Screening of Extended Family Members of Thalassemia Major Children as a Thalassemia Preventive Strategy

BACKGROUND: Thalassemia is considered as the most common single gene disorder worldwide. Preventive measures include identification of thalassemia carriers (traits) through screening, genetic counselling and prenatal diagnosis to reduce the incidence. This study aims at estimating the prevalence of carrier status detection among the extended family members of children having thalassemia major so as to use it as a screening prevention strategy with appropriate counselling. METHODS: This cross-sectional study was conducted in thalassemia unit of Pediatric Department of a tertiary care teaching hospital over a period of 18 months. Blood samples were collected from 117 extended family members (EFM) of 23 children with thalassemia major to carry out investigations such as Complete Blood Counts (CBC), Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT), Reticulocyte count, High Performance Liquid Chromatography(HPLC) and serum ferritin. Reports were analysed to find out the prevalence of carriers. RESULTS: Among 117 EFM, 62 (52.9%) were males while 55(47.1%) were females. Mean age distribution in this study was 16.49 years (8.5). Prevalence of thalassemia trait (carrier) was 35%. NESTROFT test was positive in 57(48.7%) participants. The binary logistic regression found only positive NESTROFT test as a predictor (adjusted OR=0.022, P=0.001) of having raised HbA2 (HbA2≥3.5 %). CONCLUSION: Screening of thalassemia carrier by targeting extended family members of thalassemia major children could yield more carrier cases and targeted counselling could help effectively in decreasing the number of children born with thalassemia major. This strategy could be included in future plan of national prevention programme for thalassemia

Feasibility of breast crawl in a tertiary care teaching institute

Background: Early initiation of breastfeeding has many beneficial effects for both the mother and the baby. The breast crawl has been established as the ideal method for promoting early skin-to-skin contact and early initiation of breastfeeding. Objective: The objective of the study was to assess the feasibility of breast crawl in a busy tertiary care institute. Materials and Methods: An observational study was performed including 50 mother-baby pairs, admitted to the labor room of Sassoon General Hospital, Pune, from January2018 for 6 months. Observations were made on patient and nurse attitude and behavior and were further analyzed. Results: Of the total subjects, 23 (46%) mothers had not received any counseling about breastfeeding during the antenatal period and none of them were familiar with the idea of breast crawl from the antenatal period. Of the 50 mothers, 27 mothers (54%) were concerned about privacy, 8 (16%) were concerned about environmental cold, 6 (12%) were worried about exposure, and 9 mothers (18%) were concerned about the baby, whereas 6 mothers (12%) had no concerns and 6 mothers had more than one concern. The attitude of the nursing staff was favorable (enthusiastic) 19 times, indifferent 23 times, reluctant 6 times, and unfavorable (uncooperative) 2 times. Conclusion: While it is highly desirable to implement breast crawl as a routine practice, there are several roadblocks such as lack of antenatal counseling, lack of awareness and motivation, lack of specific guidelines and instructions, skewed staff-to-patient and bed-to-patient ratio, and lack of privacy

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Childhood epilepsy: Management in resource-limited setting

<b>Objective:</b> To optimize the use of phenobarbital and/or phenytoin as frontline drugs for treatment of childhood epilepsy. <b> Design:</b> Before-and -after study. <b> Setting:</b> Epilepsy clinic at paediatric OPD, Sassoon General Hospital, Pune. <b> Materials and</b> <b> Methods:</b> Epilepsy is a condition in which seizures are triggered recurrently from within the brain. For epidemiological classification purpose epilepsy is considered to be present when two or more unprovoked seizures occur at an interval greater than twenty four hours apart. Seizures were classified as generalized and partial seizures, with underlying etiology investigated with EEG, CT scan in majority of the patients. Follow - up rate, seizure - control and antiepileptic drugs used among 151 children enrolled as on 31 March 2005 were compared with 106 children with new onset epilepsy enrolled as on February 2006. Eight children with breakthrough convulsion after a seizure free period of five to eighteen months were followed up after injection vitamin D. Nineteen children with poor control of seizures receiving polytherapy with newer antiepileptic drugs were assessed with frontline antiepileptic medication of phenobarbital and/or phenytoin. Serum calcium, phosphorus, alkaline phosphatase were done in seventy two consecutive children with seizure disorder. <b> Results:</b> During post protocol period good seizure control was achieved in 84.8&#x0025; as against 80.7&#x0025; and use of phenobarbital and/or phenytoin increased to 65.11&#x0025; from 22.87&#x0025;. Of the 8 cases with breakthrough seizures seven remained seizure free after vitamin D administration and with no dose enhancement of AED medications of the nineteen. Children receiving polytherapy thirteen children could be successfully switched to phenobarbital and/or phenytoin. Forty four (61&#x0025;) children had hypocalcemia (less than 9 mg&#x0025;), fifty seven (79&#x0025;) children had raised alkaline phosphatase levels (more than 270 IU). <b> Comments:</b> Phenobarbital and/or phenytoin have been found to be effective frontline AED. Periodic administration of vitamin D plays a supportive role

2009H1N1 Infection in a 1-day-old neonate

A full-term female neonate was delivered with meconium stained amniotic fluid by cesarean section by a 2009H1N1 positive 22-year-old second gravida mother, who developed symptoms 8 days prior to delivery. The neonate was completely and immediately isolated from the mother after delivery. Oseltamivir was started at birth to the neonate who had a potential possibility of 2009H1N1 infection. At 5 hours of life, the neonate developed respiratory distress. The neonate′s throat swab sent for 2009H1N1 by real-time polymerase chain reaction (RT-PCR) assay was positive. The neonate required oxygen by hood for 3 days and made an uneventful recovery. The mother developed acute respiratory distress syndrome after delivery, requiring ventilatory care for 14 days and was discharged after 25 days stay in hospital. 2009H1N1 infection, although rare, needs a high index of suspicion and prompt therapy in neonates. Clinicians should be alert about the possibility of perinatal transmission of 2009H1N1

D-transallethrin: An unusual agent for accidental poisoning

D-trans allethrin, a pyrethroid, is commonly used as a coil mosquito repellant. There are very few reports of human toxicity due to D-trans allethrin. We present the case of an 11-month-old boy who presented to us with excessive salivation, altered sensorium and convulsions following alleged accidental ingestion of a coil containing D-transallethrin. He required mechanical ventilation for a brief period and made a full recovery. Although rare, the possibility of pyrethroid poisoning should be kept in mind in children who present with sudden onset unconsciousness or convulsions

Comparative immune responses to Mycobacterium tuberculosis in people with latent infection or sterilizing protection

Summary: There is great need for vaccines against tuberculosis (TB) more efficacious than the licensed BCG. Our goal was to identify new vaccine benchmarks by identifying immune responses that distinguish individuals able to eradicate the infection (TB-resisters) from individuals with latent infection (LTBI-participants). TB-resisters had higher frequencies of circulating CD8+ glucose monomycolate (GMM)+ Granzyme-B+ T cells than LTBI-participants and higher proportions of polyfunctional conventional and nonconventional T cells expressing Granzyme-B and/or PD-1 after ex vivo M. tuberculosis stimulation of blood mononuclear cells. LTBI-participants had higher expression of activation markers and cytokines, including IL10, and IFNγ. An exploratory analysis of BCG-recipients with minimal exposure to TB showed absence of CD8+GMM+Granzyme-B+ T cells, lower or equal proportions of Granzyme-B+PD-1+ polyfunctional T cells than TB-resisters and higher or equal than LTBI-participants. In conclusion, high Granzyme-B+PD-1+ T cell responses to M. tuberculosis and, possibly, of CD8+GMM+Granzyme-B+ T cells may be desirable for new TB vaccines

Tuberculin skin test and QuantiFERON-Gold In Tube assay for diagnosis of latent TB infection among household contacts of pulmonary TB patients in high TB burden setting

<div><p>Background</p><p>World Health Organization (WHO) recommends systematic screening of high-risk populations, including household contacts (HHCs) of adult pulmonary tuberculosis (TB) patients, as a key strategy for elimination of TB. QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and tuberculin skin test (TST) are two commonly used tools for the detection of latent tuberculosis infection (LTBI) but may yield differential results, affecting eligibility for TB preventive therapy.</p><p>Materials and methods</p><p>A prospective cohort study of adult pulmonary TB patients and their HHCs were recruited in 2 cities of India, Pune and Chennai. HHCs underwent QFT-GIT (QIAGEN) and TST (PPD SPAN 2TU/5TU). A positive QFT-GIT was defined as value ≥0.35 IU/ml and a positive TST as an induration of ≥5 mm. A secondary outcome of TST induration ≥10mm was explored. Proportion positive by either or both assays, discordant positives and negatives were calculated; test concordance was assessed using percentage agreement and kappa statistics; and risk factors for concordance and discordance including age categories were assessed using logistic regression. Sensitivity and specificity was estimated by latent class model.</p><p>Results</p><p>Of 1048 HHCs enrolled, 869 [median (IQR) age: 27 years (15–40)] had both TST and QFT-GIT results available and prevalence of LTBI by QFT-GIT was 54% [95% CI (51, 57)], by TST was 55% [95% CI (52, 58)], by either test was 74% [95% CI (71, 77) and by both tests was 35% [95% CI (31, 38)]. Discordance of TST+/QFT-GIT- was 21% while TST-/QFT-GIT+ was 26%. Poor to fair agreement occurred with TST 5mm or 10mm cutoff (60 and 61% agreement with kappa value of 0.20 and 0.25 respectively). Test agreement varied by age, TST strength and induration cut-off. In multivariate analysis, span PPD was a risk factor for QFT-GIT+ and TST- while absence of BCG scar was for TST+ and QFT-GIT-. Being employed and exposure to TB case outside the household case were associated with positivity by both the tests. Sensitivity of TST and QFT-GIT to diagnose LTBI was 77% and 69%. Probability of having LTBI was >90% when both tests were positive irrespective of exposure gradient.</p><p>Conclusion</p><p>Prevalence of LTBI among HHCs of adult pulmonary TB patients in India is very high and varies by test type, age, and exposure gradient. In our high TB burden setting, a strategy to treat all HHCs or a targeted strategy whereby an exposure index is used should be assessed in future preventive therapy and vaccine studies as HHCs have several factors that place them at high risk for progression to TB disease.</p></div