Effect of Antiretroviral Therapy on Neutrophil Oxidative Burst in Children

Objective To ascertain the efect of human immunodefciency virus (HIV) infection, as well as, antiretroviral therapy (ART) on neutrophil oxidative burst in children. Methods Fifty-fve children living with HIV infection (30 receiving ART for?2 y, 25 treatment-naïve) and 30 healthy controls, aged 18 mo–18 y, were assessed for hemogram and neutrophil oxidative burst. The treatment-naïve children were followed up and the above tests were repeated after 6 mo of ART. Results Mean (SD) serum MPO activity at 6 mo after ART [32.1 (±19.9) U/L] was comparable to that at disease onset [17.2 (±23.0) U/L], although it was signifcantly higher compared to that in children on ART?2 y [13.3 (±15.8) U/L] and controls [12.1 (±11.9) U/L]. Median fuorescence intensity (MFI) of unstimulated DHR was highest at 6 mo after ART and in the treatment-naïve group, which was signifcantly higher than in the controls, as well as, children receiving ART?2 y. Stimulation index was highest in the control group [442.4 (341.9–562.9)], which was comparable to that in children on ART?2 y [304.2 (153.2–664.8)], but was signifcantly higher than the treatment-naïve cohort [266.1 (148.2–339.4)] and children on ART for 6 mo [318.8 (154.9–395.6)]. Conclusion A hyperinfammatory state caused by an increased serum myeloperoxidase enzyme activity and increased basal neutrophil oxidative burst was seen in untreated HIV infection and during initial 6 mo of ART. ART given for?2 y normalized the impaired neutrophilic phagocytic functions.

Diagnosis, Treatment and Prevention of Nutritional Anemia in Children: Recommendations of the Joint Committee of Pediatric HematologyOncology Chapter and Pediatric and Adolescent Nutrition Society of the Indian Academy of Pediatrics

Justification: Anemia in children is a significant public health problem in our country. Comprehensive National Nutrition Survey 2016-18 provides evidence that more than 50% of childhood anemia is due to an underlying nutritional deficiency. The National Family Health Survey-5 has reported an increase in the prevalence of anemia in the under-five age group from 59% to 67.1% over the last 5 years. Clearly, the existing public health programs to decrease the prevalence of anemia have not shown the desired results. Hence, there is a need to develop nationally acceptable guidelines for the diagnosis, treatment and prevention of nutritional anemia. Objective: To review the available literature and collate evidence-based observations to formulate guidelines for diagnosis, treatment and prevention of nutritional anemia in children. Process: These guidelines have been developed by the experts from the Pediatric Hematology-Oncology Chapter and the Pediatric and Adolescent Nutrition (PAN) Society of the Indian Academy of Pediatrics (IAP). Key areas were identified as: epidemiology, nomenclature and definitions, etiology and diagnosis of iron deficiency anemia (IDA), treatment of IDA, etiology and diagnosis of vitamin B12 and/or folic acid deficiency, treatment of vitamin B12 and/or folic acid deficiency anemia and prevention of nutritional anemia. Each of these key areas were reviewed by at least 2 to 3 experts. Four virtual meetings were held in November, 2021 and all the key issues were deliberated upon. Based on review and inputs received during meetings, draft recommendations were prepared. After this, a writing group was constituted which prepared the draft guidelines. The draft was circulated and approved by all the expert group members. Recommendations: We recommend use of World Health Organization (WHO) cut-off hemoglobin levels to define anemia in children and adolescents. Most cases suspected to have IDA can be started on treatment based on a compatible history, physical examination and hemogram report. Serum ferritin assay is recommended for the confirmation of the diagnosis of IDA. Most cases of IDA can be managed with oral iron therapy using 2-3 mg/kg elemental iron daily. The presence of macro-ovalocytes and hypersegmented neutrophils, along with an elevated mean corpuscular volume (MCV), should raise the suspicion of underlying vitamin B12 (cobalamin) or folic acid deficiency. Estimation of serum vitamin B12 and folate level are advisable in children with macrocytic anemia prior to starting treatment. When serum vitamin B12 and folate levels are unavailable, patients should be treated using both drugs. Vitamin B12 should preferably be started 10-14 days ahead of oral folic acid to avoid precipitating neurological symptoms. Children with macrocytic anemia in whom a quick response to treatment is required, such as those with pancytopenia, severe anemia, developmental delay and infantile tremor syndrome, should be managed using parenteral vitamin B12. Children with vitamin B12 deficiency having mild or moderate anemia may be managed using oral vitamin B12 preparations. After completing therapy for nutritional anemia, all infants and children should be advised to continue prophylactic iron-folic acid (IFA) supplementation as prescribed under Anemia Mukt Bharat guidelines. For prevention of anemia, in addition to age-appropriate IFA prophylaxis, routine screening of infants for anemia at 9 months during immunization visit is recommended.

Pulmonary Dysfunction in Transfusion-Dependent Thalassemia and Response to Intensive Chelation Therapy

Objectives: To evaluate pulmonary functions in children with transfusion-dependent thalassemia, and its reversal (lung dysfunction) using intensive intravenous chelation with desferrioxamine (DFO) (4 weeks). Methods: This descriptive study enrolled 77 children with transfusion-dependent thalassemia. Pulmonary function test (PFT) and iron load (serum ferritin (SF) & T2* MRI of heart and liver) were done. PFT included spirometry, total lung capacity (TLC) by helium dilution test and diffusion capacity by carbon monoxide (DLCO). Follow-up PFT was available for 13 children with moderate to severe lung dysfunction given intravenous DFO. Results: 50 (68.8%) patients had lung dysfunction, most commonly diffusional impairment (48; 96%), and reduced TLC (11; 22%); and none had obstructive pattern. 9 (81.8%) patients with restrictive defect had moderate to severely deranged DLCO. PFT and T2* MRI values were inversely correlated with serum ferritin. Among 13 patients receiving intensive chelation for 4 weeks, significant improvement was noticed in forced expiratory volume in one minute/ forced vital capacity ratio (?FEV1/FVC) (P=0.009), ?DLCO (P=0.006) and ?SF (P=0.01). Conclusions: Pulmonary dysfunction is common in children with multi-transfused thalassemia, and routine screening by PFT needs to be part of the management guidelines.

Cephalic Tetanus Presenting as Ptosis

A 7-year-old unimmunized boy developed cephalic tetanusfollowing chronic suppurative otitis media. We wish to emphasizethat possibility of cephalic tetanus should be considered in anunimmunized child presenting with ptosis.

A prospective cohort study of enteric pathogens in human immunodeficiency virus-infected Indian children and their relationship with diarrheal recurrence

Background: Opportunistic intestinal infections can increase the risk of death 11- fold in Human immunodeficiency virus (HIV) infected children presenting with diarrhea. Understanding the etiology of diarrhea and its predictors can help strategize a targeted approach to reduce child mortality due to diarrhea in this vulnerable group. Authors aim was' to compare the enteric pathogens in HIV-infected children with and without acute diarrhea, to assess the association between carriage of enteric pathogens in HIV-infected children and the occurrence of diarrhea within the next 3 months and to ascertain the relationship between enteric pathogens in HIV-infected children with their immunological and nutritional status.Methods: Stool samples were collected from HIV-infected children with acute diarrhea (n=41) and without diarrhea (n=52). All samples were subjected to microscopic examination, modified acid-fast and Trichrome staining, hanging drop examination, and bacterial culture. Serology for Cryptosporidium parvum was determined. Children who had received any antimicrobial therapy within the previous 2 weeks were excluded. Participants were followed up for three months for occurrence of diarrhea.Results: Intestinal pathogens were isolated in 48.8% and 42% of children in the diarrheal and non-diarrheal group respectively. The most common pathogens isolated in the diarrheal and non-diarrheal group were Cryptosporidium parvum and Escherichia coli (29.3% vs. 17.3%). During follow up, 8 children in each group had diarrheal occurrence. The pathogen isolated in subsequent episodes matched with the initial isolate in 3 children in each group.Conclusions: HIV-infected children without diarrhea also harbour enteric pathogens in comparable proportions to symptomatic children, which can predispose them to diarrheal occurrence in future, hence indicating need for assessing the need for preventive screening and prophylactic antibiotic regimens in this vulnerable group.

Comparative Efficacy and Safety of Oral Iron Chelators and their Novel Combination in Children with Thalassemia.

Objective: To compare the efficacy and safety of oral iron chelators (Deferiprone and Deferasirox) when used singly and in combination in multi-transfused children with thalassemia. Design: Prospective comparative study. Setting: Thalassemia Center of a medical college affiliated hospital Participants and Intervention: 49 multi-transfused children with thalassemia with a mean (SD) age 11.6 (6.21) y received daily chelation therapy with either deferiprone alone (75 mg/kg/day in 3 divided doses), deferasirox alone (30 mg/kg/day single dose) or their daily combination (same dose as monotherapy) for 12 months. Outcome measures: Serum ferritin levels at the start of study, after 6 months and after 12 months. MRI T2* of liver and heart initially and after 6 months of follow up. 24-hour urinary iron excretion values at the outset and after 12 months of chelation therapy. At every visit for blood transfusion, all patients were clinically assessed for any adverse effects; liver and renal functions were monitored 6-monthly. Results: After 12 months of respective chelation therapy, serum ferritin values decreased from a mean of 3140.5 ng/mL to 2910.0 ng/mL in deferiprone alone group, 3859.2 ng/mL to 3417.4 ng/mL in deferasirox alone group and from 3696.5 ng/mL to 2572.1 ng/mL in the combination group. The combination therapy was more efficacious in causing fall in serum ferritin levels compared to deferiprone and deferasirox monotherapy (P=0.035 and 0.040, respectively). Results of MRI T2* were equivocal. Combined drug usage produced maximum negative iron balance in the body by maximally increasing the iron excretion in urine from 61.1 µmol/day to 343.3 µmol/day (P=0.002). No significant adverse reactions were noticed in either the monotherapy or the combination group. Conclusion: Oral combination therapy of deferiprone and deferasirox appears to be an efficacious and safe modality to reduce serum ferritin in multi-transfused children with thalassemia.

Assessment of Quality of Life during Treatment of Pediatric Oncology Patients.

Background: The objective of this study was to assess health-related quality of life (HRQOL) of pediatric cancer patients and their parents in North India. Materials and Methods: Seventy-fi ve cancer children were assessed for HRQOL, using Lansky play performance scale and health utility index-2 (HUI-2). Fifty-seven patients were followedup after 4 months after therapy and reassessed. Their parents were also assessed using World Health Organisation (WHO) QOL BREF. Seventy fi ve controls were also assessed and compared. Results: Lansky and HUI-2 scores of patients, as well as WHO QOL BREF of parents were signifi cantly poor in cancer patients when compared to controls. There was signifi cant improvement after therapy in patients with lymphomas and miscellaneous tumors. Pain and self-care were found to be maximally affected domains on HUI-2. Conclusions: Large prospective multicenter studies may be undertaken and hence that need based interventions can be planned.

Clinical and Epidemiological Profiles of Severe Malaria in Children from Delhi, India.

Plasmodium vivax is traditionally known to cause benign tertian malaria, although recent reports suggest that P. vivax can also cause severe life-threatening disease analogous to severe infection due to P. falciparum. There are limited published data on the clinical and epidemiological profiles of children suffering from ‘severe malaria’ in an urban setting of India. To assess the clinical and epidemiological profiles of children with severe malaria, a prospective study was carried out during June 2008–December 2008 in the Department of Pediatrics, Guru Teg Bahadur Hospital, a tertiary hospital located in East Delhi, India. Data on children aged ≤12 years, diagnosed with severe malaria, were analyzed for their demographic, clinical and laboratory parameters. All patients were categorized and treated as per the guidelines of the World Health Organization. In total, 1,680 children were screened for malaria at the paediatric outpatient and casualty facilities of the hospital. Thirty-eight children tested positive for malaria on peripheral smear examination (2.26% slide positivity rate). Of these, 27 (71%) were admitted and categorized as severe malaria as per the definition of the WHO while another 11 (29%) received treatment on outpatient basis. Most (24/27; 88.8%) cases of severe malaria (n=27) were infected with P. vivax. Among the cases of severe malaria caused by Plasmodium vivax (n=24), 12 (50%) presented with altered sensorium (cerebral malaria), seven (29.1%) had severe anaemia (haemoglobin <5 g/dL), and 17 (70.8%) had thrombocytopaenia, of which two had spontaneous bleeding (epistaxis). Cases of severe vivax malaria are clinically indistinguishable from severe falciparum malaria. Our study demonstrated that majority (88.8%) of severe malaria cases in children from Delhi and adjoining districts of Uttar Pradesh were due to P. vivax-associated infection. P. vivax should, thus, be regarded as an important causative agent for severe malaria in children.

Immune response to second dose of MMR vaccine in Indian children.

Background & objectives: MMR vaccine in a two dose schedule has successfully eliminated measles, mumps and rubella from many developed countries. In India, it is not a part of national immunization programme but is included in the State immunization programme of Delhi as a single dose between 15-18 months. This prospective study was carried out to assess the extent of seroprotection against these three diseases in immunized children and to study the immune response to a second dose of MMR. Methods: Consecutive children aged 4-6 yr, attending the immunization clinic of a tertiary care hospital in Delhi for routine DT vaccination, were enrolled. Second dose of MMR was given and pre- and post-vaccination antibody levels were compared. Results: The pre-vaccination percentage seropositivity observed in the 103 children recruited, was 20.4 per cent for measles, 87.4 per cent for mumps and 75.7 per cent for rubella. Amongst the 84 children who were followed up after the second dose, the percentage seroprotection for measles rose from 21.4 (18/84) to 72.6 per cent (61/84) and 100 per cent became seroprotected to mumps and rubella. Interpretation & conclusions: The percentage of children protected against measles was found to be alarmingly low which needs to be investigated. Though the observed protection against mumps and rubella was adequate, its durability was not known. The need for re-appraisal of the current MMR immunization policy is called for by carrying out longitudinal studies on a larger sample.

Profile of HIV Infected Children from Delhi and Their Response to Antiretroviral Treatment.

Objectives: (i) To study the clinical and immunological profile of HIV infected children attending the ART centre; (ii) To correlate CD4 count with clinical staging at diagnosis; and, iii) To study the clinical and immunological response to antiretroviral treatment. Setting: Antiretroviral therapy (ART) centres of two tertiary care hospitals of Delhi. Patients: 100 children attending the centres between December 2008 to June 2009. Methods: The clinical features, immunological profile (CD4 count) and response to ART were recorded in a structured proforma. Design: Prospective follow-up. Results: Average age of enrolled children was 6.24 y (range 1-14 years) and mode of transmission was parent to child in 92%. Most common clinical presentation was fever (83%), cough (50.8%) and diarrhea (38.9%). Tuberculosis was the most common opportunistic infection seen in 11% of children. 59% of enrolled children were malnourished. Antiretroviral treatment (ART) was initiated in 33 children. Children who were initiated on ART had a significant improvement in both clinical and immunological staging at the 6 months follow up. Immunological response (rise in CD4 count) to ART was better in children with lesser degree of immunosuppression. The measure of agreement between the clinical and immunological stage at presentation was poor. Conclusions: Baseline CD4 counts rather than clinical staging can be a primary determinant for initiation of antiretroviral treatment in HIV infected children.

Efficacy and Safety of Azithromycin for Uncomplicated Typhoid Fever: An Open Label Non-comparative Study.

An open-labelled, non-comparative study was conducted in 117 children aged 2- 12 years to evaluate the efficacy and safety of azithromycin (20mg/ kg/day for 6 days) for the treatment of uncomplicated typhoid fever. Of the patients enrolled based on a clinical definition of typhoid fever, 109 (93.1%) completed the study. Mean (SD) of duration of fever at presentation was 9.1(4.5) days. Clinical cure was seen in 102 (93.5%) subjects, while 7 were withdrawn from the study because of clinical deterioration. Mean day of response was 3.45±1.97. BACTEC blood culture was positive for Salmonella typhi in 17/109 (15.5%) and all achieved bacteriological cure. No serious adverse event was observed. Global well being assessed by the investigator and subjects was good in 95% cases which was done at the end of the treatment. Azithromycin was found to be safe and efficacious for the management of uncomplicated typhoid fever.

Immunization Status of Children Admitted to a Tertiary-care Hospital of North India: Reasons for Partial Immunization or Non-immunization.

Reasons for the low coverage of immunization vary from logistic ones to those dependent on human behaviour. The study was planned to find out: (a) the immunization status of children admitted to a paediatric ward of tertiary-care hospital in Delhi, India and (b) reasons for partial immunization and nonimmunization. Parents of 325 consecutively-admitted children aged 12-60 months were interviewed using a semi-structured questionnaire. A child who had missed any of the vaccines given under the national immunization programme till one year of age was classified as partially-immunized while those who had not received any vaccine up to 12 months of age or received only pulse polio vaccine were classified as non-immunized. Reasons for partial/non-immunization were recorded using open-ended questions. Of the 325 children (148 males, 177 females), 58 (17.84%) were completely immunized, 156 (48%) were partially immunized, and 111 (34.15%) were non-immunized. Mothers were the primary respondents in 84% of the cases. The immunization card was available with 31.3% of the patients. All 214 partially- or completely-immunized children received BCG, 207 received OPV/DPT1, 182 received OPV/DPT2, 180 received OPV/DPT3, and 115 received measles vaccines. Most (96%) received pulse polio immunization, including 98 of the 111 non-immunized children. The immunization status varied significantly (p<0.05) with sex, education of parents, urban/rural background, route and place of delivery. On logistic regression, place of delivery [odds ratio (OR): 2.3, 95% confidence interval (CI) 1.3-4.1], maternal education (OR=6.94, 95% CI 3.1-15.1), and religion (OR=1.75, 95% CI 1.2-3.1) were significant (p<0.05). The most common reasons for partial or non-immunization were: inadequate knowledge about immunization or subsequent dose (n=140, 52.4%); belief that vaccine has side-effects (n=77, 28.8%); lack of faith in immunization (n=58, 21.7%); or oral polio vaccine is the only vaccine required (n=56, 20.9%. Most (82.5%) children admitted to a tertiary-care hospital were partially immunized or non-immunized. The immunization status needs to be improved by education, increasing awareness, and counselling of parents and caregivers regarding immunizations and associated misconceptions as observed in the study.

Vincristine induced neurotoxicity in cancer patients.

Ten out of 20 children, treated with usual doses of vincristine for various types of childhood cancers, developed neurotoxicity during treatment. Peripheral neurotoxicity (mixed motor-sensory 4/10, pure motor 3/10, pure sensory 3/10) was seen in the form of weakness of lower limbs, areflexia, neuropathic pain, or sensory loss. Autonomic neuropathy presented as constipation and urinary retention in 2 children, while 2 children developed encephalopathy in form of seizures, confusion, aphasia, and transient blindness. In children with severe neuropathy, vincristine administration was withheld/dose reduced till clinical improvement started, which took about 2-3 weeks time. Nerve conduction velocity showed motor-sensory axonal polyneuropathy. Electrophysiological abnormalities were found to persist even six months after clinical recovery in children with neurotoxicity. We found a relatively higher incidence of vincristine induced neuropathy in Indian children, which was probably due to coexistence of severe malnutrition in them.

Thinner intoxication manifesting as methemoglobinemia.

Lacquer thinner, commonly used for removing household paints is known to contain mixture of various arometic hydrocarbons; halogenated hydrocarbons and naptha, if ingested may rarely cause methemoglobinemia. We report a 3 year old child who presented to us with history of accidental ingestion of thinner, used for removing household paint. Child was having cyanosis with minimal tachypnoea & the colour of his blood was chocolate brown. Later methemoglibulin level estimations were also done, which were suggestive of this diagnosis. Child was managed conservatively with oxygen therapy & vital monitoring, which lead to complete recovery and discharge from hospital later.

Transient thrombocytosis with megathrombocytes in a case of acute myeloblastic leukemia.

Thrombocytosis is commonly seen in reactive conditions and certain neoplastic states, such as chronic myeloproliferative disorders. It is rarely seen in acute leukemia. A 12-year-old girl with acute myeloblastic leukemia (FAB M2) in remission presented with pyoderma. Her hemogram revealed anemia (Hb-6.4g/dl), leucopenia (TLC - 1.2 x 109/L) and thrombocytosis (platelet count- 580 x 109/L). A peripheral blood film showed numerous abnormally large platelets with few atypical cells. The thrombocytosis subsided with the clearance of infection but atypical cells persisted. One month later, she relapsed. Cytogenetic analysis revealed variable results (trisomy 9 and deletion 3). This case has been presented because thrombocytosis is rare in AML and its appearance calls for a close follow-up.

Congenital syphilis presenting as swelling of fingers and toes.

Congenital syphilis has varied manifestations in first two years of life. A case of 4-month-old child who was presented with painless swelling of finger and toes is reported. Family history was suggestive of syphilis in parents and one sibling. VDRL test in serum was positive in 1:128 dilution. Treponema pallidum haemagglutination test was positive. The child was treated with crystalline penicillin and responded favourably.

Physical growth patterns and dental caries in thalassemia.

This study was conducted to assess the effect of age, ferritin level, hemoglobin level and chelating agents on the physical growth in thalassemic children and to determine the prevalence of dental caries in thalassemic children. Weight, standing height, sitting height and subischial leg length were measured in 65 children attending the Thalassemia day care center at a tertiary hospital in Delhi. Their mean pre transfusion hemoglobin and ferritin levels over the previous two years were calculated. Dental caries indices, DMFT and DMFS were measured and compared with age matched controls. Weight, standing height, sitting height and subischial leg length expressed as percentage for age in children >or=10 y were significantly lower than those of children < 6 y, and those 6 to 10 y. Mean hemoglobin and ferritin did not affect growth significantly. Sitting height for age in children receiving Desferrioxamine alone or Desferrioxamine with Deferiprone was significantly lower than that of children receiving Deferiprone alone or no chelating agent. Dental caries were significantly higher in thalassemics.