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Biomedical subjects

L W Pang

Publications and source records attributed to L W Pang.

32 records · Page 2Linked to original sources

Malaria prophylaxis with proguanil and sulfisoxazole in children living in a malaria endemic area.

The effects of three separate antimalarial prophylactic regimens (proguanil, sulfisoxazole, and proguanil plus sulfisoxazole) and of vitamins in a control group were compared in a study population of 380 children living in a malaria endemic area along the Thai-Burmese border. The subjects, aged 5-16 years, were matched for age, weight, and presence of splenomegaly, then randomly assigned to one of the four groups. All medications were administered daily by the investigators and malaria smears were performed on a weekly basis. Among 99 subjects taking proguanil plus sulfisoxazole for a total of 1464 man-weeks, there was only one case of falciparum and no vivax malaria. Statistically, this regimen proved superior to each of the other groups against both Plasmodium falciparum and P. vivax. The data show that proguanil alone, as a causal or suppressive prophylatic, has poor efficacy against P. falciparum. Side-effects were infrequent and generally mild, except for two subjects whose sulfisoxazole prophylaxis was discontinued because of urticarial rash.

Adolescent↗

Malaria prophylaxis with proguanil in children living in a malaria-endemic area.

We studied the effects of daily proguanil compared to weekly chloroquine as malaria prophylaxis in 170 children living in a malaria-endemic area along the Thai-Burmese border. Children aged 5-10 years were matched for age, weight, and presence of splenomegaly then randomly assigned to receive either proguanil (equivalent of 200 mg daily adult dose) or chloroquine (equivalent of 300 mg base weekly). All medications were administered by the investigators and malaria smears were performed on a weekly basis. Among 85 children taking proguanil for 524 human-weeks, there were 17 cases of falciparum malaria and 11 cases of vivax. Of 85 children on chloroquine for 537 human-weeks, there were 24 cases of falciparum and 1 case of vivax. There were no statistically significant differences between the two regimens when analyzed either as suppressive or as causal Plasmodium falciparum prophylactics. The data were suggestive that proguanil may have some causal prophylactic effect against falciparum malaria. There were significantly more vivax prophylactic failures (P less than 0.01) in the proguanil group. Side effects were infrequent, mild, and comparable in both groups.

Animals↗

Circumsporozoite antibodies and falciparum malaria incidence in children living in a malaria endemic area.

In a case-control study we examined the association of Plasmodium falciparum circumsporozoite antibodies (anti-R32tet32) with subsequent P. falciparum infections. A study population of 140 children living in an endemic area was followed longitudinally for 25 weeks with weekly blood smears for malaria parasites and, once every two weeks, serum samples for circumsporozoite antibody determinations. From the malaria cases, antibody measurements occurring between two and six weeks prior to the onset of parasitaemia were utilized. For each case, two controls were selected. The results from 17 cases and 34 controls failed to show a statistically significant difference in antibody levels prior to the infection (P=0.07, one-tailed Student's t-test). However, 8 of the 17 cases had antibody present, indicating a level that was not protective against patent infection.

Animals↗

Malaria: treatment efficacy of halofantrine (WR 171,669) in initial field trials in Thailand.

Halofantrine (WR 171,669) hydrochloride was administered orally to 82 patients infected with Plasmodium falciparum malaria on the Thai-Kampuchean border between June 1982 and December 1983 in a randomized double-blind treatment trial which compared the efficacy of halofantrine with that of mefloquine. Halofantrine was curative with oral treatment on a single day in 65% of patients (13/20) who received 1000 mg followed 6 hours later by an additional 500 mg, and in 88% of patients (53/60) who received 500 mg every 6 hours for 3 doses. Mefloquine was curative in 88% of patients (22/25) given a single oral dose of 1000 mg and in 97% of patients (38/39) given a single oral dose of 1500 mg. The difference in cure rates between the 3-dose halofantrine regimen and either of the mefloquine regimens was not significant. The mean parasite clearance time for all regimens ranged from 75 to 84 hours. The mean fever clearance time for all four treatment groups was in the range 50-60 hours, with no significant differences between groups. Post-dosing side-effects in patients treated with halofantrine consisted of nausea, vomiting, abdominal pain and diarrhoea and were not significantly different from those treated with mefloquine. Halofantrine therefore appeared to be of comparable efficacy to mefloquine in the treatment of multidrug-resistant P. falciparum malaria.

Adult↗

Doxycycline prophylaxis for falciparum malaria.

188 schoolchildren aged 10-15 living in a malaria endemic area along the Thai-Burmese border were matched for age, splenomegaly, and weight and were then randomly assigned to receive either doxycycline (adult equivalent of 100 mg daily) or chloroquine (adult equivalent of 300 mg base weekly). All drugs were administered by the investigators and blood smears were done weekly. In 95 subjects taking doxycycline for 597 man-weeks there were 5 cases of falciparum malaria and in the 93 controls taking chloroquine for 488 man-weeks there were 31. Doxycycline was more effective than chloroquine in the prevention of falciparum malaria infections (p less than 0.0001). The doxycycline group did not have significantly more side-effects than the chloroquine group.

Adolescent↗

Development of immunity in natural Plasmodium falciparum malaria: antibodies to the falciparum sporozoite vaccine 1 antigen (R32tet32).

Antibodies that reacted with a candidate sporozoite vaccine antigen (R32tet32) were found in 20 of 21 patients treated for acute infection with Plasmodium falciparum and monitored longitudinally over 67 days. R32tet32 contains 32 tandem copies of a tetrapeptide sequence that constitutes the immunodominant epitope of the circumsporozoite surface protein. The magnitude of the antibody response varied considerably among individuals and appeared to be independent of the number of previous clinical infections. Recrudescence of infection or infection with Plasmodium vivax had no demonstrable effect on antibody levels, although reinfection with P. falciparum produced a rapid rise in antibody titer. Antibody levels were observed to decline rapidly after treatment of clinical infection with mefloquine. The apparent antibody half-life was 27 days, which is comparable to the half-life of circulating immunoglobulin G in humans. The data suggest that antisporozoite antibody production ceased on about day 4 after treatment of acute infection. A similar pattern of response was observed for antibodies against the erythrocytic forms of the parasite. The cessation of antibody synthesis was interpreted as being due to immunosuppression induced by the presence of intraerythrocytic parasites and may explain in part why protective immunity is poorly developed in natural malaria infections.

Acute Disease↗

Some entomological observations on malaria transmission in a remote village in northwestern Thailand.

Anopheline mosquitoes and their relation to malaria transmission were studied during the months of March, May and July in the Karen village of Mae Tha Waw located in the northwestern mountains of Tak Province. Thirteen species were captured on human bait during 80 man-nights of collecting. Four additional species were collected during routine larval surveys. Anopheles minimus and An. maculatus comprised 92.5% of the specimens captured biting man. Anopheles minimus and An. nivipes were implicated as vectors based on the detection of sporozoite infections using enzyme-linked immunosorbent assays for Plasmodium falciparum and P. vivax. Anopheles dirus was rarely encountered and probably played little part in transmission in Mae Tha Waw during the period of study. Information is provided on nightly biting activity, incidence of disease, infectivity and larval bionomics.

Animals↗

Genetics of esterases and 6-phosphogluconate dehydrogenase in the Anopheles maculatus complex.

Electromorphic variation for some esterases and 6-phosphogluconate dehydrogenase enzymes in the Anopheles maculatus complex is controlled by four loci which are unlinked to sex. Esterase loci are linked to each other: Est-1-36%-Est-4-16.5%-Est-3; but unlinked to Pgd-2. Linkage data were obtained by selfing the F1 generation from selected parents and analysing genotypes in the F2; the classical dihybrid-cross. The analysis consists of testing observed data for goodness of fit to a) ratios expected from Mendelian ratios without linkage and b) if they do not fit then computing a likely degree of linkage and computing expected ratios with such linkage for further tests. Confidence limits are given for the most likely levels of linkage. This method can provide useful information for population-genetic studies on anopheline mosquitoes, whose laboratory rearing is generally difficult. Through indirect evidence, the enzyme loci are correlated to polytene chromosomes. The esterases probably lie on chromosome three (polytene arms 3 and 4) and Pgd-2 on the second chromosome (arms 2 and 5).

Animals↗

Antimalarial drug susceptibility testing of Plasmodium falciparum in Thailand using a microdilution radioisotope method.

Antimalarial activity of chloroquine, quinine, mefloquine and halofantrine against 33 strains of P. falciparum isolated from naturally acquired malaria infections in Thailand was determined using a radioisotope microdilution method. A microtitration procedure was used to test isolates of P. falciparum against the 4 drugs simultaneously. The mean ID50 for chloroquine and quinine reflected known resistance to those drugs in Thailand. The mean ID50 for mefloquine and halofantrine showed susceptibility to these drugs. Four isolates of P. falciparum however had markedly decreased susceptibility to mefloquine (ID50 greater than 15 ng/ml); one case of which was confirmed as the first case of RII resistance for mefloquine in Thailand. Several parasite isolates were also observed to have decreased susceptibility to the new drug, halofantrine. These studies strongly recommend that in vitro testing be done in conjunction with field evaluation of new antimalarial drugs.

Adult↗

Failure of large-dose erythromycin in combination with a standard dose of chloroquine or quinine in the treatment of human falciparum malaria.

In eastern Thailand, falciparum malaria is highly chloroquine-resistant and is quickly becoming quinine-resistant. In the present study, ten patients with falciparum malaria were given large doses of erythromycin, combined with standard doses of chloroquine; the cure rate was 0 out of 10 (4 RIII failures, 6 RII failures). A further ten patients were given erythromycin with standard doses of quinine; 2 of the 10 patients were cured (8 RI failures). These regimens thus appear to have no appreciable effect against falciparum infections in eastern Thailand.

Adult↗

Failure to achieve predicted antibody responses with intradermal and intramuscular human diploid cell rabies vaccine.

In a study to compare the immunogenicity of human diploid cell rabies vaccine (HDCV) given by intramuscular or automatic intradermal jet injection, neither method of administration resulted in antibody levels predicted by previous studies. 49 days after starting a series of three 0.1 ml doses of HDCV given intradermally, 85 volunteers had a geometric mean titre (GMT) of neutralising antibody to rabies of 1:170. 9 concurrent control subjects who received 1.0 ml doses of vaccine intramuscularly had a GMT of only 1:269. Although standard potency testing did not demonstrate that the vaccine used was subpotent , these results strongly suggest that the immunogenicity of HDCV is substantially less than previously reported.

Antibodies, Viral↗

Development of a ceuE-based multiplex polymerase chain reaction (PCR) assay for direct detection and differentiation of Campylobacter jejuni and Campylobacter coli in Thailand.

A novel ceuE-based multiplex PCR system was developed as an efficient diagnostics test to detect and differentiate C. jejuni and C. coli. There is no cross reactivity between C. jejuni and C. coli. In addition, the assay does not produce a positive signal from other enteric bacteria including Salmonella, Shigella and Escherichia coli strains. Campylobacter detection sensitivity was determined to be equivalent to previously reported PCR for other enteric bacteria. We also noticed that silicon dioxide extraction can improve Campylobacter detection sensitivity from infected stool samples. It was demonstrated that the PCR assay developed in this study had a much better Campylobacter detection rate than the traditional culturing method (77% versus 56%). However, we also identified small numbers of culture positive stools (8%, or 16 out of 202 samples) that did not yield PCR positive results for Campylobacter. These PCR negative/culture positive stools were proven to be inhibitory to PCR amplification.

Bacterial Proteins↗

Antimalarial drug susceptibility testing of Plasmodium falciparum in Brazil using a radioisotope method.

From March 1996 to August 1997, a study was carried out in a malaria endemic area of the Brazilian Amazon region. In vivo sensitivity evaluation to antimalarial drugs was performed in 129 patients. Blood samples (0.5 ml) were drawn from each patient and cryopreserved to proceed to in vitro studies. In vitro sensitivity evaluation performed using a radioisotope method was carried out with the cryopreserved samples from September to December 1997. Thirty-one samples were tested for chloroquine, mefloquine, halofantrine, quinine, arteether and atovaquone. Resistance was evidenced in 96.6% (29/30) of the samples tested for chloroquine, 3. 3% (1/30) for quinine, none (0/30) for mefloquine and none for halofantrine (0/30). Overall low sensitivity was evidenced in 10% of the samples tested for quinine, 22.5% tested for halofantrine and in 20% tested for mefloquine. Means of IC 50 values were 132.2 (SD: 46. 5) ng/ml for chloroquine, 130.6 (SD: 49.6) ng/ml for quinine, 3.4 (SD: 1.3) ng/ml for mefloquine, 0.7 (SD: 0.3) ng/ml for halofantrine, 1 (SD: 0.6) ng/ml for arteether and 0.4 (SD: 0.2) ng/ml for atovaquone. Means of chloroquine IC 50 of the tested samples were comparable to that of the chloroquine-resistant strain W2 (137.57 ng/ml) and nearly nine times higher than that of the chloroquine-sensitive strain D6 (15.09 ng/ml). Means of quinine IC 50 of the tested samples were 1.7 times higher than that of the low sensitivity strain W2 (74.84 ng/ml) and nearly five times higher than that of the quinine-sensitive strain D6 (27.53 ng/ml). These results disclose in vitro high resistance levels to chloroquine, low sensitivity to quinine and evidence of decreasing sensitivity to mefloquine and halofantrine in the area under evaluation.

Animals↗

Malaria in Brazilian military personnel deployed to Angola.

BACKGROUND: Malaria represents one of the most important infectious disease threats to deployed military forces; most personnel from developed countries are nonimmune personnel and are at high risk of infection and clinical malaria. This is especially true for forces deployed to highly-endemic areas in Africa and Southeast Asia where drug-resistant malaria is common. METHODS: We conducted an outbreak investigation of malaria cases in Angola where a total of 439 nonimmune Brazilian troops were deployed for a 6-month period in 1995-1996. A post-travel medical evaluation was also performed on 338 (77%) of the 439 soldiers upon return to Brazil. Questionnaire, medical record, thick/thin smear, and serum anti-Plasmodium falciparum antibody titer (by IFA) data were obtained. Peak serum mefloquine (M) and methylmefloquine (MM) metabolite levels were measured in a subsample of 66 soldiers (42 cases, 24 nonmalaria controls) who were taking weekly mefloquine prophylaxis (250 mg). RESULTS: Seventy-eight cases of malaria occurred among the 439 personnel initially interviewed in Angola (attack rate = 18%). Four soldiers were hospitalized, and 3 subsequently died of cerebral malaria. Upon return to Brazil, 63 (19%) of 338 soldiers evaluated were documented to have had clinical symptoms and a diagnosis of malaria while in Angola. In addition, 37 (11%) asymptomatically infected individuals were detected upon return (< 1% parasitemia). Elevated, post-travel anti-P. falciparum IFA titers (> or = 1:64) were seen in 101 (35%) of 292 soldiers tested, and was associated with a prior history of malaria in-country (OR = 3.67, 95% CI 1.98-6.82, p <.001). Noncompliance with weekly mefloquine prophylaxis (250 mg) was associated with a malaria diagnosis in Angola (OR = 3.75, 95% CI 0.97-17.41, p =.03) but not with recent P. falciparum infection (by IFA titer). Mean peak levels (and ratios) of serum M and MM were also found to be lower in those who gave a history of malaria while in Angola. CONCLUSIONS: Malaria was a significant cause of morbidity among Brazilian Army military personnel deployed to Angola. Mefloquine prophylaxis appeared to protect soldiers from clinical, but not subclinical, P. falciparum infections. Mefloquine noncompliance and an erratic chemoprophylaxis prevention policy contributed to this large outbreak in nonimmune personnel. This report highlights the pressing need for development of newer, more efficacious and practical, prophylactic drug regimens that will reduce the malaria threat to military forces and travelers.

Angola↗