Vaccination coverage and breakthrough infections of COVID-19 during the second wave among staff of selected medical institutions in India.

India experienced the second wave of SARS-CoV-2 infection from April 3 to June 10, 2021. During the second wave, Delta variant B.1617.2 emerged as the predominant strain, spiking cases from 12.5 million to 29.3 million (cumulative) by the end of the surge in India. Vaccines against COVID-19 are a potent tool to control and end the pandemic in addition to other control measures. India rolled out its vaccination programme on January 16, 2021, initially with two vaccines that were given emergency authorization-Covaxin (BBV152) and Covishield (ChAdOx1 nCoV- 19). Vaccination was initially started for the elderly (60+) and front-line workers and then gradually opened to different age groups. The second wave hit when vaccination was picking up pace in India. There were instances of vaccinated people (fully and partially) getting infected, and reinfections were also reported. We undertook a survey of staff (front line health care workers and supporting) of 15 medical colleges and research institutes across India to assess the vaccination coverage, incidence of breakthrough infections, and reinfections among them from June 2 to July 10, 2021. A total of 1876 staff participated, and 1484 forms were selected for analysis after removing duplicates and erroneous entries (n = 392). We found that among the respondents at the time of response, 17.6% were unvaccinated, 19.8% were partially vaccinated (received the first dose), and 62.5% were fully vaccinated (received both doses). Incidence of breakthrough infections was 8.7% among the 801 individuals (70/801) tested at least 14 days after the 2nd dose of vaccine. Eight participants reported reinfection in the overall infected group and reinfection incidence rate was 5.1%. Out of (N = 349) infected individuals 243 (69.6%) were unvaccinated and 106 (30.3%) were vaccinated. Our findings reveal the protective effect of vaccination and its role as an essential tool in the struggle against this pandemic.

Molecular detection of Orientia tsutsugamushi strains circulating in Nagaland.

The antigenic heterogeneity of Orientia in India is still unknown in many disease endemic areas. The present study aims to characterize the strains of O. tsutsugamushi circulating in Nagaland, Northeast India. Two patients clinically diagnosed with ST and hospitalized in Mon district hospital, Nagaland were identified from whom eschar tissues were collected. Both patients demonstrated antibodies against O. tsutsugamushi along with positive PCR amplification for 56 â€‹kDa gene. The prototype strain TA763 shared 90.4% homology with the sequences. Both the sequences formed a distinctive cluster demonstrating 100% similarity with strains identified from Thailand, Vietnam, China and southern parts of India.

Rickettsiae in fleas infesting domestic pets of eastern Himalayan terrains of India.

BACKGROUND: Flea-borne rickettsioses have been limitedly explored in the Indian sub-Himalayan belt, including the North Eastern Region (NER) of India. This study investigates the presence of rickettsiae hosts and their probable pathogens in the disease-endemic hilly state of the NER of India. METHODS: Entomological surveys were carried out in disease-reporting localities in a hilly state in India. Fleas collected from domesticated animals were processed for detection of a Rickettsia-specific 17-kDa gene. RESULTS: Sequence analysis revealed Rickettsia felis in six flea pools (40%), Candidatus Rickettsia senegalensis in two pools (13.3%) and Rickettsia asembonensis in one pool (6.6%). CONCLUSIONS: Our findings suggest Ctenocephalides felis, Ctenocephalides canis and Pulex irritans as potential carriers of R. felis and R. felis-like organisms in India.

Effectiveness of a single dose of Japanese encephalitis vaccine among adults, Assam, India, 2012-2018.

BACKGROUND: Japanese encephalitis virus (JEV) remains the major etiology of encephalitis throughout Asia. In India, the state of Assam alone contributes more than one-third of the national burden of JE. Between 2011 and 2014, a single dose of JE vaccine SA 14-14-2 (LAJEV) was administered among adults aged 15-65 years residing in Sivasagar and Dibrugarh districts of Assam, India. We monitored the trend of JE incidence between 2009 and 2018 using JE surveillance data, estimated the long-term effectiveness of the single dose of LAJEV and estimated the coverage of JE vaccine in two districts. METHODS: We compared the JE vaccination status of laboratory-confirmed hospitalized JE patients (case) and age, sex and locality matched healthy individuals (controls) to estimate the effectiveness of single dose of JE vaccine. We used surveillance data for 2009-2018 to calculate the incidence of JE among adults. We conducted a community-based survey to estimate the coverage of JE vaccine in the two districts. RESULTS: A total of 452 laboratory-confirmed JE case-patients and 904 matched healthy controls were enrolled in the study between 2012 and 2018. The effectiveness of a single dose of JE vaccine over the 7-year period was 77.0 (95% CI: 67.0-83.0). Vaccine effectiveness decreased from 91% (95% CI: 73.0-97.0) in first year of vaccination to 71% (95% CI: 21.0-90.0) at six years post-vaccination. The incidence of adults JE cases declined from 10.5 per 100,000 in the pre-vaccination period to 5.7 per 100,000 in the years following vaccination. The coverage of vaccine among adults in two districts was 40.1% (36.8-43.5). CONCLUSIONS: A single dose of JE vaccine offered adequate protection for at least six years. Conducting mass vaccination campaigns periodically would further reduce the incidence of JE in endemic districts in Assam.

Seroprevalence of Rickettsial Infections in Northeast India: A Population-Based Cross-Sectional Survey.

A cross-sectional survey was undertaken to estimate seroprevalence of immunoglobulin G antibodies against scrub typhus, spotted fever group rickettsiae, and typhus group rickettsiae in randomly selected 48 clusters in 12 districts of 3 Northeast states of India: Assam, Meghalaya, and Tripura. Individuals in 3 age groups (5-8, 9-17, and 18-45 years) were selected from each cluster. Sera (N = 2360) tested were collected as part of a national survey on dengue seroprevalence conducted between September 2017 and February 2018. Overall, seroprevalence of 2.5% was detected against rickettsioses, with highest positivity against spotted fever group rickettsiae, followed by scrub typhus and typhus group rickettsiae. Seroprevalence was highest in Tripura (3.7%), followed by Assam (2.6%) and Meghalaya (1.04%). Adults of 18 to 45 years of age were found to be most affected (3.8%). The study findings indicate the need for increasing testing facilities for active case detection at hospital levels. Efforts on implementing effective preventing strategies are suggested to be targeted in disease-specific endemic foci.

Spotted Fever Group Rickettsiae among Children with Acute Febrile Illness, in Gorakhpur, India.

Seasonal outbreaks of acute encephalitis syndrome have been occurring in Gorakhpur division in the Indian state of Uttar Pradesh during monsoon and post-monsoon months. Orientia tsutsugamushi was identified as the major aetiology of these outbreaks. Orientia tsutsugamushi was also identified as one of the important aetiology of febrile illness among children attending peripheral health facilities. The present study was undertaken to detect antibodies against spotted fever group rickettsiae (SFGR) and typhus group rickettsiae (TGR) among children with acute febrile illness presenting at peripheral health facilities in Gorakhpur district. Of the 224 blood samples tested, SFGR infection was detected in 13 (6%) patients. None of the samples tested positive for TGR.

Experimental study of dengue virus infection in Aedes aegypti and Aedes albopictus: A comparative analysis on susceptibility, virus transmission and reproductive success.

Epidemiology of dengue fever has substantially changed over the years with respect to prevalent strains, affected geographical locations and severity of disease. Mosquito vectors show variable response in terms of susceptibility to four different serotypes of dengue virus. Although studies have postulated that, the vectors Ae. aegypti and Ae. albopictus are crucial for transmission of dengue virus, comparative efficacy of these species for viral transmission and tolerance is still enigmatic. In this study, these two vectors were infected orally with four serotypes of the dengue virus viz. DENV-1 to DENV-4 and their co-infection. It was observed that Ae. aegypti harbors multiple serotype infections more efficiently than Ae. albopictus. We suggest that transovarial transmission is of low importance in the epidemiology of the virus due to low infection rates in the filial generation, and also that reduced fecundity and fertility in both vectors after dengue virus infection affect the ecology of the pathogen.

Dengue virus serotypes and genotypic characterization from northeast India.

Dengue is a rapidly spreading acute arboviral infection transmitted through a human and Aedes mosquito cycle. Though northeast region of India has been experiencing dengue outbreaks regularly for over a decade, reports on genetic characterization of the virus from this region are limited. The present study was undertaken to detect the genotype and genetic composition of circulating dengue virus (DENV) in this region. Blood samples were collected from 918 suspected dengue patients of five northeast Indian states. Serological investigations, viz, nonstructural 1 (NS1) enzyme-linked immunosorbent assay (ELISA), immunoglobulin M (IgM) ELISA, and immunoglobulin G (IgG) ELISA were performed followed by molecular detection. Sequence analysis and phylogenetic tree construction based on capsid-premembrane (C-prM) gene junction was done by BioEdit and MEGA6 software, respectively. Serological detection showed 35.34% NS1 and 18.12% IgM positivity. Secondary infection was observed in 24.53%. All four serotypes were detected. Phylogenetic analysis demonstrated circulation of genotype III of DENV-1, genotype IV of DENV-2, and genotype III of DENV-3. Sequences from this region form distinct clades in the phylogenetic tree. Characterization of the C-prM gene junction reveals divergence among the DENV strains. As genetic variation within the DENV is known to be associated with diverse clinical outcomes, information regarding the genetic composition of circulating virus could be beneficial in designing an effective intervention strategy.

Effectiveness of Japanese encephalitis SA 14-14-2 live attenuated vaccine among Indian children: Retrospective 1:4 matched case-control study.

OBJECTIVES: We estimate the effectiveness of Japanese encephalitis (JE) SA 14-14-2 live-attenuated vaccination single dose campaign among children aged 1-15 years in India during 2006-07. METHODS: Acute encephalitis syndrome (AES) cases hospitalized following vaccination campaigns during the years 2006-08 were investigated retrospectively. The laboratory-confirmed JE cases were detected from the surveillance laboratories based on anti-JE IgM antibody by ELISA or viral RNA detection by RT-PCR in sera or cerebrospinal fluid. Consent was sought from parents or guardians. Four community controls were chosen randomly per case during house-to-house survey employing individual matching on age, gender and residence during the risk period. Vaccination history was enquired from the child's guardian and verified from vaccination card at home or records at health centre. Conditional logistic regression was conducted on matched case-control sets. RESULTS: We studied 149 cases and matched 596 controls. Vaccination effectiveness was 43.8% (95% CI, 1.9-67.8) based on vaccination card or record. However, effectiveness was 72.2% (95% CI, 56.2-82.4) based on parental history or card/record. Vaccination effectiveness in Assam state was higher than in Uttar Pradesh state. CONCLUSIONS: We concluded that the single subcutaneous dose of SA 14-14-2 JE vaccine provided moderate effectiveness in Indian children.

Enhanced cytopathic effect of Japanese encephalitis virus strain SA14-14-2: Probable association of mutation in amino acid of its envelope protein.

Japanese encephalitis (JE) is a mosquito-borne viral disease. It is a global public health concern since it causes an acute encephalitis syndrome (AES). A large number of JE/AES cases are reported to occur in areas with established or developing JE vaccination program. Partial vaccine coverage and emergence of new variants of Japanese encephalitis virus (JEV) might be playing an important role. The envelope protein (E) of JEV is a major antigenic determinant and responsible for immunogenic responses as well as membrane fusion and virion assembly. In the present study, we have characterized the JEV live attenuated vaccine strain SA14-14-2 in baby hamster kidney cells (BHK-21). The vaccine strain showed enhanced replication following its passage in BHK-21 cells. Nucleotide sequence analysis of the E protein gene of the cell-culture adapted vaccine strain showed an important point mutation. The mutation in the E protein gene was identical to its wild-type parent strain SA14. This study suggests the possibility of reversion mutation and exaltation of vaccine strains following adaptation in the host cells.

Detection of West Nile virus in six mosquito species in synchrony with seroconversion among sentinel chickens in India.

BACKGROUND: West Nile virus (WNV) is a zoonotic flavivirus maintained in mosquito-bird transmission cycle. Although humans are accidental hosts, fatal outcomes following WNV infection have been reported from India. Studies have identified WNV as an important etiological agent causing acute encephalitis syndrome in Assam, Northeast India. While circulation of WNV is evident, the role of vectors and avian hosts involved in the transmission remains unclear. In this study we identified local mosquito species for evidence of WNV infection along with seroconversion among sentinel chickens. METHODS: Mosquitoes were collected and pooled species wise from June 2014 through December 2015. Virus was screened using reverse transcriptase PCR followed by sequencing and phylogenetic analysis. Sentinel chicken blood was screened for WNV antibody to assess their role in WNV transmission. RESULTS: A total of 52,882 mosquitoes belonging to 16 species were collected. WNV was detected in 18 pools of Culex vishnui, Culex tritaeniorhynchus, Culex quinquefasciatus, Culex whitmorei, Culex pseudovishnui and Mansonia uniformis. Phylogenetic analysis revealed that all mosquito derived sequences belonged to Lineage 5 and were 99-100% similar to the Assam strain of WNV isolated from human CSF sample in 2007. All sentinel chickens had seroconverted by the month of July that happens to be the peak WNV transmission month among humans as well. CONCLUSION: To the best of our knowledge, this is the first report of WNV identification from field-collected Cx. pseudovishnui and Mansonia uniformis in India. Our study demonstrates potential vectors which may play a crucial role in WNV transmission and should be considered in the vector control strategies. Additionally, our study highlights the role of sentinel chickens for WNV surveillance.

Scrub Typhus Leading to Acute Encephalitis Syndrome, Assam, India.

To determine the contribution of Orientia tsutsugamushi, the agent of scrub typhus, as a cause of acute encephalitis syndrome (AES) in Assam, India, we conducted a retrospective study of hospital patients with symptoms of AES during 2013-2015. Our findings suggest that O. tsutsugamushi infection leads to AES and the resulting illness and death.

Comparison of ß-Propiolactone and Formalin Inactivation on Antigenicity and Immune Response of West Nile Virus.

West Nile Virus (WNV) is a pathogenic arbovirus that belongs to genus Flavivirus under family Flaviviridae. Till now there are no approved vaccines against WNV for human use. In this study, the effect of two alkylating agents, formaldehyde and ß-PL, generally used for inactivated vaccine preparation, was assessed on the basis of antigenic and immunogenic potential of the inactivated WNV. Lineage 5 WNV isolates were inactivated by both formalin and ß-PL treatments. Inactivation was confirmed by repeated passage in BHK-21 cell line and infant mice. Viruses inactivated by both the treatments showed higher antigenicity. Immune response in mice model showed serum anti-WNV antibody titre was moderately higher in formalin inactivated antigen compared to ß-PL inactivated antigen. However, no significant differences were observed in neutralization antibody titre. In conclusion, we can state that both formaldehyde and ß-PL inactivation processes were found to be equally efficient for inactivation of WNV. However, they need to be compared with other inactivating agents along with study on cell mediated immune response.

Characterization of Japanese encephalitis virus (JEV) genotype III clinical isolates in northeast India.

BACKGROUND: Japanese encephalitis virus (JEV) is one of the major etiological agents responsible for causing large numbers of acute encephalitis syndrome (AES) cases in the northeastern region of India. This study was carried out to establish and characterize the circulating strain of JEV in the region in order to understand the disease epidemiology. METHODS: Virus isolation was attempted from 121 patients that presented with AES. Phylogenetic analysis was done using the Kimura-2-Parameter model based on envelope and pre-membrane gene sequence. A pathogenecity study was done in the Swiss albino mice model and assessed by Kaplan-Meier survival analysis. RESULTS: The phylogenetic analysis of the two JEV isolates obtained placed them within genotype (G)III, where they form a subclade within the Vellore group of Indian JEV strains. Neutralization assays suggested similarity between the study isolates and prototype Vellore JEV strain P20778. Pathogenesis in mice suggested that the circulating GIII JEV strains were neuroinvasive. CONCLUSIONS: This study showed that a pathogenic GIII JEV strain was circulating in the northeastern region of India. This finding is important as it is contrary to the belief that GI is gradually replacing GIII as the dominant genotype in Asia. GenBank accession numbers: HQ270470, JQ434468, HQ246155, JX018170.

Forecasting Japanese encephalitis incidence from historical morbidity patterns: Statistical analysis with 27 years of observation in Assam, India.

BACKGROUND & OBJECTIVES: Japanese encephalitis (JE) is one of the dreaded mosquito-borne viral diseases mostly prevalent in south Asian countries including India. Early warning of the disease in terms of disease intensity is crucial for taking adequate and appropriate intervention measures. The present study was carried out in Dibrugarh district in the state of Assam located in the northeastern region of India to assess the accuracy of selected forecasting methods based on historical morbidity patterns of JE incidence during the past 22 years (1985-2006). METHODS: Four selected forecasting methods, viz. seasonal average (SA), seasonal adjustment with last three observations (SAT), modified method adjusting long-term and cyclic trend (MSAT), and autoregressive integrated moving average (ARIMA) have been employed to assess the accuracy of each of the forecasting methods. The forecasting methods were validated for five consecutive years from 2007-2012 and accuracy of each method has been assessed. RESULTS: The forecasting method utilising seasonal adjustment with long-term and cyclic trend emerged as best forecasting method among the four selected forecasting methods and outperformed the even statistically more advanced ARIMA method. Peak of the disease incidence could effectively be predicted with all the methods, but there are significant variations in magnitude of forecast errors among the selected methods. As expected, variation in forecasts at primary health centre (PHC) level is wide as compared to that of district level forecasts. INTERPRETATION & CONCLUSION: The study showed that adopted forecasting techniques could reasonably forecast the intensity of JE cases at PHC level without considering the external variables. The results indicate that the understanding of long-term and cyclic trend of the disease intensity will improve the accuracy of the forecasts, but there is a need for making the forecast models more robust to explain sudden variation in the disease intensity with detail analysis of parasite and host population dynamics.

Dengue outbreak in a hilly state of Arunachal Pradesh in Northeast India.

Dengue has been reported from plains as well as hilly regions of India including some parts of Northeast India. In July-August 2012, outbreak of fever with unknown origin (FUO) indicative of Dengue was reported in Pasighat, East Siang district of Arunachal Pradesh (AP) state. Serum samples (n = 164) collected from patients from Health Training and Research Centre General Hospital, Pasighat, were tested for NS1 antigen and IgM antibodies. NS1-positive samples were analyzed by RT-PCR assay and entomological surveys were carried out. The majority of suspected cases reported NS1 antigen positivity. Females and young adults were mostly affected. The majority of the amplified NS1-positive samples showed Dengue serotype 3 infection. Aedes (Stegomyia) albopictus, known as semiurban breeding mosquitoes, was the only potential vector species identified from the affected areas of Pasighat which single handedly contributed to the outbreak. Thus, the present work identifies Dengue as an emerging arboviral infection in hilly state of AP along with a looming risk of its spread to neighbouring areas.