An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial.

Here we conducted a multicenter open-label, randomized phase 2 and 3 study to assess the safety and immunogenicity of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-specific (BA.1/B.1.1.529), monovalent, thermostable, self-amplifying mRNA vaccine, GEMCOVAC-OM, when administered intradermally as a booster in healthy adults who had received two doses of BBV152 or ChAdOx1 nCoV-19. GEMCOVAC-OM was well tolerated with no related serious adverse events in both phase 2 and phase 3. In phase 2, the safety and immunogenicity of GEMCOVAC-OM was compared with our prototype mRNA vaccine GEMCOVAC-19 (D614G variant-specific) in 140 participants. At day 29 after vaccination, there was a significant rise in anti-spike (BA.1) IgG antibodies with GEMCOVAC-OM (P < 0.0001) and GEMCOVAC-19 (P < 0.0001). However, the IgG titers (primary endpoint) and seroconversion were higher with GEMCOVAC-OM (P < 0.0001). In phase 3, GEMCOVAC-OM was compared with ChAdOx1 nCoV-19 in 3,140 participants (safety cohort), which included an immunogenicity cohort of 420 participants. At day 29, neutralizing antibody titers against the BA.1 variant of SARS-CoV-2 were significantly higher than baseline in the GEMCOVAC-OM arm (P < 0.0001), but not in the ChAdOx1 nCoV-19 arm (P = 0.1490). GEMCOVAC-OM was noninferior (primary endpoint) and superior to ChAdOx1 nCoV-19 in terms of neutralizing antibody titers and seroconversion rate (lower bound 95% confidence interval of least square geometric mean ratio >1 and difference in seroconversion >0% for superiority). At day 29, anti-spike IgG antibodies and seroconversion (secondary endpoints) were significantly higher with GEMCOVAC-OM (P < 0.0001). These results demonstrate that GEMCOVAC-OM is safe and boosts immune responses against the B.1.1.529 variant. Clinical Trial Registry India identifier: CTRI/2022/10/046475 .

High-temperature Josephson diode.

Many superconducting systems with broken time-reversal and inversion symmetry show a superconducting diode effect, a non-reciprocal phenomenon analogous to semiconducting p-n-junction diodes. While the superconducting diode effect lays the foundation for realizing ultralow dissipative circuits, Josephson-phenomena-based diode effect (JDE) can enable the realization of protected qubits. The superconducting diode effect and JDE reported thus far are at low temperatures (~4 K), limiting their applications. Here we demonstrate JDE persisting up to 77 K using an artificial Josephson junction of twisted layers of Bi2Sr2CaCu2O8+δ. JDE manifests as an asymmetry in the magnitude and distributions of switching currents, attaining the maximum at 45° twist. The asymmetry is induced by and tunable with a very small magnetic field applied perpendicular to the junction and arises due to interaction between Josephson and Abrikosov vortices. We report a large asymmetry of 60% at 20 K. Our results provide a path towards realizing superconducting Josephson circuits at liquid-nitrogen temperature.

Hospital-based norovirus surveillance in children <5 years of age from 2017 to 2019 in India.

After the introduction of the rotavirus vaccine into the Universal Immunization Program in India in 2016, relatively few studies have assessed the prevalence and epidemiological patterns of acute gastroenteritis (AGE) among hospitalized children ≤5 years of age. We used a uniform protocol to recruit children with AGE as well as standardized testing and typing protocols. Stool specimens from children with AGE younger than 5 years of age admitted to six hospitals in three cities in India were collected from January 2017 through December 2019. Norovirus was detected by real-time reverse transcription-polymerase chain reaction (RT-qPCR) followed by typing positive specimens by conventional RT-PCR and Sanger sequencing. Norovirus was detected in 322 (14.8%) of 2182 specimens with the highest rate in 2018 (17.6%, 146/829), followed by 2019 (14.4%, 122/849) and 2017 (10.7%, 54/504). Rotavirus vaccine status was known for 91.6% of the children of which 70.4% were vaccinated and 29.6% not. Norovirus positivity in rotavirus-vaccinated children was 16.3% and 12% in unvaccinated children. GII.4 Sydney[P16] (39.3%), GII.4 Sydney[P31] (18.7%), GII.2[P16] (10%), GI.3[P13] (6.8%), GII.3[P16] (5.9%), and GII.13[P16] (5%) accounted for 85.8% (188/219) of the typed strains. Our data highlight the importance of norovirus in Indian children hospitalized with AGE.

Crossover from gapped-to-gapless Dirac surface states in magnetic topologicalinsulator MnBi2Te4.

Intrinsic magnetic topological insulators (MTI) host exotic topological phases such as quantized anomalous Hall insulating phase, arising due to the large magnetic exchange gap. However, the interplay of magnetism and topology in these systems in different temperature regimes remains elusive. In this work, we present the logarithmic temperature-dependence of conductivity for sub-100 nm thick exfoliated flakes of MTI MnBi2Te4 in the presence of out-of-plane magnetic fields and extracted the linear slope, κ. We observed a characteristic change, ∆κ ∼ -0.5 in the low-temperature regime, indicating the gapped Dirac surface state according to Lu-Shen theory. We also report the recovery of topological properties in the system via the weak-antilocalization (WAL) effect in the vicinity of antiferromagnetic to paramagnetic transition and in the paramagnetic regime. Hikami-Larkin-Nagaoka (HLN) analysis suggested the presence of topological surface states. Therefore, our study helps in understanding how intrinsic magnetism masks topological properties in an MTI as long as magnetic ordering persists. .

Immunogenicity of two COVID-19 vaccines used in India: An observational cohort study in health care workers from a tertiary care hospital.

COVID-19 pandemic witnessed rapid development and use of several vaccines. In India, a country-wide immunization was initiated in January 2021. COVISHIELD, the chimpanzee adenoviral-vectored vaccine with full-length SARS-COV-2 spike insert and COVAXIN, the whole virus-inactivated vaccines were used. To assess and compare immune response of health-care-workers to COVISHIELD (n=187) and COVAXIN (n=21), blood samples were collected pre-vaccination, 1month post-1/post-2 doses and 6months post-dose-2 and tested for IgG-anti-SARS-CoV-2 (ELISA) and neutralizing (Nab,PRNT50) antibodies. Spike-protein-specific T cells were quantitated by IFN-γ-ELISPOT. In pre-vaccination-antibody-negative COVISHIELD recipients (pre-negatives, n=120), %Nab seroconversion (median, IQR Nab titers) increased from 55.1% (16, 2.5-36.3) post-dose-1 to 95.6% (64.5, 4.5-154.2, p<0.001) post-dose-2 that were independent of age/gender/BMI. Nab response was higher among pre-positives with hybrid immunity at all-time points (p<0.01-0.0001) and independent of age/gender/BMI/Comorbidities. Post-dose-2-seroconversion (50%, p<0.001) and Nab titers (6.75, 2.5-24.8, p<0.001) in COVAXIN-recipients were lower than COVISHIELD. COVAXIN elicited a superior IFN-γ-T cell response as measured by ELISPOT (100%; 1226, 811-1532 spot forming units, SFU/million PBMCs v/s 57.8%; 21.7,1.6-169.2; p<0.001). At 6months, 28.3% (15/53) COVISHIELD and 3/3COVAXIN recipients were Nab-negative. T cell response remained unchanged. During immunization, COVID-19 cases were detected among COVISHIELD (n=4) and COVAXIN (n=2) recipients. At 6months, 9cases were recorded in COVISHIELD-recipients. This first-time, systematic, real-world assessment and long-term follow up revealed generation of higher neutralizing antibody titers by COVISHIELD and stronger T-cell response by COVAXIN. Diminished Nab titers at 6months emphasize early booster. Immunogenicity/efficacy of vaccines will change with the progression of the pandemic needing careful evaluations in the field-settings.

Immunoglobulin G Subclass Response After Chikungunya Virus Infection.

Various vaccines are under development to prevent chikungunya (CHIKV) infection. For the assessment of the CHIKV vaccine-induced antibody response, it is extremely important to understand antibody response after the infection has occurred. Previously, we assessed IgG response in samples from healthy donors using I-CHIKV and found that IgG1 was the predominant subclass induced after CHIKV infection followed by IgG4. However, IgG3 subclass induction is reported in serum samples from patients with acute CHIKV infection. Therefore, in this study, we evaluated serum/plasma from samples of patients with acute CHIKV infection for the presence of IgG and IgG subclasses against I-CHIKV and recombinant E2 protein (rE2). Out of 44 samples that were positive against I-CHIKV, 43 were found reactive against rE2. The positivity of IgG1 either alone or together with other IgG subclasses using I-CHIKV was 89% samples, while 86% samples were positive using rE2. High titers of IgG1 are obtained with I-CHIKV (67%), while raised IgG4 levels are detected using rE2p (72%) in the samples that are positive for both these subclasses. Testing of 22 samples for neutralizing antibodies revealed 100% IgG1 positivity and neutralizing antibodies in 21, 1 sample negative for both. Overall, these data will be useful in assessing IgG subclass-specific CHIKV neutralization and response after CHIKV immunization.

Orthorhombic charge density wave on the tetragonal lattice of EuAl4.

EuAl4 possesses the BaAl4 crystal structure type with tetragonal symmetry I4/mmm. It undergoes a charge density wave (CDW) transition at T CDW = 145 K and features four consecutive antiferromagnetic phase transitions below 16 K. Here we use single-crystal X-ray diffraction to determine the incommensurately modulated crystal structure of EuAl4 in its CDW state. The CDW is shown to be incommensurate with modulation wave vector q = (0,0,0.1781 (3)) at 70 K. The symmetry of the incommensurately modulated crystal structure is orthorhombic with superspace group Fmmm(00σ)s00, where Fmmm is a subgroup of I4/mmm of index 2. Both the lattice and the atomic coordinates of the basic structure remain tetragonal. Symmetry breaking is entirely due to the modulation wave, where atoms Eu and Al1 have displacements exclusively along a, while the fourfold rotation would require equal displacement amplitudes along a and b. The calculated band structure of the basic structure and interatomic distances in the modulated crystal structure both indicate the Al atoms as the location of the CDW. The tem-per-ature dependence of the specific heat reveals an anomaly at T CDW = 145 K of a magnitude similar to canonical CDW systems. The present discovery of orthorhombic symmetry for the CDW state of EuAl4 leads to the suggestion of monoclinic instead of orthorhombic symmetry for the third AFM state.

Perinatal transmission of SARS-CoV-2 and transfer of maternal IgG/neutralizing anti-SARS-CoV-2 antibodies from mothers with asymptomatic infection during pregnancy.

PURPOSE: COVID-19 pandemic remains a serious public health threat worldwide. In view of the limited data on the risk of perinatal transmission of SARS-CoV-2 and transfer of maternal anti-SARS-CoV-2 antibodies, the present study was undertaken. METHODS: A prospective study including 57 pregnant women with a positive SARS-CoV-2 RNA test (SARS-CoV-2-RNA+) and 59 neonates born to them was conducted at Pune, India. 39 viral RNA negative (SARS-CoV-2-RNA-negative) pregnant women and their 39 neonates were included as controls. Neonatal nasal swab/cord blood samples were subjected to SARS-CoV-2 RNA detection by RT-PCR for investigation of perinatal transmission. Transfer of maternal antibodies was studied using ELISA and PRNT. RESULTS: 10/57 SARS-CoV-2-RNA+ mothers were symptomatic. The duration between COVID-19 diagnosis and delivery was ≤ 7 days for 82.4%. Perinatal transmission as evidenced by viral RNA in the neonatal nasal swab/cord blood (CB) was 3.6%. IgG-anti-SARS-CoV-2 positivity was 21.6%. Of the 39 neonates born to SARS-CoV-2-RNA-negative mothers, 20 (51%) and none, respectively, were positive for IgG-anti-SARS-CoV-2 and viral RNA. Preterm deliveries were higher in SARS-CoV-2-RNA+ (18.6%) than SARS-CoV-2 RNA-negative (0/39) mothers (p < 0.005). Respiratory distress at birth (< 4 h) was higher among neonates of SARS-CoV-2-RNA+ (20/59, 33.9%) than SARS-CoV-2-RNA-negative mothers (3/39, 7.7%; p < 0.001). ~ 75% IgG-positives exhibited neutralization potential with mean PRNT titers of 42.4 ± 24 (SARS-CoV-2-RNA+) and 72.3 ± 46.7 (SARS-CoV-2 RNA-negative); higher in the latter (p < 0.05). CONCLUSION: The rate of perinatal transmission was low. Transfer of maternal antibodies was lower among SARS-CoV-2-RNA+ mothers than SARS-CoV-2-RNA-negative mothers with subclinical infection during pregnancy. Presence of neutralizing antibodies in majority of IgG-positives suggests protection from SARS-CoV-2 in early life.

SARS-CoV-2 breakthrough infections during the second wave of COVID-19 at Pune, India.

Breakthrough infections following SARS-CoV-2 vaccination remain the global concern. The current study was conducted during the second wave of COVID-19 (1st March-7th July 2021) in Pune, India, at two tertiary care hospitals. Of the 6,159 patients diagnosed as COVID-19, 372/2,210 (16.8%) were breakthrough infections. Of these, 81.1 and 18.8% received one or two doses of Covishield or Covaxin, respectively. Of note, 30.7% patients were with comorbidities, hypertension being the commonest (12.44%). The majority of infections were mild (81.2%). Forty-three patients with breakthrough infections were hospitalized with severe (n = 27, 62.8%) or moderate (n = 16, 37.2%) disease. The receptor binding domain (RBD) sequences from vaccinated (n = 126) and non-vaccinated (n = 168) samples were used for variant analysis. The delta variant was predominant followed by kappa in both vaccinated and non-vaccinated groups. Viral load (qRT-PCR) was not different among these categories. Full-genome comparisons of sequences in relation to vaccination status did not identify any mutation characteristic of the vaccinated group. Irrespective of the number of doses, neutralizing antibody titers (PRNT50) during the first week of clinical disease were higher in the vaccinated patients than the unvaccinated category. In conclusion, though not completely, SARS-CoV-2 vaccines used for country-wide immunization did reduce disease severity among the individuals without any comorbidity by inducing rapid immune response against distinctly different delta and kappa variants. The utility against emerging variants with further mutations need to be carefully examined.

Performance assessment of SARS-CoV-2 IgM & IgG ELISAs in comparison with plaque reduction neutralization test.

Background & objectives: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) continues to be a devastating pandemic. This study was aimed at performance assessment of SARS-CoV-2 IgM and IgG ELISAs, and investigation of their utility for patient diagnosis and sero-epidemiologic investigations. Methods: Serum/plasma samples from COVID-19 patients or asymptomatic contacts (n=180) and healthy donors (n=90) were tested in parallel using two commercial IgM ELISAs (Erbalisa and Inbios), and four IgG ELISAs (Kavach, Euroimmun, Erbalisa and Inbios) along with an indigenous ß-propiolactone inactivated virus-based ELISA (IRSHA-IgG-ELISA). Plaque reduction neutralization test (PRNT) was used as reference test. Results: Among 180 COVID-19 patients, 125 tested positive by PRNT. Inbios-IgM-ELISA showed sensitivity (Se)/specificity (Sp)/positive predictive value (PPV)/negative predictive value (NPV) of 93.6/97.8/98.4/94.4 per cent in relation to PRNT, and performed better than Erbalisa-IgM-ELISA (Se: 48%, Sp: 95.6%, PPV: 95.2%, NPV: 65.2%). During the first week of disease, only 47.4 per cent of the COVID-19 patients tested IgM positive by Inbios-IgM-ELISA, detection improving at two weeks and beyond (~86-100%). Among IgG tests, Inbios-IgG-ELISA ranked first in terms of sensitivity (83.2%), followed by IRSHA (64.8%), Euroimmun (64%), Erbalisa (57.6%) and Kavach (56%) tests. For all IgG tests, sensitivity improved during the third (73.9-95.7%) and fourth week (100%) of illness. The specificity (96.7-100%) and PPV (96.2-100%) of all IgG tests were high; NPV ranged between 71.9 and 87.1 per cent with Inbios-IgG-ELISA scoring highest. Interpretation & conclusions: Our results show that IgM detection by the current, most sensitive ELISAs cannot replace molecular diagnosis, but may aid as a supplement test. The available IgG tests are suitable for serosurveys for the assessment of previous virus exposure.

Clinical, epidemiological, and molecular aspects of picornaviruses (entero, parecho) in acute gastroenteritis: A study from Pune (Maharashtra), Western India.

Among enteric viruses, rotavirus A (RVA), norovirus (NoV), adenovirus, and astrovirus (AstV) are the major etiological agents associated in acute gastroenteritis. The present study highlights, clinical, epidemiological, and molecular aspects with respect to RVA, NoV, enterovirus (EV), and human parechovirus (HPeVs) in sporadic cases (n = 305) of acute gastroenteritis, Pune (Maharashtra), Western India. Detection of RVA was carried out by enzyme-linked immunosorbent assay, NoV, EV, and HPeVs by reverse transcription PCR. Prevalence of 36.06%, 20.32%, 14.09%, 3.93%, respectively was observed for RVA, EV, HPeVs, and NoV along with coinfections. Infections occurred in children less than 2 years old, with peak infections within 12 months age. The disease severity in RV infections was found high (70.90%) with severe disease, followed by EV (62.9%), NoV (58.33%), and HPeV (44.58%). Predominant strains of RV G1P[8], G2P[4] types with unusual G9P[4], NoV Genogroup II of genotype 4 strains and multiple EV types with EV-B species, E14 and E17 and two novel EV-75, EV-107 types were detected. Circulation of heterogeneous HPeV genotypes (HPeV1-5, 7, 8, 13, 14, 16) with predominance of HPeV-1 was noticed. Changing trends in circulation of a rare HPeV-2 genotype, with emerging and reemerging strains was noted. The study highlights association of RVA, NoV, EV, and HPeV and their mono-infections, genotype distribution, and changing trends in acute gastroenteritis, and added more knowledge on rota and nonrota enteric viruses in acute gastroenteritis. More such studies in rota vaccinated era are required across the country, as Indian rotavirus vaccine has been implemented under the National Immunization program.

Anti-SARS-CoV-2 IgG antibody response among Indian COVID-19 patients using ß-propiolactone-inactivated, whole virus-based indirect ELISA.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome - coronavirus-2 (SARS-CoV-2) continues to affect many countries and large populations. Serologic assays for antibody detection aid patient diagnosis and seroepidemiologic investigations. METHODS: An indirect IgG ELISA was developed indigenously using ß-propiolactone (BPL) inactivated SARS-CoV-2. This assay was used for screening 200 healthy donor sera collected prior to COVID-19 emergence (2017-2019), 185 serum/plasma samples of confirmed COVID-19 patients (n = 137) and 57 samples of viral RNA positive asymptomatic contacts (n = 51). The IgG response was studied in relation to duration and severity of illness. RESULTS: The ELISA demonstrated 97 % specificity and IgG detection in >50 %, 80 %, 93.8 % and 100 % of the patients respectively during the first, second, third and fourth week of illness. IgG detection rate was higher in patients with severe disease (SD, 90.9 %) than those with mild disease (MD, 68.8 %) during the second week of illness (P = 0.027). IgG seropositivity among asymptomatic contacts was 64.7 %. IgG ELISA absorbance values were higher in SD than MD patients during the first 2 weeks of illness (P < 0.05). No significant difference was observed between the absorbance values of asymptomatic subjects and MD patients (P = 0.94). CONCLUSION: The BPL inactivated virus-based ELISA could detect IgG antibodies early and in a significant proportion of COVID-19 patients suggesting its potential utility as a supplement to the currently used viral RNA detection tests in patient diagnosis and contact screening algorithms.

On-Demand Local Modification of High-Tc Superconductivity in Few Unit-Cell Thick Bi2 Sr2 CaCu2 O8+δ.

High-temperature superconductors (HTSs) are important for potential applications and for understanding the origin of strong correlations. Bi2 Sr2 CaCu2 O8+δ (BSCCO), a van der Waals material, offers a platform to probe the physics down to a unit-cell. Guiding the flow of electrons by patterning 2DEGS and oxide heterostructures has brought new functionality and access to new science. Similarly, modifying superconductivity in HTS locally, on a small length scale, is of immense interest for superconducting electronics. A route to modify superconductivity locally by depositing metal on the surface is reported here by transport studies on few unit-cell thick BSCCO. Deposition of chromium (Cr) on the surface over a selected area of BSCCO results in insulating behavior of the underlying region. Cr locally depletes oxygen in CuO2 planes and disrupts the superconductivity in the layers below. This technique of modifying superconductivity is suitable for making sub-micrometer superconducting wires and more complex superconducting devices.

Correlation of serostatus and viraemia levels among Indian dengue patients at the time of first diagnosis.

BACKGROUND: Dengue is a public health problem worldwide. Therapeutic monoclonal antibodies (MAbs) against dengue virus (DENV) are likely to be available soon. In view of the feasibility issues pertaining to pretreatment viraemia quantitation for therapy decisions, we conducted this study for investigation of a correlation between patient serostatus (NS1/immunoglobulin M [IgM]/IgG) and viraemia levels among Indian dengue patients at the time of first diagnosis. METHODS: The study included 297 serum samples from dengue patients in Pune, India. The samples were tested for NS1, IgM and IgG (capture enzyme-linked immunosorbent assay [ELISA] for identifying secondary dengue) using Panbio ELISAs. Quantitation of viraemia was conducted using an NS1 ELISA-based 50% tissue culture infectious dose (TCID50) test in Vero cells. RESULTS: Viraemia was detectable only among NS1-positive patients (n = 229, range 0.5-8.3 logTCID50/ml) with a mean titre of 1.9 logTCID50/ml. Among the NS1-positive patients, DENV titres were higher in IgM-negative than IgM-positive patients (p < 0.0001) and in primary (IgG < 18 Panbio units) versus secondary (IgG > 22 Panbio units) dengue patients (p = 0.002). Virus titres were higher during the first 3 days of illness and decreased later (p = 0.005). CONCLUSIONS: The study provides a range of infectious DENV titres in relation to serologic status among dengue patients in India. The data suggest the possibility of using serological markers (NS1/IgM) as a basis for treatment decisions.

Magnetotransport properties of noncentrosymmetric CaAgBi single crystal.

We report on the single crystal growth and transport properties of a topological semimetal CaAgBi which crystallizes in the hexagonal ABC-type structure with the non-centrosymmetric space group P63 mc (No. 186). The transverse magnetoresistance measurements with current in the basal plane of the hexagonal crystal structure reveal a value of about 30% for I∥[10̄0] direction and about 50% for I∥[1̅10] direction at 10 K in an applied magnetic field of 14 T. The magnetoresistance shows a cusp-like behavior in the low magnetic field region, suggesting the presence of weak antilocalization effect for temperatures less than 100 K. The Hall measurements reveal that predominant charge carriers are p-type, exhibiting a linear behavior at high fields. The magnetoconductance of CaAgBi is analyzed based on the modified Hikami-Larkin-Nagaoka model. Our first-principle calculations within a density-functional theory framework reveal that the Fermi surface of CaAgBi consists of both the electron and hole pockets and the size of the hole pocket is much larger than electron pockets suggesting the dominant p-type carriers in accordance with our experimental results.

Comparative assessment of commercial enzyme-linked immunosorbent assay & rapid diagnostic tests used for dengue diagnosis in India.

Background & objectives: Dengue diagnosis is routinely carried out by detection of dengue virus (DENV) antigen NS1 and/or anti-DENV IgM antibodies using enzyme-linked immunosorbent assays (ELISAs) and rapid diagnostic tests (RDTs). This study was aimed at evaluation of quality of diagnostic assays currently in use in India for the identification of DENV infection. Methods: During 2016 dengue season (July-November) in Pune, India, comparative assessment of a few immunoassays was undertaken using (i) WHO-approved Panbio-Dengue-Early-(NS1)-ELISA and Panbio-Dengue-IgM-Capture-ELISA as reference tests, and (ii) Bayesian latent class analysis (BLCA) which assumes that no test is perfect. The assays included J.Mitra-Dengue-NS1-Ag-MICROLISA (JME-NS1), J.Mitra-Dengue-IgM-MICROLISA (JME-IgM), and two RDTs, namely, J.Mitra-Dengue-Day-1-Test (JM-RDT) and SD-BIOLINE-Dengue-Duo (SDB-RDT). Serum samples from patients seeking dengue diagnosis (n=809) were tested using the diagnostic kits. The presence of NS1 and/or IgM was taken as evidence for dengue-positive diagnosis. Results: Panbio-NS1/IgM-ELISAs identified 38.6 per cent patients as dengue positive. With Panbio-ELISA as reference, all the tests were less sensitive for IgM detection, while for NS1, JM-RDT was less sensitive. For combined diagnosis (both markers), sensitivity of all the tests was low (55.7-76.6%). According to BLCA, Panbio-ELISA was 84 per cent sensitive for NS1, 86 per cent specific for IgM and 87 per cent specific for combined diagnosis. Accordingly, performance of the other tests was substantially improved with BLCA; however, sensitivity of both the RDTs for IgM detection remained unacceptable. The NS1 ELISAs and RDTs detected all four DENV serotypes, JME being most efficient. All IgM tests exhibited higher sensitivity in secondary infections. Interpretation & conclusions: These results confirmed superiority of ELISAs, and testing for both NS1 and IgM markers for dengue diagnosis, and emphasized on improvement in sensitivity of RDTs.

Use of Paley Classification and SUPERankle Procedure in the Management of Fibular Hemimelia.

BACKGROUND: Fibular hemimelia is the most common deficiency involving the long bones. Paley classification is based on the ankle joint morphology, identifies the basic pathology, and helps in planning the surgical management. Reconstruction surgery encompasses foot deformity correction and limb length equalization. The SUPERankle procedure is a combination of bone and soft tissue procedures that stabilizes the foot and addresses all deformities. METHODS: We retrospectively reviewed 29 consecutive patients (29 limb segments), surgically treated between December 2000 and December 2014. Among the 29 patients, 27 were treated with reconstructive procedures. Type 1 (8 patients) cases were treated with only limb lengthening, and correction of tibial deformities. Type 2 (7 patients) cases were treated by distal tibial medial hemiepiphysiodesis or supramalleolar varus osteotomy. In type 3 (10 patients) cases, the foot deformity was corrected using the SUPERankle procedure. Type 4 (2 patients) cases were treated with supramalleolar osteotomy along with posteromedial release and lateral column shortening. In a second stage, limb lengthening was performed, using the Ilizarov technique. In the remaining 2 patients (type 3A and type 3C), amputation was performed using Syme technique as a first choice of treatment. RESULTS: The results were evaluated using Association for the Study and Application of Methods of Ilizarov scoring. Excellent results were obtained in 15 of 27 (55%) patients. Six (22%) patients had good results, 4 (14.8%) had fair results, and 2 (7%) had poor results. Mean limb length discrepancy at initial presentation was 3.55 cm (range: 2 to 5.5 cm) which significantly improved to 1.01 cm (range: 0 to 3 cm) after treatment (P=0.015). CONCLUSIONS: Our results and a review of the literature clearly suggest that limb reconstruction according to Paley classification, is an excellent option in the management of fibular hemimelia. Our 2-staged procedure (SUPERankle procedure followed by limb lengthening) helps in reducing the complications of limb lengthening and incidence of ankle stiffness. Performing the first surgery at an earlier age (below 5 y) plays a significant role in preventing recurrent foot deformities. LEVEL OF EVIDENCE: Level IV.

Seroepidemiology of respiratory syncytial virus in western India with special reference to appropriate age for infant vaccination.

Respiratory syncytial virus (RSV) causes significant infant mortality worldwide and a vaccine may be available soon. This study determined age-stratified anti-RSV antibody positivity (enzyme-linked immunosorbent assay [ELISA]) at Pune, India (cord blood-85 years). Antibody positivity declined from 100% at birth to 71.3% (3 months), and 0.7% (6 months). A significant rise was noted at 15 months (16%), 16 to 24 months (64.5%) and 4 years (95.2%) with concomitant IgM-anti-RSV positivity indicative of recent infection. Antibody decline was higher in infants born preterm than full-term. Across subsequent age groups including the elderly, antibody positivity was similar and comparable, suggestive of repeated exposure to the virus. Early protection/vaccination is essential for the infant population.

Early disappearance of maternal anti-measles, mumps, rubella, and varicella antibodies in Indian infants.

BACKGROUND: Immunization of children with vaccines against Measles, Mumps, Rubella, and Varicella (MMRV) is practiced globally with varied recommendations. In India, measles vaccine is administered alone or as MMR at 9 months age. Varicella vaccine is not routinely used. Immunization age is a function of disappearance of maternal antibodies and natural exposure of the children to the pathogens. In view of the measles-WHO-initiative, we aimed to assess if the current immunization age for measles is still valid. In addition, the kinetics of IgG and IgM antibodies against rubella, mumps and varicella viruses was also examined. METHODS: This cross-sectional study was conducted at a tertiary care hospital in Pune, India. A total of 600 children, 150 each in 6-month/9-month (no vaccination) and 12-month/15-month (minimum 4 weeks post-measles-vaccine) cohorts were included. History of these infections and birth status (term/preterm) was recorded. All serum samples were screened for IgG-anti-MMRV-antibodies while IgG-positives were tested for specific IgM antibodies (ELISA). RESULTS: At 6-months, the prevalence of MMRV antibodies was 4.7%, 2.7%, 10.7%, 5.3% respectively depicting disappearance of maternal antibodies in majority of the children. Birth status did not influence antibody positivity. Despite vaccination at ∼9-months, >25% children were still susceptible to measles virus at the age of 12/15-months. The ratio of clinical:subclinical infections was 4:10 (measles) and 12:1 (varicella). All the mumps/rubella IgM positives (1 and 2 respectively) represented subclinical infections. CONCLUSION: Demonstration of early disappearance of maternal antibodies against MMRV viruses leading to the risk of these infections at an early age emphasize need for early immunization of Indian children. Suboptimal response to measles vaccine needs to be seriously addressed especially in view of the WHO's initiative for measles eradication.

Age-stratified anti-HAV positivity in Pune, India after two decades: Has voluntary vaccination impacted overall exposure to HAV?

The degree of transmission of hepatitis A virus (HAV) is inversely proportional to the socioeconomic status of a community. Serosurveys conducted at Pune, India during 1982-98 documented significant reduction in HAV exposure of paediatric, higher socioeconomic status (HSS) population. Anti-HAV positivity (ELISA) in age-stratified Pune population representing HSS and lower middle socioeconomic status (LMSS) (n = 1065) and infants till the age of 15 months (n = 690) was determined in 2017. Anti-HAV positivity in the LMSS population decreased significantly in 2017 while an increase was seen in the HSS category. The surprising rise in anti-HAV positivity in the HSS population reflected vaccine- and infection-induced antibodies while only infection-induced antibodies were present in the LMSS category. Lowest antibody prevalence in infants was at 12 months, the recommended age for hepatitis A vaccination. Improved hygiene and selective immunization practices impacted HAV exposure of the LMSS population. The data emphasize the need for hepatitis A vaccination irrespective of socioeconomic status.