Omicron infection increases IgG binding to spike protein of predecessor variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in India in 2020-2022 was driven predominantly by Wild (Wuhan-Hu-1 and D614G), Delta, and Omicron variants. The aim of this study was to examine the effect of infections on the humoral immune response and cross-reactivity to spike proteins of Wuhan-Hu-1, Delta, C.1.2., and Omicron. Residual archival sera (N = 81) received between January 2020 and March 2022 were included. Infection status was inferred by a positive SARS-CoV-2 RT-PCR and/or serology (anti-N and anti-S antibodies) and sequencing of contemporaneous samples (N = 18) to infer lineage. We estimated the levels and cross-reactivity of infection-induced sera including Wild, Delta, Omicron as well as vaccine breakthrough infections (Delta and Omicron). We found an approximately two-fold increase in spike-specific IgG antibody binding in post-Omicron infection compared with the pre-Omicron period, whilst the change in pre- and post-Delta infections were similar. Further investigation of Omicron-specific humoral responses revealed primary Omicron infection as an inducer of cross-reactive antibodies against predecessor variants, in spite of the weaker degree of humoral response compared to Wuhan-Hu-1 and Delta infection. Intriguingly, Omicron vaccine-breakthrough infections when compared with primary infections, exhibited increased humoral responses against RBD (7.7-fold) and Trimeric S (Trimeric form of spike protein) (34.6-fold) in addition to increased binding of IgGs towards previously circulating variants (4.2 - 6.5-fold). Despite Delta breakthrough infections showing a higher level of humoral response against RBD (2.9-fold) and Trimeric S (5.7-fold) compared to primary Delta sera, a demonstrably reduced binding (36%-49%) was observed to Omicron spike protein. Omicron vaccine breakthrough infection results in increased intensity of humoral response and wider breadth of IgG binding to spike proteins of antigenically-distinct, predecessor variants.

Sensitivity and specificity of phrenic nerve electrophysiology to predict mechanical ventilation in the Guillain-Barré syndrome.

INTRODUCTION/AIMS: In Guillain-Barré syndrome (GBS), the sensitivity and specificity of phrenic compound muscle action potential (CMAP) measurements to predict endotracheal mechanical ventilation are unknown. Hence, we sought to estimate sensitivity and specificity. METHODS: We performed a 10-year retrospective analysis of adult GBS patients from our single-center laboratory database (2009 to 2019). The phrenic nerve amplitudes and latencies before ventilation were recorded along with other clinical and demographic features. Receiver operating curve (ROC) analysis with area under the curve (AUC) was used to determine the sensitivity and specificity with 95% confidence interval (CI) for phrenic amplitudes and latencies in predicting the need for mechanical ventilation. RESULTS: Two hundred five phrenic nerves were analyzed in 105 patients. The mean age was 46.1 ± 16.2 years, with 60% of them being male. Fourteen patients (13.3%) required mechanical ventilation. The average phrenic amplitudes were lower in the ventilated group (P = .003), but average latencies did not differ (P = .133). ROC analysis confirmed that phrenic amplitudes could predict respiratory failure (AUC = 0.76; 95% CI, 0.61 to 0.91; P < .002), but phrenic latencies could not (AUC = 0.60; 95% CI, 0.46 to 0.73; P = .256). The best threshold for amplitude was ≥0.6 mV, with sensitivity, specificity, and positive and negative predictive values of 85.7%, 58.2%, 24.0%, and 96.4%, respectively. DISCUSSION: Our study suggests that phrenic CMAP amplitudes can predict the need for mechanical ventilation in GBS. In contrast, phrenic CMAP latencies are not reliable. The high negative predictive value of phrenic CMAP amplitudes ≥0.6 mV can preclude mechanical ventilation, making these a useful adjunct to clinical decision-making.

Persistent bacteremia predicts poor outcomes among neutropenic patients with carbapenem-resistant gram-negative bloodstream infections receiving appropriate therapy.

PURPOSE: Identifying persistent bacteremia early in patients with neutropenia may improve outcome. This study evaluated the role of follow-up blood cultures (FUBC) positivity in predicting outcomes among patients with neutropenia and carbapenem-resistant gram-negative bloodstream infections (CRGNBSI). METHODS: This retrospective cohort study conducted between December 2017 and April 2022 included patients more than 15 years old with neutropenia and CRGNBSI, who survived for ≥ 48 h, receiving appropriate antibiotic therapy and had FUBCs. Patients with polymicrobial bacteremia within 30 days were excluded. The primary outcome was 30 day mortality. Persistent bacteremia, septic shock, recovery from neutropenia, prolonged or profound neutropenia, requirement of intensive care and dialysis, and initiation of appropriate empirical therapy were also studied. RESULTS: In our study cohort of 155 patients, the 30 day mortality rate was 47.7%. Persistent bacteremia was common in our patient cohort (43.8%). Carbapenem resistant isolates identified in the study were K.pneumoniae (80%), E.coli (12.26%), P.aeruginosa (5.16%), A.baumanii (1.94%) and E.cloacae (0.65%). The median time for sending a FUBC was 2 days (IQR, 1-3 days). Patients with persistent bacteremia had higher mortality than those without (56.76% versus 32.1%; p < 0.001). Appropriate initial empirical therapy was given to 70.9%. Recovery from neutropenia occurred in 57.4% while 25.8% had prolonged or profound neutropenia. Sixty-nine percent (107/155) had septic shock and needed intensive care; 12.2% of patients required dialysis. Non-recovery from neutropenia (aHR, 4.28; 95% CI 2.53-7.23), presence of septic shock (aHR, 4.42; 95%CI 1.47-13.28), requirement of intensive care (aHR,3.12;95%CI 1.23-7.93), and persistent bacteremia (aHR,1.74; 95%CI 1.05-2.89) significantly predicted poor outcomes in multivariable analysis. CONCLUSION: FUBC showing persistent bacteremia predicted poor outcomes among neutropenic patients with carbapenem-resistant gram-negative bloodstream infections (CRGNBSI) and should be routinely reported.

Virtual microscopy as a teaching-learning tool for histology in a competency-based medical curriculum.

Background: Histology forms an important component of first-year medical education. Unfortunately, it is limited to the practical laboratory due to the need for a microscope and good quality slides. Virtual microscopy is a recent advancement, which uses computers as an alternative to microscopes. The aim of the study was to compare virtual microscopy (VM)-based practical classes with traditional microscopy (TM)-based practical classes for two cohorts of first-year medical students, by comparing learning achieved using two different test scores as well as a qualitative assessment of student and faculty perspectives regarding the feasibility and usefulness of VM. Methods: Each cohort of students was divided into two equal batches and each batch underwent eight histology modules of which, four utilised traditional microscopes and four utilised virtual microscopes. Quantitative analysis was performed using a theory test (which assessed preparation, theory knowledge and understanding) as well as a spotter test (which assessed identification skills, reasoning, and recall). Qualitative analysis was performed using a structured questionnaire and focus group discussions. Results: Modules using VM were better when compared with those using TM, showing statistically significant and better grades. Qualitative analysis performed, yielded important information as to how this technology can serve as a good adjunct to traditional histology classes in the competency-based curriculum by increasing student interest, enabling self-study, and reducing students dependence on the tutor. Conclusions: VM forms a good adjunct as well as a standalone modality of learning to TM, as it improves accessibility to slides and promotes self-learning.

Functional principal component analysis for identifying the child growth pattern using longitudinal birth cohort data.

BACKGROUND: Longitudinal studies are important to understand patterns of growth in children and limited in India. It is important to identify an approach for characterising growth trajectories to distinguish between children who have healthy growth and those growth is poor. Many statistical approaches are available to assess the longitudinal growth data and which are difficult to recognize the pattern. In this research study, we employed functional principal component analysis (FPCA) as a statistical method to find the pattern of growth data. The purpose of this study is to describe the longitudinal child growth trajectory pattern under 3 years of age using functional principal component method. METHODS: Children born between March 2002 and August 2003 (n = 290) were followed until their third birthday in three neighbouring slums in Vellore, South India. Field workers visited homes to collect details of morbidity twice a week. Height and weight were measured monthly from 1 month of age in a study-run clinic. Longitudinal child growth trajectory pattern were extracted using Functional Principal Component analysis using B-spline basis functions with smoothing parameters. Functional linear model was used to assess the factors association with the growth functions. RESULTS: We have obtained four FPCs explained by 86.5, 3.9, 3.1 and 2.2% of the variation respectively for the height functions. For height, 38% of the children's had poor growth trajectories. Similarly, three FPCs explained 76.2, 8.8, and 4.7% respectively for the weight functions and 44% of the children's had poor growth in their weight trajectories. Results show that gender, socio-economic status, parent's education, breast feeding, and gravida are associated and, influence the growth pattern in children. CONCLUSIONS: The FPC approach deals with subjects' dynamics of growth and not with specific values at given times. FPC could be a better alternate approach for both dimension reduction and pattern detection. FPC may be used to offer greater insight for classification.

Anemia requiring transfusion in breast cancer patients on dose-dense chemotherapy: Prevalence, risk factors, cost and effect on disease outcome.

PURPOSE: Dose-dense chemotherapy improves survival but with increased toxicity and treatment-related cost. We report the prevalence of anemia and the possible risk factors associated with chemotherapy-related anemia and determine the cost and time-delay associated with transfusion requirement in Indian patients with non-metastatic breast cancer on dose-dense preoperative chemotherapy. METHODS: In this study, triple-negative breast cancer (TNBC) patients were treated preoperatively with docetaxel and cyclophosphamide alternating with epirubicin and cisplatin every 2 weeks. Patients were evaluated for anemia pre- and post-chemotherapy. We examined trends in the red cell indices, transfusion requirement, time to transfusion, as well as risk factors associated with transfusion during treatment, along with delay in treatment due to anemia and the additional cost incurred. RESULTS: A total of 116 consecutive women with nonmetastatic TNBC were treated with preoperative chemotherapy. The median age was 44.5 years. 56.1% of patients had stage III disease. Anemia was detected at baseline in 54 (46.5%) patients with mild anemia (10-12 g/dl) in 42 (36.2%) patients and moderate anemia (8-10 g/dl) in 12 (10.3%) patients. During the course of treatment, all patients developed anemia. A total of 44 patients (37.9%) required transfusion during chemotherapy, with 55(47.4%) patients developing grade 1-2 anemia and 40 (34.5%) patients developing grade 3 anemia. The factors associated with anemia requiring transfusion were a steeper decline in hemoglobin after two cycles (OR 1.65, p = 0.02), low-grade tumor (OR 2.48, p = 0.03), and thrombocytopenia grade 3 or 4 (OR 4.35, p = 0.034), of which tumor grade and thrombocytopenia remained significant in multivariate analysis. Nearly one-fourth of the study population had a delay between two cycles of chemotherapy due to anemia. A median additional cost of INR 7000 was incurred among those requiring blood transfusion. CONCLUSION: Anemia is a common toxicity associated with dose-dense chemotherapy during curative breast cancer treatment leading to delay in treatment and increased cost. Low-grade tumor, grade 3 or 4 thrombocytopenia, and grade 2 or higher anemia after two cycles of chemotherapy are risk factors for blood transfusions during treatment.

Cost of Illness Due to Severe Enteric Fever in India.

BACKGROUND: Lack of robust data on economic burden due to enteric fever in India has made decision making on typhoid vaccination a challenge. Surveillance for Enteric Fever network was established to address gaps in typhoid disease and economic burden. METHODS: Patients hospitalized with blood culture-confirmed enteric fever and nontraumatic ileal perforation were identified at 14 hospitals. These sites represent urban referral hospitals (tier 3) and smaller hospitals in urban slums, remote rural, and tribal settings (tier 2). Cost of illness and productivity loss data from onset to 28 days after discharge from hospital were collected using a structured questionnaire. The direct and indirect costs of an illness episode were analyzed by type of setting. RESULTS: In total, 274 patients from tier 2 surveillance, 891 patients from tier 3 surveillance, and 110 ileal perforation patients provided the cost of illness data. The mean direct cost of severe enteric fever was US$119.1 (95% confidence interval [CI], US$85.8-152.4) in tier 2 and US$405.7 (95% CI, 366.9-444.4) in tier 3; 16.9% of patients in tier 3 experienced catastrophic expenditure. CONCLUSIONS: The cost of treating enteric fever is considerable and likely to increase with emerging antimicrobial resistance. Equitable preventive strategies are urgently needed.

Natural History of Cryptosporidiosis in a Birth Cohort in Southern India.

BACKGROUND: Cryptosporidium is a leading cause of moderate to severe childhood diarrhea in resource-poor settings. Understanding the natural history of cryptosporidiosis and the correlates of protection are essential to develop effective and sustainable approaches to disease control and prevention. METHODS: Children (N = 497) were recruited at birth in semiurban slums in Vellore, India, and followed for 3 years with twice-weekly home visits. Stool samples were collected every 2 weeks and during diarrheal episodes were tested for Cryptosporidium species by polymerase chain reaction (PCR). Serum samples obtained every 6 months were evaluated for seroconversion, defined as a 4-fold increase in immunoglobulin G directed against Cryptosporidium gp15 and/or Cp23 antigens between consecutive sera. RESULTS: Of 410 children completing follow-up, 397 (97%) acquired cryptosporidiosis by 3 years of age. PCR identified 1053 episodes of cryptosporidiosis, with an overall incidence of 0.86 infections per child-year by stool and serology. The median age for the first infection was 9 (interquartile range, 4-17) months, indicating early exposure. Although infections were mainly asymptomatic (693 [66%]), Cryptosporidium was identified in 9.4% of diarrheal episodes. The proportion of reinfected children was high (81%) and there was clustering of asymptomatic and symptomatic infections (P < .0001 for both). Protection against infection increased with the order of infection but was only 69% after 4 infections. Cryptosporidium hominis (73.3%) was the predominant Cryptosporidium species, and there was no species-specific protection. CONCLUSIONS: There is a high burden of endemic cryptosporidiosis in southern India. Clustering of infection is suggestive of host susceptibility. Multiple reinfections conferred some protection against subsequent infection.

Prevalence and risk factors for scrub typhus in South India.

OBJECTIVE: To determine the prevalence and risk factors of scrub typhus in Tamil Nadu, South India. METHODS: We performed a clustered seroprevalence study of the areas around Vellore. All participants completed a risk factor survey, with seropositive and seronegative participants acting as cases and controls, respectively, in a risk factor analysis. After univariate analysis, variables found to be significant underwent multivariate analysis. RESULTS: Of 721 people participating in this study, 31.8% tested seropositive. By univariate analysis, after accounting for clustering, having a house that was clustered with other houses, having a fewer rooms in a house, having fewer people living in a household, defecating outside, female sex, age >60 years, shorter height, lower weight, smaller body mass index and smaller mid-upper arm circumference were found to be significantly associated with seropositivity. After multivariate regression modelling, living in a house clustered with other houses, female sex and age >60 years were significantly associated with scrub typhus exposure. CONCLUSIONS: Overall, scrub typhus is much more common than previously thought. Previously described individual environmental and habitual risk factors seem to have less importance in South India, perhaps because of the overall scrub typhus-conducive nature of the environment in this region.

Conditional random slope: A new approach for estimating individual child growth velocity in epidemiological research.

OBJECTIVES: Conditioning child growth measures on baseline accounts for regression to the mean (RTM). Here, we present the "conditional random slope" (CRS) model, based on a linear-mixed effects model that incorporates a baseline-time interaction term that can accommodate multiple data points for a child while also directly accounting for RTM. METHODS: In two birth cohorts, we applied five approaches to estimate child growth velocities from 0 to 12 months to assess the effect of increasing data density (number of measures per child) on the magnitude of RTM of unconditional estimates, and the correlation and concordance between the CRS and four alternative metrics. Further, we demonstrated the differential effect of the choice of velocity metric on the magnitude of the association between infant growth and stunting at 2 years. RESULTS: RTM was minimally attenuated by increasing data density for unconditional growth modeling approaches. CRS and classical conditional models gave nearly identical estimates with two measures per child. Compared to the CRS estimates, unconditional metrics had moderate correlation (r = 0.65-0.91), but poor agreement in the classification of infants with relatively slow growth (kappa = 0.38-0.78). Estimates of the velocity-stunting association were the same for CRS and classical conditional models but differed substantially between conditional versus unconditional metrics. CONCLUSION: The CRS can leverage the flexibility of linear mixed models while addressing RTM in longitudinal analyses.

Birth weight centiles by gestational age for twins born in south India.

BACKGROUND: Birth weight centile curves are commonly used as a screening tool and to assess the position of a newborn on a given reference distribution. Birth weight of twins are known to be less than those of comparable singletons and twin-specific birth weight centile curves are recommended for use. In this study, we aim to construct gestational age specific birth weight centile curves for twins born in south India. METHODS: The study was conducted at the Christian Medical College, Vellore, south India. The birth records of all consecutive pregnancies resulting in twin births between 1991 and 2005 were reviewed. Only live twin births between 24 and 42 weeks of gestation were included. Birth weight centiles for gestational age were obtained using the methodology of generalized additive models for location, scale and shape (GAMLSS). Centiles curves were obtained separately for monochorionic and dichorionic twins. RESULTS: Of 1530 twin pregnancies delivered during the study period (1991-2005), 1304 were included in the analysis. The median gestational age at birth was 36 weeks (1st quartile 34, 3rd quartile 38 weeks). Smoothed percentile curves for birth weight by gestational age increased progressively till 38 weeks and levels off thereafter. Compared with dichorionic twins, monochorionic twins had lower birth weight for gestational age from after 27 weeks. CONCLUSIONS: We provide centile values of birth weight at 24 to 42 completed weeks of gestation for twins born in south India. These charts could be used both in routine clinical assessments and epidemiological studies.

Reduced rotavirus vaccine effectiveness among children born during the rotavirus season: a pooled analysis of 5 case-control studies from the Americas.

Using data from rotavirus vaccine effectiveness (VE) studies, we assessed whether rotavirus season modifies rotavirus VE in infants. In the first year of life, adjusted VE was 72% for children born during rotavirus season and 84% for children born in other months (P = .01). Seasonal factors may interfere with vaccine performance.

Environmental Factors Associated with High Fly Densities and Diarrhea in Vellore, India.

Diarrhea causes significant morbidity and mortality in Indian children under 5 years of age. Flies carry enteric pathogens and may mediate foodborne infections. In this study, we characterized fly densities as a determinant of infectious diarrhea in a longitudinal cohort of 160 urban and 80 rural households with 1,274 individuals (27% under 5 years of age) in Vellore, India. Household questionnaires on living conditions were completed at enrollment. Fly abundance was measured during the wet and dry seasons using fly ribbons placed in kitchens. PCRs for enteric bacteria, viruses, and protozoa were performed on 60 fly samples. Forty-three (72%) fly samples were positive for the following pathogens: norovirus (50%), Salmonella spp. (46.7%), rotavirus (6.7%), and Escherichia coli (6.7%). Ninety-one episodes of diarrhea occurred (89% in children under 5 years of age). Stool pathogens isolated in 24 of 77 (31%) samples included E. coli, Shigella spp., Vibrio spp., Giardia, Cryptosporidium, and rotavirus. Multivariate log-linear models were used to explore the relationships between diarrhea and fly densities, controlling for demographics, hygiene, and human-animal interactions. Fly abundance was 6 times higher in rural than urban sites (P < 0.0001). Disposal of garbage close to homes and rural living were significant risk factors for high fly densities. The presence of latrines was protective against high fly densities and diarrhea. The adjusted relative risks of diarrheal episodes and duration of diarrhea, associated with fly density at the 75th percentile, were 1.18 (95% confidence interval [CI], 1.03 to 1.34) and 1.15 (95% CI, 1.02 to 1.29), respectively. Flies harbored enteric pathogens, including norovirus, a poorly documented pathogen on flies.

Effect of Non-Rotavirus Enteric Infections on Vaccine Efficacy in a ROTASIIL Clinical Trial.

This study examined the relative proportion of enteric pathogens associated with severe gastroenteritis (GE) among children younger than 2 years in a phase III efficacy trial of the ROTASIIL® vaccine in India, evaluated the impact of co-infections on vaccine efficacy (VE), and characterized the association between specific pathogens and the clinical profile of severe GE. Stored stool samples collected from cases of severe GE in the phase III trial were tested by quantitative polymerase chain reaction using TaqMan™ Array Cards. Etiology was attributed by calculating the adjusted attributable fraction (AF) for each pathogen. A test-negative design was used to estimate VE. The pathogens with the highest AFs for severe diarrhea were rotavirus (23.5%), adenovirus 40/41 (17.0%), Shigella spp./enteroinvasive Escherichia coli, norovirus GII, enterotoxigenic E. coli, and Cryptosporidium spp. A considerable proportion of the disease in these children could not be explained by the pathogens tested. Severe GE cases associated with rotavirus and Shigella spp. were more likely to have a longer duration of vomiting and diarrhea, respectively. Cases attributed to Cryptosporidium spp. were more severe and required hospitalization. In the intention-to-treat population, VE was estimated to be 43.9% before and 46.5% after adjustment for co-infections; in the per-protocol population, VE was 46.7% before and 49.1% after adjustments. Rotavirus continued to be the leading cause of severe GE in this age group. The adjusted VE estimates obtained did not support co-infections as a major cause of lower vaccine performance in low- and middle-income countries.

Rural South Indian spirometry values show wide variation compared to existing prediction equations.

Background and Objective: India, a highly heterogeneous country, has no common reference standards for predicting spirometry values, with very few recent studies from south India. This study aimed to create reference equations for rural south Indian adults, based on a population-based survey in Vellore, south India and compare it with other equations from India. Methods: The data from 583 non-smoking, asymptomatic participants (30 years and older) from a spirometry-based survey for airflow obstruction (rural Vellore, 2018), were used to develop equations for FEV1, FEV1/FVC, and FVC. The dataset was divided for development (70%) and validation (30%), by gender. Differences between observed and predicted values were assessed using the new equations and comparisons made with other equations from India. Results: Predictions with Vellore rural equations were closest to the previous south Indian equations from urban Bangalore. However, the Bangalore equations led to overestimation of FVC values in males, and of both FEV1 and FVC values in females. Using the rural Vellore equations also led to a higher percent of males being classified as having airflow obstruction, compared to the Bangalore equations which underestimated airflow obstruction in this rural population. Comparison with previously derived Indian equations from other parts of the country showed pronounced variations. Conclusions: Our study reiterates the need for representative rural and urban studies of adults from various parts of India, to obtain region specific reference equations, given the wide variations in spirometry values in "normal" individuals, due to social heterogeneities of the Indian population and resulting complexities in defining normal.

Common polymorphisms of protein tyrosine phosphate non-receptor type 2 gene are not associated with risk of Crohn's disease in Indian.

BACKGROUND: Multiple genetic risk factors for Crohn's disease (CD) have been identified. However, these observations are not consistent across different populations. The protein tyrosine phosphate non-receptor type 2 (PTPN2) gene plays a role in various aspects of host defense including epithelial barrier function, autophagy, and innate and adaptive immune response. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) have been associated with risk of CD in Western countries. AIM: To evaluate the association of PTPN2 gene polymorphisms with risk of CD in Indian population. METHODS: We conducted a prospective case-control study. Patients with CD were recruited, and their clinical and investigation details were noted. Controls were patients without organic gastrointestinal disease or other comorbid illnesses. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) were assessed. DNA was extracted from peripheral blood samples of cases and controls and target DNA was amplified using specific sets of primers. The amplified fragments were digested with restriction enzymes and the presence of polymorphism was detected by restriction fragment length polymorphism. The frequency of alleles was determined. The frequencies of genotypes and alleles were compared between cases and controls to look for significant differences. RESULTS: A total of 108 patients with CD (mean age 37.5 ± 12.7 years, females 42.6%) and 100 controls (mean age 39.9 ± 13.5 years, females 37%) were recruited. For the single nucleotide polymorphism (SNP) rs7234029, the overall frequency of G variant genotype (AG or GG) was noted to be significantly lower in the cases compared to controls (35.2% vs 50%, P = 0.05). For the SNP rs2542151, the overall frequency of G variant genotype (GT or GG) was noted to be similar in cases compared to controls (43.6% vs 47%, P = 0.73). There were no significant differences in minor allele (G) frequency for both polymorphisms between the cases and controls. Both the SNPs had no significant association with age of onset of illness, gender, disease location, disease behaviour, perianal disease, or extraintestinal manifestations of CD. CONCLUSION: Unlike observation form the West, polymorphisms in the PTPN2 gene (rs7234029 and rs2542151) are not associated with an increased risk of developing CD in Indian patients.

Toll-Like Receptors and Mannose Binding Lectin Gene Polymorphisms Associated with Cryptosporidial Diarrhea in Children in Southern India.

In low-resource settings, Cryptosporidium spp. is a common cause of diarrheal disease in children under the age of 3 years. In addition to diarrhea, these children also experience subclinical episodes that have been shown to affect growth and cognitive function. In this study, we screened polymorphisms in the promoter and exon1 regions of the mannose binding lectin 2 (MBL2) gene, as well as single nucleotide polymorphisms (SNPs) described in toll-like receptors (TLR) TLR1, TLR2, TLR4, and TLR9 and TIR domain-containing adaptor protein (TIRAP) genes among children with cryptosporidial diarrhea (cases) and children who only experienced asymptomatic (subclinical) cryptosporidiosis (controls). Among the polymorphisms screened, the variant allele B at codon 54 (rs1800450) of the MBL2 gene was associated with susceptibility to cryptosporidial diarrhea (odds ratio [OR] = 2.2, 95% confidence interval [CI] 1.1-4.5). When plasma MBL levels were compared, 72% of cases were found to be deficient compared with 32% among controls (OR = 5.09). Among TLR polymorphisms screened, multivariate analysis showed that heterozygous genotypes of TLR4 896A/G (rs4986790, OR = 0.33, 95% CI: 0.11-0.98) and TIRAP 539 C/T (rs8177374, OR = 0.19, 95% CI: 0.06-0.64) SNPs were associated with protection from cryptosporidial diarrhea. Although not statistically significant, these findings suggest that polymorphisms of MBL2 and TLR genes influence susceptibility to symptomatic cryptosporidial diarrhea even in settings with high exposure levels. Further studies to validate these findings in a larger cohort and to understand the role of these polymorphisms in mediating innate and adaptive immune responses to cryptosporidial infection are necessary.

Influence of publicly funded conditional cash transfer programms on utilization patterns of healthcare services for acute childhood illness.

BACKGROUND: Conditional cash transfers are widespread and effective for utilization of targeted health services, but there is little evidence of their influence on the utilization of non-targeted or extended general healthcare services. Using data from a population-based health utilization survey, we evaluated the influence of conditional cash transfers for maternal and immunization services on the utilization of healthcare services for acute childhood illnesses. METHODS: Participants included mothers or primary caretakers of children <2 y of age residing in 2407 households in urban Vellore, Tamil Nadu, India. Mothers of children with illness in the preceding month were interviewed on presenting symptoms, provider choice and beneficiary status of maternal and immunization-based conditional cash transfer programs. RESULTS: Of 2407 children <2 y of age, about 48% reported being beneficiaries of maternal and immunization-based conditional cash transfers. Beneficiary status was associated with an increased use of public services (adjusted relative risk [aRR] 3.14 [95% confidence interval {CI} 1.96 - 5.02]) but not the use of private services (aRR 1.42 [95% CI 0.97 - 2.08]) relative to home or informal care. CONCLUSIONS: Our findings indicate financial incentives for use of maternal and immunization services could have an indirect, non-targeted effect on utilization of formal healthcare for acute childhood illnesses.

Iron homeostasis is dysregulated, but the iron-hepcidin axis is functional, in chronic liver disease.

BACKGROUND: Perturbations in iron homeostasis have been reported to be associated with irreversible liver injury in chronic liver disease (CLD). However, it is not clear whether liver dysfunction per se underlies such dysregulation or whether other factors also contribute to it. This study attempted to examine the issues involved. METHODS: Patients diagnosed to have chronic liver disease (n = 63), who underwent a medically-indicated upper gastrointestinal endoscopy, were the subjects of this study. Patients with dyspepsia, who underwent such a procedure, and were found to have no endoscopic abnormalities, were used as control subjects (n = 49). Duodenal mucosal samples were obtained to study mRNA and protein levels of duodenal proteins involved in iron absorption. A blood sample was also obtained for estimation of hematological, iron-related, inflammatory and liver function-related parameters. RESULTS: Patients with CLD had impaired liver function, anemia of inflammation and lower serum levels of hepcidin than control subjects. Gene (mRNA) expression levels of duodenal ferroportin and duodenal cytochrome b (proteins involved in iron absorption) were decreased, while that of divalent metal transporter-1 (DMT-1) was unchanged. Protein expression of DMT-1 was, however, decreased while that of ferroportin was unchanged. In the CLD group, serum hepcidin was predicted independently by serum ferritin and hemoglobin, but not by C-reactive protein (a marker of inflammation). CLD patients with serum ferritin greater than 300 µg/dL had significantly greater liver dysfunction (as indicated by significantly higher serum concentrations of bilirubin, AST and ALT, and MELD scores), higher serum concentrations of CRP and hepcidin, and higher ferroportin protein expression, than those with serum ferritin ≤ 300 µg/dL. CONCLUSIONS: In patients with CLD, anemia of inflammation and low serum hepcidin levels were found to paradoxically co-exist. Expression of duodenal proteins involved in iron absorption were either decreased or unaltered in these patients. The hepcidin response to higher body iron levels and/or inflammation appeared to be functional in these patients, despite the presence of liver disease.

Time to debridement in open high-grade lower limb fractures and its effect on union and infections: A prospective study in a tropical setting.

PURPOSE: To prospectively evaluate whether time to debridement has any correlation with union, infection, and quality of life in high-grade lower limb fractures in a tropical setting. METHODS: A prospective cohort study was conducted at a tertiary care center in South India. Two hundred fifty-four adult skeletally mature patients with 301 grade 3 fractures involving the femur, tibia, or fibula were recruited. The cohort was empirically divided into two groups (early and late) based on the time to debridement (less than or more than 12 h from injury). OUTCOME: The primary outcome was nonunion. Secondary outcomes were deep infection rates and patients' quality of life. Short form-36 (SF-36) and short musculoskeletal functional assessment (SMFA) questionnaires were also used. Patients were followed up for 9 months. RESULTS: The follow-up rate was 93%. The late group had a significantly higher risk of nonunion (odds ratio(OR): 6.5, 95% confidence interval (CI): 2.82-14.95) and infections (OR: 6.05, 95% CI: 2.85-12.82). There was a 4% increase in the infection risk for each hour of delay for the initial 50 h (p < 0.0001). SF-36 and SMFA scores were superior in the early group (p < 0.0001). CONCLUSION: The study contradicts findings reported in the literature from the West. Our study was in agreement with our hypothesis and proved that debridement within 12 h resulted in significantly lower rates of nonunion and infections and an overall improved quality of life in high-grade open lower limb fractures in a developing country. LEVEL OF EVIDENCE: Level II. TRIAL REGISTRATION: German Clinical Trials Register DRKS00015186.