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Genotype III (GIII) Japanese encephalitis virus (JEV) predominance has gradually been replaced by genotype I (GI) over the last 20 years in many Asian countries. This genotype shift raises concerns about the protective efficacy of Japanese encephalitis (JE) vaccines, as all of the currently licensed JE vaccines are derived from GIII strains. In this study, we conducted vaccination-challenge protection assays to evaluate the cross-protective efficacy of GI- or GIII-derived vaccines against the challenge of a heterologous genotype using a mouse challenge model. Titration of the neutralizing antibodies elicited by SA14-14-2 live-attenuated JE vaccine (SA14-14-2 vaccine), a GIII-derived vaccine, indicated that the titer of neutralizing antibodies specific to heterologous genotype GI stain was significantly lower than that specific to homologous genotype GIII strain in both pigs and mice immunized with the SA14-14-2 vaccine. Vaccination of mice with SA14-14-2 vaccine or a GIII-inactivated vaccine at high and medium doses completely protected vaccinated mice against challenge with the homologous genotype GIII strains, but failed to provide the vaccinated mice complete protection against the challenge of heterologous genotype GI strains. The protection rates against GI strain challenge were 60%–80%, showing that these vaccines were partially protective against GI strain challenge. Additionally, vaccination of mice with a GI-inactivated vaccine conferred 100% protection against the challenge of homologous genotype GI strains, but 50%–90% protection against the challenge of heterologous genotype GIII strains, showing a reduced protective efficacy of a GI-derived vaccine against GIII strain challenge. Overall, these observations demonstrated a partial cross-protection between GI and GIII strains and suggested a potential need for new JE vaccine strategies, including options like a bivalent vaccine, to control both genotype infection. [ABSTRACT FROM AUTHOR]

Nipah virus (NiV) is a highly pathogenic re-emerging virus that causes outbreaks in South East Asia. Currently, no approved and licensed vaccine or antivirals exist. Here, we investigated the efficacy of ChAdOx1 NiVB, a simian adenovirus-based vaccine encoding NiV glycoprotein (G) Bangladesh, in Syrian hamsters. Prime-only as well as prime-boost vaccination resulted in uniform protection against a lethal challenge with NiV Bangladesh: all animals survived challenge and we were unable to find infectious virus either in oral swabs, lung or brain tissue. Furthermore, no pathological lung damage was observed. A single-dose of ChAdOx1 NiVB also prevented disease and lethality from heterologous challenge with NiV Malaysia. While we were unable to detect infectious virus in swabs or tissue of animals challenged with the heterologous strain, a very limited amount of viral RNA could be found in lung tissue by in situ hybridization. A single dose of ChAdOx1 NiVB also provided partial protection against Hendra virus and passive transfer of antibodies elicited by ChAdOx1 NiVB vaccination partially protected Syrian hamsters against NiV Bangladesh. From these data, we conclude that ChAdOx1 NiVB is a suitable candidate for further NiV vaccine pre-clinical development. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic Leishmania donovani infections outnumber clinical presentations, however the predictors for development of active disease are not well known. We aimed to identify serological, immunological and genetic markers for progression from L. donovani infection to clinical Visceral Leishmaniasis (VL). Methods: We enrolled all residents >2 years of age in 27 VL endemic villages in Bihar (India). Blood samples collected on filter paper on two occasions 6–12 months apart, were tested for antibodies against L. donovani with rK39-ELISA and DAT. Sero converters, (negative for both tests in the first round but positive on either of the two during the second round) and controls (negative on both tests on both occasions) were followed for three years. At the start of follow-up venous blood was collected for the following tests: DAT, rK39- ELISA, Quantiferon assay, SNP/HLA genotyping and L.donovani specific quantitative PCR. Results: Among 1,606 subjects enrolled,17 (8/476 seroconverters and 9/1,130 controls) developed VL (OR 3.1; 95% CI 1.1–8.3). High DAT and rK39 ELISA antibody titers as well as positive qPCR were strongly and significantly associated with progression from seroconversion to VL with odds ratios of 19.1, 30.3 and 20.9 respectively. Most VL cases arose early (median 5 months) during follow-up. Conclusion: We confirmed the strong association between high DAT and/or rK39 titers and progression to disease among asymptomatic subjects and identified qPCR as an additional predictor. Low predictive values do not warrant prophylactic treatment but as most progressed to VL early during follow-up, careful oberservation of these subjects for at least 6 months is indicated. [ABSTRACT FROM AUTHOR]

Background: Cholera remains a substantial health burden in Asia and Africa particularly in resource poor settings. The standard procedures to identify the etiological organism V. cholerae are isolation from microbiological culture from stool as well as Polymerase Chain Reaction (PCR). Both the processes are highly lab oriented, labor extensive, time consuming, and expensive. In an effort to control for outbreaks and epidemics; an effective, convenient, quick and relatively less expensive detection method is imperative, without compromising the sensitivity and specificity that exists at present. The objective of this component of the study was to evaluate the effectiveness of a locally produced rapid diagnostic test (RDT) for cholera diagnosis. Methods: In Bangladesh, nationwide cholera surveillance is ongoing in 22 hospitals covering all 8 divisions of the country since June, 2016. In the surveillance, stool samples have been collected from patients presenting to hospitals with acute watery diarrhea. Crystal VCTM (Span diagnostics, India) and Cholkit (locally produced RDT) have been used to detect V. cholerae from stool samples. Samples have also been sent to the main laboratory at icddr,b where the culture based isolation is routinely performed. All the tests were carried out for both direct and enriched stool samples. RDT sensitivity and specificity were calculated using stool culture as the gold standard. Results: A total of 7720 samples were tested. Among these, 5865 samples were solely tested with Crystal VC and 1355 samples with Cholkit whereas 381 samples were tested with both the RDTs. In comparison with culture, direct testing with Crystal VC showed a sensitivity of 72% (95% CI: 50.6% to 87.9%) and specificity of 86.8% (95% CI: 82.8% to 90.1%). After enrichment the sensitivity and specificity was 68% (95% CI: 46.5% to 85.1%) and 97.5% (95% CI: 95.3% to 98.8%) respectively. The direct Cholkit test showed sensitivity of 76% (95% CI: 54.9% to 90.6%) and specificity of 90.2% (95% CI: 86.6% to 93.1%). Conclusion: This evaluation has demonstrated that the sensitivity and specificity of Cholkit is similar to the commercially available test, Crystal VC when used in field settings for detecting V. cholerae from stool specimens. The findings from this study suggest that the Cholkit could be a possible alternative for cholera endemic regions where V. cholerae O1 is the major causative organism causing cholera. [ABSTRACT FROM AUTHOR]