Global seroprevalence of scrub typhus: a systematic review and meta-analysis.

Scrub typhus, a neglected disease, is a significant health concern in the Tsutsugamushi triangle of the Asia-Pacific and has raised global concerns due to recent cases occurring outside this region. To estimate the global prevalence of scrub typhus, we conducted a systematic review and meta-analysis. We conducted a systematic search of PubMed, Scopus, and Embase databases for observational studies on scrub typhus. Using a random-effects model, we combined the prevalence estimates with inverse-variance weights while also evaluating heterogeneity and publication bias. Among 3551 reports screened, we identified 181 studies with 1,48,251 samples for inclusion in our synthesis. The overall pooled seroprevalence (95% confidence intervals) of scrub typhus infections was 24.93% (23.27-26.60). Gender-wise pooled prevalence was estimated to be 50.23% (47.05-53.40) for males and 48.84% (45.87-51.80) for females. Eschar prevalence was observed to be 30.34% (22.54-38.15) among the positive cases. One-fourth of all the samples tested positive for scrub typhus and eschar was present in one-third of these total positive cases, encompassing regions beyond the Tsutsugamushi triangle. This estimation underlines the importance of this neglected disease as a public health problem. Strengthening surveillance and implementing disease control measures are needed in the affected regions.

Hospital-based norovirus surveillance in children <5 years of age from 2017 to 2019 in India.

After the introduction of the rotavirus vaccine into the Universal Immunization Program in India in 2016, relatively few studies have assessed the prevalence and epidemiological patterns of acute gastroenteritis (AGE) among hospitalized children ≤5 years of age. We used a uniform protocol to recruit children with AGE as well as standardized testing and typing protocols. Stool specimens from children with AGE younger than 5 years of age admitted to six hospitals in three cities in India were collected from January 2017 through December 2019. Norovirus was detected by real-time reverse transcription-polymerase chain reaction (RT-qPCR) followed by typing positive specimens by conventional RT-PCR and Sanger sequencing. Norovirus was detected in 322 (14.8%) of 2182 specimens with the highest rate in 2018 (17.6%, 146/829), followed by 2019 (14.4%, 122/849) and 2017 (10.7%, 54/504). Rotavirus vaccine status was known for 91.6% of the children of which 70.4% were vaccinated and 29.6% not. Norovirus positivity in rotavirus-vaccinated children was 16.3% and 12% in unvaccinated children. GII.4 Sydney[P16] (39.3%), GII.4 Sydney[P31] (18.7%), GII.2[P16] (10%), GI.3[P13] (6.8%), GII.3[P16] (5.9%), and GII.13[P16] (5%) accounted for 85.8% (188/219) of the typed strains. Our data highlight the importance of norovirus in Indian children hospitalized with AGE.

Characterization of IL-10 Family of Cytokines in Acute and Convalescent COVID-19 Individuals.

Cytokines are major players in orchestrating inflammation, disease pathogenesis, and severity during COVID-19. Members of the interleukin (IL)-10 family of cytokines play important roles in regulating immune responses to various inflammatory and infectious diseases. However, the role of the IL-10 family of cytokines in COVID-19 remains elusive. Hence, we determined the plasma levels of the IL-10 family of cytokines (IL-10, IL-19, IL-20, IL-22, and IL-24) in 7 groups of COVID-19 individuals, based on days since real-time reverse transcriptase-polymerase chain reaction confirmation of SARS-CoV-2 infection. Our data show that the levels of IL-10, IL-19, IL-20, IL-22, and IL-24 cytokines decreased from days 15-30 to days 61-90 and plateaued thereafter. Severe COVID-19 patients exhibit increased plasma levels of IL-10, IL-19, IL-20, IL-22, and IL-24 compared to mild patients. Thus, our study provides evidence of alterations in the plasma levels of the IL-10 family of cytokines in convalescent COVID-19 individuals.

Sero-Surveillance to Monitor the Trend of SARS-CoV-2 Infection Transmission in India: Study Protocol for a Multi Site, Community Based Longitudinal Cohort Study.

Introduction: Large-scale sero-prevalence studies with representation from all age groups are required to estimate the true burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the community. Serial serological surveys in fixed cohorts enable study of dynamics of viral transmission and correlates of immune response over time in the context of gradual introduction of COVID-19 vaccines and repeated upsurge of cases during the pandemic. Methods: This longitudinal study will involve follow-up of a cohort of 25,000 individuals (5,000 per site) aged 2 years and above recruited from five existing demographic surveillance sites in India. The cohort will be tested for the presence of IgG antibodies against S1/S2 spike protein subunits of SARS-CoV-2 in four rounds; once at baseline and subsequently, at intervals of 4 months for a year between January 2021 and January 2022. Neutralization assays will be carried out in a subset of seropositive samples in each round to quantify the antibody response and to estimate the durability of antibody response. Serial serological surveys will be complemented by fortnightly phone based syndromic surveillance to assess the burden of symptomatic acute febrile illness/ influenza like illness in the same cohort. A bio-repository will also be established to store the serum samples collected in all rounds of serological surveys. Discussion: The population based sero-epidemiological studies will help to determine the burden of COVID-19 at the community level in urban and rural Indian populations and guide in monitoring the trends in the transmission of SARS-CoV-2 infection. Risk factors for infection will be identified to inform future control strategies. The serial serological surveys in the same set of participants will help determine the viral transmission dynamics and durability of neutralizing immune response in participants with or without symptomatic COVID infection.

Characterization of memory T cell subsets and common γ-chain cytokines in convalescent COVID-19 individuals.

T cells are thought to be an important correlates of protection against SARS-CoV2 infection. However, the composition of T cell subsets in convalescent individuals of SARS-CoV2 infection has not been well studied. The authors determined the lymphocyte absolute counts, the frequency of memory T cell subsets, and the plasma levels of common γ-chain in 7 groups of COVID-19 individuals, based on days since RT-PCR confirmation of SARS-CoV-2 infection. The data show that both absolute counts and frequencies of lymphocytes as well as, the frequencies of CD4+ central and effector memory cells increased, and the frequencies of CD4+ naïve T cells, transitional memory, stem cell memory T cells, and regulatory cells decreased from Days 15-30 to Days 61-90 and plateaued thereafter. In addition, the frequencies of CD8+ central memory, effector, and terminal effector memory T cells increased, and the frequencies of CD8+ naïve cells, transitional memory, and stem cell memory T cells decreased from Days 15-30 to Days 61-90 and plateaued thereafter. The plasma levels of IL-2, IL-7, IL-15, and IL-21-common γc cytokines started decreasing from Days 15-30 till Days 151-180. Severe COVID-19 patients exhibit decreased levels of lymphocyte counts and frequencies, higher frequencies of naïve cells, regulatory T cells, lower frequencies of central memory, effector memory, and stem cell memory, and elevated plasma levels of IL-2, IL-7, IL-15, and IL-21. Finally, there was a significant correlation between memory T cell subsets and common γc cytokines. Thus, the study provides evidence of alterations in lymphocyte counts, memory T cell subset frequencies, and common γ-chain cytokines in convalescent COVID-19 individuals.

Low risk of relapse and deformity among leprosy patients who completed multi-drug therapy regimen from 2005 to 2010: A cohort study from four districts in South India.

INTRODUCTION: Relapse of leprosy among patients released from treatment (RFT) is an indicator of the success of anti-leprosy treatment. Due to inadequate follow-up, relapse in leprosy patients after RFT is not systematically documented in India. Relapsed leprosy patients pose a risk in the transmission of leprosy bacilli. We determined the incidence of relapse and deformity among the patients RFT from the leprosy control programme in four districts in South India. METHODS: We conducted two follow-up surveys in 2012 and 2014 among the leprosy patients RFT between 2005 and 2010. We assessed them for any symptoms or signs of relapse, persistence and deformity. We collected slit skin samples (SSS) for smear examination. We calculated overall incidence of relapse and deformity per 1000 person-years (PY) with 95% confidence intervals (CI) and cumulative risk of relapse. RESULTS: Overall, we identified 69 relapse events, 58 and 11, during the first and second follow-up surveys, respectively. The incidence of relapse was 5.42 per 1000 PY, which declined over the years after RFT. The cumulative risk of relapse was 2.24%. The rate of deformity among the relapsed patients was 30.9%. The overall incidence of deformity was 1.65 per 1000 person years. The duration of M. leprae detection in smears ranged between 2.38 and 7.67 years. CONCLUSIONS: Low relapse and deformity rates in leprosy RFT patients are indicative of treatment effectiveness. However, a higher proportion of detection of deformity among relapsed cases is a cause for concern. Periodic follow-up of RFT patients for up to 3 years to detect relapses early and ensure appropriate treatment will minimize the development of deformity among relapsed patients.

Burden of bacterial meningitis in India: Preliminary data from a hospital based sentinel surveillance network.

BACKGROUND: Worldwide, acute bacterial meningitis is a major cause of high morbidity and mortality among under five children, particularly in settings where vaccination for H. influenzae type b, S. pneumoniae and N. meningitidis is yet to be introduced in the national immunization programs. Estimation of disease burden of bacterial meningitis associated with these pathogens can guide the policy makers to consider inclusion of these newer vaccines in the immunization programs. A network of hospital based sentinel surveillance was established to generate baseline data on the burden of bacterial meningitis among children aged less than 5 years in India and to provide a platform for impact assessment following introduction of the Pentavalent and Pneumococcal Conjugate Vaccines (PCV). METHODS: During surveillance carried out in select hospitals across India in 2012-2013, information regarding demographics, immunization history, clinical history, treatment details and laboratory investigations viz. CSF biochemistry, culture, latex agglutination and PCR was collected from children aged 1 to 59 months admitted with suspected bacterial meningitis. RESULTS: A total of 3104 suspected meningitis cases were enrolled from 19,670 children admitted with fever at the surveillance hospitals. Of these, 257 cases were confirmed as cases of meningitis. They were due to S. pneumoniae (82.9%), H. influenzae type b (14.4%) and N. meningitidis (2.7%). Highest prevalence (55.3%) was observed among children 1 to 11 months. Antimicrobial susceptibility testing revealed considerable resistance among S. pneumoniae isolates against commonly used antibiotics such as cotrimoxazole, erythromycin, penicillin, and cefotaxime. More commonly prevalent serotypes of S. pneumoniae in circulation included 6B, 14, 6A and 19F. More than 90% of serotypes identified were covered by Pneumococcal Conjugate Vaccine 13. CONCLUSIONS: We observed that S. pneumoniae was the commonest cause of bacterial meningitis in hospitalized children under five years of age in India. Continued surveillance is expected to provide valuable information and trends in future, to take an informed decision on introduction of pneumococcal vaccination in Universal Immunization Programme in India and will also eventually help in post-vaccination impact evaluation.