Kailash Chandra Aggarwal

Comparison of Human Neonatal and Adult Blood Leukocyte Subset Composition Phenotypes

The human peripheral leukocyte subset composition depends on genotype variation and pre-natal and post-natal environmental influence diversity. We quantified this composition in adults and neonates, and compared the median values and dispersal ranges of various subsets in them. We confirmed higher frequencies of monocytes and regulatory T cells (Tregs), similar frequencies of neutrophils, and lower frequencies of CD8 T cells, NKT cells, B1 B cells and gamma-delta T cells in neonatal umbilical cord blood. Unlike previous reports, we found higher frequencies of eosinophils and B cells, higher CD4:CD8 ratios, lower frequencies of T cells and iNKT cells, and similar frequencies of CD4 T cells and NK cells in neonates. We characterized monocyte subsets and dendritic cell (DC) subsets in far greater detail than previously reported, using recently described surface markers and gating strategies and observed that neonates had lower frequencies of patrolling monocytes and lower myeloid dendritic cell (mDC):plasmacytoid DC (pDC) ratios. Our data contribute to South Asian reference values for these parameters. We found that dispersal ranges differ between different leukocyte subsets, suggesting differential determination of variation. Further, some subsets were more dispersed in adults than in neonates suggesting influences of postnatal sources of variation, while some show the opposite pattern suggesting influences of developmental process variation. Together, these data and analyses provide interesting biological possibilities for future exploration.

Platelet functions and coagulation changes in Indian children with nephrotic syndrome.

INTRODUCTION Only little is known on the effect of the platelet function in the paediatric nephrotic syndrome. The earlier studies which had been done on hypercoagulability have mainly featured the secondary forms of the nephrotic syndrome and the data on the minimal change type of disease is limited. We therefore, made an effort to study the platelet functions and the coagulation profile in children with the nephrotic syndrome,to find the relationship between the steroid response and the coagulation profile, and to look for the correlation between thromboembolism and the hypercoagulable states. METHODOLOGY Twenty nine children with the steroid responsive nephrotic syndromewere studied to see the platelet aggregation and the coagulation parameters and their response to the steroid therapy. Doppler studies were done for the renal vein and the inferior vena cava (IVC) thrombus. RESULTS It was seen that an increased aggregability of the platelets occurred with Adenosine diphosphate (ADP) and collagen (out of the four agonists, ADP, Collagen, Ristocetin and Arachidonic acid) which were used as agonists for the assay. We also observed that the Partial thromboplastin time (PTT) had become prolonged and a significant decline in the high values of the procoagulant proteins (Protein C and Protein S) was seen after the steroid therapy and when the children went into remission. These findings were suggestive of a reversibility of the changes in the steroid responsive nephrotic syndrome with the steroid therapy. One child was found to have thrombosis of the inferior vena cava (IVC) on Doppler studies, which resolved with treatment subsequently. CONCLUSIONS An increased platelet aggregability contributes to the hypercoagulable states, that may increase the incidence of thrombosis in such patients. Although the incidence of such complications is very low, in a given child with the hypercoagulable states, Doppler may be used to look for any evidence of a latent thrombus and, an early intervention could be instituted. A change in the coagulation parameters points to the reversibility of the changes which are produced in a diseased state.

The Unusual Presentation of a Usual Organism - the Changing Spectrum of the Clinical Manifestations of Plasmodium Vivax Malaria in Children: A Retrospective Study

BACKGROUND Malaria is a major public health problem in the south-east Asian region. Among all countries in the SE Asian region the highest number of cases and deaths are reported from India. Children below 14 years of age contribute to approximately 42% of all the deaths. A majority of the deaths are attributed to severe malaria which is caused by Plasmodium falciparum. It is considered that causes a benign causing febrile illness without significant complications. However, in recent years, the spectrum of is shifting from being the cause of benign fever, to more severe complications. There have been case reports of complications like thrombocytopaenia, cerebral malaria, a disseminated intravascular coagulation, the acute respiratory distress syndrome, hepatic dysfunction and renal involvement. Most of the case reports are from the adult population, with an occasional occurrence of paediatric cases. OBJECTIVE To highlight the increasing number of severe manifestations in P.vivax malaria in the children who were admitted in the malaria transmission season of 2011, at a tertiary care hospital. DESIGN A descriptive, cross-sectional study. MATERIAL AND METHODS STUDY SUBJECTS Children with an acute febrile illness of a duration of < 7 days, which was confirmed as Plasmodium vivax positive malaria by testing the peripheral smears and/or by Rapid Diagnostic Testing, who were admitted in the paediatric ward of a tertiary care hospital in New Delhi (India), during May 2011 to October 2011, Case records of context cases were analysed retrospectively. STATISTICS The data was summarised by calculating the rates, ratios, proportions, means, standard deviations and the 95% confidence intervals. The Chi square test was applied to assess the significant difference between two qualitative variables. RESULTS Among the case records of 54 patients, 40.7% were below 5 years. 61% were males and 38.9% were females. Besides hepatomegaly and splenomegaly which were the most common symptoms, which were seen in 81.5% and 72.2% children respectively, the various unusual manifestations seen were severe thrombocytopaenia (37%), jaundice with deranged LFT values (25.9%), abnormal bleeding (18.5%), impaired consciousness with a GCS of < 9 (18.5%), severe anaemia (14.8%), hypotension (11.1%), repeated convulsions (7.6%), pulmonary oedema/ARDS (5.6%) and ascites (5.6%). One case each showed haemoglobinuria, and pleural effusion. CONCLUSION Plasmodium vivax is emerging as a cause of severe malaria. There is a further need to study the pathophysiology, virulence factors and the molecular mechanisms which are involved in malaria.

Complementary feeding at 4 versus 6 months of age for preterm infants born at less than 34 weeks of gestation: a randomised, open-label, multicentre trial

Summary Background Evidence on the optimal time to initiation of complementary feeding in preterm infants is scarce. We examined the effect of initiation of complementary feeding at 4 months versus 6 months of corrected age on weight for age at 12 months corrected age in preterm infants less than 34 weeks of gestation. Methods In this open-label, randomised trial, we enrolled infants born at less than 34 weeks of gestation with no major malformation from three public health facilities in India. Eligible infants were tracked from birth and randomly assigned (1:1) at 4 months corrected age to receive complementary feeding at 4 months corrected age (4 month group), or continuation of milk feeding and initiation of complementary feeding at 6 months corrected age (6 month group), using computer generated randomisation schedule of variable block size, stratified by gestation (30 weeks or less, and 31–33 weeks). Iron supplementation was provided as standard. Participants and the implementation team could not be masked to group assignment, but outcome assessors were masked. Primary outcome was weight for age Z-score at 12 months corrected age (WAZ12) based on WHO Multicentre Growth Reference Study growth standards. Analyses were by intention to treat. The trial is registered with Clinical Trials Registry of India, number CTRI/2012/11/003149. Findings Between March 20, 2013, and April 24, 2015, 403 infants were randomly assigned: 206 to receive complementary feeding from 4 months and 197 to receive complementary feeding from 6 months. 22 infants in the 4 month group (four deaths, two withdrawals, 16 lost to follow-up) and eight infants in the 6 month group (two deaths, six lost to follow-up) were excluded from analysis of primary outcome. There was no difference in WAZ12 between two groups: −1·6 (SD 1·2) in the 4 month group versus −1·6 (SD 1·3) in the 6 month group (mean difference 0·005, 95% CI −0·24 to 0·25; p=0·965). There were more hospital admissions in the 4 month group compared with the 6 month group: 2·5 episodes per 100 infant-months in the 4 month group versus 1·4 episodes per 100 infant-months in the 6 month group (incidence rate ratio 1·8, 95% CI 1·0–3·1, p=0·03). 34 (18%) of 188 infants in the 4 month group required hospital admission, compared with 18 (9%) of 192 infants in the 6 month group. Interpretation Although there was no evidence of effect for the primary endpoint of WAZ12, the higher rate of hospital admission in the 4 month group suggests a recommendation to initiate complementary feeding at 6 months over 4 months of corrected age in infants less than 34 weeks of gestation. Funding Indian Council of Medical Research supported the study until Nov 14, 2015. Subsequently, Shuchita Guptas salary was supported for 2 months by an institute fellowship from All India Institute Of Medical Sciences, and a grant by Wellcome Trust thereafter.

Underweight Full-Term Indian Neonates Show Differences in Umbilical Cord Blood Leukocyte Phenotype: A Cross-Sectional Study

Background While infections are a major cause of neonatal mortality in India even in full-term neonates, this is an especial problem in the large proportion (~20%) of neonates born underweight (or small-for-gestational-age; SGA). One potential contributory factor for this susceptibility is the possibility that immune system maturation may be affected along with intrauterine growth retardation. Methods In order to examine the possibility that differences in immune status may underlie the susceptibility of SGA neonates to infections, we enumerated the frequencies and concentrations of 22 leukocyte subset populations as well as IgM and IgA levels in umbilical cord blood from full-term SGA neonates and compared them with values from normal-weight (or appropriate-for-gestational-age; AGA) full-term neonates. We eliminated most SGA-associated risk factors in the exclusion criteria so as to ensure that AGA-SGA differences, if any, would be more likely to be associated with the underweight status itself. Results An analysis of 502 such samples, including 50 from SGA neonates, showed that SGA neonates have significantly fewer plasmacytoid dendritic cells (pDCs), a higher myeloid DC (mDC) to pDC ratio, more natural killer (NK) cells, and higher IgM levels in cord blood in comparison with AGA neonates. Other differences were also observed such as tendencies to lower CD4:CD8 ratios and greater prominence of inflammatory monocytes, mDCs and neutrophils, but while some of them had substantial differences, they did not quite reach the standard level of statistical significance. Conclusions These differences in cellular lineages of the immune system possibly reflect stress responses in utero associated with growth restriction. Increased susceptibility to infections may thus be linked to complex immune system dysregulation rather than simply retarded immune system maturation.

Giant Cerebral Cysticercosis in an Infant Confused With a Thalamic Glioma

Neurocysticercosis is a common parasitic infection of the central nervous system. Intraparenchymal giant cysticercosis has been described in literature, but this is a rare report of a thalamic giant cysticercosis in a young child where the diagnosis could be made on follow-up. A 1½-year-old male child presented with seizures, hemiparesis, and features of raised intracranial pressure. Initial neuroimaging findings of thalamic swelling with minimal edema and contrast enhancement with choline peak on magnetic resonance spectroscopy were attributed to thalamic glioma. Subsequent imaging revealed a ring enhancing lesion with an eccentric nodule suggestive of neurocysticercosis. It later resolved with residual gliosis. The presence of a pathognomic scolex and the resolution of size and symptoms without definitive treatment helped in making the diagnosis. This report reinforces the importance of considering cysticercosis in diagnosis of acute presentations of large cerebral masses in infants, particularly in prevalent regions, and emphasizes the follow-up of these patients.

Alarming rates of antimicrobial resistance and fungal sepsis in outborn neonates in North India.

Background There is a paucity of data on the epidemiology of sepsis in outborn neonates being referred to level-3 units in low- and middle-income countries (LMIC). The objective of the present study was to evaluate the prevalence of sepsis and outcomes of outborn neonates with sepsis, and to characterize the pathogen profile and antimicrobial resistance (AMR) patterns of common isolates in them. Methods In this prospective observational cohort study (2011–2015), a dedicated research team enrolled all neonates admitted to an outborn level-3 neonatal unit and followed them until discharge/death. Sepsis work-up including blood culture(s) was performed upon suspicion of sepsis. All the isolates were identified and tested for antimicrobial susceptibility. Gram-negative pathogens resistant to any three of the five antibiotic classes (extended-spectrum cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and piperacillin-tazobactam) were labeled multi-drug resistant. Results Of the total of 2588 neonates enrolled, culture positive sepsis and total sepsis–i.e. culture positive and/or culture negative sepsis–was diagnosed in 13.1% (95% CI 11.8% to 14.5%) and 54.7% (95% CI 52.8% to 56.6%), respectively. The case fatality rates were 23.4% and 11.0% in culture-positive and total sepsis, respectively. Sepsis accounted for two-thirds of total neonatal deaths (153/235, 63.0%). Bacterial isolates caused about three-fourths (296/401; 73.8%) of the infections. The two common pathogens–Klebsiella pneumoniae (n = 50, 12.5%) and Acinetobacter baumannii (n = 46, 11.5%)–showed high degree of multi-drug resistance (78.0% and 91.3%, respectively) and carbapenem resistance (84.0% and 91.3%, respectively). About a quarter of infections were caused by Candida spp. (n = 91; 22.7%); almost three-fourths (73.7%) of these infections occurred in neonates born at or after 32 weeks’ gestation and about two-thirds (62.1%) in those weighing 1500 g or more at birth. Conclusions In this large outborn cohort, we report high burden of sepsis, high prevalence of systemic fungal infections, and alarming rates of antimicrobial resistance among bacterial pathogens.

Improving quality of care during childbirth in primary health centres: a stepped-wedge cluster-randomised trial in India

Background Low/middle-income countries need a large-scale improvement in the quality of care (QoC) around the time of childbirth in order to reduce high maternal, fetal and neonatal mortality. However, there is a paucity of scalable models. Methods We conducted a stepped-wedge cluster-randomised trial in 15 primary health centres (PHC) of the state of Haryana in India to test the effectiveness of a multipronged quality management strategy comprising capacity building of providers, periodic assessments of the PHCs to identify quality gaps and undertaking improvement activities for closure of the gaps. The 21-month duration of the study was divided into seven periods (steps) of 3  months each. Starting from the second period, a set of randomly selected three PHCs (cluster) crossed over to the intervention arm for rest of the period of the study. The primary outcomes included the number of women approaching the PHCs for childbirth and 12 directly observed essential practices related to the childbirth. Outcomes were adjusted with random effect for cluster (PHC) and fixed effect for ‘months of intervention’. Results The intervention strategy led to increase in the number of women approaching PHCs for childbirth (26 vs 21 women per PHC-month, adjusted incidence rate ratio: 1.22; 95% CI 1.17 to 1.28). Of the 12 practices, 6 improved modestly, 2 remained near universal during both intervention and control periods, 3 did not change and 1 worsened. There was no evidence of change in mortality with a majority of deaths occurring either during referral transport or at the referral facilities. Conclusion A multipronged quality management strategy enhanced utilisation of services and modestly improved key practices around the time of childbirth in PHCs in India. Trial registration number CTRI/2016/05/006963.