Transmission event of SARS-CoV-2 delta variant reveals multiple vaccine breakthrough infections.

BACKGROUND: This study aims to identify the causative strain of SARS-CoV-2 in a cluster of vaccine breakthroughs. Vaccine breakthrough by a highly transmissible SARS-CoV-2 strain is a risk to global public health. METHODS: Nasopharyngeal swabs from suspected vaccine breakthrough cases were tested for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) by qPCR (quantitative polymerase chain reaction) for Wuhan-Hu1 and alpha variant. Positive samples were then sequenced by Swift Normalase Amplicon Panels to determine the causal variant. GATK (genome analysis toolkit) variants were filtered with allele fraction ≥80 and min read depth 30x. RESULTS: Viral sequencing revealed an infection cluster of 6 vaccinated patients infected with the delta (B.1.617.2) SARS-CoV-2 variant. With no history of vaccine breakthrough, this suggests the delta variant may possess immune evasion in patients that received the Pfizer BNT162b2, Moderna mRNA-1273, and Covaxin BBV152. CONCLUSIONS: Delta variant may pose the highest risk out of any currently circulating SARS-CoV-2 variants, with previously described increased transmissibility over alpha variant and now, possible vaccine breakthrough. FUNDING: Parts of this work was supported by the National Institute of Allergy and Infectious Diseases (1U19AI144297) and Baylor College of Medicine internal funding.

Transmission event of SARS-CoV-2 Delta variant reveals multiple vaccine breakthrough infections.

Importance: Vaccine breakthrough by an emergent SARS-CoV-2 variant poses a great risk to global public health. Objective: To determine the SARS-CoV-2 variant responsible for 6 cases of vaccine breakthrough. Design: Nasopharyngeal swabs from suspected vaccine breakthrough cases were tested for SARS-CoV-2 by qPCR for Wuhan-Hu1 and Alpha variant. Positive samples were then sequenced by Swift Normalase Amplicon Panels to determine the causal variant. Setting: Transmission event occurred at events surrounding a wedding outside of Houston, TX. Two patients from India, likely transmitted the Delta variant to other guests. Participants: Following a positive SARS-CoV-2 qPCR test at a third-party site, six fully vaccinated patients were investigated. Three males and three females ranged from 53 to 69 years old. One patient suffered from diabetes while three others were classified as overweight. No significant other comorbidities were identified. None of the patients had a history of failed vaccination.

Etiological causes and epidemiological characteristics of patients with occupational corneal foreign bodies: A prospective study in a hospital-based setting in India.

Purpose: Corneal foreign bodies (CFBs) due to occupational exposure have been largely ignored in Indian literature, especially nonmetal workers. Our study looks at a broad range of occupations and settings that contribute to CFB in our local Indian population. The study objective was to: determine the occupations, level of education and demographics of patients presenting with CFB acquired during occupational work. Methods: Prospective hospital-based study at a tertiary eye hospital in Gurgaon, Haryana, India, within duration of 9 months. Patients presenting with CFB were asked a set of questions relating to their occupation, level of education, understanding of the potential complications of CFB, and demographics. Results: A total of 83 patients were included in the study. CFB were attributed only to males. 66% of patients were in the age group of 14--29 years. 30% of patients were in the age group 30--44 years and 4% of patients were between 45 and 60 years old. The metal work industry was responsible for 47% of presentations. The construction industry was responsible for 27% of presentations. Electricians and carpenters combined were responsible for 10% of presentations and 17% of presentations occurred in other sectors. Conclusion: CFB occur across a number of occupations in the construction industry, not just metallic workers. Among a population that is generally poorly educated and have nominal understanding of the impact that CFB can have on vision, occupational hazard education is necessary to address this problem.

Management of phenytoin-induced gingival enlargement in a patient with antiphospholipid antibody syndrome: A rare case report.

Antiphospholipid antibody (APLA) syndrome is a noninflammatory autoimmune disease, with innumerable clinical manifestations ranging from recurrent thrombosis and pregnancy morbidity to valvular lesions, transverse myelitis, thrombocytopenia, and hemolytic anemia. APLAs in antiphospholipid syndrome (APS) are well-known risk factors for cerebrovascular accidents. Stroke is the most common manifestation of APS in the central nervous system. Gingival enlargement is a known side effect of phenytoin which is an antiepileptic drug. This can have a significant effect on the quality of life as well as increasing the oral bacterial load by generating plaque retention sites. The management of gingival overgrowth seems to be directed at controlling gingival inflammation through a good oral hygiene regimen. Thus, this case report aims to describe the conservative management of phenytoin-induced gingival enlargement combined with inflammatory enlargement in a patient with APLA syndrome.

Tumor necrosis factor-alpha microsatellite polymorphism association with rheumatoid arthritis in Indian patients.

BACKGROUND: Level of TNF-alpha increases significantly in synovial fluid of rheumatoid arthritis (RA) patients. It is proposed that tumor necrosis factor (TNF) microsatellite alleles may influence its expression and presumably can contribute to the disease severity. However, there is a lack of such study to predict any such association with RA in an Indian population. METHODS: In this study, we investigated the differential pattern of distribution of TNF microsatellite alleles in an Indian population and its association with RA. One hundred eighteen RA patients and 120 healthy individuals were genotyped for TNF microsatellite alleles using Genescan. Odds ratio was calculated to demonstrate the correlation between allelic distribution and clinical severity. RESULTS: The study shows that distribution of TNF microsatellite alleles in an Indian population is very different from other Asian Oriental and Western populations, except for some similarities with an Italian population. Frequency of microsatellite TNFd3 allele (9.24 vs. 3.85%, chi(2)=5.6, p < or =0.0179, OR=0.393, 95% CI=0.177-0.87) and more interestingly TNFd3 containing haplotypes has been found significantly reduced in patients. On the contrary, TNFb5 allele frequency increased in the patients (22.3 vs. 30.8%, chi(2)=4.4, p < or =0.036, OR=1.55, 95% CI=1.027-2.344) as compared to controls. Furthermore, significant increase in frequency of this allele in severe patients (22.3 vs. 33.8%, chi(2)=6.22, p < or =0.013, OR=1.78, 95% CI=1.132-2.798) along with the significant increase in haplotypes containing this allele supports the association of TNFb5 with disease severity. CONCLUSIONS: In an Indian population, TNFb5 may be considered as a risk factor, whereas TNFd3, unlike others, may be protective for RA.

Methicillin Resistant Staphylococcus aureus: Inconsistencies in Vancomycin Susceptibility Testing Methods, Limitations and Advantages of each Method.

BACKGROUND: Vancomycin may be ineffective against an increasing proportion of methicillin resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentrations (MICs) well within the susceptible range. On the other hand it is common knowledge that determination of vancomycin MICs is method dependent. Therefore, given the apparent variability in vancomycin MIC results obtained with the different methods, the use of the vancomycin MIC to predict the outcome of serious S. aureus infections needs to take into account the method used and the results of studies using that particular method. AIM: Comparative study was carried out to evaluate the MICs obtained by BMD method, E-test, and Vitek 2 method and to detect inconsistencies in these vancomycin for 66 MRSA isolates obtained from various samples of patients attending the OPDs & IPDs within a period of one year. MATERIALS AND METHODS: A comparative study was carried out to evaluate the MICs obtained by BMD method, E-test, and Vitek 2 method to detect vancomycin susceptibility in 66 clinical isolates of MRSA obtained from various samples of patients attending the OPDs & IPDs within a period of one year. The study was conducted in Department of Microbiology, Subharti Medical College, Meerut from January to December 2012. RESULTS: On determination of MICs for vancomycin for the MRSA isolates, all were identified as VSSA by BMD, E-Test & Vitek 2 methods. However, the vancomycin MIC values obtained by E-test correlated better with BMD method (correlation factor= 0.6727) than Vitek 2 (correlation factor=0.5316), indicating E-Test to be a better method for determination of vancomycin MICs as compared to Vitek 2. CONCLUSION: MRSA isolates with higher vancomycin MICs, even within the susceptibility range, are being observed more frequently which result in treatment failures with vancomycin. Because of the discrepancy that exists in vancomycin MIC results from different methods, the prediction of outcome of serious S.aureus infections should take into account the method used & results of studies using that particular method.

Antibiotic overuse as a risk factor for candidemia in an Indian pediatric ICU.

OBJECTIVE: To identify risk factors and mycological characteristics of candidemia in Pediatric ICU of a tertiary-care hospital. METHODS: Patients were screened for candidemia by blood culture. Recovered isolates were speciated and subjected to antifungal susceptibility testing. For every candidemic patient, three controls were matched for age, underlying diagnosis and period of hospitalization. Premature neonates were also matched for birth-weight. Proportion of cases and controls on specific antibiotics or indwelling devices was compared using Chi-square test, while unpaired t-test was used for comparing the number of antibiotics used and the number of days of antibiotic administration. Concordance between susceptibility testing methods was evaluated using Chi-square test. RESULTS: Significantly wider spectrum of antibiotic coverage was observed among the 28 candidemic patients. While every patient received antibiotic against enteric gram-negative bacilli, antibiotic usage for additional groups of microorganisms was significantly higher among cases. Association of candidemia with increasing use of indwelling devices was also observed. Endogenous colonization was higher in candidemic infants. Candida albicans was the commonest species (n = 18), followed by C. tropicalis (n = 7). Fluconazole and ketoconazole resistance was observed in 10.7 % cases. CONCLUSIONS: This information on pediatric candidemia could be used to devise locally-tailored strategies for identifying at-risk patients, underline the importance of routine antifungal susceptibility testing and formulate appropriate guidelines for management.

A Rare Case of Apical Root Resorption during Orthodontic Treatment of Patient with Multiple Aplasia.

External apical root resorption is an adverse effect of orthodontic treatment. It reduces the length of root and breaks the integrity of teeth and dental arch. Orthodontics is the only dental specialty that clinically uses the inflammatory process to correct the mal-aligned teeth. Hence, it is necessary to know the risk factors of root resorption and do everything to reduce the rate of root resorption. Hence, all predisposing factors which are systemic as well as local should be considered before treatment begins. This case report describes the incidence of root resorption following orthodontic treatment and the teeth affected in the patient with multiple aplasia.

Spinal tuberculosis due to dissemination of atypical mycobacteria.

There has been an increase in disease caused by Non Tuberculous Mycobacteria (NTM) since the early 1980s. Though ubiquitous in environment, they may act as clinically important pathogens in various conditions. More importantly they are resistant to the conventional anti-tuberculous therapy (ATT) and respond to antibiotics such as quinolones and aminoglycosides and need an aggressive surgical intervention. Missing these atypical mycobacteria may lead to unnecessary administration of ATT and hence delay in proper management of the case. We report a case of spinal tuberculosis due to a Non Tuberculous Mycobacteria, M. fortuitum (Rapid grower). Relevant literature is also reviewed.

Eumycetoma due to Madurella grisea--a case report.

Mycetoma due to Madurella grisea has not been previously reported from Gujarat. We report a case in whom identification of the strain was made through the structure and texture of grains, morphology in Sabouraud's dextrose agar and histopathology.

Genotype MTBDR plus assay for molecular detection of rifampicin and isoniazid resistance in Mycobacterium tuberculosis.

AIM: This study was performed for the rapid identification of Mycobacterium tuberculosis complex and its resistance to rifampicin and isoniazid, directly from the sputum samples of pulmonary tuberculosis patients. MATERIALS AND METHODS: A commercially available genotype MTBDR plus assay was used for the identification and detection of mutations in Mycobacterial isolates. A total of 100 sputum samples of pulmonary tuberculosis patients were analyzed by using the genotype MTBDR plus assay. The MTBDR plus assay is designed to detect the mutations in the hotspot region of rpoB gene, katG and regulatory region of inhA gene. RESULTS: The genotype MTBDR plus assay detected 22% multidrug resistant (MDR), 2% rifampicin (RMP) monoresistant and 1% isoniazid (INH) monoresistant isolates. In 22 MDR isolates, the codons most frequently involved in RMP-associated mutations were codon 531 (54.55%), 516 (31.82%) and 526 (13.63%), and 90.90% of MDR isolates showed KatG S315T mutations and 9.1% showed inhA C-15T mutations associated with INH resistance. CONCLUSION: The new genotype MTBDR plus assay represents a rapid, reliable tool for the detection of MDR-TB, wherein results are obtained in 5 h allowing early and appropriate treatment, which is essential to cut the transmission path and reduce the spread of MDR-TB. The genotype MTBDR plus assay can readily be included in a routine laboratory work for the early diagnosis and control of MDR-TB.

Successful outcome of mucormycosis in two children on induction therapy for acute lymphoblastic leukemia.

Zygomycetes are one of the less common causes of invasive fungal infections in patients with the hematological malignancies. We report two cases of acute lymphoblastic leukemia in the pediatric age group, complicated by disseminated cutaneous mucormycosis during induction chemotherapy. In one of our cases, cutaneous mucormycosis progressed to osteomyelitis of the proximal ulna while in the other it disseminated to lungs and distant cutaneous site. Aggressive treatment, which included intravenous administration of amphotericin B; radical surgical intervention in the form of serial wound debridement in the former and wedge pulmonary resection in the later, allowed successful salvage, and administration of planned anti-leukemia treatment in both of our cases. High index of suspicion, timely diagnosis, and appropriate treatment are key components of a successful outcome.

Paratyphoid sepsis.

A large for gestational age male baby was born to a healthy young primigravida, on L-thyroxime, at 40 weeks by caesarean delivery in a tertiary care hospital. The baby had episodes of hypoglycemia during his immediate four postnatal days in the nursery that were successfully managed with intravenous glucose administration. The baby became unwell on day 5 and had a positive sepsis-screening test. Blood culture revealed a multidrug susceptible S. Paratyphi A strain, which he probably acquired on the first or second postnatal day from the contaminated expressed breast milk or the formula feed.

Anti-MBL autoantibodies in patients with rheumatoid arthritis: prevalence and clinical significance.

Occurrence of autoantibodies in patients' sera is the characteristic feature of autoimmune disorders. We assessed the presence of anti-mannose binding lectin (MBL) autoantibodies in the sera of 107 rheumatoid arthritis (RA) patients and 121 control subjects by enzyme immunoassay. Elevated levels of anti-MBL autoantibodies in the sera of RA patients (P<0.0001) was detected for the first time. The ratios of anti-MBL positive in RA patients and controls were respectively 60.7% and 1.65%. Experiments were then designed to understand the functional relevance of these autoantibodies. An inverse correlation of anti-MBL autoantibodies with serum MBL levels (P=0.001) and MBL complex activity (P=0.02) was observed without genetic association between MBL polymorphisms and anti-MBL autoantibody secretion. A significant increase (P=0.038) in the level of anti-MBL autoantibodies was observed in 23 synovial fluid samples in comparison to the serum samples. Moreover, the anti-MBL autoantibodies were found to be more often present in the sera of RA patients (60.75% sensitivity, 98.35% specificity and 0.913 area under the ROC curve) in comparison to the IgM and IgG isotypes of rheumatoid factors (RF). Anti-MBL autoantibodies were still positive in 25.23% RA patients when both the RF isotypes were negative. Also, in RA patients, at all stages of disease activity and joint deformity, anti-MBL autoantibodies were more often present than both the RF isotypes. Therefore, the significant presence of anti-MBL autoantibodies enunciates that anti-MBL autoantibodies might have a diagnostic value; however, more studies are needed to confirm the role of anti-MBL autoantibodies in the diagnosis of rheumatoid arthritis.

Expression of TNF-alpha and related signaling molecules in the peripheral blood mononuclear cells of rheumatoid arthritis patients.

We examined the role of tumor necrosis factor (TNF-alpha) and its related signaling intermediates leading to apoptosis/proliferation in the peripheral blood mononuclear cells (PBMCs) of RA patients. The constitutive expression of mRNA for TNF-alpha receptors (TNFR-I and TNFR-II) and the adapter molecules, such as the TNF receptor-associated death domain protein (TRADD), Fas-associated death domain protein (FADD), receptor interacting protein (RIP), and TNF receptor-associated factor 2 (TRAF-2) were analyzed by reverse transcriptase-PCR (RT-PCR) in PBMCs from control and RA cases. PBMCs of RA patients showed a significant increase in TNF-alpha and TNFR-I expression as compared with that from control subjects along with significantly increased constitutive expression of TRADD, RIP, and TRAF-2 mRNA. There was a decrease in expression of FADD in RA patients, but the difference was not significant as compared to controls. These data suggested enhanced signaling by the TNFR-I-TRADD-RIP-TRAF-2 pathway and suppressed signaling by the TNFR-I-TRADD-FADD pathway in PBMCs of RA patients. However, the regulatory mechanisms for TNF-alpha induced signaling may not be explained only by these pathways.

Altered expression and glycosylation of plasma proteins in rheumatoid arthritis.

Altered glycosylation of plasma proteins has been directly implicated in the pathogenesis of rheumatoid arthritis (RA). The present study investigated the changes in the Concanavalin-A (Con-A)-bound plasma proteins in the RA patients in comparison to that of the healthy controls. Two proteins (MW approximately 32 kDa and approximately 62 kDa) showed an alteration in expression while an altered monosaccharide profile (high mannose) was observed in the approximately 62 kDa protein in the samples collected from RA patients. The 2-dimensional polyacrylamide gel electrophoresis analysis of the Con-A-bound plasma samples showed a large number of protein spots, a few of which were differentially expressed in the RA patients. Some unidentified proteins were detected in the RA patients which were absent in the control samples. The present study, therefore, enunciates the role of carbohydrates as well as that of the acute phase response in the disease pathogenesis.

Association of mannose-binding lectin gene (MBL2) polymorphisms with rheumatoid arthritis in an Indian cohort of case-control samples.

Single nucleotide polymorphisms in the mannose-binding lectin (MBL2) gene, as well as the serum MBL2 level, have been associated with various autoimmune diseases. We investigated whether such polymorphisms and/or the serum MBL2 level were associated with rheumatoid arthritis (RA) in an Indian population. The frequency of the B variant (codon 54) of the MBL2 gene was quite frequent in the healthy Indian population and was significantly (P=6.35x10(-6)) lower in RA patients. We replicated this association (P=1.78x10(-5)) in an independent cohort of control individuals. Promoter polymorphism at -550 nt showed a significant overrepresentation (P=0.003) of the minor allele G in severe RA patients compared with the less severe group. Haplotype LYA frequency was significantly (P=0.03) high in the less severe group, while the frequency of the HYA haplotype was significantly (P=0.04) increased in the severe RA patients. No statistically significant difference in serum MBL2 was observed as a whole, but the individuals homozygous for the LYA haplotype had significantly lower (P=0.017) serum MBL2 levels compared with individuals homozygous for the HYA haplotype. Therefore, the B variant of the MBL2 gene may be associated with protection from RA in our study population, and the promoter polymorphism (-550 nt) seems to have some role in disease progression.