Utpal Kant Singh

Miltefosine: an oral drug for visceral leishmaniasis.

Miltefosine, a phosphocholine analogue originally developed as antimalignant drug, has been found to be highly active against leishmaniain vitro and animal model. 1,2 Based on these experiences this drug was tried against human visceral leishmaniasis and found to be highly effective and achieved 97% and 94% cure in phase 2 and phase 3 trial in children.

Miltefosine in Children with Visceral Leishmaniasis: A Prospective, Multicentric, Cross-Sectional Study

ObjectiveMiltefosine, an alkyl phospholipid has been found effective against visceral leishmaniasis (VL) in adults in various studies. The authors safety, tolerance and efficacy of Miltefosine and compared with available gold standard anti-leishmanial drug, Amphotericin B, a parenteral formulation in children with VL.MethodsAll consecutive children aged 1 yr to 14 yr, presented with fever, splenomegaly and positive LD body in splenic smear examination, admitted in pediatric ward of Nalanda Medical college and Child care center between 1st July 03 to 30th June 05 were taken for study. Patients were randomized into four groups. Group-1 and 2 patients were given Miltefosine in dose of 2.5 mg/Kg day o.d. or b.i.d. per orally to a maxilpum of 100 mg and group 3 and 4 Amphotericin B at a dose of 1 mg/Kg/day (total: 15 mg/Kg). All patients were followed at completion of therapy, 3 months and 6 months for clinical response, splenic size and parasitologically.ResultsOut of 125 children, 44 were in group-1, 20 in group-2, 38 in group-3 and 23 in group 4, 124 patients had parasitological cure with relapse in one patient of group 1 during follow up. One patient in-group II had no response with first course but became parasitologically negative with 2nd course of Miltefosine. In-group I, one patient had persistent splenomegaly and found to have associated portal hypertension. Final cure rate with Miltefosine and Amphotericin B was 93.2%, 95%, 92.1% and 91.3% in-group 1, 2, 3 and 4 respectively, which are statistically insignificant. Majority of patients had pancytopenia. Eievated″. AL T (>3 times of normal) were seen in 28, 11, 19 and 13 patients of group 1, 2, 3 and group 4 respectively which returned to normal in subsequent follow up. Raised BUN was observed more in patients who got Amphotericin B i.e. 65.42% and 73.91% in-group 3 and 4 respectively. GI side effects i.e. diarrhea and vomiting were observed in 26 and 23 patients in-group 1 and 2 respectively.ConclusionMiltefosine is safe, well tolerable, and highly effective and has same efficacy as Amphotericin B in newly diagnosed and SAG resistant children with visceral leishmaniasis.

Fulminant hepatitis in Kala-azar

One hundred and fifty cases of Kala-azar were studied for evidence of hepatic involvement. The hepatic function was mildly affected in 25 cases and 3 cases had fulminate hepatitis. Most of the cases were cured after anti-Kala-azar therapy except 2 cases, who died of hepatic failure. This study suggests that fulminant hepatitis may be the outcome of Kala-azar, itself.

Prognostic value of serum C-reactive protein in kala-azar

The currently recommended protocol for treatment of kala-azar (KA) necessitates repeated bone marrow/splenic aspiration to monitor the response and duration of therapy as well as to detect resistance and change to alternative drugs. These procedures being invasive, there is a pressing need for less invasive diagnostic tools for this purpose. We have evaluated the role of C-reactive protein (CRP) in 201 children with visceral leishmaniasis at different stages of the disease to work out the relationship, if any, between CRP levels and disease activity, including response to therapy. The subjects belonged to the 2-12 year age group in whom CRP estimation was done on admission, every 5th day during treatment, and repeated on follow-up at 2 and 6 months. The levels were compared with those of 50 randomly chosen age-matched healthy children who served as controls. The mean serum CRP value in the study group before the commencement of treatment was 62.96 +/- 1.03 mg/l, which was significantly higher (p < 0.001) in comparison to the control group. Commencement of treatment resulted in a simultaneous decline in serum CRP. Parasitic clearance from the spleen was faster in patients with an initial low serum CRP level (< 60 mg/l) in comparison to patients with high levels (> 60 mg/l). During treatment, mean serum CRP levels were significantly higher in late responders than in early responders (p < 0.001). Correlation of CRP levels to indicate the presence or absence of parasites suggested a cut-off level of 12 mg/l by day 10, with a sensitivity of 82.5 per cent, specificity of 78.5 per cent, positive predictive value of 92 per cent, and negative predictive value of 60.2 per cent. Our observations suggest a promising role for CRP estimation every 5-10 days during therapy in visceral leishmaniasis for monitoring the response to therapy and to detect possible resistance.

Amphotericin B therapy in children with visceral leishmaniasis: daily vs. alternate day, a randomized trial.

A randomized study was carried out to compare the efficacy and adverse reactions of daily vs. alternate day regimens of amphotericin B in children with visceral leishmaniasis (VL). Six hundred and five children of VL below 14 years of age were randomized into two groups; Group A (302), who received amphotericin B at a dose of 1 mg kg(-1) day(-1) for 15 days and Group B (303); same doses but on alternate days. All patients in both groups were cured, who had completed course of amphotericin B therapy. None had relapsed at 1 and 6 months of follow-up. Adverse reactions in both groups were non-significant. The duration of stay and cost of therapy was significantly lower in Group A children who left the hospital against medical advice, which was also significantly more in Group B. Thus, daily regimen of amphotericin B is equally effective, well tolerated, not more toxic and cost-effective than alternate day regimen, which is currently practiced.

Ciprofloxacin in children: Is arthropathy a limitation?

Two hundred and nineteen children treated with Ciprofloxacin were observed for drug related adverse reactions (ADR). ADR was observed in 35/219 (15.98%) children, arthropathy in 2/219 (0.9%) children only. All the ADR were reversible even on continuation of therapy except one child with arthropathy and no permanent sequele or death occurred as a drug related ADR.

Congenital hypertrophic pyloric stenosis.

Congenital hypertrophic pyloric stenosis, an important cause of intractable vomiting in infants is diagnosed clinically and confirmed ultrasonographically. Other useful interventions are plain radiography and berium study. Differential diagnosis includes pylorospasm and gastroesophageal reflux. Management protocol includes correction of dehydration and electrolyte imbalance and either Fredet Ramstedt pyloromyotomy or medical treatment with atropine sulphate. Atropine is initially given intravenously till vomiting is controlled and then orally at double the effective I.V. done for another 3 weeks. Atropine sulphate is generally well tolerated and side effects are few like tachycardia, raised SGPT and hyperthermia. Atropine sulphate is very effective, cheap, safe and perhaps more acceptable treatment option for CHPS.

Serum prolactin and cortisol in children with some paroxysmal disorders

Postictal serum prolactin and cortisol levels were estimated in 73 children having either epilepsy, febrile seizures, breath-holding spells, or fever without other manifestation and in 20 normal controls. Mean serum prolactin levels (28.6±2.3 ng/ml) were significantly higher (p < 0.001) in the epileptic group than in the group with febrile seizures (12.7±2.8 ng/ml), non-specific febrile illness (12.2±2.4 ng/ml), breath-holding spells (8.8±1.1 ng/ml) and normal controls (9.8±2.6 ng/ml) Mean serum cortisol levels were non-specifically elevated in children with epilepsy (32.8±2.2 ug/dl), febrile convulsion (34.2±4.1 ug/dl) and non-specific febrile illness (30.6±2.4 ug/dl). Our observations suggest that elevated prolactin levels associated with afebrile epileptic seizures may help in differentiating epilepsy from febrile seizures and breath-holding spells. Cortisol levels appear to be non-specifically elevated in all stressful conditions.

Evaluating the Impact of Breastfeeding on Rotavirus Antigenemia and Disease Severity in Indian Children

Objectives To evaluate the contribution of breastfeeding to Rotavirus (RV)-induced antigenemia and/or RNAemia and disease severity in Indian children (<2 yrs age). Methods Paired stool and serum samples were collected from (a) hospitalized infants with diarrhea (n = 145) and (b) healthy control infants without diarrhea (n = 28). Stool RV-antigen was screened in both groups by commercial rapid-test and enzyme immunoassay. The disease severity was scored and real-time-PCR was used for viral-load estimation. Serum was evaluated for RV-antigenemia by EIA and RV-RNAemia by RT-PCR. Data was stratified by age-group and breastfeeding status and compared. Results Presence of RV-antigenemia and RV-RNAemia was positively related with presence of RV in stool. Disease severity and stool viral-load was significantly associated with RV-antigenemia[(r = 0.74; CI:0.66 to 0.84; P<0.0001,R2 = 0.59) and (r = -0.55; CI:-0.68 to -0.39; P<0.0001,R2 = 0.31) respectively], but not with RV-RNAemia. There was significant reduction in RV-antigenemiarate in the breast-fed group compared to non-breastfed infants, especially in 0–6 month age group (P<0.001). Non-breastfed infants were at risk for RV-antigenemia with severe disease manifestations in form of high Vesikari scores correlating with high fever, more vomiting episodes and dehydration. Conclusion RV-antigenemia was common in nonbreastfed children with severe RV-diarrhea and correlated with stool RV-load and disease severity.

Cognitive and behaviour dysfunction of children with neurocysticercosis: a cross-sectional study.

Eighty-three confirmed cases of neurocysticercosis diagnosed as per modified delBrutto criteria were enrolled in the study (Group-I) to observe cognitive and behavioural changes. Controls consisted of two groups: children with idiopathic generalized tonic-clonic seizure (Group-II) and normal children with non-specific cough (Group-III). Cases and controls were subjected to cognitive and behaviour assessment. There was significant difference in the intelligence quotient (IQ) of cases in domains of visual perception, immediate recall, analysis synthesis and reasoning, verbal ability, memory and spatial ability. In the age group of 6-18 years, cases had significantly more behaviour problems than control without seizure, in domains of anxious depressed, withdrawn depressed, somatic problems, social problems and rule-breaking behaviour. Neurocysticercosis causes decline in cognitive function and behaviours in older children, which should be recognized early for appropriate management and to avoid undue parental anxiety.