PubMed Health⌕ Search

Biomedical subjects

S Looareesuwan

Publications and source records attributed to S Looareesuwan.

At least 19 recordsLinked to original sources
PubMed2001

A human volunteer challenge model using frozen bacteria of the new epidemic serotype, V. cholerae O139 in Thai volunteers.

A total of 35 volunteers were recruited for an IRB-approved inpatient dose-escalation challenge. The goal was to identify a dose that produced an observed cholera attack rate > or =80% and an illness of sufficient severity during the defined study period such that the model would be useful for determining vaccine protection. Volunteers were challenged in groups of 5 with V. cholerae O139 that had been reconstituted immediately before use. Only 2 out of 5 volunteers who received the lowest dose (4.3 x 10(4) cfu) had diarrhea. As the inoculum size increased, the attack rate of diarrhea increased to 3-4 of 5 volunteers. At the highest dose tested, approximately 5 x 10(7) cfu, the attack rate was 73%. We recommend the use of frozen V. Cholera O139 in a human experimental challenge model to assess cholera vaccine efficacy (VE) in a cholera endemic area but with 4 days observation period before initiation of tetracycline to allow assessment of severity.

Adult↗
PubMed2001

Artemisinin antimalarials in pregnancy: a prospective treatment study of 539 episodes of multidrug-resistant Plasmodium falciparum.

The emergence and spread of multidrug-resistant Plasmodium falciparum compromises the treatment of malaria, especially during pregnancy, where the choice of antimalarials is already limited. Artesunate (n=528) or artemether (n=11) was used to treat 539 episodes of acute P. falciparum malaria in 461 pregnant women, including 44 first-trimester episodes. Most patients (310 [57.5%]) received re-treatments after earlier treatment with quinine or mefloquine. By use of survival analysis, the cumulative artemisinin failure rate for primary infections was 6.6% (95% confidence interval, 1.0-12.3), compared with the re-treatment failure rate of 21.7% (95% confidence interval, 15.4-28.0; P=.004). The artemisinins were well tolerated with no evidence of adverse effects. Birth outcomes did not differ significantly to community rates for abortion, stillbirth, congenital abnormality, and mean gestation at delivery. These results are reassuring, but further information about the safety of these valuable antimalarials in pregnancy is needed.

Animals↗
PubMed2001

Antimalarial activity of azithromycin, artemisinin and dihydroartemisinin in fresh isolates of Plasmodium falciparum in Thailand.

Antibiotics with antimalarial activity may offer an interesting alternative for the treatment of multidrug-resistant falciparum malaria. Azithromycin, a relatively recent semisynthetic derivative of erythromycin, was tested for its in vitro activity against fresh isolates of Plasmodium falciparum. As the reportedly slow onset of action of azithromycin suggests its combination with fast-acting substances, such as artemisinin-derivatives, dihydroartemisinin (DHA) was tested parallel as a possible combination partner. The effective concentrations found for azithromycin in this study (EC(50) = 29.3 micromol/l, EC(90) = 77.1 micromol/l blood medium mixture (BMM)) are comparable to those of other antimalarials in the antibiotics class and are considerably higher than those found for mefloquine or quinine. The absence of an activity correlation between azithromycin and chloroquine, quinine and artemisinin emphasises the independence of azithromycin drug response from the sensitivity to these drugs. A weak activity correlation (rho(EC90) = 0.352; p = 0.028), which could point to a potential cross-sensitivity but is probably of little clinical importance, was found with mefloquine above the EC(50) level. Provided that further clinical trials support the combination of these drugs, DHA may offer an interesting combination partner for azithromycin owing to its rapid onset of action and the comparatively low effective concentrations (EC(50) = 1.65 nmol/l, EC(90) = 7.10 nmol/l BMM). This combination may serve as an interesting alternative for tetracycline and doxycycline, which cannot be used in pregnant women and children, and exhibit phototoxicity. Nevertheless, the relatively high cost of this combination, as well as the controversial reports of the clinical efficacy, may limit the usefulness of azithromycin in malaria therapy and require an adjustment of previously used treatment regimens.

Animals↗
PubMed2001

A comparison of the in vivo kinetics of Plasmodium falciparum ring-infected erythrocyte surface antigen-positive and -negative erythrocytes.

Ring-infected erythrocyte surface antigen (RESA)-positive, Plasmodium falciparum-negative red blood cells (RBCs) are cells from which the malaria parasite has been removed by the host without the destruction of the erythrocyte ("pitting"). The survival of RESA-RBCs in vivo was assessed in 14 severe and 6 uncomplicated falciparum malaria patients. The mean RESA-RBC life of 183 hours (95% confidence interval [CI], 136-246) was longer than the median parasite clearance time of 66 hours (range, 30-108 hours) but shorter than the mean red cell life of 1027 hours (95% CI, 840-1213) (P =.0004), with a median ratio of 0.2:1.0 (range, 0.1-0.7). The estimated median percentage of parasites pitted/body transit was 0.003% (range, 0.001%-0.05%). The rate of rise of the RESA-RBC count during the first 24 hours after antimalarial treatment was significantly faster (P =.036) and the subsequent RESA-RBC survival significantly shorter (P =.017) after treatment with an artemisinin derivative than after treatment with quinine. Parasitization of red cells leads to changes in the erythrocyte that shorten their survival even if the parasite is removed subsequently.

Adolescent↗
PubMed2001

Fake artesunate in southeast Asia.

Artesunate is a key antimalarial drug in the treatment of multidrug-resistant Plasmodium falciparum malaria in southeast Asia. We investigated the distribution of counterfeit artesunate tablets by use of the validated, simple, and inexpensive Fast Red TR dye technique. We also aimed to identify distinguishing characteristics of the fake drugs. Of 104 shop-bought "artesunate" samples from Cambodia, Laos, Myanmar (Burma), Thailand, and Vietnam, 38% did not contain artesunate. Characteristics such as cost and physical appearance of the tablets and packaging reliably predicted authenticity. The illicit trade in counterfeit antimalarials is a great threat to the lives of patients with malaria. The dye test will assist national malaria control authorities in urgently needed campaigns to stop this murderous trade.

Antimalarials↗
PubMed2001

Socio-economic and environmental protective/risk factors for severe malaria in Thailand.

We conducted a cross-sectional study to identify the socio-economic and environmental protective/risk factors for severe malaria in Thailand. Forty-six cases of severe malaria, 72 cases of non-severe malaria with high parasite biomass and 40 mild malaria cases were included. When comparing severe malaria and non-severe malaria with high parasite biomass, specific logistic regression models showed a significant protective effect for helminths, adjusted odds ratio 0.24 (0.07-0.78) for low body mass index (BMI), adjusted odds ratio 0.11 (0.02-0.58). When comparing severe and mild malaria, a longer residence duration, adjusted odds ratio 0.36 (0.09-0.83) and the use of antimalarial self-medication, adjusted odds ratio 0.08 (0.009-0.84) were associated with protection from severe malaria. Using stepwise logistic regression with all the variables inserted in the model yielded similar results. These findings suggest specific immunity and self-medication control parasite multiplication whereas helminths and malnutrition more specifically affect the pathogenesis of severe malaria.

Adult↗
PubMed2001

Association of adhesion molecule PECAM-1/CD31 polymorphism with susceptibility to cerebral malaria in Thais.

Adhesion molecules on endothelial cells are known to be important ligands for malaria infected red blood cells (PRBC) [Mol Biochem Parasitol, 76, (1996) 1], and may be involved in the pathogenic process of cerebral malaria (CM) which is the most serious complication of falciparum malaria, through enhancing micro embolism or sequestration in the capillaries of the brain. PECAM-1/CD31 is one of these candidate ligands and is coded by a polymorphic gene. Two hundred and ten Thai malaria patients (43 cerebral, 89 severe and 78 uncomplicated) were analyzed for their genetic polymorphism of CD31 to examine the clinical relationship between the disease and specific genotypes. Four alleles were defined 125 valine (V)-563 asparagine (N); 125V-563 serine (S); 125 leucine (L)-563N; and 125L-563S. We found that the frequency of the 125 V/V 563 N/N genotype was significantly high in CM patients as compared with severe cases without CM (P<0.01, OR=2.92), suggesting that this genotype is one of the risk factors for CM.

Adult↗
PubMed2001

Case-control studies on host factors in severe malaria.

Although molecular biology has illustrated the phenotypic heterogeneity of Plasmodium falciparum, there are still no specific markers of virulence. As parasite virulence is an important determinant of severe malaria, the choice of comparison groups in the study of host factors influencing severity is a delicate issue. Ignoring parasite factors in the selection of controls potentially leads to biased comparisons between a majority of cases with virulent parasites and a majority of controls with non-virulent parasites. This article discusses how to avoid this virulence bias in the absence of specific markers of virulence.

Animals↗
PubMed2001

Association of genetic mutations in Plasmodium vivax dhfr with resistance to sulfadoxine-pyrimethamine: geographical and clinical correlates.

Mutations in the Plasmodium falciparum gene (dhfr) encoding dihydrofolate reductase are associated with resistance to antifols. Plasmodium vivax, the more prevalent malaria parasite in Asia and the Americas, is considered antifol resistant. Functional polymorphisms in the dhfr gene of P. vivax (pvdhfr) were assessed by PCR-restriction fragment length polymorphism using blood samples taken from 125 patients with acute vivax malaria from three widely separated locations, Thailand (n = 100), India (n = 16), and Madagascar and the Comoros Islands (n = 9). Upon evaluation of the three important codons (encoding residues 57, 58, and 117) of P. vivax dhfr (pvdhfr), double- or triple-mutation genotypes were found in all but one case from Thailand (99%), in only three cases from India (19%) and in no cases from Madagascar or the Comoros Islands (P < 0.0001). The dhfr PCR products of P. vivax from 32 Thai patients treated with the antifolate sulfadoxine-pyrimethamine (S-P) were investigated. All samples showed either double (53%) or triple (47%) mutations. Following treatment, 34% of the patients had early treatment failures and only 10 (31%) of the patients cleared their parasitemias for 28 days. There were no significant differences in cure rates, but parasite reduction ratios at 48 h were significantly lower for patients whose samples showed triple mutations than for those whose samples showed double mutations (P = 0.01). The three mutations at the pvdhfr codons for residues 57, 58, and 117 are associated with high levels of S-P resistance in P. vivax. These mutations presumably arose from selection pressure.

Adult↗
PubMed2001

Contemporaneous and successive mixed Plasmodium falciparum and Plasmodium vivax infections are associated with Ascaris lumbricoides: an immunomodulating effect?

Following an investigation suggesting a protective role for Ascaris against cerebral malaria, possibly through immunomodulation, we examined whether Ascaris had any impact on mixed Plasmodium falciparum and Plasmodium vivax infections. We studied a cross section of 928 patient files between 1991 and 1999. Forty patients had contemporaneous mixed infections and 40 patients had P. falciparum infections, followed by P. vivax infections. There was a significant association between Ascaris infection and risk of having both contemporaneous or successive mixed P. falciparum and P. vivax infections (adjusted odds ratios respectively 6 [2-18] P = 0.001 and 3.6 [1.2-11.1] P = 0.02). There was a positive linear trend between the burden of Ascaris and the risk of mixed infections P < 0.0001. These results suggested the possibility that pre-existing Ascaris infection may increase tolerance of the host to different Plasmodium spp., thus facilitating their coexistence.

Animals↗
PubMed2001

Short report: Hookworm infection is associated with decreased body temperature during mild Plasmodium falciparum malaria.

Malaria's pyrogenic threshold seems to depend on factors such as age and transmission patterns. We studied the temperature at admission of 200 patients with mild malaria and observed that after adjusting for body mass index, the presence of other helminths, and other confounders, only hookworm-infected patients had lower fever at admission that those without hookworm infection (37.5 +/- 0.9 and 38 +/- 0.8, respectively; P < 0.001). Thus, we suggest the age dependence of the pyrogenic threshold could have been confounded by the epidemiology of iron deficiency.

Adolescent↗
PubMed2001

Safety of the insect repellent N,N-diethyl-M-toluamide (DEET) in pregnancy.

The safety of daily application of N, N-diethyl-m-toluamide (DEET) (1.7 g of DEET/day) in the second and third trimesters of pregnancy was assessed as part of a double-blind, randomized, therapeutic trial of insect repellents for the prevention of malaria in pregnancy (n = 897). No adverse neurologic, gastrointestinal, or dermatologic effects were observed for women who applied a median total dose of 214.2 g of DEET per pregnancy (range = 0-345.1 g). DEET crossed the placenta and was detected in 8% (95% confidence interval = 2.6-18.2) of cord blood samples from a randomly selected subgroup of DEET users (n = 50). No adverse effects on survival, growth, or development at birth, or at one year, were found. This is the first study to document the safety of DEET applied regularly in the second and third trimesters of pregnancy. The results suggest that the risk of DEET accumulating in the fetus is low and that DEET is safe to use in later pregnancy.

Administration, Cutaneous↗
PubMed2001

Association of helminth infection with decreased reticulocyte counts and hemoglobin concentration in Thai falciparum malaria.

Following a study showing an association between Ascaris and protection from cerebral malaria, we conducted a cross-sectional study comparing admission hemoglobin concentrations in relation to exposure to helminth infection in 2 separate groups of patients: 111 cerebral malaria cases and 180 mild Plasmodium falciparum malaria cases. Hookworm infections were excluded. Mean hemoglobin concentrations were significantly lower in helminth-infected patients compared to those without helminths, both in the cerebral malaria group (10.1+/-3 [n = 47] versus 11.2+/-2.4 g/dl [n = 64], P = 0.04) and the mild malaria group (11+/-2.5 [n = 89] vs 12.2+/-2.7 g/dl [n = 91], P = 0.004). Median reticulocyte counts, only available in the cerebral malaria group, were lower in helminth-infected patients compared to those without helminths (15,340/23,760 per microl, P = 0.03). Adjustments for confounders such as body mass index did not alter these associations. These data are consistent with a mechanism causing anemia linked to differences in the immune response of helminth-infected patients during malaria.

Animals↗
PubMed2001

Identification of cryptic coinfection with Plasmodium falciparum in patients presenting with vivax malaria.

In Thailand, approximately 8% of patients treated for vivax malaria are found subsequently to have coinfection with Plasmodium falciparum. A P. falciparum histidine rich protein 2 (PfHRP-2) dipstick test was evaluated as a predictor of mixed infections with subpatent P. falciparum in a prospective study of 238 patients admitted to the hospital with acute vivax malaria. Of these, 23 (10%) had subsequent development of falciparum malaria without reexposure. Patients with cryptic P. falciparum infection had a significantly lower mean (standard deviation) hematocrit than those with P. vivax alone: 29.6 (7.6%) versus 37.2 (6.4%) (P < 0.0001). Using microscopic appearance of P. falciparum after the start of treatment as the reference standard, the PfHRP-2 test was 74% sensitive and 99% specific in predicting mixed infections with subpatent P. falciparum parasitemia at presentation. The PfHRP-2 dipstick test may be a useful adjunct to microscopy in areas where mixed infections are common.

Adult↗
PubMed2001

Association of splenomegaly with cerebral malaria and decreased concentrations of reactive nitrogen intermediates in Thailand.

The role of the spleen during Plasmodium falciparum malaria in humans is unclear. In Thailand, malaria transmission is low and splenomegaly is rarer than in high transmission areas. We compared the prevalence of splenomegaly between 52 cerebral malaria patients and 191 patients without complications despite a high parasite biomass. We also measured concentrations of reactive nitrogen intermediates (RNIs) in a fraction of these cases recruited in 1998 (24 cerebral malaria and 56 controls). Splenomegaly was significantly associated with cerebral malaria (adjusted odds ratio = 2.07 [95% confidence interval = 1-4.2]; P = 0.048). There was a linear trend for this association (P = 0.0003). After adjusting for potential confounders, concentrations of RNIs were significantly lower in the presence of splenomegaly (P = 0.01). These results suggest that in humans, as in animal models, the spleen may be involved in the pathogenesis of cerebral malaria. The relationship between RNI concentrations and the spleen suggest that nitric oxide may have a regulating role in the complex physiology of the spleen during malaria.

Adult↗
PubMed2001

Association of helminth infections with increased gametocyte carriage during mild falciparum malaria in Thailand.

The objective of this study was to determine whether pre-existing helminth infections could affect sexual forms of Plasmodium falciparum. A cross-sectional case record study compared 120 mild P. falciparum malaria cases with patent gametocyte carriage and 187 without gametocytes for helminth exposure. Relevant crude odds ratios and potential confounders were included in a logistic regression model. Helminth infections were associated with the presence of gametocytes with a crude odds ratio of 1.9 (95% confidence interval = 1.1-3.3) (P = 0.01). A positive linear trend was observed between the odds of having patent gametocytemia and the number of different helminth species (P = 0.003). However, when adjusting for hemoglobin concentration the significance of the association between helminths and gametocytes disappeared (P = 0.15). Pre-existing helminth infections may increase the severity of malarial anemia and therefore increase the likelihood of carrying gametocytes. At a population level, helminth infections may thus have a significant influence on malaria transmission.

Adolescent↗