Unveiling Neurobrucellosis: A Case Report Emphasizing Early Diagnosis for Better Outcomes.

Introduction: Brucellosis is a pervasive zoonotic disease causing considerable human morbidity worldwide. This report focuses on a case of neurobrucellosis in a rural Indian patient, emphasizing the need for timely microbiological confirmation given its nonspecific clinical presentation. Case Presentation: A 55-year-old rural Indian farmer presented with a 3 week history of insidious, low-grade fever, myalgia, and arthralgia. He developed acute right-sided weakness and neurological symptoms, including disorientation and neck rigidity. Laboratory tests indicated abnormal blood counts, elevated inflammatory markers, and liver dysfunction. Cerebrospinal fluid analysis showed pleocytosis with lymphomononuclear cells and elevated protein levels. Blood cultures eventually grew Gram-negative coccobacilli. Serological tests confirmed neurobrucellosis. Prompt antibiotic therapy led to clinical and laboratory improvement. Conclusion: This case underscores the importance of recognizing neurobrucellosis, particularly in endemic areas, given its nonspecific clinical presentation. Early microbiological diagnosis, supported by positive blood cultures and serological tests, was crucial. The patient's rapid response to appropriate antibiotics emphasizes the significance of timely recognition and management.

Molecular appraisal of Giardia intestinalis from Western India: A prospective observational study.

Background: Giardia intestinalis is an intestinal protozoan which commonly causes parasitic gastroenteritis globally. It is a species complex consisting of at least eight assemblages (genotypes). In India, Giardia is mostly underreported and missed in asymptomatic cases. Aim: The aim of this study was to genotype the G. intestinalis isolates from stool samples of patients at a tertiary care center in Rajasthan, India, and to clinically correlate it. Methods: This prospective pilot cross-sectional study was conducted from 2019 to 2021 in a tertiary care center in western India. Patients who were microscopically positive for giardiasis were enrolled. DNA was extracted from their stool samples and amplified by polymerase chain reaction (PCR) using 4E1-HP as the target sequence. Anthropometric measurements and analysis were done for children by using Anthrocal application. Results: A total of 50 patients were enrolled. Diarrhea was present in 18 patients (36%). Among these, 6 were immunocompromised and had different comorbidities. Among the children <12 years of age, 55.17% (n = 16/29) were stunted (<-2 S.D.), and among <5 years, 44.4% (n = 4/9) showed wasting (<-2 S.D.). A PCR product corresponding to assemblage B of G. intestinalis was amplified in 47 stool specimens. Only three stool samples were negative for both assemblages A and B and posed an interesting enigma. Conclusion: In this study, a predominance of assemblage B of G. intestinalis was detected in 94% of the isolates. Furthermore, the possibility of zoonotic transmission could not be ruled out.

Correlation of severity & clinical outcomes of COVID-19 with virus variants: A prospective, multicentre hospital network study.

BACKGROUND OBJECTIVES: The clinical course of COVID-19 and its prognosis are influenced by both viral and host factors. The objectives of this study were to develop a nationwide platform to investigate the molecular epidemiology of SARS-CoV-2 (Severe acute respiratory syndrome Corona virus 2) and correlate the severity and clinical outcomes of COVID-19 with virus variants. METHODS: A nationwide, longitudinal, prospective cohort study was conducted from September 2021 to December 2022 at 14 hospitals across the country that were linked to a viral sequencing laboratory under the Indian SARS-CoV-2 Genomics Consortium. All participants (18 yr and above) who attended the hospital with a suspicion of SARS-CoV-2 infection and tested positive by the reverse transcription-PCR method were included. The participant population consisted of both hospitalized as well as outpatients. Their clinical course and outcomes were studied prospectively. Nasopharyngeal samples collected were subjected to whole genome sequencing to detect SARS-CoV-2 variants. RESULTS: Of the 4972 participants enrolled, 3397 provided samples for viral sequencing and 2723 samples were successfully sequenced. From this, the evolution of virus variants of concern including Omicron subvariants which emerged over time was observed and the same reported here. The mean age of the study participants was 41 yr and overall 49.3 per cent were female. The common symptoms were fever and cough and 32.5 per cent had comorbidities. Infection with the Delta variant evidently increased the risk of severe COVID-19 (adjusted odds ratio: 2.53, 95% confidence interval: 1.52, 4.2), while Omicron was milder independent of vaccination status. The independent risk factors for mortality were age >65 yr, presence of comorbidities and no vaccination. INTERPRETATION CONCLUSIONS: The authors believe that this is a first-of-its-kind study in the country that provides real-time data of virus evolution from a pan-India network of hospitals closely linked to the genome sequencing laboratories. The severity of COVID-19 could be correlated with virus variants with Omicron being the milder variant.

An unusual co-reactivation of herpes genitalis and shingles in a young male with primary genital herpes in partner.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcers in industrialized countries. Herpes zoster (HZ) is an acute, cutaneous viral infection caused by the reactivation of the varicella-zoster virus (VZV). CASE SUMMARY: A 27-year-old male presented with painful vesicles over the trunk for the last 5 days with painful genital erosions for the last 2 days. His spouse also developed painful genital erosions with systemic complaints for the last 2 days. VZV Polymerase Chain reaction (PCR) from trunk vesicles and type-specific anti-HSV antibody from serum were positive from the index case. DISCUSSION: Here, we report an unusual case of co-reactivation of herpes zoster and genitalis in an immunocompetent male. We recommend the use of molecular testing to confirm the diagnosis of VZV or HSV infection in all cases of genital herpes-like lesions to exclude multi-segmental herpes zoster.

Effectiveness of ayurvedic formulation, NAOQ19 along with standard care in the treatment of mild-moderate COVID-19 patients: A double blind, randomized, placebo-controlled, multicentric trial.

BACKGROUND: Medicines in indigenous systems such as Ayurveda have strong antimicrobial activity but double-blind randomized control trials are infrequent in this system of medicine. The efficacy of a new ayurvedic formulation was evaluated during the pandemic. METHODS: 150 mild-moderate COVID-19 patients were enrolled and randomized in 1:1 to NAOQ19 and placebo group. RT-PCR was done on Day 3, 5 and 7. CBC, CRP, LFT, and KFT were assessed at baseline and exit. Duration of hospital stay was noted and clinical assessment was also performed. RESULT: The results demonstrated more people turning RT-PCR negative in the NAOQ19 group compared to the placebo group on day 3 (p-value = 0.033). The mean time duration to turn RT-PCR negative was significantly lower in the NAOQ19 group (4.6 days) compared to placebo group (5.2 days) (p-value = 0.018). There was significant reduction in hospital stay among patients in the NAOQ19 arm who were discharged earlier (5.6 days) compared to placebo group (6.4 days) (p-value = 0.046). Patients in NAOQ19 arm did not show any adverse life-threatening events. CONCLUSION: The ayurvedic preparation given along with standard of care therapy reduced the duration of hospital stay and there was earlier conversion to RT-PCR negative.The integrated approach can help to reduce patient workload in the hospitals as well as limit the transmission of the virus in the community. STUDY REGISTRATION: CTRI/2021/05/033790.

Identification of consensus hairpin loop structure among the negative sense subgenomic RNAs of SARS-CoV-2.

Background: SARS-CoV-2 is the causative agent of worldwide pandemic disease coronavirus disease 19. SARS-CoV-2 bears positive sense RNA genome that has organized and complex pattern of replication/transcription process including the generation of subgenomic RNAs. Transcription regulatory sequences have important role in the pausing of replication/transcription and generation of subgenomic RNAs. Results: In the present bioinformatics analysis, a consensus secondary structure was identified among negative sense subgenomic RNAs of SARS-CoV-2. This consensus region is present at the adjacent of initiation codon. Conclusions: This study proposed that consensus structured domain could involve in mediating the long pausing of replication/transcription complex and responsible for subgenomic RNA production. Supplementary Information: The online version contains supplementary material available at 10.1186/s42269-023-01002-3.

Post-COVID-19 Immune-Mediated Neurological Complications in Children: An Ambispective Study.

BACKGROUND: The neurological manifestation following a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is varied, and till now, only a few studies have reported the same. METHODS: We used retrospective data from May to July 2021 and prospective study data from August to September 2021, including that from children aged between one month and 18 years who presented to a tertiary care referral center with the neurological manifestation and had a history of coronavirus disease 2019 (COVID-19) infection or exposure and positive SARS-CoV-2 serology. The neuroradiological manifestations were further categorized as in a predesigned proforma. RESULTS: Case records of the 18 children who fulfilled the criteria were included in the study; among them, seven (38.8%) were male and 11 (61.1%) were female. Predominant presentation in our study group was status epilepticus (six of 18) and Guillain-Barré syndrome (five of 18). Other manifestations included stroke (two of 18), demyelinating syndromes (three of 18), and autoimmune encephalitis (two of 18). Most of the children had favorable outcomes except for one mortality in our cohort. CONCLUSIONS: Delayed complications following SARS-CoV-2 infection are seen in children. A temporal correlation was noted between the COVID-19 infection and the increasing number of neurological cases after the second wave. Steroids could be beneficial while treating such patients, especially in the presence of high inflammatory markers. Testing for SARS-CoV-2 serology during the pandemic can give a clue to the underlying etiology. Further multicentric studies are required to understand the varied neurological manifestations following SARS-CoV-2 infection in children.

Effectiveness of BBV152/Covaxin and AZD1222/Covishield vaccines against severe COVID-19 and B.1.617.2/Delta variant in India, 2021: a multi-centric hospital-based case-control study.

OBJECTIVES: India introduced BBV152/Covaxin and AZD1222/Covishield vaccines in January 2021. We estimated the effectiveness of these vaccines against severe COVID-19 among individuals aged ≥45 years. METHODS: We did a multi-centric, hospital-based, case-control study between May and July 2021. Cases were severe COVID-19 patients, and controls were COVID-19 negative individuals from 11 hospitals. Vaccine effectiveness (VE) was estimated for complete (2 doses ≥ 14 days) and partial (1 dose ≥ 21 days) vaccination; interval between two vaccine doses and vaccination against the Delta variant. We used the random effects logistic regression model to calculate the adjusted odds ratios (aOR) with a 95% confidence interval (CI) after adjusting for relevant known confounders. RESULTS: We enrolled 1143 cases and 2541 control patients. The VE of complete vaccination was 85% (95% CI: 79-89%) with AZD1222/Covishield and 71% (95% CI: 57-81%) with BBV152/Covaxin. The VE was highest for 6-8 weeks between two doses of AZD1222/Covishield (94%, 95% CI: 86-97%) and BBV152/Covaxin (93%, 95% CI: 34-99%). The VE estimates were similar against the Delta strain and sub-lineages. CONCLUSION: BBV152/Covaxin and AZD1222/Covishield were effective against severe COVID-19 among the Indian population during the period of dominance of the highly transmissible Delta variant in the second wave of the pandemic. An escalation of two-dose coverage with COVID-19 vaccines is critical to reduce severe COVID-19 and further mitigate the pandemic in the country.

Delta variant SARS-CoV-2 infections in pediatric cases during the second wave in India.

BACKGROUND: During October 2020, Delta variant was detected for the first time in India and rampantly spread across the globe. It also led to second wave of pandemic in India which affected millions of people. However, there is limited information pertaining to the SARS-CoV-2 strain infecting the children in India. METHODS: Here, we assessed the SARS-CoV-2 lineages circulating in the pediatric population of India during the second wave of the pandemic. Clinical and demographic details linked with the nasopharyngeal/oropharyngeal swabs (NPS/OPS) collected from SARS-CoV-2 cases (n = 583) aged 0-18 year and tested positive by real-time RT-PCR were retrieved from March to June 2021. RESULTS: Symptoms were reported among 37.2% of patients and 14.8% reported to be hospitalized. The E gene CT value had significant statistical difference at the point of sample collection when compared to that observed in the sequencing laboratory. Out of these 512 sequences 372 were VOCs, 51 were VOIs. Most common lineages observed were Delta, followed by Kappa, Alpha and B.1.36, seen in 65.82%, 9.96%, 6.83% and 4.68%, respectively in the study population. CONCLUSION: Overall, it was observed that Delta strain was the leading cause of SARS-CoV-2 infection in Indian children during the second wave of the pandemic. We emphasize on the need of continuous genomic surveillance in SARS-CoV-2 infection even amongst children.

Zika a Vector Borne Disease Detected in Newer States of India Amidst the COVID-19 Pandemic.

Background: During the second wave of the COVID-19 pandemic, outbreaks of Zika were reported from Kerala, Uttar Pradesh, and Maharashtra, India in 2021. The Dengue and Chikungunya negative samples were retrospectively screened to determine the presence of the Zika virus from different geographical regions of India. Methods: During May to October 2021, the clinical samples of 1475 patients, across 13 states and a union territory of India were screened and re-tested for Dengue, Chikungunya and Zika by CDC Trioplex Real time RT-PCR. The Zika rRTPCR positive samples were further screened with anti-Zika IgM and Plaque Reduction Neutralization Test. Next generation sequencing was used for further molecular characterization. Results: The positivity was observed for Zika (67), Dengue (121), and Chikungunya (10) amongst screened cases. The co-infections of Dengue/Chikungunya, Dengue/Zika, and Dengue/Chikungunya/Zika were also observed. All Zika cases were symptomatic with fever (84%) and rash (78%) as major presenting symptoms. Of them, four patients had respiratory distress, one presented with seizures, and one with suspected microcephaly at birth. The Asian Lineage of Zika and all four serotypes of Dengue were found in circulation. Conclusion: Our study indicates the spread of the Zika virus to several states of India and an urgent need to strengthen its surveillance.

Immune profile and responses of a novel dengue DNA vaccine encoding an EDIII-NS1 consensus design based on Indo-African sequences.

The ongoing COVID-19 pandemic highlights the need to tackle viral variants, expand the number of antigens, and assess diverse delivery systems for vaccines against emerging viruses. In the present study, a DNA vaccine candidate was generated by combining in tandem envelope protein domain III (EDIII) of dengue virus serotypes 1-4 and a dengue virus (DENV)-2 non-structural protein 1 (NS1) protein-coding region. Each domain was designed as a serotype-specific consensus coding sequence derived from different genotypes based on the whole genome sequencing of clinical isolates in India and complemented with data from Africa. This sequence was further optimized for protein expression. In silico structural analysis of the EDIII consensus sequence revealed that epitopes are structurally conserved and immunogenic. The vaccination of mice with this construct induced pan-serotype neutralizing antibodies and antigen-specific T cell responses. Assaying intracellular interferon (IFN)-γ staining, immunoglobulin IgG2(a/c)/IgG1 ratios, and immune gene profiling suggests a strong Th1-dominant immune response. Finally, the passive transfer of immune sera protected AG129 mice challenged with a virulent, non-mouse-adapted DENV-2 strain. Our findings collectively suggest an alternative strategy for dengue vaccine design by offering a novel vaccine candidate with a possible broad-spectrum protection and a successful clinical translation either as a stand alone or in a mix and match strategy.

Neonatal dengue: an under-diagnosed entity.

Neonatal dengue is an under-diagnosed disease likely due to low index of suspicion along with its resemblance to sepsis. We hereby report two cases of neonatal dengue, highlighting the need of high degree of suspicion in infants born to febrile mothers even with maternal serology being negative. Moreover, severity of neonatal illness positively correlates with the maternal disease.

Predictors of Clinical Outcomes in Adult COVID-19 Patients Admitted to a Tertiary Care Hospital in India: an analytical cross-sectional study.

BACKGROUND: The outbreak ofsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted inexponential rise in the number of patients getting hospitalised with corona virus disease 2019 (COVID-19). There is a paucity of data from South East Asian Region related to the predictors of clinical outcomes in these patients. This formed the basis of conducting our study. METHODS: This was an analytical cross-sectional study. Demographic, clinical, radiological and laboratory data of 125 patients was collected on admission. The study outcome was death or discharge after recovery. For univariate analysis, unpaired t-test, Chi-square and Fisher's Exact test were used. Receiver operating characteristic (ROC) curves were plotted for Sequential Organ Failure Assessment (SOFA) score and few laboratory parameters. Logistic regression was applied for multivariate analysis. RESULTS: Elderly age, ischemic heart disease and smoking were significantly associated with mortality. Elevated levels of D-dimer and lactate dehydrogenase (LDH) and reduced lymphocyte counts were the predictors of mortality. The ROCs for SOFA score curve showed a cut-off value ≥ 3.5 (sensitivity- 91.7% and specificity- 87.5%), for IL-6 the cut-off value was ≥ 37.9 (sensitivity- 96% and specificity- 78%) and for lymphocyte counts, a cut off was calculated to be less than and equal to 1.46 x 109per litre (sensitivity-75.2%and specificity- 83.3%). CONCLUSION: Old age, smoking history, ischemic heart disease and laboratory parameters including elevated D-dimer, raised LDH and low lymphocyte counts at baseline are associated with COVID-19 mortality. A higher SOFA score at admission is a poor prognosticator in COVID-19 patients.

Viral Ribonucleic Acid Shedding and Transmission Potential of Asymptomatic and Paucisymptomatic Coronavirus Disease 2019 Patients.

We studied the pattern and duration of viral ribonucleic acid (RNA) shedding in 32 asymptomatic and 11 paucisymptomatic coronavirus disease 2019 cases. Viral RNA shedding in exhaled breath progressively diminished and became negative after 6 days of a positive reverse-transcription polymerase chain reaction test. Therefore, the duration of isolation can be minimized to 6 days.

A 5-year study of dengue seropositivity among suspected cases attending a teaching hospital of North-Western region of India.

Dengue virus infection is estimated to cause infection in approximately 390 million people globally each year, of which 96 million develop clinical disease. Dengue serotype 2 (DEN-2) is the most prevalent serotype over the past 50 years in India, but serotypes 3 and 4 have appeared in some epidemics as well. A retrospective study was conducted in a teaching hospital, western India, between January 2014 and December 2018. The records of dengue serological test were analyzed. In total, 40 randomly selected nonstructural protein 1 (NS1) antigen-positive samples were analyzed by a reverse transcription-polymerase chain reaction. The demographic data, that is, age and sex, along with geographic location and platelet count level, were recorded from the Serology laboratory register and Hospital Information System. In total, 14.85% (735/4948) samples tested positive for dengue serology. Most of the laboratory-confirmed dengue cases, 34.97% (257/735), were observed in the 21-30 years of age group. The most common serotype detected in the tested samples was DEN-3 in 55% cases (22/40, 13 monoinfection and 9 coinfection with DEN-1 and DEN-2). The present study gives an insight into the trend of dengue seropositivity among suspected cases in the western part of Rajasthan, India. This study showed a higher seroprevalence of dengue infection as well as a gradual increase in the seroprevalence in this part of India.

The Enigma of Low COVID-19 Fatality Rate in India.

Coronavirus disease 2019 (COVID-19), an acute onset pneumonia caused by a novel Betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly evolved into a pandemic. Though its origin has been linked to the Wuhan City of China's Hubei Province in December 2019, recent reports claim that the original animal-to-human transmission of the virus probably happened sometime between September and October 2019 in Guangdong Province, rather than Hubei. As of July 3, 2020, India has reported a case positivity rate of 6.5% and a fatality rate of 2.8%, which are among the lowest in the world. Also, the severity of the disease is much less among Indians as evidenced by the low rate of ICU admission (15.3%) and the need for mechanical ventilation (4.16%). As per the World Health Organization (WHO) situation report 165 on July 3, 2020, India has one of the lowest deaths per 100,000 population (1.32 deaths against a global average of 6.04). Several factors related to the pathogen, host and environment might have some role in reducing the susceptibility of Indians to COVID-19. These include some ongoing mutations that can alter the virulence of the circulating SARS-CoV-2 strains, host factors like innate immunity, genetic diversity in immune responses, epigenetic factors, genetic polymorphisms of ACE2 receptors, micro RNAs and universal BCG vaccination, and environmental factors like high temperature and humidity which may alter the viability and transmissibility of the strain. This perspective -highlights the potential factors that might be responsible for the observed low COVID-19 fatality rate in Indian population. It puts forward several hypotheses which can be a ground for future studies determining individual and population susceptibility to COVID-19 and thus, may offer a new dimension to our current understanding of the disease.