We retrieved Nipah virus (NiV) sequences from 4 human and 3 fruit bat (Pteropus medius) samples from a 2018 outbreak in Kerala, India. Phylogenetic analysis demonstrated that NiV from humans was ...96.15% similar to a Bangladesh strain but 99.7%-100% similar to virus from Pteropus spp. bats, indicating bats were the source of the outbreak.
Neonatal diabetes mellitus (NDM) is a rare monogenic disorder of pancreatic beta cell mass and/or function. In the present study we aimed to evaluate the INS gene mutations in a cohort of children ...with Permanent Neonatal Diabetes Mellitus (PNDM) and to explore the clinical and genetic characteristics of PNDM caused by INS mutations.
Direct sequencing of all exons of INS genes was carried out in 189 children with PNDM. Clinical and biochemical data were collected and correlated. The pathogenicity of mutations was determined based on the American College of Medical Genetics and Genomics and Association of Medical Pathology guidelines.
Two novel mutations (His34Pro, Leu35Met) in a compound heterozygous state and seven known mutations (Gly32Ser, Phe48Cys, Arg89Cys, Cys96Tyr, Ser98Ile, Try108Asp and Cys109Phe) in the INS gene were identified in 8 patients out of the total of 189 PNDM children studied. Four mutations were involved in defects with disulphide bond formation and hence were in crucial regions of the gene. All the mutations were de novo in origin.
This is the first comprehensive study from India to investigate the insulin gene mutations in PNDM and to show that INS gene mutations also contribute to the causation of PNDM.
•This is the first study describing the spectrum of INS gene mutations in Indian PNDM patients.•Four mutations that created unpaired cysteine and five mutations that involved non-cysteine residues were identified.•Five mutations that involved non cysteine residues were G32S, H34P, L35M, S98I and Y108D•Bioinformatics analysis and ACMG guidelines predicted that these variations could be damaging or disease causing.•NDM children in this study are on insulin therapy, were born to non- consanguineous parents and carried de novo mutations.
Skull base osteomyelitis is a potentially life-threatening infection, usually seen in elderly immunocompromised patients secondary to malignant otitis externa (MOE) caused by Pseudomonas. Central or ...atypical skull base osteomyelitis often poses a diagnostic challenge as they present as head-ache with or without cranial nerve palsy often without any obvious source of infection. Although the incidence of fungal skull base osteomyelitis is increasing central skull base osteomyelitis due to invasive fungal sinusitis presenting with isolated hypoglossal nerve palsy has not been reported in the literature, to our knowledge. We report a case of a 59-year-old diabetic patient on regular treatment including steroid for acetylcholine receptor binding antibody positive myasthenia gravis with thymoma who presented with persistent head-ache and on evaluation, was found to have 12th cranial nerve palsy on the right side. She was diagnosed to have invasive fungal sphenoid sinusitis and central skull base osteomyelitis involving the clivus and was successfully treated with endoscopic transnasal transsphenoidal debridement followed by antifungal therapy.
Maturity-onset diabetes of the young (MODY) is an early-onset, autosomal dominant form of non-insulin dependent diabetes. Genetic diagnosis of MODY can transform patient management. Earlier data on ...the genetic predisposition to MODY have come primarily from familial studies in populations of European origin.
In this study, we carried out a comprehensive genomic analysis of 289 individuals from India that included 152 clinically diagnosed MODY cases to identify variants in known MODY genes. Further, we have analyzed exome data to identify putative MODY relevant variants in genes previously not implicated in MODY. Functional validation of MODY relevant variants was also performed.
We found MODY 3 (HNF1A; 7.2%) to be most frequently mutated followed by MODY 12 (ABCC8; 3.3%). They together account for ~ 11% of the cases. In addition to known MODY genes, we report the identification of variants in RFX6, WFS1, AKT2, NKX6-1 that may contribute to development of MODY. Functional assessment of the NKX6-1 variants showed that they are functionally impaired.
Our findings showed HNF1A and ABCC8 to be the most frequently mutated MODY genes in south India. Further we provide evidence for additional MODY relevant genes, such as NKX6-1, and these require further validation.
We conducted a serosurvey of 155 healthcare workers and 124 household and community members who had close contact with 18 patients who had laboratory-confirmed Nipah virus infections in Kerala, ...India. We detected 3 subclinical infections; 2 persons had IgM and IgG and 1 only IgM against Nipah virus.
We report here a Nipah virus (NiV) outbreak in Kozhikode district of Kerala state, India, which had caused fatal encephalitis in a 12-year-old boy and the outbreak response, which led to the ...successful containment of the disease and the related investigations. Quantitative real-time reverse transcription (RT)-PCR, ELISA-based antibody detection, and whole genome sequencing (WGS) were performed to confirm the NiV infection. Contacts of the index case were traced and isolated based on risk categorization. Bats from the areas near the epicenter of the outbreak were sampled for throat swabs, rectal swabs, and blood samples for NiV screening by real-time RT-PCR and anti-NiV bat immunoglobulin G (IgG) ELISA. A plaque reduction neutralization test was performed for the detection of neutralizing antibodies. Nipah viral RNA could be detected from blood, bronchial wash, endotracheal (ET) secretion, and cerebrospinal fluid (CSF) and anti-NiV immunoglobulin M (IgM) antibodies from the serum sample of the index case. Rapid establishment of an onsite NiV diagnostic facility and contact tracing helped in quick containment of the outbreak. NiV sequences retrieved from the clinical specimen of the index case formed a sub-cluster with the earlier reported Nipah I genotype sequences from India with more than 95% similarity. Anti-NiV IgG positivity could be detected in 21% of
(
) and 37.73% of
(
). Neutralizing antibodies against NiV could be detected in
. Stringent surveillance and awareness campaigns need to be implemented in the area to reduce human-bat interactions and minimize spillover events, which can lead to sporadic outbreaks of NiV.
Background: Gestational diabetes mellitus (GDM) and thyroid dysfunction are the two common endocrine disorders affecting pregnancy. Some association was hypothesized between GDM and thyroid ...dysfunction in the literature. The main aim of this study was to unveil this metabolic interplay as better understanding may facilitate early diagnosis and intervention thereby limiting major fetal and maternal adverse events. Here we estimated the prevalence of abnormal thyroid function and anti-thyroid peroxidase (anti-TPO) antibody and also studied the risk factors for thyroid disorders in patients with GDM. Materials and Methods: This cross-sectional study was conducted between February 2014 and January 2015. A total of 100 consecutive pregnant women diagnosed to have GDM as per the American Diabetes Association 2013 recommendations were recruited and thyroid stimulating hormone, free triiodothyronine (T3), free thyroxine (T4), and anti-TPO antibody assays were done. Details regarding pregnancy outcome and any complications if present were also obtained and analyzed. The prevalence is expressed as proportions, and the statistical significance of risk factors was assessed using the chi-square test and independent t-test. Results: Abnormal thyroid function was detected in 31 (31%) patients, which includes 17 cases of subclinical hypothyroidism (54%), 10 hypothyroidism (32%), 2 (6%) subclinical hyperthyroidism, and one case each of isolated low T3 and isolated low T4. Anti-TPO antibody was positive in 35 patients (35%). History of GDM in previous pregnancy, family history of diabetes mellitus, presence of clinically detectable thyroid gland enlargement, and presence of anti-TPO antibody in serum were found to increase the risk of thyroid dysfunction. Majority of the subjects had uneventful delivery, and no significant increase in maternal or fetal complications was reported. Conclusions: This study showed a high prevalence of thyroid dysfunction and anti-TPO antibody in GDM patients. The significant thyroid abnormalities detected were subclinical hypothyroidism and hypothyroidism. The risk of thyroid dysfunction is elevated in patients with the presence of anti-TPO antibody. This scenario provides a strong ground to recommend meticulous assessment of thyroid function in GDM patients.
Coronavirus disease 2019 (COVID-19) rapidly spread from a city in China to almost every country in the world, affecting millions of individuals. The rapid increase in the COVID-19 cases in the state ...of Kerala in India has necessitated the understanding of SARS-CoV-2 genetic epidemiology. We sequenced 200 samples from patients in Kerala using COVIDSeq protocol amplicon-based sequencing. The analysis identified 166 high-quality single-nucleotide variants encompassing four novel variants and 89 new variants in the Indian isolated SARS-CoV-2. Phylogenetic and haplotype analysis revealed that the virus was dominated by three distinct introductions followed by local spread suggesting recent outbreaks and that it belongs to the A2a clade. Further analysis of the functional variants revealed that two variants in the
gene associated with increased infectivity and five variants mapped in primer binding sites affect the efficacy of RT-PCR. To the best of our knowledge, this is the first and most comprehensive report of SARS-CoV-2 genetic epidemiology from Kerala.
Background
Quarantine is one of the best measures to prevent the community spread of any infectious diseases. The study focused on the psychosocial impacts of quarantine among the survivors of the ...highly fatal viral disease, Nipah virus infection (NiV), and their family members. Objective of the study was to examine the psychosocial impact of quarantine on NiV survivors and families being quarantined because of exposure to NiV infection.
Methods
We used qualitative in-depth interviews, Focus group discussions and Narratives of a participant observer to explore the psychosocial impacts of Quarantine during the NiV outbreak. We identified 2 major themes for doing the in-depth interview and focus group discussions: (i) quarantine experience, (ii) its impact on the family and social living and subject’s working environment.
Results
The identified major themes are the following, Stroke on the community structure, public mistrust, psychosocial sequelae experienced by the grass root level health care workers, stigma in the community and social percussions.
Conclusions
Quarantine measures were effective when controlling an infectious disease spread, but it imparts many long lasting consequences on the psychological and social wellbeing of the individual. Better understanding these consequences will help to plan interventions incorporating this knowledge in future outbreaks of similar types.
Next Generation Sequencing (NGS) is the gold standard for the detection of new variants of SARS-CoV-2 including those which have immune escape properties, high infectivity, and variable severity. ...This test is helpful in genomic surveillance, for planning appropriate and timely public health interventions. But labs with NGS facilities are not available in small or medium research settings due to the high cost of setting up such a facility. Transportation of samples from many places to few centers for NGS testing also produces delays due to transportation and sample overload leading in turn to delays in patient management and community interventions. This becomes more important for patients traveling from hotspot regions or those suspected of harboring a new variant. Another major issue is the high cost of NGS-based tests. Thus, it may not be a good option for an economically viable surveillance program requiring immediate result generation and patient follow-up. The current study used a cost-effective facility which can be set up in a common research lab and which is replicable in similar centers with expertise in Sanger nucleotide sequencing. More samples can be processed at a time and can generate the results in a maximum of 2 days (1 day for a 24 h working lab). We analyzed the nucleotide sequence of the Receptor Binding Domain (RBD) region of SARS-CoV-2 by the Sanger sequencing using in-house developed methods. The SARS-CoV-2 variant surveillance was done during the period of March 2021 to May 2022 in the Northern region of Kerala, a state in India with a population of 36.4 million, for implementing appropriate timely interventions. Our findings broadly agree with those from elsewhere in India and other countries during the period.
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