Imported cutaneous leishmaniasis in Thailand.

Eleven cases of imported cutaneous leishmaniasis are described based on clinical features such as sex, age, occupation, country visited prior to consultation, sites and numbers of lesions, duration of illness, treatment and outcomes. Ketoconazole was shown to be effective against imported cutaneous leishmaniasis. With the increasing numbers of cutaneous leishmaniasis due to exchange workers going to the endemic areas and the presence of vectors in some localities in Thailand, primary transmission of the disease in this country is possible if feeding habits of the vectors change.

Pharmacokinetics of proguanil in malaria patients treated with proguanil plus atovaquone.

Clinical studies have shown atovaquone (ATQ), a new blood schizontocidal drug, in combination with proguanil (PROG) to be very effective in the treatment of acute multidrug-resistant falciparum malaria. The multiple dose pharmacokinetics of PROG were determined in Thai patients with acute falciparum malaria given PROG alone (200 mg PROG twice a day for 3 days, n = 4) and concurrently PROG and ATQ (200 mg PROG and 500 mg ATQ twice a day for 3 days, n = 12). There were no statistical differences (p > 0.05) in the area under the plasma drug concentration-time curve (AUC), apparent oral clearance (CL/F) and elimination half-life (t1/2) of PROG between patients given PROG alone and PROG/ ATQ. The median (range) kinetic values of PROG in patients given PROG alone and PROG/ATQ were respectively: CL/F = 1.25 l/h/kg (0.99-1.45) and 0.95 (0.73-1.32) l/h/kg, and t1/2 = 14.2 hours (9.3-16.8) and 13.6 hours (9.1-17.6). The CL/F and t1/2 of PROG in the Thai patients treated with the 2 treatment regimens were also comparable to values reported in healthy Thai volunteers given a standard prophylactic dose (200 mg PROG). The results of this preliminary study suggest that ATQ is unlikely to affect the pharmacokinetics of PROG to a clinically important extent at an ATQ dosage of 500 mg twice a day for 3 days in malaria infected patients.

Intestinal sarcocystosis in Thai laborers.

To determine the prevalence of Sarcocystis and other intestinal parasites in Thai laborers who were going abroad for work, stool examinations of 362 asymptomatic laborers were studied. The four most frequently parasites found in stool were Sarcocystis sp (23.2%), Opisthorchis viverini (40.3%), hookworm (21.5%), and Strongyloides stercoralis (14.1%). Giardia intestinalis (5.2%), Entamoeba coli (1.7%), Endolimax nana (2.5%), Blastocystis hominis (4.1%), Echinostoma sp (3.6%), Trichuris trichiura (0.3%), Taenia sp (1.7%), Hymenolepis nana (0.6%), and Enterobius vermicularis (0.3%) were present at low rates. Sarcocystis were frequently found in male laborers (83.3%) (p < .01). The laborers from northeastern Thailand (n = 278) had a higher prevalence (26.6%) of Sarcocystis infection (p < .01). This study shows that Thai laborers, particularly from northeastern Thailand, are commonly infected with intestinal parasites. The high prevalence rates of Sarcocystis and other intestinal parasites in this study were indicative of the local habit of eating raw beef and pork, poor living conditions, and low levels of hygiene in Thai laborers. Sarcocystosis could be a significant food-borne zoonotic infection in Thailand.

Treatment of acute uncomplicated falciparum malaria with a short course of artesunate followed by mefloquine.

The clinical results of this study indicate that a half-dose regimen of artesunate followed by mefloquine produces an acceptable cure rate when compared to other commonly available drugs for treating acute uncomplicated falciparum malaria in Thailand. The 90% cure rate was comparable to the results with either a full dose of artesunate (600 mg over 5 days) or mefloquine (25 mg/kg in divided doses six hours apart) as well as the combination of quinine-tetracycline administered for seven days. This abbreviated regimen, however was less effective than the full dose regimen of both drugs previously reported.

Clinical trials with halofantrine in acute uncomplicated falciparum malaria in Thailand.

The antimalarial efficacy of halofantrine was compared with mefloquine in an open-label, randomized comparative trial in adult male patients with acute uncomplicated falciparum malaria. Twenty-eight patients received halofantrine and 27 received mefloquine. Halofantrine was administered in 3 doses of 500 mg at 6 hour intervals and mefloquine was administered in divided doses of 1,250 mg or 1,500 mg depending on whether the patients weighed less than or more than 60 kg. The patients were followed for 42 days and observed for drug tolerance and evidence of recrudescence. Response to treatment was favorable with both drugs, but three patients (two treated with halofantrine and one with mefloquine) did not completely eliminate malaria parasites from peripheral blood films in seven days. The parasite and fever clearance times were 75.6 and 55.7 hours, and 80.1 and 61.3 hours, respectively for halofantrine and mefloquine. However, 12 patients recrudesced during the 42 day follow-up period. Nine of these had been treated with halofantrine and three with mefloquine. The 42-day cure rate for the two drugs was 56% and 84%, respectively. The side-effects of halofantrine and mefloquine were comparable and transient. These are diarrhea, dizziness, orthostatic hypotension and black out. However, vomiting was found to be more common in mefloquine group (41% vs 22%).

Clinical trials of mefloquine with tetracycline.

A comparative trial of the combination of mefloquine or MSP with tetracycline was carried out in fifty-one adult Thai male patients with acute falciparum malaria. The patients were randomized to receive either the combination of tetracycline (250 mg qid for 7 days) with mefloquine 4 tablets (1,000 mg) or with MSP 4 tablets (one tablet contains 250 mg mefloquine, 500 mg sulfadoxine and 25 mg pyrimethamine). Fifty patients had a complete 28-day follow-up period. Both regimens produced similar efficacy with no difference in adverse effects. In the mefloquine plus tetracycline group, the cure rate was 72% (18/25). One patient had an RIII response, the others showed initial response to the treatment with FCT and PCT of 40.7 +/- 27.4 and 76.2 +/- 34.2 hours (mean +/- SD) respectively. However, 6 patients developed recrudescence between days 17 and 29 (RI), 3 of these had vomiting. In the MSP plus tetracycline group, the cure rate was 76% (19/25). The means (+/- SD) of FCT and PCT were 44.7 +/- 38.0 and 80.6 +/- 25.0 hours, respectively. Six patients had recrudescence between days 17 and 31 (RI), 2 of these had vomiting. Although the addition of tetracycline improved the cure rate of mefloquine when compared with standard dose of mefloquine alone (3 tablets), these combinations seem to be useful in areas where alternative drugs are not available.

Double blind randomised clinical trial of oral artesunate at once or twice daily dose in falciparum malaria.

A double blind randomised comparative trial of the efficacy of daily dose (200 mg as an initial dose followed by 100 mg daily for another 4 days) and twice daily dose (100 mg 12 hourly for 2 doses on the first day, followed by 50 mg 12 hourly for another 8 doses) regimens of oral artesunate at 600 mg was studied in 59 Thai patients with uncomplicated falciparum malaria. Fifty patients had a complete 28-day follow-up period. Both regimens produced similar efficacy with no difference in adverse effects. The patients with the daily artesunate regimen had mean fever and parasite clearance times of 20 and 40 hours, respectively. The cure rate was 72%. Eight patients had recrudescence during days 15 to 28 while 8 showed P. vivax in their peripheral blood between days 12 and 21. The patients with the twice daily regimen had mean fever and parasite clearance time of 28 and 40 hours, respectively. The cure rate was 76%. Six patients had recrudescence during days 15 and 27 while 7 showed P. vivax during days 12 and 23. We suggest that the duration of the treatment may be a more important factor determining the efficacy of artesunate rather than the frequency of the doses. Further studies based on pharmacokinetics are therefore needed to improve the cure rate to 100% to prevent the spread of P. falciparum, particularly in areas where there are high numbers of multi-drug resistant strains.

Double blind randomised clinical trial of two different regimens of oral artesunate in falciparum malaria.

A double blind randomized comparative trial of the efficacy of 7-day and 5-day courses of oral artesunate at 600 mg was studied in 89 Thai patients with uncomplicated falciparum malaria. Eighty patients completed the 28-day follow-up period. Artesunate was found to be well tolerated in either regimen. There was an increase of 7% in the cure rate obtained from a 7-day regimen. In 43 patients with a 7-day regimen, the cure rate was 92.5% and 15 patients showed P. vivax in their peripheral blood between days 12 and 34. The mean fever and parasite clearance times were 20 and 40 hours, respectively. In 46 patients with a 5-day regimen, the cure rate was 85% and 8 patients showed P. vivax during days 13 and 24. The mean fever and parasite clearance times were 29 and 40 hours, respectively. Although the cure rates of oral artesunate were high in both regimens, the efficacy was considered unsatisfactory since the aim of the treatment is to achieve 100% cure rate. We suggest however that the extension of the duration of treatment to 7 days together with the increase in total dose may improve therapeutic efficacy of artesunate in falciparum malaria.

Clinical trial of artesunate and artemether on multidrug resistant falciparum malaria in Thailand. A preliminary report.

A 5-day course of oral artesunate at total doses of 1200, 600, 650 mg and intramuscular artemether 480 mg proved effective (90-100% cured) in the treatment of multidrug resistant falciparum malaria in Thailand. Shorter courses yielded high recrudescence rates. The fever clearance and parasite clearance times were short. The side effects were mild and transient including occasional abnormal electrocardiograms and pain at the injection site. Slight reduction of neutrophil leucocytes and reticulocytes was observed. Further studies of artesunate and artemether should be carried out to find the optimum dosage regimen and to clarify the hematological effects.

Enzyme-linked immunosorbent assay for diagnosis of human strongyloidiasis.

Crude antigen (CA) was prepared from Strongyloides stercoralis filariform larvae obtained from in vitro culture of the human feces containing rhabditiform larvae. The lyophilized filariform larvae were ground and ultrasonicated in distilled water then the soluble antigenic preparation was delipidized. The protein content of the crude soluble antigen was 20% of the original dried larvae. The CA was passed through a gel filtration chromatography column and yielded three different protein fractions namely F1, F2 and F3. CA and its fractions were used in the indirect enzyme-linked immunosorbent assay (ELISA) for detecting antibodies to S. stercoralis in serum samples of 5 groups of individuals. These were patients with parasitologically confirmed strongyloidiasis (group 1), patients with mixed S. stercoralis and other parasitic infections (group 2), non-strongyloidiasis patients with other worm infestation(s) (group 3), normal parasite-free Thais (group 4) and normal parasite-free Swedes (group 5). It was found that F2 was the best antigen in the ELISA. The sensitivity, specificity and positive and negative predictive values of the test using F2 as the antigen were 95.0%, 96.4%, 95.0% and 96.4%, respectively.

Clinical field trial of praziquantel in opisthorchiasis in Nong Rangya Village, Khon Kaen Province, Thailand.

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.

Clinical trial of albendazole in hookworm infection.

A clinical trial of albendazole (Zentel R) was carried out at the Hospital for Tropical Diseases in 1981. Thirty-five patients with hookworm infection were divided into 2 groups A, B and treated with a single dose of albendazole 400 mg and 600 mg respectively. The age of the patients ranged from 12 to 66 years and their weights ranged from 25 to 62 kilograms. Concentration and Stoll egg count methods were done at pretreatment, day 14 and day 21. At each interval two aliquots from each of the two faecal specimens were collected. The geometrical mean of EPG in Group A and B were 5406 and 5617 respectively. The cure rate in patients with less than 5000 EPG was 75% on day 21 in Group A and 67% in Group B. The mean percentage egg reduction was 95% in Group A and 99% in Group B. In patients with a higher egg out-put, the cure rate on day 21 was 50% in Group A and 29% in Group B. The mean percentage egg reduction was 91% in Group A and 93% in B. The side effects were mild and transient.

Serum cholinesterase activity in patients with malaria infection.

Serum cholinesterase activities were determined in 87 patients of both sexes with P. falciparum malaria in comparison to those of 80 blood donors. Patients with acute P. falciparum malaria had significantly lower serum cholinesterase activity than those of the control group. After treatment, their serum cholinesterase levels returned to the normal level. Serum albumin concentration also showed the same pattern and had a direct relationship to those of serum cholinesterase levels. These findings indicated that malarial parasites had some effect on the liver cells which resulted in impaired hepatic synthesis of serum cholinesterase and albumin concentrations. This result therefore add new information that there was a disturbance of enzyme cholinesterase among many liver enzymes that have been shown to be altered during an acute malarial attack.

Clinical trial of flubendazole on hookworm, Trichuris trichiura and Ascaris lumbricoides infections.

Flubendazole, a parafluoro analoque of mebendazole, was given to 89 service men with hookworm, Trichuris trichiura and Ascaris lumbricoides infections. The drug was given either as two doses of 300 mg at 12 hour interval (regimen A) or as two doses of 300 mg at 24 hour interval (regimen B). At four weeks follow-up the mean percentage egg reduction for hookworm was 88% and 96% in regimen A and B respectively. There were too few cases of Trichuris and Ascaris infection to allow comparison of the two regimens, but flubendazole appeared to be as effective and the single day regimen more convenient than difetasone for trichuriasis and levamisole for ascariasis. Side effects were few, mild and transient.