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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Vibrio cholerae O1 serotype Ogawa in a neonate.

In India, cholera is endemic and affects usually the 3 to 5-year-old age group. There have been occasional reports in the neonatal period with Vibrio cholerae O139 Bengal. We report here a case of Vibrio cholerae O1 diarrhea in a 2-day-old, breastfed male, who had been delivered in the hospital and developed severe dehydration.

Health for all and rural Medicare.

PIP: The goals of the "Health for All" (HFA) by the year 2000 remain unfulfilled, as preschool child mortality is almost 10 to 20 times higher than developed countries. 75% of the population of Indian still lives in villages and 70% of farmers are landless. The Community Health Volunteer (CHV) scheme was launched in 1977 to implement the health policy formulated by the Bhore Committee calling for extension of primary health centers and rural hospitals with 50 beds. Although CHV was changed to community health worker (CHW), and later to village health guide (VHG), this Indian version of the Chinese barefoot doctor scheme never took root. The population coverage of primary health centers was reduced from 100,000 to 30,000 and that of a subcenters to just 3,000 to 5,000. The Bhore panel proposed to set up 7,200, 30-bed community health centers (CHC's) in the rural areas by 2000 calling for 90% of all beds to be at the village, taluk or district levels with 40% set aside for maternal and child health. In 40 years of health planning, the government has been able to create only 30,000 medical jobs to serve 600 million people living in the rural areas, while there are more 90,000 jobs for 200 million urban people. Only 750 (20%) of about 3800 posts of specialists have been sanctioned for the CHC's established in the rural areas by March 1987. It is necessary to provide primary care through a network of specially trained voluntary workers. It is incumbent on the government to establish more than 3 lakh hospital beds in the next 13 years to meet the target of 1 bed for 1,000 people in concordance with the objectives of the Bhore Committee. In addition, it is advisable to implement the recommendations of the National Workshop on Child Health & Manpower: 2000 A.D.^ieng

Health services in urban India.

PIP: At the time of independence 340 million lived in urban areas in India, and currently 200 million of an estimated population of 800 million live in 3000 cities and towns with inhabitants over 10.000. There are 90.000 government-employed doctors in urban areas: 1 doctor per 2200 residents. Another 180.000 are practicing in such areas providing a ratio of 1 doctor for every 800 urban people. In Delhi in 1986 there were 63 allopathic hospitals with 15.000 beds and 561 dispensaries. Government employees receive preferential treatment, while the public waits long hours. In frustration the poor often turn to private practitioners even if their qualifications are dubious. Despite 35 years of socialistic planning, only 10-15% of children living in a Delhi colony received adequate vaccination. To rectify this inequality a system is recommended guaranteeing public access to dispensaries on the same fee-basis as that accorded to government employees. A health card could prevent misuse, and it would ensure optimal utilization of existing health facilities. Future development of 50-100 bed hospitals within 2-3 km of clients' homes and the attachment of 5-10 of them to a large hospital or medical school is proposed. A central health board could oversee and coordinate area-based health services.^ieng

Non invasive continuous anterior fontanel tension monitoring in neonates.

Anterior fontanel tension (AFT) has been shown to reflect the intracranial pressure (ICP). A new transducer was designed for AFT measurement which overcomes the problems of replacement in subsequent use. Using the transducer AFT was monitored noninvasively over extended periods in about 200 normal and sick neonates. The results indicate that the technique can be used to identify elevated pressure due to different disease conditions and it has a potential to help in understanding physiological and pathological mechanisms causing alterations in the normal cerebrospinal dynamics. Further studies are underway to establish the full potentials of the technique.

Intellectual psycho-educational and functional status of low birth weight survivors beyond 5 years of age.

To determine the intellectual, psycho-educational and functional status of low birth weight (LBW) survivors (birth weight < or = 2000 gms) beyond 5 years of age and to compare their status with normal birth weight counterparts. This was cross-sectional study. On hospital based cohort on longitudinal follow-up at the High Risk and Well Baby Clinics of a teaching hospital. The demographic data of these children was recorded. A detailed physical examination was performed. The tests of cognition included the Stanford Binet and the Raven's Progressive Matrices. Academic achievement was evaluated by the Wide range achievement test-Revised (WRAT-R). Assessment of visuo motor integration was done by the Bender Gestalt Test. The proportion of children having soft neurological signs was determined. Vineland Social Maturity Scale was performed on all children. Fifty-nine LBW children and fifty-seven matched control children participated in the study. 27 of LBW children were examined at a mean age of 7.0 +/- 1.1 years (group I) and 32 were examined at a mean age of 10.6 +/- 1.2 years (group II). The LBW children as a group performed in the normal range on the tests of cognition and academic achievement, but were significantly disadvantaged (p < 0.005) as compared to controls. A higher percentage of LBW children had low scores on the Bender Gestalt. Test as compared to controls but the difference was not significant. A significantly higher proportion of LBW children of both the groups showed the presence of soft neurological signs as compared to controls. The social quotient as assessed by the vineland Social Maturity Scale was significantly lower in the LBW children as compared to controls. Thus, though the LBW children were performing in the normal range on various measures, comparison with the control group showed that they were clearly disadvantaged on nearly every measure tested, emphasizing the need for early detection and referral for special education.

Mediastinal enteric duplication cyst containing aberrant pancreas.

OBJECTIVE: The purpose of the study is to report a unique association of clinical and pathological findings in a neonate. Foregut enteric duplication cysts--rare developmental anomalies that are associated with midline vertebral fusion anomalies. METHODS: We had a neonate with foregut duplication cyst who presented at birth with respiratory distress. The child also had associated communicating hydrocephalus. The patient underwent excision of the duplication cyst along with a ventriculo-peritoneal shunt. RESULT: The excised specimen revealed a duplication cyst lined by aberrant pancreatic tissue. CONCLUSION: The present case demonstrates histologically the presence of both pancreatic and gastric tissue.

MCH indicators in south Asia.

PIP: This article presents some statistical indicators of maternal and child health in countries of South Asia, including Afghanistan, Bangladesh, Bhutan, India, Nepal, Pakistan, and Sri Lanka. Statistical tables aggregate data for the entire South Asia region and industrialized countries, for comparative purposes. South Asia has about 22% of world population, 33% of births annually, about 37% of annual global child mortality (CM), and the second highest maternal mortality ratio (MMR). In 1995, Sri Lanka had the lowest CM. Afghanistan had the highest CM. CM in the region was 121, or 15 times more than in industrialized countries. Countries with higher CM rates tended to have higher birthrates. Total fertility rates ranged from 2.4 in Sri Lanka, to 6.6 in Afghanistan. The total fertility rate in the region was 3.9. 29% of births in the region were attended by a trained attendant during 1990-96. Under 10% of births were attended by a trained attendant in Nepal (7%) and Afghanistan (9%). India had the highest proportion of births attended by a trained attendant (34%). Contraceptive prevalence ranged from a low of 2% in Afghanistan, to a high of 66% in Sri Lanka. Contraceptive prevalence for the region was 38%. Female literacy was lowest in Nepal (14%) and Afghanistan (15%). Sri Lanka had the highest female literacy of 87%, followed by India with 38%. Female literacy for the region was 36%. Countries with high fertility rates tended to have high MMRs. MMR was inversely related to contraceptive prevalence rates, presence of trained attendants during delivery, and adult female literacy rates. 90% of the region had coverage with BCG immunization, followed by DPT, OPV, and measles immunization. Maternal tetanus toxoid was 69%.^ieng

Slow versus fast enteral feed advancement in very low birth weight infants: a randomized control trial.

OBJECTIVE: To evaluate the tolerance of rapid advancement of enteral feeds in VLBW babies. SETTING: Tertiary teaching hospital. DESIGN: Randomized controlled trial. METHODS: All stable neonates with birth weight less than 1250 grams were included in the study. The primary outcome variable was the time taken to achieve full enteral feeds (defined as 180 ml/kg/day). The secondary outcome variables were incidence of Necrotizing enterocolitis (NNEC) and incidence of apnea. At 48 hours, the infants were randomized into the slow advancement group (enteral feeds advanced by increments of 15 ml/kg/day) or fast advancement group (enteral feeds advanced by increments of 30 ml/kg/day). The monitoring during feeding included daily weight record, two hourly abdominal girth charting, gastric aspirates, apnea, time taken to reach full enteral feedings and for NNEC. RESULTS: There were 53 infants who were enrolled for the study (27 in the fast advancement group and 26 in the slow advancement group). In the fast advancement group, 20 percent completed the trial; whereas 14 (53.8 percent;) in the slow advancement group completed the study. The two groups were comparable for birth weights, gestational age, sex, intrauterine growth status, Apgar and CRIB scores. The infants in the fast group reached full enteral intake of 180 ml/kg/day significantly earlier (10 +/- 1.8 days) than in the slow group (14.8 +/- 1.5 days). The two groups were comparable for episodes of feed intolerance, apnea, NNEC. Infants in the fast group regained birth weight significantly earlier (median 18 days) than in the slow advancement group (median 23 days). CONCLUSIONS: Stable VLBW neonates can tolerate rapid advancements of enteral feeding without increased risk of adverse effects.

Midazolam sedation in mechanically ventilated newborns: a double blind randomized placebo controlled trial.

OBJECTIVE: To determine efficacy of midazolam as a sedative in mechanically ventilated newborns. DESIGN: Double blind randomized placebo controlled trial. SETTING: Neonatal Unit of Tertiary Hospital. OUTCOME: Sedation over 48 h of observation. METHODS: Neonates with birth weight less than 2000 g who were mechanically ventilated within 7 days of life were randomly assigned to midazolam and placebo group. Midazolam and placebo were administered as bolus (0.2 mg/kg) followed by continuous infusion (0.06 mg/kg/h). Both groups received morphine infusion (10 microg/kg/h). Sedation score was noted at 6 hourly intervals for 48 hours. Hemodynamic variables, ventilatory variables, complications and side effects of treatments were also recorded. RESULTS: Thirty-three neonates were enrolled (17 in midazolam, 16 in placebo group). The groups were comparable for birth weights and gestation. The midazolam group had significantly better sedation from 18-24 hours after enrollment compared to placebo group. At 48 h there were no significant differences in proportion of infants with adequate sedation between midazolam and placebo group. The two groups were comparable with respect to heart rate, perfusion, ventilatory indices and blood gas parameters. None of the infants were noted to have hypotension on loading with midazolam or placebo. Seizures were noted in 2 neonates in placebo group 24 hours after enrollment (insignificant statistically). CONCLUSION: Sedation provided by continuous infusion of midazolam and morphine appears to be comparable to morphine alone in newborn babies on mechanical ventilation, with no significant adverse effects. The course of mechanical ventilation is not influenced by use of midazolam.