A preliminary randomized double blind placebo-controlled trial of intravenous immunoglobulin for Japanese encephalitis in Nepal.

BACKGROUND: Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG's anti-inflammatory properties may also be beneficial. METHODOLOGY/PRINCIPAL FINDINGS: We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2), which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group. CONCLUSIONS/SIGNIFICANCE: A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT01856205.

Systemic lupus erythematosus in childhood--a review of 11 patients at a single center in eastern Nepal.

We retrospectively evaluated the clinico-laboratory features of 11 children and adolescents with Systemic Lupus Erythematosus between the period of 2001 and 2006. All of them (100.0%) had renal involvement at the first visit in the hospital. Female to male ratio was 10:1. Skin and or mucosal involvement (90.9%), periorbital puffiness and or pedal edema (81.8%), fever (72.7%), hypertension (72.7%), and reticuloendothelial involvement (72.7%), were the commonest presentations. All patients had anemia (8.6 +/- 1.5 gm/dl), raised ESR (46.7 +/- 9.4 mm in first hour), proteinuria, and in disease activity as evident by raised ESR and positive anti-dsDNA antibody at the first visit. The mean duration of disease was 7.6 months and the average duration of disease activity was 63.18 days. Renal biopsy was performed in 8 patients: class IV lupus nephritis in 4 patients (50.0%), class II in 2 patients (25.0%), class III and V in patient (12.5%) each. Nephrotic range proteinuria and hypertension was observed in all patients of class IV and V of lupus nephritis. Class II and III lupus nephritis patients' were normotensive and had non-nephrotic range proteinuria. Three out of 11 patients (27.2%) expired. The commonest primary determinant of mortality was uncontrolled disease activity in 2 patients (66.6%). The third one had infection and developed disseminated intravascular coagulation. The mean duration of disease activity in patients who died (mean 30 days) was statistically lower than the survival group (75.6 days) (p < 0.01). Renal involvement during first visit and mortality could be attributed by late referrals and diagnosis at hospital.

Epidemiological dynamics of antimonial resistance in Leishmania donovani: genotyping reveals a polyclonal population structure among naturally-resistant clinical isolates from Nepal.

Pentavalent antimonials (SbV) are the first line drug against leishmaniasis worldwide, but drug resistance is increasingly reported, particularly in the Indian sub-continent, where it represents a major threat for the control of anthroponotic visceral leishmaniasis (VL). In order to understand the epidemiological dynamics of antimonial resistance in anthroponotic VL, we analysed here the population structure of 24 Leishmania donovani stocks isolated from anthroponotic VL-patients from Eastern Nepal: 13 SbV-naturally resistant and 11 SbV-sensitive, as demonstrated by in vitro drug susceptibility assays. The parasites were genotyped by PCR-RFLP analysis of kDNA minicircles and by microsatellite analysis and the encountered polymorphism revealed a polyclonal structure among resistant isolates. Furthermore, analysis of paired samples obtained from the same patients before treatment and after failure revealed primary as well as acquired resistance. The hypothesis of independent events of drug resistance emergence is proposed and confronted to alternative explanations. Our results show the dynamics of drug resistance epidemiology and highlight the importance of surveillance networks.

Acute renal failure following multiple wasp stings.

We report the cases of two patients who developed acute renal failure following multiple wasp stings. Both patients required dialysis and recovered within 4 weeks. The kidney biopsy from one patient showed acute tubular necrosis with interstitial nephritis. One patient had complete recovery of renal function on follow-up, while the other was lost to follow-up.

Lateral sinus thrombosis in neurocysticercosis.

Cysticercosis is a frequent parasitic infection in developing countries including Nepal and is related to poverty, ignorance and pig-rearing practices at home in the community. A variety of structural involvements such as brain parenchyma, cerebellum, ventricular system, brain stem, meninges, subarachnoid space, spinal cord and orbit have been reported, but cysticercus involving the lateral sinus causing thrombosis is extremely rare.

Caudal regression syndrome--case report and review of literature.

Caudal regression syndrome is a rare disorder of distal spinal segments affecting the development of the spinal cord, with attendant sequelae. Intelligence is preserved. The exact etiology is elusive, though maternal diabetes, genetic factors, and hypoperfusion might play roles. Recently, the role of teratogens has been studied in animal models. Treatment is difficult, multidisciplinary, and largely supportive. Lower limb deformities with sensory and motor loss and neurogenic bladder call for intensive and long-term attention.

A comparative study of the effectiveness of diagnostic tests for visceral leishmaniasis.

We compared the validity of pancytopenia, the formol-gel test (FGT), the indirect fluorescence antibody test (IFAT), the direct agglutination test (DAT), and the rK39 dipstick test as diagnostic criteria for visceral leishmaniasis (VL) in Nepal. Between September 2000 and January 2002, 310 clinical suspects had a bone marrow aspirate, and if negative, a spleen aspirate smear examined for Leishmania donovani. Sensitivity and specificity of all tests were determined compared with parasitology and by latent class analysis (LCA). Compared with parasitology, the sensitivities of the other tests were as follows: pancytopenia = 16.3% (95% confidence interval [CI] = 11.3-22.5%), FGT = 39.9% (95% CI = 32.7-47.4%), IFAT = 28.4% (95% CI = 22.0-35.5%), DAT = 95.1% (95% CI = 90.8-97.7%), and the rK39 dipstick test = 87.4% (95% CI = 81.7-91.9%). Sensitivity estimates obtained by LCA were similar, but specificity estimates were substantially higher (DAT = 93.7% versus 77.8%; rK39 dipstick test = 93.1% versus 77.0%). The DAT or the rK39 dipstick test can replace parasitology as the basis of a decision to treat VL in Nepalese peripheral health services.