Production and preclinical assessment of camelid immunoglobulins against Echis sochureki venom from desert of Rajasthan, India.

Snakebite is a significant cause of death and disability in subsistent farming populations of rural India. Antivenom is the most effective treatment of envenoming and is manufactured from IgG of venom-immunised horses. Because of complex fiscal reasons, the production, testing and delivery of antivenoms designed to treat envenoming by the most medically-important snakes in the region has been questioned time to time. In this study, we report successful immunisation of dromedaries (Camelus dromedarius) against the venom of Indian saw-scaled Viper- Echis carinatus sochureki. This study assessed the specificity and potential of camels immunised with venom of medically most important snake of Western India, the saw-scaled viper (Echis c. sochureki). Using WHO standard pre-clinical in vivo tests the neutralisation of the venom responsible for the lethal, haemorrhagic, coagulant and local necrotizing activities were measured, since these are the most significant effects that characterize envenoming by this species. The anti-venom was found significantly effective in the neutralisation of all these effects tested and thus, revealed further an immunological perspective, that camel IgG anti-venom (monospecific) would be as efficacious as specific equine anti-venoms or even of better choice in treating snake specific envenoming.

A prospective study on adult patients of severe malaria caused by Plasmodium falciparum, Plasmodium vivax and mixed infection from Bikaner, northwest India.

BACKGROUND & OBJECTIVES: Description of severe vivax malaria and mixed species infection requires good clinical study. The present study was undertaken to evalute the characteristics of severe malaria patients in Bikaner, northwest India. METHODS: This prospective study included 539 admitted adult patients of severe malaria (Plasmodium falciparum 274, P. vivax 221, and mixed infection of Pv + Pf 44). The diagnosis was confirmed by polymerase chain reaction. The categorization of severe malaria was done strictly as per WHO criteria. RESULTS: The distribution of severe manifestation was similar in severe vivax, falciparum and mixed infections except more cases of thrombocytopenia in P. vivax (p=0.030) and in mixed infection (p=0.004). The risk of developing severe malaria was greatest in patients of mixed infection [53.01% (44/83)] in comparison to Plasmodium falciparum malaria [49.37% (274/555), RR= 1.135; p=0.616] and P. vivax malaria [45.38% (221/ 487), RR = 1.299, p=0.243]. Hepatic dysfunction was the commonest pernicious syndrome [P. falciparum 50% (137/274), P. vivax 43.89% (97/221), and mixed infections 54.55% (24/44)]. Multiorgan dysfunction was present in 40.26% (217/539) patients, the risk was greatest in mixed infection [90.90% (40/44)] in comparison to P. falciparum monoinfection [37.59% (103/274), RR = 12.238; p=0.0001] or P. vivax monoinfection [33.48% (74/ 221), RR = 13.25; p=0.0001]. The risk of mortality in severe malaria was 6.31% (34/539) in which mixed infection had greater risk [9.09% (4/44)] in comparison to P. falciparum [7.30% (20/274); OR = 1.270 (CI 0.347-4.217); p=0.757] or P. vivax [4.52% (10/221); 0R 2.110 (CI 0.527-7.826); p=0.260]. INTERPRETATION & CONCLUSION: Severe vivax or falciparum malaria had almost similar features and prognosis including mortality. Risk of developing severe malaria, multiorgan dysfunction and mortality was more in patients of mixed infection in comparison to P. falciparum or P. vivax monoinfection. A multicentric study on larger number of patients requires further confirmation.

Clinical profiles of 13 children with Plasmodium vivax cerebral malaria.

BACKGROUND: Bikaner region is endemic for both P. vivax and P. falciparum malaria. Usually, cerebral malaria is caused by P. falciparum but it has been reported recently also in P. vivax mono-infection. Epidemiologic studies and clinical descriptions of P. vivax cerebral malaria in children are rare. AIMS: To describe the clinical features of PCR-confirmed cerebral malaria owing to P. vivax mono-infection and its clinico-laboratory profile in Bikaner, Northwest India. METHODS: This observational prospective study was based on detailed clinical and laboratory investigation of children admitted with cerebral malaria owing to P. vivax between November 2008 and December 2010. Cerebral malaria was categorised according to the WHO (2000) criteria for P. falciparum and the diagnosis of P. vivax mono-infection was established by peripheral blood film and rapid diagnostic tests and confirmed by polymerase chain reaction. The possibility of other diseases/infections causing similar illness were investigated thoroughly. RESULTS: Thirteen children with P. vivax cerebral malaria were studied, eight of whom (61·5%) had multi-organ (two or more organs) dysfunction. Other associated severe manifestations included severe anaemia (7), hepatic dysfunction (2), renal dysfunction (2), bleeding manifestation (2), respiratory distress (2), metabolic acidosis (2) and shock (one). Hypoglycaemia was not observed in any patient. There was no evidence of neurological sequelae. All the children were managed according to WHO guidelines using intravenous artisunate. Thrombocytopenia was detected in five and hyponatraemia in four children. CONCLUSION: P. vivax mono-infection can cause cerebral malaria and multi-organ dysfunction.

A rare cause of heart failure--primary hypoparathyroidism.

We report a patient who presented with congestive heart failure (ejection fraction 24.4%) and who had previous history of convulsions. Our investigations found him to be a case of primary hypoparathyroidism. He showed a dramatic response with the addition of calcium infusion therapy with almost full recovery of left ventricular function (67% ejection fraction after 16 days of the initial echo). We conclude that in a young patient a thorough investigation for heart failure is never complete without looking for endocrine and metabolic causes. The prognosis in these cases is much better, identification and treatment of the same will yield dramatic results.

A double blind, randomised placebo controlled trial of rifampicin with omeprazole in the treatment of human cutaneous leishmaniasis.

BACKGROUND & OBJECTIVES: This study was conducted on 50 patients of Anthroponotic cutaneous leishmaniasis (oriental sore) to assess the efficacy of rifampicin and omeprazole through a double blind, randomised placebo control study. METHODS: The diagnosis of Anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica was done by demonstration of Leishmania tropica (LT) bodies from the painless, dry ulcerative lesion. Each patient was assessed clinically in the beginning of the study, at the end of 2,4 and 6 weeks and all observations were compared in both the groups. Twenty-five patients received rifampicin with omeprazole (Group A) whereas other 25 patients received placebo (Group B) for a period of six weeks. RESULTS: Altogether 23 cases in group Aand 21 cases in group B completed the study. About 16 (69.7%) cases in group A and 3 (14.29%) cases in group B had complete healing, whereas 3 patients (13.04%) of group A and 4 patients (19.05%) of group B had partial response and 4 patients (17.93%) of group A and 14 patients (66.67%) of group B had no response at the end of study. The difference of two groups was statistically highly significant (p < 0.00025). All patients tolerated the drug and placebo very well and no side effect was reported. INTERPRETATION & CONCLUSION: In our opinion rifampicin and omeprazole is a highly effective, less toxic and cheaper alternative for the management of cutaneous leishmaniasis.

The changing spectrum of severe falciparum malaria: a clinical study from Bikaner (northwest India).

BACKGROUND & OBJECTIVES: Recently there were reports from all over India about changing spectrum of clinical presentation of severe malaria. The present study was planned to study the same in the northwest India. METHODS: This prospective study was conducted on patients of severe malaria admitted in a classified malaria ward of a tertiary care hospital in Bikaner, Rajasthan (northwest India) during 1994 and 2001. It included adult patients of both sexes belonging to all age groups. The diagnosis of Plasmodium falciparum was confirmed by demonstrating asexual form of parasites in peripheral blood smear. All patients were treated with i.v./oral quinine. The specific complications were treated by standard WHO protocol. The data for individual complications for both the years were analysed by applying chi-square test. RESULTS: In a prospective study in 1994 the spectrum of complication was dominated by cerebral malaria (25.75%) followed by jaundice (11.47%), bleeding tendencies (9.59%), severe anaemia (5.83%), shock (5.26%), Acute respiratory distress syndrome-ARDS (3.01%), renal failure (2.07%) and hypoglycemia (2.07%) whereas in 2001 it was dominated by jaundice (58.85%) followed by severe anaemia (26.04%), bleeding tendencies (25.52%), shock (10.94%), cerebral malaria (10.94%), renal failure (6.25%), ARDS (2.08%) and hypoglycemia (1.56%). The sharp difference for presence of jaundice and severe anaemia in 2001 and cerebral malaria in 1994 was statistically significant. Similarly, the important cause of mortality in 2001 was multiple organ dysfunction syndrome (71.10%) with predominant presentation of jaundice and renal failure, whereas in 1994, it was cerebral malaria (77.96%). INTERPRETATION & CONCLUSION: The observation of changing spectrum of severe malaria in this study and a significant increase in presentation with jaundice as an important manifestation is highly essential for primary, secondary and tertiary level health care providers for proper diagnosis and management.

A comparative study of regression of jaundice in patients of malaria and acute viral hepatitis.

BACKGROUND & OBJECTIVES: Jaundice is one of the common manifestations of severe malaria in adults. The purpose of this study is to compare the pattern of clinical and biochemical parameters such as serum bilirubin and liver enzyme levels in patients of malaria with jaundice and acute viral hepatitis. METHODOLOGY: The present study was conducted on 34 patients of malaria with jaundice and 15 patients of acute viral hepatitis. Estimation of serum bilirubin, aspartate amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase was done daily using standard procedures in malaria patients and weekly in acute viral hepatitis patients. RESULTS: Mean level of serum bilirubin on first day in malaria and acute viral hepatitis patients was 7.07 +/- 3.94 and 10.38 +/- 7.87 mg%, whereas on Day 8 it was 1.19 +/- 1.43 and 7.88 +/- 7.02 mg% respectively. Mean level of AST on Day 1 in malaria and acute viral hepatitis patients was 158.47 +/- 120.35 and 1418.6 +/- 834.11 IU/L, whereas on Day 8 it was 41 +/- 28.33 and 775.3 +/- 399.01 IU/L respectively. Mean level of ALT on Day 1 in malaria and acute viral hepatitis patients was 220.14 +/- 145.61 and 1666.67 +/- 1112.77 IU/L, whereas on Day 8 it was 50.85 +/- 37.31 and 823.8 +/- 475.06 IU/L respectively. Mean level of serum alkaline phosphatase on Day 1 in malaria and acute viral hepatitis patients was 394.74 +/- 267.78 and 513.4 +/- 324.7 IU/L, whereas on Day 8 it was 84.76 +/- 68.50 and 369.27 +/- 207.75 IU/L respectively. INTERPRETATION & CONCLUSION: We observed that resolution of jaundice in malaria took 1-2 weeks in contrast 6 to 8 weeks in viral hepatitis. This difference in duration was statistically significant. Thus, jaundice not resolving in 1-2 weeks time in a patient of malaria requires serious consideration for presence of other concomitant diseases including viral hepatitis.

Divalproex sodium in the management of post-herpetic neuralgia: a randomized double-blind placebo-controlled study.

BACKGROUND: Post-herpetic neuralgia is difficult to treat. Divalproex sodium (valproic acid and sodium valproate in molar ratio 1:1) has been used successfully in the management of various painful neuropathies. AIM: To study the effectiveness and safety of divalproex sodium in the management of post-herpetic neuralgia. DESIGN: Randomized double-blind placebo-controlled trial. METHODS: We enrolled 48 consecutively attending out-patients with post-herpetic neuralgia, out of whom three were excluded (two had insufficient pain, one withdrew consent). Quantification of pain was by Short Form-McGill pain questionnaire (SF-MPQ), visual analogue scale (VAS), present pain intensity score (PPI) and 11 point Likert scale (11 PLS) at the beginning of the study, after 2 weeks, 4 weeks and at the end of the study (8 weeks). We also assessed patients' global impression of change by questionnaire at the end of the study. RESULTS: After 8 weeks treatment with 1000 mg/day divalproex sodium, there was significant reduction in pain: SF-MPQ, 20.47 +/- 2.29 to 11.90 +/- 6.52 (p < 0.0001); PPI 4.0 +/- 0.52 to 1.95 +/- 1.29 (p < 0.0001); VAS 70.17 +/- 9.21 to 31.27 +/- 29.74 (p < 0.0001) and 11 PLS 6.97 +/- 0.73 to 3.63 +/- 2.34 (p < 0.0001) in comparison to placebo (means +/- SEM). The 'global impression of change' questionnaire showed much or moderate improvement in pain in 58.2% of patients receiving divalproex vs. 14.8% of those receiving placebo. The drug was well tolerated by all patients, except one who developed severe vertigo after 10 days of treatment. DISCUSSION: Divalproex sodium provides significant pain relief in patients of post-herpetic neuralgia, with very little incidence of adverse reactions. These data provide a basis for longer trials in a larger group of patients.

Sodium valproate for painful diabetic neuropathy: a randomized double-blind placebo-controlled study.

BACKGROUND: Various drugs are effective in the management of painful diabetic neuropathy, but none is completely satisfactory. We previously found sodium valproate to be effective and safe in a short-term study. AIM: To test the effectiveness and safety of sodium valproate in the management of painful diabetic neuropathy over 3 months. DESIGN: Randomized double-blind placebo-controlled study. METHODS: Consecutive attending patients with type 2 diabetes mellitus with painful neuropathy were asked to participate in the trial: 48 agreed. Five were excluded: three with HbA(1c) > 11, one with too low a pain level and one who withdrew consent. The remaining 43 were given either drug (group A) or placebo (group B). Each patient was assessed clinically. Quantitative assessment of pain was done by McGill Pain Questionnaire, Visual Analogue Score and Present Pain Intensity, at the beginning of the study, after 1 month and after 3 months. Motor and sensory nerve conduction velocities were measured initially and after 3 months. Liver function tests and other adverse drug-related effects were assessed periodically. RESULTS: Of the 43 patients, four dropped out: one in group A and three in group B. There was significant improvement in pain score in group A, compared to group B, at 3 months (p < 0.001). Changes in electrophysiological data were not significant. The drug was well-tolerated by all patients, except one, who had raised serum AST and ALT levels after 1 month of treatment, and whose treatment was discontinued. DISCUSSION: Sodium valproate is well-tolerated, and provides significant subjective improvement in painful diabetic neuropathy.

Hepatocyte dysfunction and hepatic encephalopathy in Plasmodium falciparum malaria.

BACKGROUND: According to the WHO, signs of hepatic dysfunction are unusual, and hepatic encephalopathy is never seen in malaria. However, in recent years, isolated cases have been reported from different parts of world. AIM: To identify the evidence for hepatocyte dysfunction and/or encephalopathy in jaundiced patients with falciparum malaria. DESIGN: Prospective observational study. METHODS: We studied 86 adult patients of both sexes who had malaria with jaundice (serum bilirubin > 3 mg%). The main outcome measures were: flapping tremor, deranged psychometric test, level of consciousness, serum bilirubin level, serum aspartate transaminase (AST) and alanine transaminase (ALT) levels, blood ammonia level, viral markers for hepatitis, ultrasonography of liver and gall bladder and electroencephalography (EEG). RESULTS: The range of serum bilirubin was 3-48.2 mg% (mean +/- SD 10.44 +/- 8.71 mg%). The ranges of AST and ALT levels were 40-1120 IU/l (294.47 +/- 250.67 IU/l) and 40-1245 IU/l (371.12 +/- 296.76 IU/l), respectively. Evidence of hepatic encephalopathy was seen in 15 patients. Asterexis was observed in 9 patients, impaired psychometric tests in 12 and altered mental state in 13. Arterial blood ammonia level was 120-427 meq/l (310 +/- 98.39 meq/l). EEG findings included presence of large bilateral synchronous slow waves, pseudo burst suppression and triphasic waves. Four patients died due to multiple organ dysfunction; the others made rapid recoveries. DISCUSSION: There is strong evidence of hepatocyte dysfunction and hepatic encephalopathy in some of these patients, with no obvious non-malarial explanation. Current guidelines may need to be revised.

Malarial hepatitis.

AIMS AND OBJECTIVE: To study the clinical, biochemical and histopathological changes in the liver of patients of Plasmodium falciparum malaria with jaundice. MATERIAL AND METHOD: This study was conducted on 50 PBF confirmed cases of Plasmodium falciparum malaria with jaundice. Detailed history, clinical examination, biochemical parameters for liver function test and blood for hepatitis B and C was done in all patients. Liver biopsy was done for detailed histopathological examination in all the 20 patients having serum bilirubin between 3 to 10 mg%. All patients were treated by IV/oral quinine using standard regimen. RESULTS: Age of the patient was ranging from 15-45 years. All patients had jaundice, 70% had pallor, 56% had splenomegaly, 48% had hepatomegaly and 24% of cases had coma. Based on serum bilirubin level, the patients were categorized in group A (18 patients, serum bilirubin < 3 mg%), in group B (20 patients, serum bilirubin 3-10 mg%) and in group C (12 patients, serum bilirubin >10 mg%). Histopathological examination done in all the 20 patients of group B, showed evidence of swollen hepatocytes (100%), malarial pigment deposition (75%), inflammatory infiltrates (60%), congestion of hepatocyte (50%) alongwith centrizonal necrosis in 25% of cases. CONCLUSION: The evidence of predominant conjugated hyperbilirubinemia, increased levels of AST and ALT along with evidence of hepatocellular necrosis in histopathological examination are strong evidence of gross hepatocytic dysfunction in patients of Plasmodium falciparum malaria with jaundice. Therefore the term malarial hepatitis should not be taken as a misnomer.

Cerebral malaria in Indian adults: a prospective study of 441 patients from Bikaner, north-west India.

AIMS OF THE STUDY: As per WHO (1993) the assessment and analysis of local problems and an appropriate epidemiological information system is an essential part of a control programme before embarking any control activity. METHODOLOGY: Four hundred and fourty one (441) adults of strictly defined admitted cerebral malaria patients were studied. Detailed clinical/neurological examination was done at the time of admission, daily thereafter, at the time of regaining consciousness, at the time of discharge and at weekly intervals in those having neurological sequelae. All patients were treated by i.v./oral quinine and specific syndromes were managed according to WHO guidelines. RESULTS: Apart from fever and unconsciousness in all the patients, other features were convulsion (21.31%), neck rigidity (19%), psychosis (5.21%), conjugate deviation of eyes (2.26%), extrapyramidal rigidity (2.25%), trismus (1.31%), decorticate rigidity (1.13%) and decerebrate rigidity (0.90%). One hundred forty five (32.87%) patients expired and mortality was highest in pregnant ladies (39.28%). The important neurological sequelae in survivors were psychosis in 15 (5.06%), cerebellar ataxia in 14 (4.72%), hemiplegia in five (1.68%), extrapyramidal rigidity (EPR) in four (1.35%), peripheral neuropathy in three (1.01%), EPR with trismus in one (0.33%) and isolated sixth nerve palsy in one (0.33%) patients and all showed complete recovery in further follow up. CONCLUSION: The important observations of this study were stormy presentation, increased incidence of haemoglobinuria and jaundice, presence of neck rigidity, no prognostic relation to fundus abnormalities and high incidence of cerebellar ataxia and psychosis as neurological sequelae in survivors. Knowledge of self-limiting course of neurological sequelae may be helpful in reducing economic strain of expensive investigations and treatment.

Brainstem auditory evoked potentials and somatosensory evoked potentials in cerebral malaria--a prognostic significance.

OBJECTIVE: To study the changes in brainstem auditory evoked potentials (BAEPs) and somatosensory evoked potentials (SSEPs) in cerebral malaria and to see their prognostic significance. METHODS: BAEPs and right median nerve SSEPs were performed in 25 adult patients of strictly defined cerebral malaria in acute stage in a semi-dark, sound proof chamber on four channel computerized multi-basis OTE-Biomedica machine in department of neurology, SP Medical College, Bikaner. RESULTS: The abnormalities of BAEPs were delayed peak latency of wave III in 13/25 (52%) and wave V in 20/25 (80%) patients and delayed interpeak latencies (IPLs) of wave I-III in 9/25 (36%), wave I-V in 15/25 (60%) and wave III-V in 12/25 (48%) patients. In SSEPs delayed N20 was seen in 11/25 (44%); delayed IPLs of N13-N20 (central conduction time; CCT) in 12/25 (48%) patients. Distorted N20 was recorded in 12/25 (48%) patients. Both N13-N20 IPLs in SSEPs and wave III-V IPLs in BAEPs were delayed in five patients and all of them expired. Delayed N13-N20 with normal III-V IPLs was present in seven patients and two of them died, whereas delayed III-V IPLs with normal N13-N20 was present in seven patients, and one of them expired. In remaining six patients both the parameters were normal and one of them died. CONCLUSIONS: The values of BAEPs and SSEPs were abnormal in patients of cerebral malaria and it was observed that BAEPs/SSEPs alone was not useful for predicting the outcome of coma, whereas abnormalities in both was predictive of worst prognosis. The changes in evoked potentials (BAEPs and SSEPs) could be due to either interruption of conduction in central pathways because of structural changes due to petechial hemorrhages and malarial granuloma at multiple levels in the brain including brainstem or due to metabolic abnormalities.

Building related illnesses and indoor air pollution.

Building related illnesses are a common problem in developed countries and are expected to increase rapidly in urban India. Although objective physical abnormalities are not generally found except in a few specific diseases like Legionnaires' disease, the symptoms can be uncomfortable and even disabling. In this review we initially introduce the concept of indoor air pollution and building related illnesses. Subsequently we review the sources of and exposure to the pollutants along with their health effects and the approach to a patient of suspected building related illness. We conclude by discussing the measures for the control of indoor air pollution.