Serum ferritin level as a prognostic biomarker for predicting dengue disease severity: A systematic review and meta-analysis.

Serum ferritin levels serves as biomarkers in many inflammatory and infectious diseases. This current systematic review and meta-analysis evaluated whether serum ferritin levels are associated with severe dengue and its utility as a biomarker of disease severity. Literature searches were conducted in PubMed, Scopus, ScienceDirect, the Cochrane library, and Google Scholar. A total of 18 studies examining the serum ferritin levels in dengue cases in the context of disease severity (nine studies having dengue classification as non-severe vs. severe dengue cases, and nine studies having dengue classification as dengue without warning signs (DwoWS), dengue with warning signs (DwWS), and severe dengue cases) were included and the quality of the studies was assessed using the Quality in Prognostic Factor Studies tool. The meta-analysis was performed using STATA software to calculate the effect size as a standardized mean difference (SMD) or Hedges 'g' for the continuous outcome. Higher serum ferritin levels were found in severe dengue cases compared to non-severe cases [SMD (Hedges 'g') 4.05 (95% C.I. 2.09-6.00), (I2  = 98.8%)]. In the second group, DwWS cases showed high serum ferritin levels compared to DwoWS [SMD 2.01 (95% C.I. 0.92-3.10), (I2  = 97.89%)], and severe dengue cases showed higher levels of serum ferritin compared to DwWS [SMD 2.66 (95% C.I. 1.72-4.48), (I2  = 98.78%)] and DwoWS cases [SMD 6.65 (95% C.I. 1.72-11.59), (I2  = 99.78%]. Subgroup analysis for the country of study (India vs. others), ferritin testing methods, and ferritin measurement day revealed testing method as a significant contributor to heterogeneity. To conclude, the present study suggests serum ferritin as a prognostic marker for dengue disease severity. Multi-centric studies involving a large number of dengue patients with a uniform case definition accounting for all the confounding variables might help in determining a universal cut-off value to discriminate between non-severe and severe dengue.

Understanding the resurgence of chikungunya virus during 2020-2021 in Pune, India, based on genomic analyses: A seven year study.

A surge in chikungunya was observed during 2020-21 in Pune district of Maharashtra, India. Whole genome sequencing and phylogenetic analysis of 21 samples/sequences revealed them as Indian ocean lineage of East Central South African genotype. Two distinct sequence clusters were found to circulate during 2020-21; one with E1:K211E and E2:V264A mutations while the other had E1:I317V mutation along with E1:K211E and E2: V264A mutations. The former, the predominant cluster (n = 18), clustered with chikungunya virus (CHIKV) strains of pre 2014 period while the latter (n = 3) clustered with 2016-2018 period Indian strains. Though E1: A226V was not detected in any of the 21 sequences, several unique mutations were detected in the strains which might have played key roles in the enhanced virus transmission during the period. The study highlights parallel evolution, introduction from the neighboring regions and cocirculation of two sequence clusters of CHIKV in Pune. The complete genome data can be useful to determine how the circulating strains differ from candidate vaccines and might help to predict the protective efficacy of chikungunya vaccine candidates.

Cost estimation of COVID Kavach test developed in 2020: A National Reference Laboratory initiative during early phase of Indian pandemic mitigation.

BACKGROUND OBJECTIVES: A new indigenously developed technology, coronavirus disease (COVID) Kavach, an IgG immunoglobulin-based enzyme-linked immunosorbent assay (ELISA) kit, was developed in 2020 by the Indian Council of Medical Research-National Institute of Virology (ICMR-NIV), Pune, India. The primary objective of this study was to determine the total cost of development of COVID Kavach IgG ELISA and estimate the unit cost (UC) as well. METHODS: The total development cost (TDC) of COVID Kavach and its UC during the early phase of pandemic mitigation were estimated through a micro-costing approach from provider's perspective. An activity-based bottom-up costing approach was used to facilitate data collection from all resources, and analysis was performed using Microsoft Excel version 2016. The micro-costing data were utilized to interpret the breakdown of cost across all inputs and different levels of activity. RESULTS: The TDC of COVID Kavach was estimated to be JOURNAL/ijmer/04.03/02223309-202310000-00007/363FF04/v/2023-11-25T134903Z/r/image-tiff 2,884,032 (US$ 38,265). The UC of providing test results for exposure to severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) was estimated to be JOURNAL/ijmer/04.03/02223309-202310000-00007/363FF04/v/2023-11-25T134903Z/r/image-tiff 300 (US$ 4) during July 2020. The capital and recurrent cost were incurred around 5-10 per cent and 90-95 per cent, respectively, in both the development and UC of COVID Kavach. The major portion of funds (70-80%) was utilized for procurement of laboratory consumables, followed by human resources (8-12%) in the development as well as for UC of COVID Kavach. INTERPRETATION CONCLUSIONS: The estimates from this study can be useful for conducting economic evaluations, which will help in deciding upon the subsidy in government health facilities. The data may be useful to set up laboratory facilities analogous to the National Reference Laboratory located at the ICMR-NIV, Pune and for allotting sufficient budget to develop such assays in government-funded laboratories.

Outbreaks and sporadic cases of japanese encephalitis in the state of Odisha, India: Outcome of 7 years of laboratory surveillance.

Acute encephalitis syndrome (AES) is a major public health challenge in India. We report here the epidemiology of sporadics and outbreaks of Japanese Encephalitis (JE) in Odisha state during 2012-2018. A total of 4235 AES cases (sporadics - 3394, outbreak cases - 841) recorded including 42 outbreaks; majority (n = 18) of which were during 2016. Overall JE virus (JEV) positivity was 11.78% (outbreak cases - 24.5%, sporadic cases - 8.6%). Age ≤15 years were largely affected during outbreaks, while 16-60 years population was dominant among sporadics. The major outbreak (2016) involved 336 patients from a tribal dominated district, spread over 173 villages. JEV seropositivity was high (43.45%) with 28.57% mortality. Epidemiological linkage with pig rearing was documented through JEV neutralizing antibodies in 50% of pig serum samples. Although the postvaccination period (2017-18) showed increase in AES case reporting but low JE proportion. Ongoing surveillance and preparedness of the health system would be of importance, especially in tribal-dominated districts.

Economic evaluation of hepatitis A vaccines by income level of the country: A systematic review.

Background & objectives: Although several reviews of economic evaluation (EE) studies on hepatitis A virus (HAV) vaccine exist, there remains a need to corroborate such data from time to time. This study aimed to systematically review the literature for reports on EE of HAV vaccination by type of population, characteristics of intervention and income level of the country. Methods: PubMed and Scopus were searched to identify relevant studies from inception up to May 2021 using topic-specific key words in various combinaiton. Full EE studies comparing HAV vaccination to no vaccine or immunoglobulin were included. The risk of bias was assessed by using the ECOBIAS checklist. Results: Among the 1984 identified studies, 43 were found eligible. Of these, 27 were from high-income countries (HICs), 15 from middle-income countries (MICs), and one from low income country. Majority of the studies used Markov model and/or decision tree (n=26). Eight studies used a dynamic model. The discount rate, perspective and time horizon varied across the studies. Universal HAV vaccination without screening was cost-effective among children (14/16, 87.5%) and adolescents (1/5, 20%) but not in adults (0/4, 0%). Analysis by the level of income found that universal HAV vaccination among children without screening was cost-effective in 81.8 per cent of the studies conducted in MICs (9/11) as compared to 66.7 per cent in HICs (4/6). About one-third of the studies conducted among children found that screening and HAV vaccination were cost-effective compared to no vaccination. Interpretation & conclusions: The finding of this review suggest that universal vaccination of children without screening was likely to be cost-effective, especially in MICs. Nevertheless, it should be noted that the methodology varied across studies. Several aspects should also be considered in transferring the EE results across jurisdictions.

Peripheral lymphocyte subset alteration in patients with COVID-19 having differential clinical manifestations.

Background & objectives: The COVID-19 disease profile in Indian patients has been found to be different from the Western world. Changes in lymphocyte compartment have been correlated with disease course, illness severity and clinical outcome. This study was aimed to assess the peripheral lymphocyte phenotype and subset distribution in patients with COVID-19 disease from India with differential clinical manifestations. Methods: Percentages of peripheral lymphocyte subsets were measured by flow cytometry in hospitalized asymptomatic (n=53), mild symptomatic (n=36), moderate and severe (n=30) patients with SARS-CoV-2 infection, recovered individuals (n=40) and uninfected controls (n=56) from Pune, Maharashtra, India. Results: Percentages of CD4+Th cells were significantly high in asymptomatic, mild symptomatic, moderate and severe patients and recovered individuals compared to controls. Percentages of Th memory (CD3+CD4+CD45RO+), Tc memory (CD3+CD8+CD45RO+) and B memory (CD19+CD27+) cells were significantly higher in the recovered group compared to both asymptomatic, mild symptomatic patient and uninfected control groups. NK cell (CD56+CD3-) percentages were comparable among moderate +severe patient and uninfected control groups. Interpretation & conclusions: The observed lower CD4+Th cells in moderate+severe group requiring oxygen support compared to asymptomatic+mild symptomatic group not requiring oxygen support could be indicative of poor prognosis. Higher Th memory, Tc memory and B memory cells in the recovered group compared to mild symptomatic patient groups might be markers of recovery from mild infection; however, it remains to be established if the persistence of any of these cells could be considered as a correlate of protection.

Understanding the dynamics of IgM & IgG antibodies in COVID-19-positive patients.

Background & objectives: The pandemic caused by the SARS-CoV-2 has been a threat to humankind due to the rapid spread of infection and appearance of multiple new variants. In the present study, we report the dynamics and persistence of immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies in asymptomatic and symptomatic COVID-19 patients by chemiluminescent assay. Methods: A total of 463 serum samples from 218 SARS-CoV-2 PCR-positive patients were collected over a period of 124 days post-onset of disease (POD). Antibody levels were measured by chemiluminescence bioanalyzer. Neutralizing antibody titres were assessed by plaque reduction neutralization test (PRNT) for SARS-CoV-2. Results: Both IgM and IgG started appearing from day five post-infection in symptomatic and asymptomatic patients. IgM antibody response peaked around day 35 POD and rapidly diminished thereafter, with the last IgM-positive sample observed at 90 days POD. IgG antibody response peaked around 45 days POD and persisted till 124 days. The chemiluminescence immunoassay (CLIA) results showed a moderate correlation (R=0.5846, P<0.001) compared with PRNT. Additional analysis indicated a neutralizing titre of 250 corresponded to 12.948 AU/ml of YHLO iFlash SARS-CoV-2 IgG units. Interpretation & conclusions: Both symptomatic and asymptomatic COVID-19 patients seem to initiate production of antibody responses from day five of onset of disease. Although the CLIA gives high sensitivity and specificity and also its binding IgG antibody titres may correlate moderately with protective immunity, our results indicate that the values of binding antibody alone may not be a perfect guide to represent virus neutralization titre during donor selection for plasma therapy. However, IgM and IgG antibody detection may help in monitoring the status of disease progression and burden in the community.

Performance assessment of seven SARS-CoV-2 IgG enzyme-linked immunosorbent assays.

The pandemic of COVID-19 has caused enormous fatalities worldwide. Serological assays are important for detection of asymptomatic or mild cases of COVID-19, and sero-prevalence and vaccine efficacy studies. Here, we evaluated and compared the performance of seven commercially available enzyme-linked immunosorbent assay (ELISA)s for detection of anti-severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) immunoglobulin G (IgG). The ELISAs were evaluated with a characterized panel of 100 serum samples from qRT-PCR confirmed COVID-19 patients, collected 14 days post onset disease, 100 SARS-CoV-2 negative samples and compared the results with that of neutralization assay. Results were analysed by creating the receiver operating characteristic curve of all the assays in reference to the neutralization assay. All kits, were found to be suitable for detection of IgG against SARS-CoV-2 with high accuracy. The DiaPro COVID-19 IgG ELISA showed the highest sensitivity (98%) among the kits. The assays demonstrated high sensitivity and specificity in detecting the IgG antibodies against SARS-CoV-2. However, the presence of IgG antibodies does not always correspond to neutralizing antibodies. Due to their good accuracy indices, these assays can also aid in tracing mild infections, in cohort studies and in pre-vaccine evaluations.

Pro-inflammatory CXCL-10, TNF-α, IL-1ß, and IL-6: biomarkers of SARS-CoV-2 infection.

Currently, the world is witnessing the pandemic of COVID-19, a disease caused by the novel coronavirus SARS-CoV-2. Reported differences in clinical manifestations and outcomes in SARS-CoV-2 infection could be attributed to factors such as virus replication, infiltration of inflammatory cells, and altered cytokine production. Virus-induced aberrant and excessive cytokine production has been linked to the morbidity and mortality of several viral infections. Using a Luminex platform, we investigated plasma cytokine and chemokine levels of 27 analytes from hospitalized asymptomatic (n = 39) and mildly symptomatic (n = 35) SARS-CoV-2-infected patients (in the early phase of infection), recovered individuals (45-60 days postinfection) (n = 40), and uninfected controls (n = 36) from the city of Pune located in the state of Maharashtra in India. Levels of the pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α and the chemokine CXCL-10 were significantly higher, while those of the antiviral cytokines IFN-γ and IL-12 p70 were significantly lower in both asymptomatic and mildly symptomatic patients than in controls. Comparison among the patient categories revealed no difference in the levels of the cytokines/chemokines except for CXCL-10 being significantly higher and IL-17, IL-4, and VEGF being significantly lower in the mildly symptomatic patients. Interestingly, levels of all key analytes were significantly lower in recovered individuals than in those in both patient categories. Nevertheless, the level of CXCL10 was significantly higher in the recovered patients than in the controls, indicating that the immune system of SARS-CoV-2 patients may take a longer time to normalize. Our data suggest that IL-6, IL-1ß, TNF-α, CXCL-10, and reduced antiviral cytokines could be used as biomarkers of SARS-CoV-2 infection.

Epidemiological characterization of COVID-19 - Pune, 2020-2021.

The present study describes the epidemiological characteristics of 3,08,259 suspected cases of COVID-19 from the Pune district, India. The samples were referred for COVID-19 testing between January 24, 2020 and April 30, 2021. Demographic and clinical data were extracted from the ICMR-portal as a single dataset and analyzed. Of the 3,08,259 samples tested, 2,63,833 (85.6%) were asymptomatic. Symptomatic cases ratio in the first and the second COVID-19 wave was 1:2. Among symptomatic cases, cough was the most common complaint, followed by fever. Among the COVID-19 positives, one-fifth were asymptomatic, highlighting the necessity for close contact tracing even among apparently healthy contacts. The second wave of COVID-19 had double the per cent of symptomatic individuals as compared to the first wave.

Declining trends in Hepatitis A seroprevalence over the past two decades, 1998-2017, in Pune, Western India.

Reduction in seroprevalence of Hepatitis A virus (HAV) is known to be associated with improvements in socioeconomic conditions of the community. National Institute of Virology, Pune has been studying seroprevalence of hepatitis viruses in Pune region over the past four decades. In total, 1438 samples were collected from urban general (UGEN), urban lower socioeconomic stratum (ULSES) and rural (RURAL) populations of the Pune district. Based on estimates in previous studies, subjects were enrolled from age groups '6-10', '15-25' and '40 + ' years. HAV seroprevalence in younger population showed a significant decline. A significant decline in HAV seroprevalence in '15-25' years age group in UGEN (from 85.9% to 73.9%; OR = 0.46, 95% CI: 0.25-0.86) and RURAL (from 98.6% to 91.4%; OR = 0.15, 95% CI: 0.05-0.45) populations suggested that the trend probably started more than a decade ago. Seroprevalence of HAV among ULSES '6-10' children was found to be significantly higher (70.4%) than that among the RURAL children (44.2%; OR = 3.0, 95%CI: 1.7-5.2) and UGEN children (40.4%; OR = 3.5, 95%CI: 1.8-6.7). In view of increasing rates of urbanisation in India, ULSES population needs special consideration while designing future studies and viral hepatitis vaccination/elimination strategies. Our findings call for robust population-based studies that consider heterogeneity within populations and dynamics of socio-economic parameters in various regions of a country.

Neutralizing antibody responses to SARS-CoV-2 in COVID-19 patients.

BACKGROUND & OBJECTIVES: The global pandemic caused by SARS-CoV-2 virus has challenged public health system worldwide due to the unavailability of approved preventive and therapeutic options. Identification of neutralizing antibodies (NAb) and understanding their role is important. However, the data on kinetics of NAb response among COVID-19 patients are unclear. To understand the NAb response in COVID-19 patients, we compared the findings of microneutralization test (MNT) and plaque reduction neutralization test (PRNT) for the SARS-CoV-2. Further, the kinetics of NAb response among COVID-19 patients was assessed. METHODS: A total of 343 blood samples (89 positive, 58 negative for SARS-CoV-2 and 17 cross-reactive and 179 serum from healthy individuals) were collected and tested by MNT and PRNT. SARS-CoV-2 virus was prepared by propagating the virus in Vero CCL-81 cells. The intra-class correlation was calculated to assess the correlation between MNT and PRNT. The neutralizing endpoint as the reduction in the number of plaque count by 90 per cent (PRNT90) was also calculated. RESULTS: The analysis of MNT and PRNT quantitative results indicated that the intra-class correlation was 0.520. Of the 89 confirmed COVID-19 patients, 64 (71.9%) showed NAb response. INTERPRETATION & CONCLUSIONS: The results of MNT and PRNT were specific with no cross-reactivity. In the early stages of infection, the NAb response was observed with variable antibody kinetics. The neutralization assays can be used for titration of NAb in recovered/vaccinated or infected COVID-19 patients.

Development of indigenous IgG ELISA for the detection of anti-SARS-CoV-2 IgG.

BACKGROUND & OBJECTIVES: Since the beginning of the year 2020, the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted humankind adversely in almost all spheres of life. The virus belongs to the genus Betacoronavirus of the family Coronaviridae. SARS-CoV-2 causes the disease known as coronavirus disease 2019 (COVID-19) with mild-to-severe respiratory illness. The currently available diagnostic tools for the diagnosis of COVID-19 are mainly based on molecular assays. Real-time reverse transcription-polymerase chain reaction is the only diagnostic method currently recommended by the World Health Organization for COVID-19. With the rapid spread of SARS-CoV-2, it is necessary to utilize other tests, which would determine the burden of the disease as well as the spread of the outbreak. Considering the need for the development of such a screening test, an attempt was made to develop and evaluate an IgG-based ELISA for COVID-19. METHODS: A total of 513 blood samples (131 positive, 382 negative for SARS-CoV-2) were collected and tested by microneutralization test (MNT). Antigen stock of SARS-CoV-2 was prepared by propagating the virus in Vero CCL-81 cells. An IgG capture ELISA was developed for serological detection of anti-SARS-CoV-2 IgG in serum samples. The end point cut-off values were determined by using receiver operating characteristic (ROC) curve. Inter-assay variability was determined. RESULTS: The developed ELISA was found to be 92.37 per cent sensitive, 97.9 per cent specific, robust and reproducible. The positive and negative predictive values were 94.44 and 98.14 per cent, respectively. INTERPRETATION & CONCLUSIONS: This indigenously developed IgG ELISA was found to be sensitive and specific for the detection of anti-SARS-CoV-2 IgG in human serum samples. This assay may be used for determining seroprevalence of SARS-CoV-2 in a population exposed to the virus.

Cost Utility of Sodium-Glucose Cotransporter 2 Inhibitors in the Treatment of Metformin Monotherapy Failed Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) and associated ailments are leading economic burdens to society. Sodium glucose cotransporter-2 (SGLT2) inhibitors are recent antidiabetic medications with beneficial clinical efficacy. This meta-analysis was conducted to quantitatively pool the incremental net benefit of SGLT2 inhibitors in T2DM patients who failed metformin monotherapy. METHODS: Relevant economic evaluation studies of T2DM patients were identified from PubMed, Scopus, ProQuest, the Cochrane Library, and the Tufts Cost-Effective Analysis Registry until June 2018. Studies were eligible if they studied T2DM patients who failed metformin monotherapy and assessed the cost-effectiveness/utility between SGLT2 inhibitors and other treatments. Details of the study characteristics, economic model inputs, costs, and outcomes were extracted. Risk of bias was assessed using the biases in economic studies (ECOBIAS) checklist. The incremental net benefit was calculated with monetary units adjusting for purchasing power parity for 2017 US dollars. This was then pooled across studies stratified by the country's level of income using a random-effect model if heterogeneity was present and with a fixed-effect model otherwise. Heterogeneity was assessed using the Q test and I2 statistic. RESULTS: A total of 13 studies with 22 comparisons, mainly from high-income countries, were eligible. Six and 4 studies compared SGLT2 with dipeptidyl peptidase-4 inhibitors (DPP4i) and sulfonylureas, respectively. The pooled incremental net benefits (95% confidence interval) for these corresponding comparisons were $164.95 (-$534.71 to $864.61; I2 = 0%) and $3675.09 ($1656.46-$5693.71; I2 = 85.4%), respectively. These results indicate that SGLT2s were cost-effective in comparison with sulfonylureas but not DPP4i. CONCLUSION: SGLT2s were cost-effective as compared with sulfonylureas but not DPP4i. Most of the evidence was from high-income countries with few comparative drug groups, and the results might not be representative of the actual global scenario. Further studies from middle and lower economies and other comparators are still required.

Crimean Congo hemorrhagic fever serosurvey in humans for identifying high-risk populations and high-risk areas in the endemic state of Gujarat, India.

BACKGROUND: Crimean Congo Hemorrhagic Fever (CCHF) is a highly infectious zoonotic disease of humans transmitted by Hyalomma ticks. Earlier studies have shown CCHF seroprevalence in livestock throughout India, yet sporadic outbreaks have been recorded mostly from the Gujarat state of India since 2011. Occupational vulnerability to CCHF for animal handlers, veterinarians, abattoir workers, and healthcare workers has been documented. The current study was planned to determine the seroprevalence of CCHF with an intention to identify the high -risk population and high -risk areas from Gujarat state, India. METHODS: Based on the socio-clinical data, the human population of Gujarat was divided into eight categories viz. A: CCHF affected person/house/close contact, B: Neighborhood contacts, C: Animal handlers, D: General population, E: Farmers, F: Abattoir workers, G: Veterinarian, H: Healthcare workers. A total of 4978 human serum samples were collected from 33 districts of Gujarat during year 2015, 2016 and 2017. All the samples were screened for the presence of anti-CCHFV IgG using indigenously developed anti-CCHFV IgG ELISA. Univariate regression analysis was performed to recognize significant risk factors for CCHF seropositivity. RESULTS: Twenty-five serum samples were found to be positive with an overall CCHF human seropositivity of 0.5% (95% CI 0.30-0.74%). Gender predisposition to CCHF prevalence was observed in males (OR: 2.80; p-value: 0.020). The risk for seropositivity increased sevenfold when a person was in contact or neighbor with a CCHF case (OR 7.02; p-value: < 0.0001). No significant difference in seropositivity was observed within different age groups. Veterinarians, healthcare workers, and control group were found to be seronegative for CCHF. CONCLUSIONS: In-spite of CCHF sporadic outbreaks reported in Gujarat, the seropositivity for CCHF in the state was low as compared to other endemic countries. Males, close contacts and neighbors were identified as a high-risk population for CCHF infection. To recognize the high-risk area, tick screening and animal serosurvey would be a wiser choice. The study also suggests circulation and under diagnoses of CCHFV in the naïve regions of Gujarat.

Kinetics of viral RNA, immunoglobulin-M & G antibodies in Kyasanur forest disease.

Background & objectives: Kyasanur forest disease (KFD) is an infectious disease discovered in Karnataka State of India in 1957; since then, the State has been known to be enzootic for KFD. In the last few years, its presence was observed in the adjoining five States of the Western Ghats of India. The present study was conducted to understand the kinetics of viral RNA, immunoglobulin M (IgM) and IgG antibody in KFD-infected humans for developing a diagnostic algorithm for KFD. Methods: A prospective follow up study was performed among KFD patients in Sindhudurg district of Maharashtra State, India. A total of 1046 suspected patients were tested, and 72 KFD patients were enrolled and followed for 17 months (January 2016 to May 2017). Serum samples of KFD patients were screened for viral RNA, and IgM and IgG antibodies. Results: KFD viral positivity was observed from 1st to 18th post-onset day (POD). Positivity of anti-KFD virus (KFDV) IgM antibodies was detected from 4th till 122nd POD and anti-KFDV IgG antibodies detected from 5th till 474th POD. A prediction probability was determined from statistical analysis using the generalized additive model in R-software to support the laboratory findings regarding viral kinetics. Interpretation & conclusions: This study demonstrated the presence of KFD viral RNA till 18th POD, IgM antibodies till 122nd POD and IgG till the last sample collected. Based on our study an algorithm was recommended for accurate laboratory diagnosis of KFDV infection. A sample collected between 1 and 3 POD can be tested using KFDV real-time reverse transcriptase polymerase chain reaction (RT-PCR); between 4 and 24 POD, the combination of real-time RT-PCR and anti-KFDV IgM enzyme-linked immunosorbent assay (ELISA) tests can be used; between POD 25 and 132, anti-KFDV IgM and IgG ELISA are recommended.

A large outbreak of Japanese encephalitis predominantly among adults in northern region of West Bengal, India.

Unusual rise of acute encephalitis syndrome cases (AES) were reported in July 2014 in the northern region of West Bengal, India. Investigations were carried out to characterize the outbreak and to identify the associated virus etiology. This observational study is based on 398 line listed AES cases, mostly (70.8%, 282/398) adults, with case fatality ratio of 28.9% (115/398). Japanese encephalitis virus infection was detected in 134 (49.4%) among 271 AES cases tested and most of them (79.1%, 106/134) were adults. The study reports a large outbreak of genotype III Japanese encephalitis among adults in northern region of West Bengal, India. J. Med. Virol. 88:2004-2011, 2016. © 2016 Wiley Periodicals, Inc.

Cost-effective analysis of hepatitis A vaccination in Kerala state, India.

Several hepatitis A outbreaks have recently been reported in Kerala state, India. To inform coverage decision of hepatitis A vaccine in Kerala, this study aimed to examine the cost-effectiveness of 1) hepatitis A vaccination among children aged 1 year and individuals aged 15 years, and 2) serological screening of individuals aged 15 years and vaccination of susceptible as compared to no vaccination or vaccination without serological screening. Both live attenuated hepatitis A vaccine and inactivated hepatitis A vaccine were considered in the analysis. A combination of decision tree and Markov models with a cycle length of one year was employed to estimate costs and benefits of different vaccination strategies. Analysis were based on both societal and payer perspectives. The lifetime costs and outcomes were discounted by 3%. Our findings indicated that all strategies were cost-saving for both societal and payer perspectives. Moreover, budget impact analysis revealed that vaccination without screening among individuals aged 15 years could save the government's budget by reducing treatment cost of hepatitis A. Our cost-effectiveness evidence supports the inclusion of hepatitis A vaccination into the vaccination program for children aged 1 year and individuals aged 15 years in Kerala state, India.