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1.
PLoS One ; 19(5): e0297452, 2024.
Article in English | MEDLINE | ID: mdl-38696397

ABSTRACT

BACKGROUND: Limited data exists regarding risk factors for adverse outcomes in older adults hospitalized with Community-Acquired Pneumonia (CAP) in low- and middle-income countries such as India. This multisite study aimed to assess outcomes and associated risk factors among adults aged ≥60 years hospitalized with pneumonia. METHODS: Between December 2018 and March 2020, we enrolled ≥60-year-old adults admitted within 48 hours for CAP treatment across 16 public and private facilities in four sites. Clinical data and nasal/oropharyngeal specimens were collected by trained nurses and tested for influenza, respiratory syncytial virus (RSV), and other respiratory viruses (ORV) using the qPCR. Participants were evaluated regularly until discharge, as well as on the 7th and 30th days post-discharge. Outcomes included ICU admission and in-hospital or 30-day post-discharge mortality. A hierarchical framework for multivariable logistic regression and Cox proportional hazard models identified risk factors (e.g., demographics, clinical features, etiologic agents) associated with critical care or death. FINDINGS: Of 1,090 CAP patients, the median age was 69 years; 38.4% were female. Influenza viruses were detected in 12.3%, RSV in 2.2%, and ORV in 6.3% of participants. Critical care was required for 39.4%, with 9.9% in-hospital mortality and 5% 30-day post-discharge mortality. Only 41% of influenza CAP patients received antiviral treatment. Admission factors independently associated with ICU admission included respiratory rate >30/min, blood urea nitrogen>19mg/dl, altered sensorium, anemia, oxygen saturation <90%, prior cardiovascular diseases, chronic respiratory diseases, and private hospital admission. Diabetes, anemia, low oxygen saturation at admission, ICU admission, and mechanical ventilation were associated with 30-day mortality. CONCLUSION: High ICU admission and 30-day mortality rates were observed among older adults with pneumonia, with a significant proportion linked to influenza and RSV infections. Comprehensive guidelines for CAP prevention and management in older adults are needed, especially with the co-circulation of SARS-CoV-2.


Subject(s)
Hospitalization , Pneumonia , Humans , Female , Male , Aged , India/epidemiology , Middle Aged , Prospective Studies , Risk Factors , Pneumonia/epidemiology , Pneumonia/mortality , Pneumonia/virology , Community-Acquired Infections/epidemiology , Community-Acquired Infections/mortality , Community-Acquired Infections/virology , Aged, 80 and over , Hospital Mortality , Intensive Care Units
2.
J Genet ; 1022023.
Article in English | MEDLINE | ID: mdl-36722210

ABSTRACT

Congenital myasthenic syndromes (CMSs) are a diverse group of diseases that have an underlying defect in transmission of signals from nerve cells to muscles that lead to muscular weakness. A 13-year-old male child born of consanguineous parents with profound motor developmental delay and normal cognition was referred to us. The younger male sibling aged 9 months was similarly affected. Electromyography (EMG) and nerve conduction studies revealed CMS. Clinical exome sequencing revealed a novel large deletion including the exons 2 to 9 of SYT2 gene which confirmed the diagnosis of presynaptic CMS type 7 in the siblings. The deletion was confirmed on a chromosomal exon microarray. The parents were confirmed carriers of the same mutation and were normal on clinical and EMG studies. This is the second case of CMS type 7 described with a large deletion of SYT2 gene, a first case with SYT2 gene mutation from India and overall 10th recessive case in the world.


Subject(s)
Synaptotagmin II , Adolescent , Child , Humans , Male , Consanguinity , Electromyography , Exome Sequencing , Exons/genetics
3.
Math Biosci Eng ; 19(11): 11114-11136, 2022 08 03.
Article in English | MEDLINE | ID: mdl-36124583

ABSTRACT

Water resources in India's Indo-Gangetic plains are over-exploited and vulnerable to impacts of climate change. The unequal spatial and temporal variation of meteorological, hydrological and hydrogeological parameters has created additional challenges for field engineers and policy planners. The groundwater and surface water are extensively utilized in the middle Gangetic plain for agriculture. The primary purpose of this study is to understand the discharge and recharge processes of groundwater system using trend analysis, and surface water and groundwater interaction using groundwater modelling. A comprehensive hydrological, and hydrogeological data analysis was carried out and a numerical groundwater model was developed for Bhojpur district, Bihar, India covering 2395 km2 geographical area, located in central Ganga basin. The groundwater level data analyses for the year 2018 revealed that depth to water level varies from 3.0 to 9.0 meter below ground level (m bgl) in the study area. The M-K test showed no significant declining trend in the groundwater level in the study area. The groundwater modelling results revealed that groundwater head is higher in the southern part of the district and the groundwater flow direction is from south-west to north-east. The groundwater head fluctuation between the monsoon and the summer seasons was observed to be 2 m, it is also witnessed that groundwater is contributing more to rivers in the monsoon season in comparison with other seasons. Impact of reduction in pumping on groundwater heads was also investigated, considering a 10% reduction in groundwater withdrawal. The results indicated an overall head rise of 2 m in the southern part and 0.2-0.5 m in the middle and northern part of the district.


Subject(s)
Groundwater , Water , Environmental Monitoring/methods , Rivers , Water Supply
4.
Indian J Anaesth ; 66(5): 375-378, 2022 May.
Article in English | MEDLINE | ID: mdl-35782659

ABSTRACT

Epidural volume extension involves injection of normal saline into the epidural space soon after an intrathecal injection, with the aim of augmenting the sensory block height. It has significant dose-sparing effect, providing adequate level of anaesthesia and analgesia with minimal haemodynamic disturbances. We present this case series that shows the successful use of this technique in high risk cardiac patients coming for elective lower segment caesarean section.

5.
J Travel Med ; 29(6)2022 09 17.
Article in English | MEDLINE | ID: mdl-35900009

ABSTRACT

BACKGROUND: Covaxin/BBV152 is one of the most widely used vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and one of the few vaccines used extensively in low- and middle-income countries (LMIC). METHODS: We investigated the effect of Covaxin on the SARS-CoV-2 specific IgG and IgA and neutralizing antibody (NAb) levels at baseline (M0) and at Months 1 (M1), 2 (M2), 3 (M3), 4 (M4), 6 (M6) and 12 (M12) following vaccination in healthcare workers. In addition, we also examined the NAb levels against variant lineages of B.1.617.2 (Delta, India), B.1.617.2.1 (Delta Plus, India), B.1.351 (Beta, SA), B.1.1.7 (Alpha, UK) and B.1.1.529 (Omicron). RESULTS: Covaxin induces enhanced SARS-CoV-2 binding antibodies of IgG and IgA responses against both spike (S) and nucleocapsid (N) antigens at M1, M2, M3, M4, M6 and M12 in comparison with M0. Our data also reveal that NAb levels against the ancestral strain (Wuhan, wild type) are elevated and sustained at M1, M2, M3, M4, M6 and M12 in comparison with M0 and against variant lineages of B.1.617.2 (Delta, India), B.1.617.2.1 (Delta Plus, India), B.1.351 (Beta, SA) and B.1.1.7 (Alpha, UK) are elevated at M3, M6 and M12 in comparison with M0. However, NAb levels against B.1.1.529 (Omicron) was consistently below the limit of detection except at M12. CONCLUSION: Thus, Covaxin induces an enhanced humoral immune response, with persistence till at least 12 months post-vaccination against most SARS-CoV-2 variants.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunoglobulin A , Immunoglobulin G , SARS-CoV-2 , Vaccines, Inactivated
6.
Front Public Health ; 10: 836454, 2022.
Article in English | MEDLINE | ID: mdl-35444976

ABSTRACT

India witnessed a very strong second wave of coronavirus disease 2019 (COVID-19) during March and June 2021. Newly emerging variants of concern can escape immunity and cause reinfection. We tested newly diagnosed COVID-19 cases during the second wave in Chennai, India for the presence of Immunoglobulin G (IgG) antibodies to estimate the extent of re-infection. Of the 902 unvaccinated COVID-19 positive individuals, 53 (26.5%) were reactive for IgG antibodies and non-reactive for Immunogobulin M (IgM) antibodies. Among the 53 IgG-positive individuals, the interval between symptom onset (or last contact with the known case in case of asymptomatic) was <5 days in 29 individuals, ≥5 days in 11 individuals, while 13 asymptomatic individuals did not know their last contact with a positive case. The possible re-infections ranged between 3.2% (95% CI: 2.2-4.5%) and 4.3% (95% CI: 3.4-6.2%). The findings indicate that re-infection was not a major reason of the surge in cases during second wave. The IgG seropositivity among recently diagnosed unvaccinated COVID-19 patients could provide early indications about the extent of re-infections in the area.


Subject(s)
COVID-19 , COVID-19/epidemiology , Humans , Immunoglobulin G , India/epidemiology , Reinfection/epidemiology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2
7.
Preprint in English | medRxiv | ID: ppmedrxiv-22273859

ABSTRACT

BackgroundIndia experienced the second wave of the COVID-19 pandemic in March 2021, driven by the delta variant. Apprehensions around the usefulness of vaccines against delta variant posed a risk to the vaccination program. Therefore, we estimated the effectiveness of two doses of the ChAdOx1 nCoV-19 (Covishield) vaccine against COVID-19 infection among individuals [≥]45 years in Chennai, India. MethodsA community-based cohort study was conducted from May to September 2021 in a selected geographic area in Chennai, Tamil Nadu. The estimated sample size was 10,232. We enumerated individuals from all eligible households and periodically updated vaccination and COVID-19 infection data. We computed vaccine effectiveness with its 95% confidence interval for two doses of the Covishield vaccine against any COVID-19 infection. ResultsWe enrolled 69,435 individuals, of which 21,793 were above 45 years. Two dose coverage of Covishield in the 18+ and 45+ age group was 18% and 31%, respectively. The overall incidence of COVID-19 infection was 1099 per 100,000 population. The vaccine effectiveness against COVID-19 disease in the [≥]45 age group was 61.3% (95% CI: 43.6 - 73.4) at least two weeks after receiving the second dose of Covishield. Genomic analysis of 74 (28 with two doses, 15 with one dose, and 31 with zero dose) out of the 90 aliquots collected from the 303 COVID-19 positive individuals in the 45+ age group showed delta variants and their sub-lineages. ConclusionWe demonstrated the effectiveness of two doses of the ChAdOx1 vaccine against the delta variant in the general population of Chennai. We recommend similar future studies considering emerging variants and newer vaccines. Two-dose vaccine coverage could be ensured to protect against COVID-19 infection.

8.
Viruses ; 14(3)2022 03 02.
Article in English | MEDLINE | ID: mdl-35336918

ABSTRACT

Background: Examination of CD4+ T cell responses during the natural course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection offers useful information for the improvement of vaccination strategies against this virus and the protective effect of these T cells. Methods: We characterized the SARS-CoV-2-specific CD4+ T cell activation marker, multifunctional cytokine and cytotoxic marker expression in recovered coronavirus disease 2019 (COVID-19) individuals. Results: CD4+ T-cell responses in late convalescent (>6 months of diagnosis) individuals are characterized by elevated frequencies of activated as well as mono, dual- and multi-functional Th1 and Th17 CD4+ T cells in comparison to early convalescent (<1 month of diagnosis) individuals following stimulation with SARS-CoV-2-specific antigens. Similarly, the frequencies of cytotoxic marker expressing CD4+ T cells were also enhanced in late convalescent compared to early convalescent individuals. Conclusion: Our findings from a low-to middle-income country suggest protective adaptive immune responses following natural infection of SARS-CoV-2 are elevated even at six months following initial symptoms, indicating the CD4+ T cell mediated immune protection lasts for six months or more in natural infection.


Subject(s)
COVID-19 , CD4-Positive T-Lymphocytes , Humans , Immunity, Humoral , Lymphocyte Activation , SARS-CoV-2
9.
PLoS Med ; 18(12): e1003877, 2021 12.
Article in English | MEDLINE | ID: mdl-34890407

ABSTRACT

BACKGROUND: India began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India experienced a severe second wave of COVID-19 during March-June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs). METHODS AND FINDINGS: We did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test-adjusted seroprevalence of IgG antibodies against SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6-9 years, 5,798 (20%) were aged 10-17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. The weighted and test-adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged ≥6 years was 67.6% (95% CI 66.4% to 68.7%). Seroprevalence increased with age (p < 0.001) and was not different in rural and urban areas (p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey. CONCLUSIONS: Nearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June-July 2021 in India. As one-third of the population is still seronegative, it is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions.


Subject(s)
COVID-19/blood , COVID-19/epidemiology , COVID-19/immunology , Immunoglobulin G/blood , SARS-CoV-2 , Adolescent , Adult , Aged , Child , Cross-Sectional Studies , Female , Health Personnel , Humans , India/epidemiology , Male , Middle Aged , Prevalence , Rural Population , Urban Population , Young Adult
10.
Sci Rep ; 11(1): 20254, 2021 10 12.
Article in English | MEDLINE | ID: mdl-34642411

ABSTRACT

Monocytes are thought to play an important role in host defence and pathogenesis of COVID-19. However, a comprehensive examination of monocyte numbers and function has not been performed longitudinally in acute and convalescent COVID-19. We examined the absolute counts of monocytes, the frequency of monocyte subsets, the plasma levels of monocyte activation markers using flowcytometry and ELISA in seven groups of COVID-19 individuals, classified based on days since RT-PCR confirmation of SARS-CoV2 infection. Our data shows that the absolute counts of total monocytes and the frequencies of intermediate and non-classical monocytes increases from Days 15-30 to Days 61-90 and plateau thereafter. In contrast, the frequency of classical monocytes decreases from Days 15-30 till Days 121-150. The plasma levels of sCD14, CRP, sCD163 and sTissue Factor (sTF)-all decrease from Days 15-30 till Days 151-180. COVID-19 patients with severe disease exhibit higher levels of monocyte counts and higher frequencies of classical monocytes and lower frequencies of intermediate and non-classical monocytes and elevated plasma levels of sCD14, CRP, sCD163 and sTF in comparison with mild disease. Thus, our study provides evidence of dynamic alterations in monocyte counts, subset frequencies and activation status in acute and convalescent COVID-19 individuals.


Subject(s)
COVID-19/immunology , Monocytes , Acute Disease , Adolescent , Adult , Aged , Biomarkers/blood , Convalescence , Female , Humans , Leukocyte Count , Male , Middle Aged , Monocytes/cytology , Monocytes/immunology , Young Adult
11.
Indian J Med Res ; 153(5&6): 671-676, 2021 05.
Article in English | MEDLINE | ID: mdl-34528524

ABSTRACT

Background & objectives: Vaccination against SARS-CoV-2 is a recommendation from the World Health Organization as the foremost preference in the current situation to control the COVID-19 pandemic. BBV152 is one of the approved vaccines against SARS-CoV-2 in India. In this study, we determined SARS-CoV-2-specific antibody levels at day 0 (baseline, before vaccination), day 28 ± 2 post-first dose (month 1) and day 56 ± 2 post-first dose (month 2) of BBV152 whole-virion-inactivated SARS-CoV-2 recipients, and compared the antibody responses of individuals with confirmed pre-vaccination SARS-CoV-2 infection to those individuals without prior evidence of infection. Methods: Blood samples were collected from 114 healthcare professionals and frontline workers who received BBV152 vaccine from February to May & June 2021. Prior infection with SARS-CoV-2 was determined at baseline. Serum samples were used to estimate SARS-CoV-2 nucleoprotein-specific IgG [IgG (N)], spike protein-specific IgG [IgG (S)] and neutralizing antibodies (NAb). Results: Participants with previous SARS-CoV-2 infection after a single vaccine dose elicited IgG (N) and IgG (S) antibody levels along with NAb binding inhibition responses levels were similar to infection-naïve vaccinated participants who had taken two doses of vaccine. Interpretation & conclusions: Our preliminary data suggested that a single dose of BBV152-induced humoral immunity in previously infected individuals was equivalent to two doses of the vaccine in infection-naïve individuals. However, these findings need to be confirmed with large sized cohort studies.


Subject(s)
Antibody Formation , COVID-19 Vaccines , COVID-19 , Antibodies, Viral , Humans , Pandemics , Pilot Projects , SARS-CoV-2
12.
Indian J Med Res ; 153(5&6): 546-549, 2021 05.
Article in English | MEDLINE | ID: mdl-34528527

ABSTRACT

Background & objectives: Infection fatality ratio (IFR) is considered a more robust and reliable indicator than case fatality ratio for severity of SARS-CoV-2 infection. Age- and sex-stratified IFRs are crucial to guide public health response. Infections estimated through representative community-based serosurveys would gauge more accurate IFRs than through modelling studies. We describe age- and sex-stratified IFR for COVID-19 estimated through serosurveys conducted in Chennai, India. Methods: Two community-based serosurveys were conducted among individuals aged ≥10 yr during July and October 2020 in 51 of the 200 wards spread across 15 zones of Chennai. Total number of SARS-CoV-2 infections were estimated by multiplying the total population of the city aged ≥10 yr with the weighted seroprevalence and IFR was calculated by dividing the number of deaths with the estimated number of infections. Results: IFR was 17.3 [95% confidence interval (CI): 14.1-21.6] and 16.6 (95% CI: 13.8-20.2) deaths/10,000 infections during July and October 2020, respectively. Individuals aged 10-19 years had the lowest IFR [first serosurvey (R1): 0.2/10,000, 95% CI: 0.2-0.3 and second serosurvey (R2): 0.2/10,000, 95% CI: 0.1-0.2], and it increased with age and was highest among individuals aged above 60 yr (R1: 140.0/10,000, 95% CI: 107.0-183.8 and R2: 111.2/10,000, 95% CI: 89.2-142.0). Interpretation & conclusions: Our findings suggested that the IFR increased with age and was high among the elderly. Therefore, elderly population need to be prioritized for public health interventions including vaccination, frequent testing in long-term care facilities and old age homes, close clinical monitoring of the infected and promoting strict adherence to non-pharmaceutical interventions.


Subject(s)
COVID-19 , Aged , COVID-19/mortality , Female , Humans , India/epidemiology , Male , SARS-CoV-2 , Seroepidemiologic Studies
13.
Am J Trop Med Hyg ; 105(5): 1255-1260, 2021 09 27.
Article in English | MEDLINE | ID: mdl-34583334

ABSTRACT

It is essential to examine the longevity of the defensive immune response engendered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We examined the SARS-CoV-2-specific antibody responses and ex vivo memory B-cell subsets in seven groups of individuals with COVID-19 classified based on days since reverse-transcription polymerase chain reaction confirmation of SARS-CoV-2 infection. Our data showed that the levels of IgG and neutralizing antibodies started increasing from days 15 to 30 to days 61 to 90, and plateaued thereafter. The frequencies of naive B cells and atypical memory B cells decreased from days 15 to 30 to days 61 to 90, and plateaued thereafter. In contrast, the frequencies of immature B cells, classical memory B cells, activated memory B cells, and plasma cells increased from days 15 to 30 to days 61 to 90, and plateaued thereafter. Patients with severe COVID-19 exhibited increased frequencies of naive cells, atypical memory B cells, and activated memory B cells, and lower frequencies of immature B cells, central memory B cells, and plasma cells when compared with patients with mild COVID-19. Therefore, our data suggest modifications in memory B-cell subset frequencies and persistence of humoral immunity in convalescent individuals with COVID-19.


Subject(s)
Antibodies, Viral/blood , B-Lymphocyte Subsets/immunology , COVID-19/immunology , Convalescence , Memory B Cells/immunology , Acute Disease , Adolescent , Adult , Aged , Antibodies, Neutralizing/blood , Cross-Sectional Studies , Female , Humans , Immunity, Humoral , India , Male , Middle Aged , Young Adult
14.
Am J Trop Med Hyg ; 105(5): 1277-1280, 2021 08 09.
Article in English | MEDLINE | ID: mdl-34370710

ABSTRACT

We conducted a nationally representative population-based survey in 60 districts from 15 Indian states covering all five geographic regions during 2017-2018 to estimate the age specific seroprevalence of dengue. Of the 12,300 sera collected, 4,955 were positive for IgG antibodies against dengue virus using IgG Indirect ELISA indicating past dengue infection. We tested 4,948 sera (seven had inadequate volume) positive for IgG antibodies on indirect ELISA using anti-dengue IgG capture ELISA to estimate the proportion of dengue infections with high antibody titers, suggestive of acute or recent secondary infection. Of the 4,948 sera tested, 529 (10.7%; 95% CI: 9.4-12.1) were seropositive on IgG capture ELISA. The proportions of dengue infections with high titers were 1.1% in the northeastern, 1.5% in the eastern, 6.2% in the western, 12.2% in the southern, and 16.7% in the northern region. The distribution of dengue infections varied across geographic regions, with a higher proportion of infections with high antibody titer in the northern and southern regions of India. The study findings could be useful for planning facilities for clinical management of dengue infections.


Subject(s)
Antibodies, Viral/blood , Dengue/blood , Dengue/immunology , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G/blood , Population Surveillance , Adolescent , Adult , Child , Child, Preschool , Dengue/epidemiology , Female , Humans , India/epidemiology , Male , Middle Aged , Prevalence , Rural Population/statistics & numerical data , Seroepidemiologic Studies , Urban Population/statistics & numerical data , Young Adult
15.
JAC Antimicrob Resist ; 3(2): dlab066, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34223128

ABSTRACT

BACKGROUND: India is among the nations reporting substantial healthcare burden linked to pneumococcal infections. Nafithromycin is a novel lactone ketolide antibiotic, which recently entered Phase 3 development in India for the indication of community-acquired bacterial pneumonia (CABP). OBJECTIVES: To assess the in vitro activity of nafithromycin against serotyped invasive and non-invasive Streptococcus pneumoniae isolates, collected from nine medical centres across India. METHODS: A total of 534 isolates of S. pneumoniae were collected during 2015-20 and serotyped as per CDC protocol. A subset of erythromycin-non-susceptible S. pneumoniae (n = 200) was screened for the presence of erm(B) and mef(A/E) genes. A subset of MDR isolates (n = 54) were also subjected to MLST. The MICs of antibiotics were determined by the reference agar-dilution method (CLSI). Susceptibilities of the comparators were interpreted as per CLSI criteria. RESULTS: Fifty-nine distinct serotypes were identified among the 534 isolates. Among erythromycin-non-susceptible isolates, erm(B) and mef(A/E) genes were found in 49% and 59% strains respectively, while MLST showed clonal diversity. Azithromycin (67.6% non-susceptible) and clindamycin (31.8% non-susceptible) showed limited activity. Penicillin (for non-meningitis) or quinolone non-susceptibility was low (<11% and <6%, respectively). Nafithromycin showed potent activity with MIC50 and MIC90 of 0.015-0.03 and 0.06 mg/L, respectively, regardless of the macrolide resistance mechanisms. CONCLUSIONS: Indian pneumococcal isolates show poor susceptibilities to macrolides, in concordance with the global trend. Nafithromycin overcomes erm as well as mef-mediated macrolide resistance mechanisms expressed individually or concurrently in S. pneumoniae. This study supports continued clinical development of nafithromycin for pneumococcal infections including CABP.

16.
BMC Public Health ; 21(1): 1412, 2021 07 16.
Article in English | MEDLINE | ID: mdl-34271883

ABSTRACT

BACKGROUND: Antimicrobial resistance is a global health emergency. Persons colonized with multidrug-resistant organisms (MDROs) are at risk for developing subsequent multidrug-resistant infections, as colonization represents an important precursor to invasive infection. Despite reports documenting the worldwide dissemination of MDROs, fundamental questions remain regarding the burden of resistance, metrics to measure prevalence, and determinants of spread. We describe a multi-site colonization survey protocol that aims to quantify the population-based prevalence and associated risk factors for colonization with high-threat MDROs among community dwelling participants and patients admitted to hospitals within a defined population-catchment area. METHODS: Researchers in five countries (Bangladesh, Chile, Guatemala, Kenya, and India) will conduct a cross-sectional, population-based prevalence survey consisting of a risk factor questionnaire and collection of specimens to evaluate colonization with three high-threat MDROs: extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCrE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Healthy adults residing in a household within the sampling area will be enrolled in addition to eligible hospitalized adults. Colonizing isolates of these MDROs will be compared by multilocus sequence typing (MLST) to routinely collected invasive clinical isolates, where available, to determine potential pathogenicity. A colonizing MDRO isolate will be categorized as potentially pathogenic if the MLST pattern of the colonizing isolate matches the MLST pattern of an invasive clinical isolate. The outcomes of this study will be estimates of the population-based prevalence of colonization with ESCrE, CRE, and MRSA; determination of the proportion of colonizing ESCrE, CRE, and MRSA with pathogenic characteristics based on MLST; identification of factors independently associated with ESCrE, CRE, and MRSA colonization; and creation an archive of ESCrE, CRE, and MRSA isolates for future study. DISCUSSION: This is the first study to use a common protocol to evaluate population-based prevalence and risk factors associated with MDRO colonization among community-dwelling and hospitalized adults in multiple countries with diverse epidemiological conditions, including low- and middle-income settings. The results will be used to better describe the global epidemiology of MDROs and guide the development of mitigation strategies in both community and healthcare settings. These standardized baseline surveys can also inform future studies seeking to further characterize MDRO epidemiology globally.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Adult , Bangladesh , Chile , Cross-Sectional Studies , Drug Resistance, Multiple, Bacterial , Guatemala , Hospitals , Humans , India , Kenya , Multilocus Sequence Typing , Prevalence , Staphylococcal Infections/drug therapy , Staphylococcal Infections/epidemiology
17.
Vaccine ; 39(28): 3737-3744, 2021 06 23.
Article in English | MEDLINE | ID: mdl-34074545

ABSTRACT

INTRODUCTION: A hospital-based sentinel surveillance network for bacterial meningitis was established in India to estimate the burden of bacterial meningitis, and the proportion of major vaccine-preventable causative organisms. This report summarises the findings of the surveillance conducted between March 2012, and September 2016 in eleven hospitals. METHODS: We enrolled eligible children with bacterial meningitis in the age group of one to 59 months. CSF samples were collected and processed for biochemistry, culture, latex agglutination, and real-time PCR. Pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. RESULTS: Among 12 941 enrolled suspected meningitis cases, 586 (4.5%) were laboratory confirmed. S. pneumoniae (74.2%) was the most commonly detected pathogen, followed by H. influenzae (22.2%), and N. meningitidis (3.6%). Overall 58.1% of confirmed bacterial meningitis cases were children aged between one, and 11 months. H. influenzae meningitis cases had a high (12.3%) case fatality rate. The serotypes covered in PCV13 caused 72% pneumococcal infections, and the most common serotypes were 14 (18.3%), 6B (12.7%) and 19F (9.9%). Non-susceptibility to penicillin was 57%. Forty-five (43.7%) isolates exhibited multidrug resistance, of which 37 were PCV13 serotype isolates. CONCLUSIONS: The results are representative of the burden of bacterial meningitis among under-five children in India. The findings were useful in rolling out PCV in the National Immunization Program. The non-susceptibility to penicillin and multidrug resistance was an important observation. Timely expansion of PCV across India will significantly reduce the burden of antimicrobial resistance. Continued surveillance is needed to understand the trend after PCV expansion in India.


Subject(s)
Meningitis, Bacterial , Pneumococcal Infections , Child , Child, Preschool , Hospitals , Humans , India/epidemiology , Infant , Meningitis, Bacterial/epidemiology , Pneumococcal Vaccines , Sentinel Surveillance , Serogroup , Serotyping
18.
Int J Infect Dis ; 108: 145-155, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34022338

ABSTRACT

BACKGROUND: Earlier serosurveys in India revealed seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) of 0.73% in May-June 2020 and 7.1% in August-September 2020. A third serosurvey was conducted between December 2020 and January 2021 to estimate the seroprevalence of SARS-CoV-2 infection among the general population and healthcare workers (HCWs) in India. METHODS: The third serosurvey was conducted in the same 70 districts as the first and second serosurveys. For each district, at least 400 individuals aged ≥10 years from the general population and 100 HCWs from subdistrict-level health facilities were enrolled. Serum samples from the general population were tested for the presence of immunoglobulin G (IgG) antibodies against the nucleocapsid (N) and spike (S1-RBD) proteins of SARS-CoV-2, whereas serum samples from HCWs were tested for anti-S1-RBD. Weighted seroprevalence adjusted for assay characteristics was estimated. RESULTS: Of the 28,598 serum samples from the general population, 4585 (16%) had IgG antibodies against the N protein, 6647 (23.2%) had IgG antibodies against the S1-RBD protein, and 7436 (26%) had IgG antibodies against either the N protein or the S1-RBD protein. Weighted and assay-characteristic-adjusted seroprevalence against either of the antibodies was 24.1% [95% confidence interval (CI) 23.0-25.3%]. Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI 23.5-27.8%). CONCLUSIONS: Nearly one in four individuals aged ≥10 years from the general population as well as HCWs in India had been exposed to SARS-CoV-2 by December 2020.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Health Personnel , Humans , Seroepidemiologic Studies
19.
Virus Res ; 300: 198439, 2021 07 15.
Article in English | MEDLINE | ID: mdl-33930486

ABSTRACT

Hepatitis B is a major co-infection among people with HIV (PWHIV) worldwide. There is a paucity of data on HBV genetic diversity in India, which would be useful for targeted preventive and management interventions. To characterize the distribution of HBV genotypes and sub-genotypes, samples of 180 HIV-HBV co-infected individuals from a study previously conducted to estimate the prevalence of HBV co-infection were analyzed. Nested PCR using type-specific primers was used to identify the various HBV genotypes. Partial HBV S sequences were generated for a subset of samples using Sanger sequencing. Mutation analysis was done using the online HBVseq program. PCR based genotyping documented D (69.4 %) and A (5.6 %) to be the major genotypes in the study population. Infection with multiple genotypes was observed in 25 % co-infected individuals. D2, D5, A2, and A1 were the sub-genotypes detected. Mutations 184K and 173L were identified. HBV genotypes/ sub-genotypes play a pivotal role in the clinical outcome of chronic hepatitis B (CHB). Therefore, monitoring of CHB cases is needed to track disease progression, including early detection of hepatocellular carcinoma.


Subject(s)
Coinfection , HIV Infections , Hepatitis B, Chronic , Hepatitis B , Coinfection/epidemiology , DNA, Viral/genetics , Genotype , HIV Infections/complications , HIV Infections/epidemiology , Hepatitis B/complications , Hepatitis B/epidemiology , Hepatitis B virus/genetics , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/epidemiology , Humans , India/epidemiology , Molecular Epidemiology , Mutation
20.
Indian Pediatr ; 58(2): 134-137, 2021 02 15.
Article in English | MEDLINE | ID: mdl-33632942

ABSTRACT

OBJECTIVE: To describe the clinical profile of children with syncope. METHODS: Hospital records were reviewed for clinical and laboratory details of children presenting with real or apparent syncope. Five diagnostic categories were identified: neurocardiogenic syncope (NCS), psychogenic pseudosyncope (PPS), cardiac, neurological and indeterminate. RESULTS: 30 children (aged 4 to 17 years)were included. The commonest cause of syncope was NCS (63.3%), followed by PPS (13.3%), cardiac (10%), neurological (10%) and indeterminate (3.3%). Exercise, loud noise or emotional triggers and family history were associated with cardiac etiology, and electrocardiogram (ECG) was diagnostic in the majority. Children with PPS and cardiacsyncope had frequent episodes when compared with other groups. Indiscriminate antiepileptic use was found in 5 children, including two cardiac cases. CONCLUSIONS: Frequent recurrences of syncope may suggest PPS or cardiac cause. Cardiac etiology may be readily identified on history and ECG alone.


Subject(s)
Electrocardiography , Syncope , Child , Humans , Recurrence , Syncope/diagnosis , Syncope/epidemiology , Syncope/etiology
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