leaving us with limited options of treatment. Methods: The purpose of this study is to find the genotypic association in drug-resistant A. baumannii isolated from different sterile body fluids. Matrix-assisted laser desorption/ionization-time of flight confirmed A. baumannii isolates were taken and minimum inhibitory concentration (MIC) was determined by VITEK-2 AST system. The presence of resistance nodulation-division (RND)-efflux pump genes AdeABC-RS was detected by multiplex polymerase chain reaction. Results: Of the total 40 A. baumannii, 32 (80%) were multidrug resistant though all isolates were susceptible to Tigecycline. Similarly, 26 (81.25%) isolates were positive for RND-efflux pump genes AdeABC-RS. Discussion: RND efflux pump AdeABC-RS system plays a significant role in emerging multi drug resistant A. baumannii. Mutation in AdeS gene deciphers the role of regulatory gene. Hence, antimicrobial stewardship should be strictly followed and efflux pump inhibiting substances should be vigorously searched to bring back the era of existing antibiotics.