Tuberculosis Pathways to Care and Transmission of Multidrug Resistance in India.

Rationale: India is experiencing a regional increase in cases of multidrug-resistant tuberculosis (MDR-TB). Objectives: Given the complexity of MDR-TB diagnosis and care, we sought to address key knowledge gaps in MDR risk factors, care delays, and drivers of delay to help guide disease control. Methods: From January 2018 to September 2019, we conducted interviews with adults registered with the National TB Elimination Program for MDR (n = 128) and non-MDR-TB (n = 269) treatment to quantitatively and qualitatively study care pathways. We collected treatment records and GeneXpert-TB/RIF diagnostic reports. Measurements and Main Results: MDR-TB was associated with young age and crowded residence. GeneXpert rifampicin resistance diversity was measured at 72.5% Probe E. Median time from symptom onset to diagnosis of MDR was 90 days versus 60 days for non-MDR, Wilcoxon P < 0.01. Delay decreased by a median of 30 days among non-MDR patients with wider access to GeneXpert, Wilcoxon P = 0.02. Pathways to care were complex, with a median (interquartile range) of 4 (3-5) and 3 (2-4) encounters for MDR and non-MDR, respectively. Of patients with MDR-TB, 68% had their first encounter in the private sector, and this was associated with a larger number of subsequent healthcare encounters and catastrophic expenditure. Conclusions: The association of MDR with young age, crowding, and low genotypic diversity raises concerns of ongoing MDR transmission fueled by long delays in care. Delays are decreasing with GeneXpert use, suggesting the need for routine use in presumptive TB. Qualitatively, we identify the need to improve patient retention in the National TB Elimination Program and highlight patients' trust relationship with private providers.

Expanding the Distinctive Neuroimaging Phenotype of ACTA2 Mutations.

BACKGROUND AND PURPOSE: Arg179His mutations in ACTA2 are associated with a distinctive neurovascular phenotype characterized by a straight course of intracranial arteries, absent basal Moyamoya collaterals, dilation of the proximal internal carotid arteries, and occlusive disease of the terminal internal carotid arteries. We now add to the distinctive neuroimaging features in these patients by describing their unique constellation of brain malformative findings that could flag the diagnosis in cases in which targeted cerebrovascular imaging has not been performed. MATERIALS AND METHODS: Neuroimaging studies from 13 patients with heterozygous Arg179His mutations in ACTA2 and 1 patient with pathognomonic clinicoradiologic findings for ACTA2 mutation were retrospectively reviewed. The presence and localization of brain malformations and other abnormal brain MR imaging findings are reported. RESULTS: Characteristics bending and hypoplasia of the anterior corpus callosum, apparent absence of the anterior gyrus cinguli, and radial frontal gyration were present in 100% of the patients; flattening of the pons on the midline and multiple indentations in the lateral surface of the pons were demonstrated in 93% of the patients; and apparent "squeezing" of the cerebral peduncles in 85% of the patients. CONCLUSIONS: Because α-actin is not expressed in the brain parenchyma, only in vascular tissue, we speculate that rather than a true malformative process, these findings represent a deformation of the brain during development related to the mechanical interaction with rigid arteries during the embryogenesis.

Normal neuroanatomical variants that may be misinterpreted as disease entities.

Variations of normal development and benign incidental anomalies are frequently observed on diagnostic neuroimaging. It is important these are recognised for what they are, as misinterpretation may result in unnecessary further investigation, follow-up imaging and anxiety. In this article, we review benign intracranial anomalies commonly referred to our unit for specialist neuroradiology advice or multidisciplinary discussion, concerning cysts of the pineal gland and pituitary fossa, vascular anomalies, and perivascular spaces. This article outlines the embryology and development, the various imaging features as well as the clinical relevance and differential diagnoses of each normal neuroanatomical variant.

Risk factors for vertical transmission of hepatitis E virus infection.

Hepatitis E virus (HEV) infection can be vertically transmitted, but the factors that transmit the disease to foetuses are still unclear. We studied a total of 144 pregnant women with HEV infection. Cord blood and newborn samples were taken for analysis. Nutritional factors were evaluated on the basis of anthropometric parameters and biochemical factors, and HEV viral load was quantified by real-time PCR. Sequencing of HEV-positive samples was performed. Approximately 14.63% (6/41) of pregnant patients with acute liver failure (ALF) died before delivery. Vertical transmission was observed in 46.09% (59/128) of HEV-IgM-positive mothers. Approximately 23.80% (10/42) of newborns in the acute viral hepatitis group and 29.41% (5/17) in the ALF group were positive for HEV-RNA. No significant difference was observed in the occurrence of vertical transmission in HEV groups. Viral load was found to be a significant predictor for vertical transmission of HEV infection adjusted with haemoglobin and folate in derivation cohort group. Incorporating these variables, a new score predicting vertical transmission of HEV was derived. Using these significant predictors, the probability for vertical transmission of HEV was well stratified in the validation group (P>.05). In conclusion, viral load was associated with vertical transmission of HEV infection. A valid prediction score model was generated that was verified in a validation cohort group.

Time-constrained mother and expanding market: emerging model of under-nutrition in India.

BACKGROUND: Persistent high levels of under-nutrition in India despite economic growth continue to challenge political leadership and policy makers at the highest level. The present inductive enquiry was conducted to map the perceptions of mothers and other key stakeholders, to identify emerging drivers of childhood under-nutrition. METHODS: We conducted a multi-centric qualitative investigation in six empowered action group states of India. The study sample included 509 in-depth interviews with mothers of undernourished and normal nourished children, policy makers, district level managers, implementer and facilitators. Sixty six focus group discussions and 72 non-formal interactions were conducted in two rounds with primary caretakers of undernourished children, Anganwadi Workers and Auxiliary Nurse Midwives. RESULTS: Based on the perceptions of the mothers and other key stakeholders, a model evolved inductively showing core themes as drivers of under-nutrition. The most forceful emerging themes were: multitasking, time constrained mother with dwindling family support; fragile food security or seasonal food paucity; child targeted market with wide availability and consumption of ready-to-eat market food items; rising non-food expenditure, in the context of rising food prices; inadequate and inappropriate feeding; delayed recognition of under-nutrition and delayed care seeking; and inadequate responsiveness of health care system and Integrated Child Development Services (ICDS). The study emphasized that the persistence of child malnutrition in India is also tied closely to the high workload and consequent time constraint of mothers who are increasingly pursuing income generating activities and enrolled in paid labour force, without robust institutional support for childcare. CONCLUSION: The emerging framework needs to be further tested through mixed and multiple method research approaches to quantify the contribution of time limitation of the mother on the current burden of child under-nutrition.

Measurement of the viscoelastic properties of blood plasma clot formation in response to tissue factor concentration-dependent activation.

The coagulation of blood plasma in response to activation with a range of tissue factor (TF) concentrations was studied with a quartz crystal microbalance (QCM), where frequency and half width at half maximum (bandwidth) values measured from the conductance spectrum near resonant frequency were used. Continuous measurement of bandwidth along with the frequency allows for an understanding of the dissipative nature of the forming viscoelastic clot, thus providing information on the complex kinetics of the viscoelastic changes occurring during the clot formation process. Using a mathematical model, these changes in frequency and bandwidth have been used to derive novel QCM parameters of effective elasticity, effective mass density and rigidity factor of the viscoelastic layer. The responses of QCM were compared with those from thromboelastography (TEG) under identical conditions. It was demonstrated that the nature of the clot formed, as determined from the QCM parameters, was highly dependent on the rate of clot formation resulting from the TF concentration used for activation. These parameters could also be related to physical clot characteristics such as fibrin fibre diameter and fibre density, as determined by scanning electron microscopic image analysis. The maximum amplitude (MA) as measured by TEG, which purports to relate to clot strength, was unable to detect these differences.

Antenatally diagnosed wilms' tumour.

Wilms' tumour (WT) is seldom seen in a neonate and prenatal diagnosis is rare. We present a case of antenatally diagnosed left sided WT with features of hydrops foetalis in a girl baby. Emergency LSCS was done at 34 weeks of gestation for foetal distress. Patient required mechanical ventilation for birth asphyxia and congestive cardiac failure. After stabilization, gross total resection of the tumour was done on day 4 of life. Histopathology HPE confirmed classical WT (stage I). Unfortunately, the patient died on the second postoperative day despite all supportive measures.

The modelling of blood coagulation using the quartz crystal microbalance.

Blood is a clinically-important analytical matrix that is routinely selected for disease monitoring. Having a clear understanding of the mechanisms involved in blood coagulation is a key consideration in haemostasis, with modern clinical practices requiring rapid, miniaturised and informative diagnostic platforms to reliably study changes in viscoelasticity (VE). Oscillatory transducers such as the Quartz Crystal Microbalance (QCM) have considerable potential in this area, provided that they present simple, linear rheometric readings which can be adequately analysed and interpreted. Hence, integrating QCM data obtained in the laboratory with mathematical modelling of acoustic interactions between quartz crystal surfaces and coagulating blood is an important consideration for modelling thrombus formation. Here, we provide a comprehensive overview of experimental and theoretical applications currently being employed to monitor and model the VE properties of coagulating blood when applied to a QCM resonator, with key emphasis on data modelling and interpretation.

Interdistrict variations in child health status and health services utilization: lessons for health sector priority setting and planning from a cross-sectional survey in rural India.

BACKGROUND: There are limited data on interdistrict variations in child health status and health services utilization within the states of India. We conducted this study to identify and understand district-wise variations in child morbidity, mortality, healthcare seeking, and the status of health facilities in India. METHODS: A cross-sectional population-based cluster survey was conducted from April to July 2007 in 16 districts of eight states in India. Two districts with similar demographic profile and health criteria were selected from each study state. RESULTS: A total of 216 794 households and 24 812 under-5 children were surveyed. There were wide interdistrict variations in the health status of children within the same state and between different states across India. Interdistrict difference of >5 points/1000 live-births was found for infant mortality rate and under-5 mortality rate in all eight study states, while in six out of eight states this difference was >10 points/1000 live-births. Four states had a difference of >10 points/1000 live-births between respective districts for neonatal mortality rate. The interdistrict differences were also noted in childhood morbidity and health-seeking behaviour. Analysis of proportion of health facilities conforming to Indian public health standards revealed that the difference was m10% for availability of vaccines in five states, emergency services in three, laboratory services and logistics in four each, and referral facility in three of the eight study states. CONCLUSION: This study underscores an important information gap in the country where planners seem to rely heavily on a few selected national-level databases that may not be adequate at the micro level. The current process of sporadic health surveys also appears inadequate and inappropriate. There is a need for district-specific data for planning, improving quality of service and generating demand for health service utilization to improve child survival in India. The findings of this study may prove useful for child health programme planning in India.

Growth from birth to adulthood and peak bone mass and density data from the New Delhi Birth Cohort.

UNLABELLED: Growth in early life may predict adult bone health. Our data showed that greater height and body mass index (BMI) gain in utero and infancy are associated with higher peak bone mass, and greater BMI gain in childhood/adolescence with higher peak bone density. These associations are mediated by attained adult height and BMI. INTRODUCTION: To study the relationship of height and BMI during childhood with adult bone mineral content (BMC), areal density (aBMD) and apparent density (BMAD, estimated volumetric density). METHODS: Participants comprised 565 men and women aged 33-39 years from the New Delhi Birth Cohort, India, whose weight and height were recorded at birth and annually during infancy (0-2 years), childhood (2-11 years) and adolescence (11 years-adult). Lumbar spine, femoral neck and forearm BMC and aBMD were measured using dual X-ray absorptiometry; lumbar spine and femoral neck BMAD were calculated. RESULTS: Birth length, and height and height gain during infancy, childhood and adolescence were positively correlated with adult BMC (p≤0.01 all sites except birth length with femoral neck). Correlations increased with height from birth to 6 years, then remained constant for later height measurements. There were no associations with BMAD. BMI at birth, and during childhood and adolescence was also positively correlated with BMC (p < 0.01 all sites). BMI at 11 years, and BMI gain in childhood and adolescence, were correlated with aBMD and BMAD (p < 0.001 for all); these correlations strengthened with increasing age of BMI measurement. The associations with height and BMI in early life became non-significant after adjustment for adult height and BMI. CONCLUSIONS: Greater skeletal growth and BMI gain in utero and during infancy are associated with higher peak BMC, and greater BMI gain in childhood and adolescence is associated with higher peak aBMD and BMAD. These associations are mediated by the attainment of adult height and BMI, respectively.

Ileal atresia with duplication cyst of terminal ileum: a rare association.

A case of ileal atresia in association with duplication of terminal ileum is being reported here.

Predicting adult metabolic syndrome from childhood body mass index: follow-up of the New Delhi birth cohort.

OBJECTIVES: To assess whether serial measurements of childhood body mass index (BMI) give clinically useful predictions of the risk of developing adult metabolic syndrome and impaired glucose tolerance or type 2 diabetes. DESIGN/SETTING: Follow-up of a community-based birth cohort in Delhi, India. PARTICIPANTS: 1492 men and women aged 26-32 years whose BMI was recorded 6-monthly throughout childhood. MAIN OUTCOME MEASURES: The predictive value of childhood BMI for adult metabolic syndrome and impaired glucose tolerance (IGT) and diabetes mellitus. RESULTS: 25% of subjects had metabolic syndrome and 15% had IGT/diabetes mellitus. Both outcomes were associated with greater childhood BMI gain (metabolic syndrome: OR 1.63 (95% CI 1.44 to 1.85); IGT/diabetes mellitus: 1.39 (1.20 to 1.60) per unit increase in within-cohort BMI SD score between 5 and 14 years). The best predictions of adult disease were obtained using a combined test comprising (i) any increase in BMI SD score between 5 and 14 years and (ii) a BMI SD score >0 at 14 years (metabolic syndrome: sensitivity 45%, specificity 78%; IGT/diabetes mellitus: 37%, 73%). Likelihood ratios were low (metabolic syndrome: 1.4-2.0; IGT/diabetes mellitus: 1.2-1.4). A single high BMI measurement at 14 years (overweight or obese, according to International Obesity Task Force criteria) was highly specific but insensitive (metabolic syndrome: sensitivity 7%, specificity 97%; IGT/diabetes mellitus: 8%, 97%). Charts for plotting BMI SD scores through childhood were produced. CONCLUSIONS: Serial measurements of childhood BMI give useful predictions of adult risk and could guide advice to children and parents on preventing later disease.

Phage immobilized magnetoelastic sensor for the detection of Salmonella typhimurium.

In this article, a phage-based magnetoelastic sensor for the detection of Salmonella typhimurium is reported. Filamentous bacteriophage specific to S. typhimurium was used as a biorecognition element in order to ensure specific and selective binding of bacteria onto the sensor surface. Phage was immobilized onto the surface of the sensors by physical adsorption. The phage immobilized magnetoelastic sensors were exposed to S. typhimurium cultures with different concentrations ranging from 5x10(1) to 5x10(8) cfu/ml, and the corresponding changes in resonance frequency response of the sensor were studied. It was experimentally established that the sensitivity of the magnetoelastic sensors was higher for sensors with smaller physical dimensions. An increase in sensitivity from 159 Hz/decade for a 2 mm sensor to 770 Hz/decade for a 1 mm sensor was observed. Scanning electron microscopy (SEM) analysis of previously assayed biosensors provided visual verification of frequency changes that were caused by S. typhimurium binding to phage immobilized on the sensor surface. The detection limit on the order of 10(3) cfu/ml was obtained for a sensor with dimensions 1x0.2x0.015 mm.

A magnetoelastic resonance biosensor immobilized with polyclonal antibody for the detection of Salmonella typhimurium.

Mass-sensitive, magnetoelastic resonance sensors have a characteristic resonant frequency that can be determined by monitoring the magnetic flux emitted by the sensor in response to an applied, time varying, magnetic field. This magnetostrictive platform has a unique advantage over conventional sensor platforms in that measurement is wireless and remote. A biosensor for the detection of Salmonella typhimurium was constructed by immobilizing a polyclonal antibody (the bio-molecular recognition element) onto the surface of a magnetostrictive platform. The biosensor was then exposed to solutions containing S. typhimurium bacteria. Binding between the antibody and antigen (bacteria) occurred and the additional mass of the bound bacteria caused a shift in the sensor's resonant frequency. Sensors with different physical dimensions were exposed to different concentrations of S. typhimurium ranging from 10(2) to 10(9)CFU/ml. Detection limits of 5x10(3) CFU/ml, 10(5) CFU/ml and 10(7) CFU/ml were obtained for sensors with the size of 2 mmx0.4 mmx15 microm, 5 mmx1 mmx15 microm and 25 mmx5 mmx15 microm, respectively. Good agreement between the measured number of bound bacterial cells (as measured by scanning electron microscopy (SEM)) and frequency shifts was obtained.

Reanimación normoxémica en la sala de partos / Normoxemic resuscitation in the delivery room

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Neurodevelopmental, functional and growth status of term low birth weight infants at eighteen months.

This study was done to evaluate the neurodevelopmental, functional and growth status of term infants weighing 2000 g or less at 18 months, and to analyze major medical and social factors associated with an adverse neurodevelopmental and/or functional outcome. All infants were assessed for growth, audio-visual, neurological impairment, and motor and mental development using Indian modification of Bayley Scales of infant development. A detailed history was also taken. Term infants with birth weight of >2500 g without any antenatal or neonatal complications served as controls. Fifty low birth weight (LBW) term infants and 30 controls were evaluated. The mean mental development Quotient for LBW infants [91.51(16.97)] was significantly lower than that of Controls [102.02(8.4)]; the mean motor development Quotient however was comparable. The LBW infants were significantly lagging in terms of weight, length and head circumference at assessment. Neonatal complications were associated with an abnormal motor outcome while lower Socio-economic status and maternal education were related to adverse mental status. We concluded that Term LBW infants are at a significant disadvantage in terms of growth and mental scores at 18 months.

Hepatitis B vaccine in the EPI schedule.

OBJECTIVE: This study was carried out to evaluate the adequacy of seroconversion when Hepatitis B vaccine is given along with other vaccines at 0, 6 weeks (along with DPT and OPV) and at 9 months (along with measles). METHODS: 725 infants born to apparently healthy mothers were enrolled to receive the hepatitis B vaccine at 0, 6 weeks and 9 months (Group A) or at 0, 1 and 6 months as per WHO schedule--(Group B). Baseline HbsAg testing was carried out and the babies were immunized with the first dose of hepatitis B vaccine within 48 hours of birth. BCG and the other EPI vaccines were given as per schedule. Serum samples were collected 4 weeks after the second and the third immunizations. 604 infants (83.3%) completed the study. The testing for HbsAg and Anti Hbs titers were conducted in the Department of Microbiology, Maulana Azad Medical College, New Delhi utilizing standard ELISA kits. RESULTS: The seroconversion rates 4 weeks after the second dose of the vaccine were 90.89% (GMT = 48.23) and 91.82% (GMT = 43.95) (P=0.8) in Group A and Group B respectively. After 4 weeks of the third dose the seroconversion rates were 98.99 (GMT = 161.12) and 98.45 (GMT = 150.12) (p=0.17) in Group A and Group B respectively. The two schedules were comparable on using the Kruskal-Wallis H method for analysis. CONCLUSION: The schedule of hepatitis B vaccination at 0, 6 weeks and 9 months has the same seroefficacy as the currently recommended schedule of 0, 1 and 6 months.

Secular change in newborn adiposity in an urban hospital.

Triceps and subscapular skinfold thickness were measured in 1080 consecutive newborns and the values were compared with an earlier study reported in 1981 from the same institution. The skinfold thickness in the present study was higher at all gestational age groups (except for 41 weeks) in both sexes. These differences were statistically significant at all periods except for males at 38 weeks and females at 39 weeks. For term infants, the mean skin fold thickness (subscapular and triceps) was significantly higher among both males (3.5 mm vs 4.0 mm; p< 0.05) and females (3.9 mm vs. 4.2 mm; p <0.05). The subscapular skin fold thickness in both males and females and triceps skin fold thickness in females were also significantly higher for all birthweight categories. The data suggests an increase in adiposity among newborns, over a period of two decades, in an urban poor population.