Quinine and quinidine in malaria in Thailand.
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Biomedical subjects
Publications and source records attributed to D Bunnag.
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An ultrastructural study was undertaken of the spleen of 13 year-old-boy who died of falciparum malaria. The spleen revealed the following: both parasitized and non-parasitized erythrocytes are phagocytosed in large numbers by macrophages, littoral and reticular cells. Blood congestion and trapping of parasitized erythrocytes are commonly seen in splenic sinusoids and cords. Erythrocytes forming rosette structure around immuno-presenting cells is observed. The results of this study provide evidence that the mechanisms underlying splenic host defence in malaria include both immunological and non-immunological interaction with erythrocytes. Splenic trapping of parasitized erythrocytes is an important defence mechanism and the phagocytosis of erythrocytes probably accounts for anaemia.
A case of subcutaneous phycomycosis involving the right thigh for 1 year duration which mimic elephantiasis was reported in a 21-year-old military man. An initial diagnosis was that of a subcutaneous tissue lesion attributed to parasitic manifestation but turned out to be that of subcutaneous fungal infection both clinically and histologically. The lesion was successfully treated with cotrimoxazole for a period of one month, and followed up for 4 1/2 months with complete cure.
Eosinophilia is common in hookworm infection but the interaction between eosinophils and the larval stage of the parasite is poorly understood. The present study was conducted to test the ability of the eosinophils to adhere to infective filariform larvae of Necator americanus in vitro. Adherence of eosinophils to the larvae was found to be serum dependent. Antibody facilitated eosinophil adherence but this was maximal in the presence of complement. The adherence was greatly diminished by EGTA treated normal human serum (NHS) and was completely abolished when NHS was treated with either EDTA or heat-inactivation, suggesting that the process can be facilitated through complement activation via the alternative pathway. As with other nematodes, the surface of hookworm larvae appeared to be both antigenic and complement-activating. Although it is not known whether eosinophil adherence has any larvicidal effect, the present study demonstrated for the first time a definite interaction between human eosinophils and hookworm filariform larvae.
Albendazole was used to treat 30 patients with Strongyloides stercoralis infections. There were 21 males and 9 females, 13 to 68 years of age, who were divided into two groups of 11 and 19, respectively. Repeated pre- and post-treatment stool examinations were done by simple direct smear and formalin-ether concentration, and larval quantitations were done by the Stoll and Sasa's technique. Group I patients were given albendazole in dosages of 400 mg/day in divided doses for 3 days. Group II patients were given similar dosages, but were treated again 7 days later on the same schedule. Patients in Group I were followed for 14 days and those in Group II for 30 days. The cure rates were 73% for Group I and 100% for Group II. Side effects were minimal and transient. Albendazole is recommended for the treatment of strongyloidiasis in dosages of 400 mg/day in divided doses for 3 days with treatment repeated one week later.
Human intestinal flukes (Fasciolopsis buski and Heterophyes heterophyes) were treated with praziquantel in vivo or in vitro and then studied by transmission (TEM) and scanning (SEM) electron microscopy. F. buski worms recovered from patients, which had been cured by oral treatment of 1 X 15, 1 X 25 or 1 X 40 mg praziquantel/kg body weight, showed typical contraction and alterations together with vacuolization and bleb formation of their tegument. H. heterophyes worms recovered from an experimentally infected dog were incubated in media containing 1 microgram praziquantel/ml for 5-60 min. Their tegument showed lesions the extent and duration of which increased with exposure time, finally leading to death. The damage observed in vitro was very similar to that found in F. buski recovered from cured patients. The cure rate was very high when using 1 X 15 mg praziquantel/kg.
A sensitive enzyme-linked immunosorbent assay is described for the detection of immunoglobulin G antibody to Gnathostoma antigen in the sera of patients with intermittent cutaneous migratory swelling who were suspected of being infected by the tissue nematode Gnathostoma spinigerum. The antigen used was a crude somatic aqueous extract of the third larval stage obtained from naturally infected eels. The 1:320 dilution of all sera from 46 patients gave enzyme-linked immunosorbent assay values above the mean (+2 standard deviations) of normal healthy controls, which was arbitrarily used as a cutoff point. The sera from patients suspected of being infected by another tissue nematode, Angiostrongylus cantonensis, as well as from patients with intestinal roundworm infections, also reacted weakly in the test system used in this study. Nonetheless, when the assay was carried out using both Gnathostoma and Angiostrongylus antigens simultaneously, it appeared to be a reliable laboratory test that can be used to support a clinical diagnosis of gnathostomiasis in patients with intermittent cutaneous migratory swelling.
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A clinical field trial of praziquantel was carried out in Nong Ranya Village, Amphoe Ban Phai, Khon Kaen Province, with a population of 309 individuals, and 94% prevalence rate of opisthorchiasis. A mass treatment was carried out using a single dose of praziquantel at 40 mg per kg body weight. Acceptance for treatment was 91%. Follow-up stool examinations performed on days 14 and 60 gave prevalence rates of 20.5% and 22.2% respectively. Side effects including dizziness, headache, abdominal discomfort, nausea, vomiting, diarrhoea, lassitude, arthralgia, sleepiness, cramps and hot sensation were the complaints from 80% of adults and 40% of children. All of these were mild and transient except in one adult female who had severe diarrhoea and required intravenous fluid infusion.
Two randomised double-blind trials were conducted to examine the activity and tolerability of mefloquine alone and in combination with sulfadoxine/pyrimethamine (MSP). In one trial mefloquine was compared with chloroquine in 40 patients with Plasmodium vivax malaria and in the other one mefloquine was compared with MSP in 40 patients with P falciparum malaria. The former trial showed that both a single oral dose of 250 mg mefloquine and a single oral dose of 450 mg chloroquine (base) were highly effective in relieving symptoms of malaria and in clearing P vivax parasitaemia. No side-effects and no changes in laboratory variables attributable to the test drugs were observed. The other trial showed that a single oral dose of 750 mg mefloquine and a single oral dose of MSP (750 mg mefloquine plus 3 tablets of 'Fansidar', were equally effective in the treatment of falciparum malaria. 2/4 treatment failures in the mefloquine group and 2/3 treatment failures in the MSP group were due to low plasma drug levels resulting from vomiting soon after ingestion of the tablets. Gametocytes of P falciparum were unaffected by either mefloquine or MSP. 5 patients in each group had side-effects such as vomiting, skin rash, diarrhoea, and transient mental confusion. Mefloquine was well tolerated by patients with glucose-6-phosphate dehydrogenase deficiency or heterozygous haemoglobin E.
Ultrastructure of erythrocytes infected with Plasmodium falciparum in human brain, obtained 3 hours post mortem revealed gross distortion of host red cells with abnormality of the red cell surface. The superficial alterations of the parasitized cells as knob-like protrusion appear to be the sites of attachment to vascular endothelium. There was evidence of platelets sticking to the injured endothelium. The endothelial vesicular membrane is in close adhesion to the parasitized red cell, and also to the platelets involved in this mechanism. Thus, explaining the sequestration of parasitized red cell and obstruction in cerebral microcirculation, cerebral oedema and low peripheral platelet count. The was no evidence of inflammation, fibrin or thrombus formation observed in our studies.
Ninety-six patients who had heavy Opisthorchis viverrini infection were studied. Egg count per gram of faeces ranged from 10,800 to 139,000 (mean 26,044.3). Praziquantel 50 mg per kg body weight was given after a morning meal. 68 patients completed the follow up period of 60 days. The cure rate was 97.0%. The side-effects occurred in 61 patients (89.7%). The common side effects were diarrhoea, dizziness, sleepiness, epigastric pain, headache, nausea and anorexia. These side-effects were mild and transient. 62 patients (91.2%) showed clinical improvement, and 20 patients were symptom free on day 60.
Thirty-six patients with uncomplicated amoebic liver abscess were treated with low dose tinidazole 1.2 g to 1.5 g in a single or divided doses, and aspiration of the abscess. No drug related toxicity was noted. All patients responded well and there was no relapse or treatment failure.
An ELISA for immunodiagnosis of human gnathostomiasis using a crude water extract of third-stage larvae of G. spinigerum as antigen, and alkaline phosphatase labelled goat antihuman IgG in the indicator system was developed and evaluated. At the titre of 1:400 and above positive results were observed in 100% of 4 parasitological confirmed and 10 eosinophilic meningo-encephalitis (EME) typical of gnathostomiasis cases, 56% of 160 cutaneous migratory swelling cases, 33% of 24 cases with EME typical of A. cantonensis infections, 23% of 92 cases with other parasitic infections and 1.5% of blood donors. The overall sensitivity was 59% and specificity 84%. The predictive value was 77%. The results indicated that ELISA is potentially useful for immunodiagnosis of gnathostomiasis but improvement of sensitivity and specificity is needed.
Clinical features of severe opisthorchiasis were studied in 88 patients. The ratio of males to females was 6.3 : 1; 75% were over 40 years old. The presenting symptoms were obstructive jaundice, 25% associated with secondary infection of biliary system; cholangitis and cholecystitis; intraabdominal mass, which was enlarged liver; 18% had palpable gallbladder; 18% had adenocarcinoma of the bile duct. High bilirubin was found in 46% of cases, high alkaline phosphatase in 80%; elevation of serum transaminase in 78% and low serum albumin in 62% of patients. There was no correlation between severity of the disease and the faecal egg output. The obstructive jaundice patients had low or no egg output. Two patients had no eggs in stool, but numerous Opisthorchis viverrini eggs and flukes were found in the gallbladder and bile ducts at operation.
Twelve patients with cysticercosis including two cases of subcutaneous cysticercosis and ten cases of combined subcutaneous and, cerebral cysticercosis were treated with praziquantel 30 mg per kilogram of body weight daily in 3 divided doses for 10 days. To minimize possible reactions due to the death of parasites prednisolone 10 mg three times a day was also given in most cases. During treatment, an intense inflammatory reaction occurred as evidenced by increased intracranial pressure and convulsions. Histopathological findings studied at 2 weeks post treatment revealed lymphocytic and plasma cell infiltrations with destruction of the larvae. Clinical response was evident at one week post treatment, manifested by a significant decrease in size of the subcutaneous cysts which gradually disappeared at the end of three months. Radiology of soft tissues showed distortion of semicalcified cysts. Brain computerized tomography at 6 months post treatment showed disappearance of the cysts presumed to be due to death of cystercerci and marked reduction in numbers and size of other stages of cysts. Mild and transient side effects were observed in 25% of cases. Two patients (17%) had severe side effects and one (8%) had convulsions during treatment.
The first finding of Episthmium sp. in man is reported. Characteristics of the worm are given in detail. The infestation is an accidental one acquired from consuming raw fish, which serves as an intermediate host of Opisthorchis viverrini. The pathogenic role of Episthmium sp. in man needs further investigations.
A total of 52 adult patients with opisthorchiasis with or without concomitant intestinal helminthic infections were treated with albendazole at dosage regimens of 400 mg twice daily for 3 days (group I with 25 patients) and 7 days (group II 27 patients). By concentration method with four examinations from two faecal specimens of each patient the cure rates and percentage egg reduction on day 30 in group I and group II were 12% and 33%, 94 and 95 respectively; by Stoll method the cure rates and percentage egg reduction were 40% and 63%, 92 and 92 in group I and group II, respectively. There were no statistically significant differences between the results of the two regimens. Twenty six patients with hookworm and 9 patients with S. stercolaris infections were cured. Opisthorchis viverrini, N. americanus, A. duodenale, A. ceylanicum, E. malayanum, E. ilocanum, S. stercolaris, E. vermicularis, and T. saginata segments were expelled in stools, mostly on days 1 to 4. Most of the patients felt relieved from symptoms of pain in the right hypochondrium and epigastrium. The side effects were mild and transient. There were no evidence of toxic effects on the bone marrow, heart, liver or kidneys. Albendazole was shown to be effective against Opisthorchis viverrini infection as well as other concomitant intestinal helminthic infections; but the optimal dosage and duration of treatment have not yet been achieved.