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Biomedical subjects

T Harinasuta

Publications and source records attributed to T Harinasuta.

At least 55 records · Page 3Linked to original sources

Splenic Fc receptor function in host defense and anemia in acute Plasmodium falciparum malaria.

To determine splenic Fc receptor function in patients with acute Plasmodium falciparum malaria, the clearance of IgG-coated autologous 51Cr-labeled erythrocytes in 20 patients and 10 normal controls was studied. Clearance half-times were directly correlated with both the absolute parasite count (r = .635, P less than .005) and hematocrit (r = .791, P less than .001). Clearance half-times in patients varied from 1.0 to 96.3 h (median, 14.8 h) while those of controls ranged from 8.0 to 80.3 h (median, 23.1 h) (P = .10). Nine of the 20 patients had clearance half-times shorter than the lower 95% confidence limit of controls (less than 12.4 h). The clearance of IgG-coated erythrocytes was accelerated after parasites were eliminated from the circulation (P less than .05) and returned toward normal 6-8 weeks after the acute infection. Although circulating immune complexes were detectable, there was no correlation between immune complex levels and clearance half-times (P greater than .05). The failure to increase Fc receptor-mediated red cell clearance in patients with high parasitemias suggests inadequate splenic phagocytic activity in the face of considerable antigenic challenge. These findings indicate that splenic Fc receptor function may be important both in the control of infection and the development of anemia in P. falciparum malaria.

Acute Disease↗

Fatal Plasmodium falciparum malaria after an inadequate response to quinine treatment.

A 24-year-old man with severe Plasmodium falciparum malaria died after 77 h of treatment with full parenteral doses of quinine. His peripheral parasitemia at death exceeded the level on admission. Plasma concentrations of quinine were abnormally low throughout. This case emphasizes the importance of pharmacokinetic factors in determining the therapeutic response in severe P. falciparum malaria.

Adult↗

Mefloquine antimalarial prophylaxis in pregnancy: dose finding and pharmacokinetic study.

1. A dose finding pharmacokinetic study was performed in 20 Karen women in the third trimester of pregnancy receiving antimalarial prophylaxis with mefloquine. Ten received 250 mg mefloquine base weekly and ten received identical tablets of 125 mg base/week. 2. Both dose regimens were well tolerated. Malaria was prevented effectively, there were no serious adverse effects, all pregnancies proceeded normally, and there were no abnormalities in the babies followed up to 2 years. 3. The median time from dose administration to peak whole blood mefloquine concentration was 6 (range 3-24) h. Mean (+/- s.d.) peak and trough concentrations in the seventh week were 722 +/- 279 and 488 +/- 155 ng ml-1 with the 250 mg/week dose, and 390 +/- 81 and 185 +/- 53 ng ml-1 with the 125 mg/week dose regimens respectively. These blood concentration values are lower than those reported previously in non-pregnant adults. 4. One and two compartmental models were fitted to the whole blood concentration-time data. Mean (+/- s.d.) clearance (CL/F) was 0.78 +/- 0.27 ml min-1 kg-1, and the apparent terminal elimination half-life (t1/2) was 11.6 +/- 7.9 days. 5. Further studies to determine the oral bioavailability of mefloquine are needed, but these results suggest that clearance may be increased in late pregnancy. These preliminary results of good efficacy without significant toxicity are encouraging, and a more extensive evaluation of mefloquine antimalarial prophylaxis in pregnancy is now warranted.

Birth Weight↗

Evidence for diversity of Plasmodium falciparum sporozoite surface antigens derived from analysis of antibodies elicited in humans.

We have compared the reactivities of antibodies developed by individuals frequently exposed to Plasmodium falciparum infections with the epitopes contained within the repeats of the circumsporozoite (CS) protein and their reactivities with the epitopes of a native molecule(s) accessible on the sporozoite surface. Results of direct-binding assays and competition assays between artificial and native molecules or between human antibodies and anti-CS monoclonal antibodies suggest that humans respond preferentially to epitopes not contained within the repeats of the CS protein and probably not contained in the whole CS protein. Human monoclonal antibodies reactive with P. falciparum sporozoite surface antigens were produced by Epstein-Barr virus transformation of human lymphocytes. Their pattern of reactivity with sporozoites from a number of different isolates indicates the existence of several distinct epitopes on the parasite surface. Differences between isolates and between sporozoites within a given sample were observed. No single human monoclonal antibody capable of detecting an epitope expressed in all the parasites studied was found.

Animals↗

Quinine resistant falciparum malaria treated with mefloquine.

Twenty eight adult male patients with acute uncomplicated falciparum malaria which showed RI or RII responses to quinine sulfate at the dosage of 600 mg 8 hourly for 7, 10 or 14 days were treated with a single dose of mefloquine (Lariam); 25 patients received 1000 mg, 2 received 750 mg and 1 received 500 mg. The initial response was good; there was no RII or RIII response. Three patients were lost to followup. Of 25 patients who stayed in the Bangkok Hospital for Tropical Diseases where there was no malaria transmission for 28-65 days, only one patient in the 1000 mg group had recrudescence on day 21. The cure rate was 96%. Our prospective study suggests that mefloquine was effective in the treatment of quinine resistant falciparum malaria and the risk of cross-resistance between quinine and mefloquine in P. falciparum in vivo is very low.

Administration, Oral↗

Fecal egg output in relation to worm burden and clinical features in human opisthorchiasis.

A study of the relation of fecal egg excretion to worm burden and clinical features was carried out in 45 opisthorchiasis patients who had no signs of biliary obstruction. The fecal egg excretion was consistent and correlated with the worm burden. Although there was no definite association between clinical signs and intensity of infection, mild hepatomegaly and thickened wall or dilatation of the gallbladder were found more commonly in heavily infected patients. Eosinophilia was observed more often than previous reports. Concomitant parasitic infections were found in 82% of the patients. After praziquantel treatment, egg counts increased greatly during the first few days then decreased to very low levels in 7 days.

Adolescent↗

Electron microscopic study of phagocytosis in human spleen in falciparum malaria.

The ultrastructure of the spleen of a patient who died of natural infection of Plasmodium falciparum was studied with emphasis on phagocytosis. Parasitized erythrocytes were shown to interact with the heterogenous populations of phagocytic cells. Phagocytosis occurred predominantly in macrophages than endothelial cells and immature forms of parasites were preferentially phagocytosed. Splenic trapping, pitting and destruction of both infected and noninfected erythrocytes were demonstrated. Other forms of interaction between phagocytic cells and parasitized erythrocytes observed include complex interdigitation, association of loose and tight phagosomes, and preferential sites of adherence, the significance of which need further investigation.

Adolescent↗

A new intestinal fluke, Plagiorchis harinasutai n.sp.

Dilution-sedimentation examination of stool specimens from four opisthorchiasis patients treated with praziquantel led to the discovery of six Plagiorchis worms. This is the first known report of plagiorchis infection in man in Thailand. The morphological features differed from those of previously described Plagiorchis species indicating that these worms belong to a new species, which we designated as Plagiorchis harinasutai n.sp. in honour of Professor Chamlong Harinasuta, former Dean of the Faculty of Tropical Medicine, Mahidol University, Bangkok. The holotype is held at the Museum and Reference Centre. Paratypes are held in the Bangkok School of Tropical Medicine, Faculty of Tropical Medicine, Mahidol University.

Adult↗

Human pathology of Opisthorchis viverrini infection: a comparison of adults and children.

The pathology of human opisthorchiasis in 22 adults (20 to 68 years) and 7 children (7 to 15 years) at autopsy is described. The changes of the liver in adults and children are similar and are summarized as follows: Enlargement of the liver was a common finding. Pericholangitis was observed in most cases. The pathology was confined to the large and medium-sized bile ducts where the flukes inhabited. The small interlobular bile ducts had minimal or unremarkable changes. Dilatation of the bile ducts with hyperplasia, desquamation and proliferation of the bile duct epithelial cells, glandular formation and fibrous connective tissue infiltration of the walls were the most common features. The pathological changes were well established within 7 to 15 years. Dilatation of the gallbladder, chronic cholecystitis and carcinoma were found only in adults. Eight of ten cases were cholangiocarcinoma and two were hepatocellular carcinoma.

Adolescent↗

Incidence of bacteremia in patients with opisthorchiasis during recurrent cholangitis.

A total of 257 haemocultures were performed in 50 patients with opisthorchiasis when they presented signs and symptoms of biliary tract infection. 19 patients showed positive haemoculture. There are no significant relationship between the age of the patient and the incidence of positive haemoculture. Septic shock occurred in 5 patients, one patient died. Out of 221 aerobic cultures, 14% were positive and of the 36 anaerobic cultures 11% were positive. The most common organism was Staphylococcus followed by Klebsiella and Bacillus spp. Anaerobic bacterias were Streptococcus spp. Clostridia spp. was not found in this study. Most organisms were sensitive to cefotaxime, cephalothin, kanamycin and chloramphenicol, and the least sensitive to ampicillin.

Adult↗

Opisthorchis viverrini eggs and adult flukes as nidus and composition of gallstones.

Three cases of opisthorchiasis with calculous cholecystitis was presented. The diagnosis of gallstones was made before praziquantel therapy in 2 cases, and 4 years after treatment in one case. The patients underwent cholecystectomy. Numerous O. viverrini eggs and one dead fluke were found in the bile in one case. A single stone was recovered from each gallbladder. All stones contained O. viverrini eggs. Fragments of flukes were also present in two cases. The stones consisted of a mixture of bilirubin pigment and calcium salts.

Adult↗

High rate of Plasmodium vivax relapse following treatment of falciparum malaria in Thailand.

Within two months of treatment for falciparum malaria, Plasmodium vivax infections developed in 58 (33%) of 174 patients who had received a quinine or quinidine regimen and in 46 (32%) of 145 patients who had received mefloquine with inpatient follow-up of more than six weeks. The time to vivax relapse was significantly longer after mefloquine treatment (median 47 days, range 30-65) than after quinine or quinidine treatment (21 days, 15-36; p less than 0.0001). All patients remained outside areas of malaria transmission. These findings suggest a very high rate of double infection in Thailand with acute suppression of vivax by falciparum malaria, and warrant evaluation of radical therapy with primaquine in certain patients with acute falciparum malaria.

Acute Disease↗

Dynamic alteration in splenic function during acute falciparum malaria.

Plasmodium-infected erythrocytes lose their normal deformability and become susceptible to splenic filtration. In animal models, this is one mechanism of antimalarial defense. To assess the effect of acute falciparum malaria on splenic filtration, we measured the clearance of heated 51Cr-labeled autologous erythrocytes in 25 patients with acute falciparum malaria and in 10 uninfected controls. Two groups of patients could be distinguished. Sixteen patients had splenomegaly, markedly accelerated clearance of the labeled erythrocytes (clearance half-time, 8.4 +/- 4.4 minutes [mean +/- SD] vs. 62.5 +/- 36.5 minutes in controls; P less than 0.001), and a lower mean hematocrit than did the patients without splenomegaly (P less than 0.001). In the nine patients without splenomegaly, clearance was normal. After institution of antimalarial chemotherapy, however, the clearance in this group accelerated to supernormal rates similar to those in the patients with splenomegaly, but without the development of detectable splenomegaly. Clearance was not significantly altered by treatment in the group with splenomegaly. Six weeks later, normal clearance rates were reestablished in most patients in both groups. We conclude that splenic clearance of labeled erythrocytes is enhanced in patients with malaria if splenomegaly is present and is enhanced only after treatment if splenomegaly is absent. Whether this enhanced splenic function applies to parasite-infected erythrocytes in patients with malaria and has any clinical benefit will require further studies.

Adult↗

Mefloquine, sulfadoxine, and pyrimethamine in the treatment of symptomatic falciparum malaria: a double-blind trial for determining the most effective dose.

A total of 89 adult male Thai patients who had acute, uncomplicated falciparum malaria were treated in a double-blind randomized trial with a single oral dose of two or three tablets, each consisting of 250 mg mefloquine, 500 mg sulfadoxine, and 25 mg pyrimethamine (MSP). The two-tablet regimen produced a cure rate (S response) of 93%, the three-tablet regimen a cure rate of 98%. The mean duration of parasitaemia for the two- and three-tablet groups was 50 and 29 hours, respectively, while the mean duration of fever was 43 and 40 hours, respectively. Differences between the groups were not statistically significant. Tolerance was good at both dose levels. The main side-effects were abdominal discomfort, nausea, vomiting, dizziness, and diarrhoea, but these were mild, transient, and required no specific treatment. The results of haematological and biochemical investigations and of urinalysis revealed no drug-related changes following administration of MSP. The electrocardiograms of some patients revealed sinus bradycardia or sinus arrythmia, but these conditions were transient, symptomless, and clinically not significant.

Administration, Oral↗