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This open-label study assessed the safety and immunogenicity of two doses (14 days apart) of an indigenously manufactured, killed, bivalent (Vibrio cholerae O1 and O139), whole-cell oral cholera vaccine (SHANCHOL; Shantha Biotechnics) in healthy adults (n = 100) and children (n = 100) in a cholera endemic area (Vellore, South India) to fulfill post-licensure regulatory requirements and post-World Health Organization (WHO) prequalification commitments. Safety and reactogenicity were assessed, and seroconversion rates (i.e. proportion of participants with a ≥ 4-fold rise from baseline in serum vibriocidal antibody titers against V. cholerae O1 Inaba, O1 Ogawa and O139, respectively) were determined 14 days after each vaccine dose. No serious adverse events were reported during the study. Commonly reported solicited adverse events were headache and general ill feeling. Seroconversion rates after the first and second dose in adults were 67.7% and 55.2%, respectively, against O1 Inaba; 47.9% and 45.8% against O1 Ogawa; and 19.8% and 20.8% against O139. In children, seroconversion rates after the first and second dose were 80.2% and 68.8%, respectively, against O1 Inaba; 72.9% and 67.7% against O1 Ogawa; and 26.0% and 18.8% against O139. The geometric mean titers against O1 Inaba, O1 Ogawa, and O139 in both adults and children were significantly higher after each vaccine dose compared to baseline titers (P < 0.001; for both age groups after each dose versus baseline). The seroconversion rates for O1 Inaba, O1 Ogawa, and O139 in both age groups were similar to those in previous studies with the vaccine. In conclusion, the killed, bivalent, whole-cell oral cholera vaccine has a good safety and reactogenicity profile, and is immunogenic in healthy adults and children. Trial Registration: ClinicalTrials.gov ; CTRI/2012/01/002354. [ABSTRACT FROM AUTHOR]

Background: Burden, phenotype and risk-factors of lung function defects in successfully treated tuberculosis cases are unclear. Methods: We performed spirometry with bronchodilators in new drug-sensitive adult (≥18 years) pulmonary tuberculosis cases during the 12 months following successful treatment in India. Airflow obstruction was defined as pre-bronchodilator FEV1/FVC<5th percentile of Global Lung Initiative mixed-ethnicity reference (lower limit of normal [LLN]). Chronic obstructive pulmonary disease (COPD) was defined as post-bronchodilator FEV1/FVC

Background: The burden of scrub typhus in endemic areas is poorly understood. This study aimed at estimating the proportion of hospitalisations and outpatient visits for undifferentiated fever in the community that may be attributable to scrub typhus. Methodology and principal findings: The study was a retrospective cohort with a nested case-control study conducted in the South Indian state of Tamil Nadu. We conducted house-to-house screening in 48 villages (42965 people, 11964 households) to identify hospitalised or outpatient cases due to undifferentiated fever during the preceding scrub typhus season. We used scrub typhus IgG to determine past infection. We calculated adjusted odds ratios for the association between IgG positivity and case status. Odds ratios were used to estimate population attributable fractions (PAF) indicating the proportion of hospitalised and outpatient fever cases attributable to scrub typhus. We identified 58 cases of hospitalisation and 236 outpatient treatments. 562 people were enrolled as control group to estimate the background IgG sero-prevalence. IgG prevalence was 20.3% in controls, 26.3% in outpatient cases and 43.1% in hospitalised cases. The PAFs suggested that 29.5% of hospitalisations and 6.1% of outpatient cases may have been due to scrub typhus. In villages with a high IgG prevalence (defined as ≥15% among controls), the corresponding PAFs were 43.4% for hospitalisations and 5.6% for outpatients. The estimated annual incidence of scrub typhus was 0.8/1000 people (0.3/1000 in low, and 1.3/1000 in high prevalence villages). Evidence for recall error suggested that the true incidences may be about twice as high as these figures. Conclusions: The study suggests scrub typhus as an important cause for febrile hospitalisations in the community. The results confirm the adequacy of empirical treatment for scrub typhus in hospitalised cases with undifferentiated fever. Since scrub typhus may be rare among stable outpatients, the use of empirical treatment remains doubtful in these. [ABSTRACT FROM AUTHOR]

Orientia tsutsugamushi (Ots) is an obligate, intracellular, mite-transmitted human pathogen which causes scrub typhus. Understanding the diversity of Ots antigens is essential for designing specific diagnostic assays and efficient vaccines. The protective immunodominant type-specific 56 kDa antigen (TSA) of Ots varies locally and across its geographic distribution. TSA contains four hypervariable domains. We bioinformatically analyzed 345 partial sequences of TSA available from India, most of which contain only the three variable domains (VDI-III) and three spacer conserved domains (SVDI, SVDII/III, SVDIII). The total number (152) of antigenic types (amino acid variants) varied from 14–36 in the six domains of TSA that we studied. Notably, 55% (787/1435) of the predicted CD4 T-cell epitopes (TCEs) from all the six domains had high binding affinities (HBA) to at least one of the prevalent Indian human leukocyte antigen (HLA) alleles. A surprisingly high proportion (61%) of such TCEs were from spacer domains; indeed 100% of the CD4 TCEs in the SVDI were HBA. TSA sequences from India had more antigenic types (AT) than TSA from Korea. Overall, >90% of predicted CD4 TCEs from spacer domains were predicted to have HBA against one or more prevalent HLA types from Indian, Korean, Asia-Pacific region or global population data sets, while only <50% of CD4 TCEs in variable domains exhibited such HBA. The phylogenetically and immunologically important amino acids in the conserved spacer domains were identified. Our results suggest that the conserved spacer domains are predicted to be functionally more important than previously appreciated in immune responses to Ots infections. Changes occurring at the TCE level of TSA may contribute to the wide range of pathogenicity of Ots in humans and mouse models. CD4 T-cell functional experiments are needed to assess the immunological significance of these HBA spacer domains and their role in clearance of Ots from Indian patients. [ABSTRACT FROM AUTHOR]