A cross sectional study on molecular prevalence of Orientia tsutsugamushi in household rat population of South India.

This study aimed to assess the molecular prevalence of mite-borne zoonotic pathogen O. tsutsugamushi in household rats of South India through nested polymerase chain reaction amplification of O. tsutsugamushi 47-kDa htrA gene and to determine the most suitable sample type for screening of O. tsutsugamushi in rats. Out of 85 rats trapped in Tamil Nadu, Karnataka, and Puducherry regions, 47 rats were found positive for the O. tsutsugamushi genome with prevalence of 55.29 %. Among different sample types screened, faecal samples exhibited the highest positivity rate, followed by liver, spleen, kidney, and blood samples. Agreement between faecal and spleen samples of rats for the presence of O. tsutsugamushi was the highest. Principal component analysis revealed a positive correlation between the spleen, liver, and faeces and a negative correlation between blood and faeces for the presence of O. tsutsugamushi genome. These findings underscore the varied distribution of O. tsutsugamushi among different samples and indicate that the faecal and liver samples of rats are an ideal choice of samples for epidemiological studies. This is the first study to report a high level of presence of O. tsutsugamushi in faecal samples of rats.

Comparison of rituximab efficacy in treatment-naive and refractory inflammatory myopathies: experiences from a tertiary care centre.

OBJECTIVES: To find out if Rituximab (RTX) is effective in "treatment naive" idiopathic inflammatory myopathies (IIM), and whether there could be differential treatment responses between the "treatment naive" and treatment "refractory" IIM. METHODS: Data obtained from a prospectively maintained database comprising patients with IIM treated with rituximab. Patient details were obtained at baseline, 3-months, 6-months intervals, and subsequent follow up visits. Treatment response was categorised as improved, worsening, or stable based on manual muscle testing (MMT8) scores, patient global and physician global improvement (PtGA and PGA) for skin and joint symptoms improvement and spirometry at 6 months. The time to clinical improvement and remission were noted and survival analysis curves were constructed. RESULTS: 60 patients with IIM (including 18 with anti-SRP myopathy) were included, out of which 33 who received RTX were treatment naïve. The remaining 27 were started on rituximab for refractory myopathy. Mean age was 39 years (SD12.58) in "treatment-naive" group and 43 years (SD 12.12) in "refractory" group. At 6 months of follow up, 48/55 (87%) patients showed response, 31/31 (100%) in "treatment-naive" and 17/24 (70%) in "refractory" cases, p 0.006*. In refractory group, 7 (29%) had stable disease. The mean changes in MMT8 were significantly more in the "treatment-naive" treatment group (13.41(SD 7.31) compared with "refractory" IIM 8.33 (SD 7.92) (p= 0.017*). Majority of patients were able to reduce dose below 5 mg/day before 6 months. No major adverse events were reported over the median follow-up of 24 (IQR 36) months. CONCLUSIONS: Rituximab is effective and safe across the spectrum of IIM. Early use in disease is associated with better outcomes.

Heterogeneity and Hierarchy of Immune Response to Primary Immunization in HIV-Infected Children on HAART and the Impact of an Additional Dose of Vaccine.

The nature of vaccine response inferiority is not well studied in children living with HIV (CLHIV). The authors investigated Hepatitis B Virus (HBV) and Diphtheria/Pertussis/Tetanus toxoid (DPT) vaccination responses following primary immunization in CLHIV (n = 42) and healthy controls (HC) (n = 38) and the effect of an additional vaccine dose. Antibody responses, CD4 and HBV-specific T/B cells were analysed using CMIA/ELISA and flow-cytometry. CLHIV had significantly lower baseline median antibody titres for all vaccines than HC (p <0.02). Differential seroprotection rates observed in CLHIV were, 4.8% for pertussis; 9.5% for HBV; 26.2% for diphtheria and 66.7% for tetanus. WHO staging significantly influenced anti-HBs levels (p = 0.0095). HBsAg-specific CD4+T-cells were significantly higher in CLHIV than HC (p = 0.042). An additional vaccine dose (HBV and Tdap) conferred a higher protection rate for tetanus and diphtheria (p <0.040) in CLHIV. These findings suggest that CLHIV exhibit a hierarchy of vaccine responses affecting antibody levels and protection rate, which was rescued by administering additional vaccine dose.

Polymerase Spiral Reaction (PSR) as a point-of-care diagnostic assay: A systematic review.

INTRODUCTION: The current systematic review aimed to collect and analyze the comprehensive evidence regarding Polymerase Spiral Reaction (PSR) and to estimate its diagnostic performance and usefulness as a point-of-care (PoC) assay. METHODS: Literature was retrieved systematically from 2015 to 2023 from PubMed and Scopus. Studies were screened and selected against pre-determined inclusion and exclusion criteria. Quality assessment and risk of bias were critiqued using QUADAS-2. A systematic, qualitative narrative synthesis was employed to synthesize the data. RESULTS: 11 studies were selected for the systematic review, testing diseases in humans utilizing PSR. Only 2 studies clinically validated the test with a sample size > 150. 5 studies were of poor quality; 3 studies were of moderate quality and 3 studies were deemed to be of high quality. 3 studies quantified the diagnostic throughput and reported clinical sensitivity and specificity of PSR approaching to be > 92% and ~ 100%, respectively. CONCLUSION: Polymerase spiral reaction promises to be an optimistic isothermal assay; however, a huge research gap can be attributed to the lack of statistical and clinical evidence to validate the assay. Adequate research, focused on optimization, coupled with statistical and clinical validation, can help in estimating its true diagnostic potential and applicability. REGISTRATION AND PROTOCOL: A detailed protocol of this review is registered and available in Prospero (registration number CRD42023406265).

Unveiling angular sweep total fluorescence Spectroscopy:A novel multidimensional technique for analysis of complex multi-fluorophoric systems.

Analyzing multi-fluorophoric real systems without pre-processing is challenging, often addressed with unconventional fluorescence techniques and chemometrics. In this context, we introduce a novel addition - 'Angular Sweep Total Fluorescence Spectroscopy (ASTFS),' to the arsenal of multidimensional steady-state fluorescence spectroscopic techniques. ASTFS utilizes a series of variable angle synchronous fluorescence spectra, strategically covering the fluorescence region between the first and second-order Rayleigh scattering ridges. The plot features a minimal data matrix size, avoids Rayleigh scattering signals, and incurs no blind regions. The study delves into the instrumental configurations for spectral acquisition, highlights the enhanced spectral resolution due to the band-narrowing effect, and discusses other notable features of the ASTFS plot. Further, this technique is reported to be effective in analyzing analytes in complex systems with strong background fluorescence, such as milk. The antibiotic- Norfloxacin is quantified via minimal pre-processing in milk samples and yields excellent analytical figures of merit.

Climate influences scrub typhus occurrence in Vellore, Tamil Nadu, India: analysis of a 15-year dataset.

Climate is one of the major factors determining the prevalence and seasonality of vector borne diseases like scrub typhus (ST). We analyzed, the association of the meteorological factors like temperature, rainfall and humidity with scrub typhus using the 15 years scrub typhus data from a tertiary care hospital in Vellore, South India. Demographic data of permanent residents of Vellore, who had IgM ELISA results for scrub typhus for the time period of May 2005 to April 2020 were included. Meteorological data was correlated with the monthly scrub typhus cases; negative binomial regression model was used to predict the relation between scrub typhus occurrence and climate factors. Maximum number of ST cases were reported between the months August and February with October recording the highest number of cases. Elderly people, farmers, agricultural workers and housewives were at higher risk for scrub typhus. For an increase of 1 °C in mean temperature, the monthly ST cases reduced by 18.8% (95% CI - 24.1, - 13.2%). On the contrary, for 1 percent increase in mean relative humidity (RH), there is an increase of 7.6% (95% CI 5.4, 9.9%) of monthly ST cases. Similarly, an increase of 1 mm of rainfall contributed to 0.5 to 0.7% of monthly ST cases (after 2 months) depending on the variables included in the analysis. This study provides information that meteorological factors influence ST occurrence in Vellore. The rise of scrub typhus cases is maximal 2 months post rainfall. Whereas a rise in relative humidity, causes a rise in scrub typhus cases in same month, while rise in temperature has a negative impact on scrub typhus during the same month. These findings based on a retrospective analysis need validation by prospective studies.

Genotyping of Orientia tsutsugamushi circulating in and around Vellore (South India) using TSA 56 gene.

PURPOSE: The immunodominant TSA 56 gene of Orientia tsutsugamushi, (scrub typhus agent) has four variable regions (VD-I to VD-IV) making it useful for genotyping. This study was undertaken to determine Orientia tsutsugamushi genotypes circulating in and around Vellore using complete and partial TSA 56 gene. METHODS: Of the 162 patients positive by 47 â€‹kDa qPCR, on 21 samples PCR to amplify the complete TSA 56 gene (≈1605 bp: Long protocol) and the partial gene sequence using the Horinouchi (≈650bp) and the Furuya (≈480 bp) protocol was performed. Sanger and Nanopore sequencing was performed to obtain sequence data for assigning genotype. For 13 amplicons partial and complete gene data was obtained. RESULTS: Phylogenetic analysis of the complete gene (Long protocol) which includes VD-I to VD-IV region and partial gene (Horinouchi) which amplifies the VD-I to VD-III regions showed identical genotypes. Twelve belonged to TA763 genotype and one belongs to Karp genotype. The Furuya sequence (in silico) correctly identified the Karp genotype and 10 of the TA763 genotypes. Two TA763 genotypes (identified by complete and 650 bp partial gene analysis) were misidentified by Furuya sequence analysis as Karp genotype. CONCLUSIONS: Analysis of the 13 complete 56 â€‹kDa gene sequences suggests that TA763 is the commonest genotype in Vellore. Sanger sequencing of the 650 bp fragment gives similar results. However, these results need to be validated by larger prospective multi-centric studies.

Clinical profile of anti-NXP-2 antibody-positive inflammatory myositis and outcome in an Indian population.

INTRODUCTION: Myositis-specific antibodies (MSA) play an important role in the clinical presentation and prognosis of patients with idiopathic inflammatory myositis (IIM). Anti-NXP-2 is one of the newly described MSA. OBJECTIVE: We aimed to describe various clinical presentations associated with anti-NXP2 antibodies and assess response to treatment. METHODS: In this retrospective study, the electronic medical records of all patients who tested positive for anti-NXP2 during June 2019 to April 2022 were screened. Details of demography, clinical presentation, and treatment data were recorded. The anti-NXP2 was tested using the Euro line test kit. Any patient who had an intensity of ≥1+ was considered testing positive. The diagnosis of IIM was reviewed after applying the 2017 European League of Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria of myositis. RESULTS: Among the 660 suspected patients, 470 (71.2%) patients were positive for IIM, and 28 (5.95%) patients were positive for anti-NXP2. From anti-NXP2-antibody positive, 21/470 (4.46%) patients fulfilled criteria for IIM. Among 12 adult (57.14%) patients with IIM, 7 (58.33%) presented as polymyositis (PM) and 5 (41.6%) as dermatomyositis (DM) with median age at presentation of 45 (IQR: 25-58) years. Calcinosis and subcutaneous oedema were observed in 4 (19%) and 2 (9.52%), respectively; myalgia in 6 (28.6%); and distal muscle weakness in 5 (23.8%) patients. Malignancy at the time of diagnosis was observed in two adults with IIM (16.7%), one with DM (intraductal breast cancer), and another with PM (anaplastic large cell lymphoma). Remaining, 9 had juvenile dermatomyositis (JDM) with a median age of 4 (IQR: 3-8) years. Seven (77.8%) patients with JDM had skin rash specific for DM (heliotrope rash and Gottron's papule). None of the patients had cardiac and lung involvement, while GI symptoms, especially dysphagia, were present in 5 (23.8%) patients. During a median follow-up of 19 months (IQR: 12-26 months), 19/19 patients reported improvement and were in remission with treatment. CONCLUSION: The current study shows that adult DM patients with anti-NXP-2 autoantibodies have a unique clinical phenotype. Its presentation differs between adult and JDM, even in different parts of the world. Muscle weakness is mild and responds to treatment. Dysphagia needs more time and aggressive IS for improvement as compared to other muscle involvement. Key Points • Anti-NXP-2 antibody presentation varied from adult to child, as in different parts of the world. • In Indian adult patients, non-specific skin manifestations were more common, whereas in JDM, specific skin features were common. • There was less likely involvement of the lung and heart. But more risk of GI involvement requiring aggressive management. • Adult with anti-NXP-2 antibody should be screened for malignancy at the time of presentation.

Opsoclonus myoclonus ataxia syndrome, ovarian teratoma and anti-NMDAR antibody: an 'unresolved' mystery.

Background: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is characterised by the combination of opsoclonus and arrhythmic action myoclonus with axial ataxia and dysarthria. In adults, a majority are paraneoplastic secondary to solid organ tumours and could harbour antibodies against intracellular epitopes; however, certain proportions have detectable antibodies to various neuronal cell surface antigens. Anti-N-methyl-D-aspartate (NMDAR) antibodies and ovarian teratomas have been implicated in OMAS. Methods: Report of two cases and review of literature. Results: Two middle-aged women presented with subacute-onset, rapidly progressive OMAS and behavioural changes consistent with psychosis. The first patient had detectable antibodies to NMDAR in the cerebrospinal fluid (CSF) alone. Evaluation for ovarian teratoma was negative. The second patient had no detectable antibodies in serum or CSF; however, she had an underlying ovarian teratoma. Patient A was treated with pulse steroids, therapeutic plasma exchange (TPE) followed by bortezomib (BOR) and dexamethasone, while patient B was treated with steroids, TPE followed by surgical resection of ovarian teratoma. Both patients had favourable outcomes and were asymptomatic at the 6 monthly follow-up. Conclusions: With coexistent neuropsychiatric manifestations, OMAS can be considered a distinct entity of autoimmune encephalitis, pathogenesis being immune activation against known/unknown neuronal cell surface antigens. The observation of absence of anti-NMDAR antibody in patients with teratoma-associated OMAS and vice versa is intriguing. Further research on the potential role of ovarian teratoma in evoking neuronal autoimmunity and its targets is required. The management challenge in both cases including the potential use of BOR has been highlighted.

Genomic analysis of Brucella melitensis reveals new insights into phylogeny and evolutionary divergence.

PURPOSE: Brucellosis is a bacterial zoonotic disease caused by genus Brucella. The disease is often transmitted to humans by direct or indirect contact with infected livestock or from laboratory exposure. In this study two clinical isolates of Brucella melitensis were subjected to whole genome sequencing (WGS) using Ion Torrent PGM and Oxford Nanopore MinIon platform. METHODS: The two hybrid complete genomes were subjected to core gene SNP analysis to identify the relative evolutionary position. To distinguish between the various lineages of B. melitensis, Pangenome analysis was carried out. RESULTS: Phylogenetic analysis revealed that both the study isolates (ST8) clustered along the other Asian isolates that formed genotype II. Genome wide analyses of 326 B melitensis isolates suggests 2171 gene clusters were shared across all the genomes while 3552 gene clusters were considered as accessory genes. CONCLUSION: Here we attempted to provide the gain and loss of six unique genes that defined the phylogenetic lineages and complex evolutionary process. As the severity and prevalence of human brucellosis is increasing a better understanding of Brucella genomics and transmission dynamics is needed.

Clinical Spectrum and Microbial Etiology of Bone and Joint Infections in Children: A Retrospective Analysis from South India.

Acute infections of bone and joints are medical emergencies. Early diagnosis and treatment are essential for limb salvage and prevention of deformities. Data from developing countries are essential to develop region-specific treatment guidelines including choice of empiric antibiotics. We reviewed electronic medical records of children (≤ 12 years old) admitted to the pediatrics or orthopedics department of a tertiary care hospital in South India from 2013 to 2017 with a diagnosis of septic arthritis and/or osteomyelitis. Clinical, microbiological, and follow-up data were collected and analyzed. The median (interquartile range, IQR) age of the children (N = 207) was 48 (7.5-105) months. Acute infections were more common in infants, whereas chronic cases were common in children > 5 years of age. Staphylococcus aureus (71%) was the most common organism identified. Gram-negative organisms were more frequently isolated in infants compared with older children. Blood and/or wound culture positivity was 78% (N = 161) overall and 78% (N = 31) in chronic cases. The median (IQR) duration of antibiotics was 7 (5-8) weeks. Sequelae and readmissions occurred in 47% (N = 81) of the 172 patients followed for a year. Culture positivity rates especially of wound were high even after receiving antibiotics.

Phenotypic and Genotypic Correlation of Antimicrobial Susceptibility of Bacteroides fragilis: Lessons Learnt.

Background Bacteroides fragilis is an opportunistic pathogen causing severe infections, including bacteremia. There have been increased reports of antimicrobial resistance in B. fragilis. However, phenotypic testing of susceptibility is time consuming and not cost effective for anaerobes. The present study investigates the correlation of phenotypic susceptibility with genotypic markers; to determine if these could be considered for deciding empirical therapy for B. fragilis. Material and methods Bacteroides fragilis isolates from various clinical samples including exudates, tissue, and body fluids were collected between November 2018 and January 2020 in the Department of Clinical Microbiology, Christian Medical College (CMC) Vellore. Species identification was done by Matrix Assisted Laser Desorption Ionization time of flight mass spectrometry (MALDI TOF) according to the manufacturer's instructions. A total number of 51 B. fragilis isolates were tested against metronidazole, clindamycin, piperacillin/tazobactam, and meropenem phenotypically by agar dilution method using Clinical & Laboratory Standards Institute (CLSI) 2019 guidelines and minimum inhibitory concentrations (MIC) were interpretated. The genotypic markers for antimicrobial resistance genes (nim, emrF, and cfiA) were studied by polymerase chain reaction (PCR) assay as per the standard protocol on all isolates to detect resistance genes. Results B. fragilis isolates in this study expressed 45%, 41%, and 16% phenotypic resistance to clindamycin, metronidazole, and meropenem, respectively, with least resistance to piperacillin/tazobactam (6%). Among the metronidazole resistant isolates, 52% harbored nim gene. Nim gene was also present in 76% (23/30) of the metronidazole susceptible isolates. Similarly, cfiA was present in all eight meropenem resistant isolates in addition to 22% (9/41) of the susceptible isolates. All cfiA negative isolates were phenotypically susceptible. Interestingly, 74% (17/23) of the clindamycin resistant isolates were positive for ermF. Conclusions Detection of a limited set of genes does not always correlate with phenotypic resistance to metronidazole and clindamycin due to the reported influence of insertion sequence (IS) elements, efflux, and other genetic determinants. Certainly, the absence of the cfiA gene can be employed to rule out meropenem resistance. However, redundant use of antibiotics such as meropenem along with metronidazole could be avoided for B. fragilis, which might otherwise elevate meropenem resistance. Recommendation of metronidazole requires prior phenotypic testing due to the reported 41% resistance.

Chronic flaccid quadriparesis from tract specific myelopathy in neurosyphilis.

INTRODUCTION: Tract-specific myelopathies with distinctive imaging features are uncommon and typically occur with metabolic or paraneoplastic syndromes. We report a unique case of tract-specific myelopathy with neurosyphilis. CASE PRESENTATION: A 53-year-old male presented with a four-month history of flaccid quadriparesis, sensory loss, and bladder dysfunction. His MRIs revealed striking symmetric T2-weighted hyperintensities in the lateral corticospinal tracts and dorsal columns of the cervical spinal cord that extended rostrally into the pyramidal decussation and medial lemnisci of the medulla oblongata. Nerve conduction and needle electromyography studies excluded axonal or demyelinating lower motor neuron disorders. The patient reported previous untreated primary syphilis and was seropositive on the T.pallidum hemagglutination assay. Penicillin therapy resulted in substantial clinical improvement. DISCUSSION: Although syphilitic meningomyelitis is well-reported, our patient was unique because of the persistent flaccidity (possibly suggesting prolonged spinal shock) and striking tract-specific MRI patterns. These features are novel in syphilitic myelitis and suggest unknown mechanisms of tract-specific tropism and neuronal injury. CONCLUSIONS: "Tract-specific" complete transverse myelopathy with persistent flaccid weakness and areflexia is a novel presentation of neurosyphilis. Early recognition and crystalline penicillin therapy can alleviate morbidity. Our report describes this patient's findings and discusses the differential diagnoses of tract-specific myelopathies.

Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

BACKGROUND: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. METHODS: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. RESULTS: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. CONCLUSIONS: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).

Geography and prevalence of rickettsial infections in Northern Tamil Nadu, India: a cross-sectional study.

Rickettsial infections and Q fever are a common cause of acute febrile illness globally. Data on the role of climate and altitude on the prevalence of these infections in lacking from Southern India. In this study, we determined the sero-prevalence of scrub typhus (ST), spotted fever (SF), murine typhus (MT) and Q Fever (QF) in 8 eight geographical regions of North Tamil Nadu by detecting IgG antibodies using ELISA. Totally we tested 2565 people from 86 localities. Among the 27.3% positives, approximately 5% were IgG positive for two or more infections. Sero-prevalence to rickettsioses and Q fever was highest for individuals from rural areas and increased with age (> 30 years). Those in the Nilgiris highlands (wetter and cooler) and Erode, which has the most land under irrigation, demonstrated the least exposure to rickettsioses and Q fever. Lowland plains (AOR: 8.4-22.9; 95% CI 3.1-55.3) and highland areas up to 1000 m (AOR: 6.1-10.3; 95% CI 2.4-23.9) showed the highest risk of exposure to scrub typhus. For spotted fever, the risk of exposure was highest in Jawadhi (AOR:10.8; 95% CI 2.6-44.3) and Kalrayan (AOR:16.6; 95% CI 4.1-66.2). Q fever positivity was most likely to be encountered in Salem (AOR: 5.60; 95% CI 1.01-31.08) and Kalrayan hills (AOR:12.3; 95% CI 2.9-51.6). Murine typhus risk was significant only in Tiruvannamalai (AOR:24.2; 95% CI 3.3-178.6). Our study suggests that prevalence of rickettsial infections and Q fever is low in areas which receive rainfall of ≥ 150 cm/year, with average minimum and maximum temperatures between 15 and 25 °C and elevation in excess of 2000 m. It is also less in well irrigated lowlands with dry climate. These preliminary findings need confirmation by active surveillance in these areas.

EAST in Children with Allergic rhinitis: Experience from Indian Tertiary Centre.

Allergic rhinitis (AR) is recognized as a growing global health disease with considerable importance among children and adolescents. This study aims to study the clinical and sensitization profile of children with allergic rhinitis using EAST. All children presenting to pediatric ENT outpatient with a clinical diagnosis of AR were prospectively recruited. Detailed demographic and clinical history including self-reported allergens, predominant symptoms and associated comorbid conditions were obtained. Severity of symptoms was graded on a visual analogue scale. Specific Ig E antibodies to 20 inhalant allergens was measured using EAST (EUROIMMUN, Germany).The pattern of sensitization was analyzed with respect to age, symptoms, associated comorbid conditions and urbanization. We recruited 328 children with a clinical diagnosis of AR (Mean age 10.3 year, IQR 8-13 years) Nasal block was the predominant symptom across all age groups, sneezing became more troublesome during adolescence. In 191 children sera were tested for allergen specific IgE, 119 (62.3%) showed positive sensitization. The most common sensitization noted was for cockroach, followed by dust mite and pollens. Majority had polysensitization (73%). Those who were predominantly sneezers were more likely to be sensitized with indoor allergens (p < 0.05). Among the comorbid conditions, asthma and atopic dermatitis accounted for maximum non ENT physician visits. The pattern of sensitization did not vary with age, urbanization or comorbid condition. This study highlights the clinical and sensitization profile of children with AR in South East India. Various peculiarities of this community has been presented which needs further attention.

Generation of a Large Repertoire of Monoclonal Antibodies against Dengue Virus NS1 Antigen and the Development of a Novel NS1 Detection Enzyme-Linked Immunosorbent Assay.

Commercial dengue virus (DENV) nonstructural-1 (NS1) Ag detection immunoassays often perform poorly, particularly in secondary DENV infection. To develop a highly sensitive NS1 ELISA, we generated a large repertoire of anti-DENV NS1 mouse mAbs (n = 95) that falls into 36 mAb classes based on binding specificities. The identified mAb pair, capable of efficiently detecting NS1 from four DENV serotypes in an immunoassay, was selected based on multiparametric analysis. The selected mAbs have subnanomolar affinities for NS1 with recognition sites outside the immunodominant wing domain. The assay was converted to an ELISA kit, which showed higher analytical sensitivity (3-fold to 83-fold) for NS1 from four DENV serotypes than commercial Platelia NS1 ELISA (Bio-Rad Laboratories). Compared to RT-PCR, the developed NS1 ELISA showed 78.57% (66 of 84) sensitivity, whereas Platelia NS1 ELISA showed a sensitivity of 60.71% (51 of 84). In a subgroup of RT-PCR-positive secondary dengue samples, our ELISA showed a sensitivity of 70.18% (40 of 57), whereas Platelia ELISA detected only 47.37% (27 of 57) samples. Furthermore, unlike Platelia ELISA, our test equally detected NS1 from four serotypes; Platelia ELISA performed poorly for the DENV-2 serotype, in which only 8 of 21 (38.10%) samples were detected compared with 17 of 21 (80.95%) in our ELISA. Moreover, our ELISA showed 100% specificity in 342 challenging dengue-negative samples. The large and diverse mAb repertoire generated against DENV NS1 and the appropriate selection of mAbs allowed us to establish an ELISA that can efficiently detect NS1 Ag even in secondary dengue and without serotype level bias.

Upward trends of syphilis in the non-pregnant adults: A six-year report on clinical and epidemiological profile of syphilis from a tertiary care center, India.

Since 2000, a resurgence of syphilis has been noted in many developed and developing countries, especially among men who have sex with men (MSM). Incidence and prevalence of syphilis in pregnant women have been reduced drastically by mandatory screening in early pregnancy. Insufficient data in other populations especially from developing countries limit targeted public health interventions. This study aimed to describe the clinical and epidemiological profile of serologically confirmed syphilis cases among the non-pregnant high-risk group reporting to a tertiary care center in Southern India. A retrospective study was carried out in a tertiary care center in Southern India for 6 years from 2015 to 2020. A total of 265 serologically confirmed syphilis patients were included. A statistically significant increase in positivity from 0.52 to 2.1% was observed in this study (2015 to 2020). Among risk factors, high-risk behavior with multiple heterosexual partners was the commonest (51.3%), followed by marital partners who tested positive (9.4%) and MSM (7.5%). The majority of the patients were diagnosed at the latent stage (79%), followed by secondary syphilis (10%) and tertiary syphilis (8%). A quarter of patients (23%) were coinfected with HIV. Serological non-responsiveness was more common among HIV infected (47 vs. 24%). Sixteen had neurosyphilis and six had ocular involvement. HIV co-infection complicated 50% (8/16) of neurosyphilis patients. Syphilis is still prevalent, especially in high-risk groups including those are attending STI clinics. Further prospective multicentric studies are needed to identify and implement public health measures.

Performance of EAST in diagnosing inhalant allergens in children with allergic rhinitis.

The performance of enzyme linked immunosorbent assays (EAST) for identifying six indoor allergens was evaluated using skin prick test (SPT) as reference tests in 154 children with allergic rhinitis. Sensitivity of EAST ranged from 9% (cat) to 54% (HDM) with specificity of 74%(cockroach) to 100% (cat) with an agreement ranged from 58 to 86%. Cut off values â€‹> â€‹0.35 kU/L showed best sensitivity and specificity. Our findings agree with extant literature which suggests that the ability of EAST to determine the precipitating allergen is moderate. Assays for definitively identifying the inhalant allergen are currently not available.

Association of a Single Post-Operative Day Three C-Reactive Protein Value with Anastomotic Complications after Colorectal Surgery: A Prospective Observational Study.

Background: Early detection and treatment of a colorectal anastomotic leak reduces leak-associated morbidity. The primary objective of this study was to assess the role of C-reactive protein (CRP) as a tool to facilitate the early diagnosis of large bowel anastomotic leak. Patients and Methods: We conducted a prospective observational study at a specialized colorectal unit of a tertiary referral teaching center where we recorded CRP levels pre-operatively and on day three for 113 patients undergoing a large bowel anastomosis. The primary outcome measure was the occurrence of anastomotic leak and its association with post-operative day three CRP levels (day one considered as 24 hours after surgery). The area under the curve of the receiver operating characteristic (ROC) curve analysis for the day three CRP value with the anastomotic leak was calculated and optimal cutoffs derived. Definitions and diagnostic criteria for a leak were established before commencing the study. Demographic, operative, diagnostic, and interventional procedure data were also recorded. Results: Twenty-two patients had an anastomotic leak (19.4%), and 14 (12.3%) required re-exploration or drain placement. The cutoff value of day three CRP with the greatest area under the ROC curve in the ROC curve analysis was 166 mg/L (area under the curve [AUC], 0.853) for open and laparoscopic procedures (sensitivity and specificity of 81.81% and 82.42%, respectively) with a negative predictive value of 93.8%. There was no difference in mean day three CRP levels between open and laparoscopic surgery (116.57 mg/L vs. 108.94 mg/L) Conclusions: A CRP value of more than 166 mg/L on day three should raise suspicion of an anastomotic leak.