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Biomedical subjects

L W Pang

Publications and source records attributed to L W Pang.

At least 19 recordsLinked to original sources

Paracoccidioidomycosis: an epidemiologic survey in a pediatric population from the Brazilian Amazon using skin tests.

Since Paracoccidioides brasiliensis and Histoplasma capsulatum are known to be present in similar environments, there have been many epidemiologic investigations regarding the prevalences of these two organisms. However, cross-reactivity can occur in paracoccidioidin and histoplasmin skin tests, and this usually results in the overestimation of the prevalence of P. brasiliensis. The prevalence of infection with P. brasiliensis was evaluated in a cross-sectional study of 298 asymptomatic school children in the Brazilian Amazon region (Mato Grosso State). In this investigation, the reactivity of children to two different P. brasiliensis antigen preparations, paracoccidioidin and a purified 43-kD glycoprotein (gp43), was compared with or without the co-administration of histoplasmin. In the group of individuals receiving paracoccidioidin who had a positive histoplasmin skin test result, the prevalence of exposure to P. brasiliensis was 44% (16 of 36). This reactivity to P. brasiliensis was significantly higher than that observed in other groups, which ranged from 4% to 6% (P < 5 x 10(-4) for each). Overall prevalence was 4.6% (95% confidence interval = 2.5-7.7%). These data suggest that gp43 provides a better estimate of exposure to P. brasiliensis when the co-administration of histoplasmin is desired.

Adolescent↗

Drug-resistant malaria in Bangladesh: an in vitro assessment.

Forty-four Plasmodium falciparum isolates from Bangladesh and 22 from western Thailand were successfully tested for their drug susceptibility. High degrees of resistance were observed against chloroquine with geometric mean IC50s of 114.25 and 120.5 nM, respectively, for Bangladesh and western Thailand. Most isolates from both sites were sensitive to quinine, and all were sensitive to artesunate. Many isolates were considered in vitro resistant to mefloquine, but the geometric mean IC50 for the Thai isolates (98.79 nM) was 1.6 times (P = 0.002) higher than that of isolates from Bangladesh (60.3 nM). The high prevalence of in vitro mefloquine resistance in Bangladesh suggests that close surveillance is necessary to delay widespread multidrug resistant problems in the area.

Animals↗

An observational clinic-based study of diarrheal illness in deployed United States military personnel in Thailand: presentation and outcome of Campylobacter infection.

Campylobacter is a leading cause of traveler's diarrhea in Thailand. Since resistance to quinolones is high among Campylobacter isolates, empiric therapy with quinolones for traveler's diarrhea may be ineffective in this region. We conducted an observational study among 169 U.S. military personnel with acute diarrhea and compared their microbiologic findings to those of 77 asymptomatic personnel deployed to Thailand in May 1998. Of 146 pathogenic bacterial isolates, the most common were nontyphoidal Salmonella (n = 31), enterotoxigenic Escherichia coli (n = 24), and C. jejuni/coli (n = 23). Campylobacter was strongly associated with disease (odds ratio = 5.9; 95% confidence interval = 1.3-37.3), with a more severe clinical presentation, and with a reduced functional ability at presentation (P = 0.02). In vitro resistance to ciprofloxacin was observed in 96% of the Campylobacter isolates. Sub-optimal treatment response to ciprofloxacin was observed in 17% of the cases of Campylobacter infection versus 6% due to other causes. These results highlight the importance of Campylobacter as a cause of severe traveler's diarrhea in Thailand and illustrates the ongoing problem with antibiotic-resistant strains and associated treatment problems.

Adult↗

Prospective study of the incidence of diarrhoea and prevalence of bacterial pathogens in a cohort of Vietnamese children along the Red River.

We prospectively studied diarrhoea incidence among 1655 children < 5 years of age in northern Vietnam for 1 year using primarily passive surveillance. Standard culture methods were used to detect bacterial pathogens. Overall 2160 cases occurred (13 cases/child per year). Peak rates of diarrhoea occurred in children < 12 months old. Rates ranged from 3.3 cases/child per year in children < 1 year old, to 0.7 cases/child per year in 4-year-olds. Campylobacter, shigella and enterotoxigenic Escherichia coli were most commonly isolated. Rates detected by active surveillance were about twice those detected passively. S. flexneri was the most common shigella serogroup (65 %). S. flexneri serotypes 6, 4, 1 and Y were most common, but 40% were untypable using commercial antisera. The data illustrate important regional differences in pathogen prevalence and shigella serotype distribution. Shigella vaccine development strategies, commonly targeting S. flexneri 2a, S. sonnei and S. dysenteriae 1, will have little impact on diarrhoea rates in Vietnam.

Age Distribution↗

In vitro susceptibility of Plasmodium falciparum isolates from Myanmar to antimalarial drugs.

In vitro drug susceptibility profiles were assessed in 75 Plasmodium falciparum isolates from 4 sites in Myanmar. Except at Mawlamyine, the site closest to the Thai border, prevalence and degree of resistance to mefloquine were lower among the Myanmar isolates as compared with those from Thailand. Geometric mean concentration that inhibits 50% (IC50) and 90% (IC90) of Mawlamyine isolates were 51 nM (95% confidence interval [CI], 40-65) and 124 nM (95% CI, 104-149), respectively. At the nearest Thai site, Maesod, known for high-level multidrug resistance, the corresponding values for mefloquine IC50 and IC90 were 92 nM (95% CI, 71-121) and 172 nM (95% CI, 140-211). Mefloquine susceptibility of P. falciparum in Myanmar, except for Mawlamyine, was consistent with clinical-parasitological efficacy in semi-immune people. High sensitivity to artemisinin compounds was observed in this geographical region. The data suggest that highly mefloquine-resistant P. falciparum is concentrated in a part of the Thai-Myanmar border region.

Animals↗

Association of subtherapeutic dosages of a standard drug regimen with failures in preventing relapses of vivax malaria.

This study evaluated the cure rate of the standard recommended regimen for Plasmodium vivax malaria in Brazil and assessed risk factors for failures. Fifty patients with vivax malaria given supervised medical treatment (standard dose of chloroquine: total dose = 1.5 g over a three-day period plus primaquine: total dose = 210 mg over a 14-day period) were followed for six months in a non-endemic area. Cox's regression was used to identify predictors of relapses. Among the 289 patient-months of follow-up, seven relapses were identified (2.4 relapses per 100 person-months) between 33 and 137 days after treatment initiation. Risk factors for relapses (P < or = 0.05) were female sex, higher parasitemia at baseline, shorter number of days with symptoms prior to baseline, and lower mg/kg dose of primaquine. Relapses following supervised vivax treatment is in principle a necessary, but not sufficient, component of in vivo parasite resistance. Results indicate that other factors, principally sub-therapeutic primaquine doses, may explain the occurrence of vivax treatment failures.

Adolescent↗

Community-based program for malaria case management in the Brazilian Amazon.

In areas of drug-resistant malaria, control programs may restrict chemotherapy until malaria has been confirmed via microscopy to contain costs and toxicity. In Brazil, patients travel to centralized laboratory posts (FNS) at great cost for diagnosis and treatment. A program was established through the bars of a mining town offering free dipstick diagnosis and mefloquine treatment on a 24-hr basis; falciparum malaria dipstick tests are accurate and easy to use. Outcomes were compared with historical data and results of a neighboring non-intervention village. Guidelines for dipstick use and treatment were followed for 98% of visits. The number of FNS visits was reduced from 2,316 (expected) to 1,097 (observed) with 626 dipstick tests applied. Ninety-five percent of those who visited the FNS experienced onset of malaria symptoms in the town where the FNS was located. There was an unexpected doubling of the malaria hospital admission rate. We demonstrate that dipstick testing can be used in a sustainable, community-based program that should be applicable in a wide variety of settings.

Animals↗

Economic advantage of a community-based malaria management program in the Brazilian Amazon.

In the Brazilian Amazon, travel costs to centralized malaria clinics for diagnosis and treatment can approach 20% of one's monthly salary. A program was established in a mining town for community-based dipstick test diagnosis and treatment. An economic analysis was performed that compared expected costs under the old program to the observed costs of the new one. Data were obtained through interviews, government reports, clinic and hospital records, and community records. There was a 53% reduction (by 1,219 visits) of clinic visits but a doubling of malaria hospitalization admissions (to 191). The new program had an overall annual savings of $60,900 ($11.8K-$160K, sensitivity limits), a 77% reduction of the old program's cost. The benefit-to-cost ratio was 9:1, where benefits were patients' savings from travel and lost wages and costs were government drug, diagnostic, training, and monitoring expenses. A community-based program incorporating dipstick tests for malaria management can have economic advantages.

Animals↗

Detection of PCR products of the ipaH gene from Shigella and enteroinvasive Escherichia coli by enzyme linked immunosorbent assay.

PCR techniques applied to diarrheal stools reliably diagnose Shigella and enteroinvasive Escherichia coli (EIEC) infections. Identification of PCR products using agarose gel electrophoresis (AGE) and hybridization with DNA probes has several shortcomings. Automated methods of identifying PCR products that process larger numbers of specimens can facilitate epidemiologic studies and standardize results. In this study, we used ELISA following PCR to detect ipaH gene sequences of Shigella and EIEC from 89 diarrheal stools. Results of ELISA were compared with AGE with and without DNA probe, and with culture. Two specimen preparation methods were compared as well: boiling/centrifugation, and purification with silicon dioxide (SiO(2)). Both PCR product-detection methods identified significantly more infections than did culture. PCR-ELISA detected significantly more infections than PCR-AGE when processed using SiO2 (P = 0.014). PCR-ELISA allows screening of larger numbers of specimens, automates test results, and avoids use of mutagenic reagents. PCR-ELISA is faster than PCR-AGE when testing large numbers of specimens, although not when testing small numbers of specimens.

Antigens, Bacterial↗

In vivo efficacy of mefloquine for the treatment of Falciparum malaria in Brazil.

Ninety-four patients with falciparum malaria were treated with mefloquine (1000-mg single dose) and remained hospitalized in a malaria-free area for a minimum of 28 days. There was 1 parasitologic failure (grade I resistance [RI]) for a 99% cure rate (95% confidence interval, 94.2%-99.7%). Mean parasite clearance time by thick smear was 45.7 h (SD, 11.4 h). The subject in whom therapy failed had a parasite clearance time (71 h) >2 SD above the population mean. His plasma mefloquine level 48 h after administration was lower (578 ng/mL) than the range of levels from 8 randomly selected cured subjects (834-2360 ng/mL). The IC50 to mefloquine for the recrudescent strain of the RI failure was in the upper 90th percentile of IC50 values from 30 cured subjects. These results show a high mefloquine cure rate but document the onset and mechanism of the emergence of resistance.

Adolescent↗

Atovaquone and proguanil for the treatment of malaria in Brazil.

The purpose of this study was to compare an experimental regimen of atovaquone plus proguanil with the standard regimen of quinine plus tetracycline for the treatment of uncomplicated falciparum malaria. The study was designed as an open, randomized study of men presenting with symptoms of uncomplicated malaria and thick-smear slide confirmation of parasitemia (1000-100,000 ring forms/microL). Subjects were hospitalized for 28 days to insure medication compliance and to rule out the possibility of reinfections. With 77 patients in each group, the cure rates were 98.7% and 100% for atovaquone plus proguanil and quinine plus tetracycline, respectively. The parasite clearance times (mean, 56 h) and fever clearance times (mean, 19 h) were significantly shorter in the atovaquone plus proguanil group, and there were significantly fewer side effects in the atovaquone plus proguanil group. Atovaquone plus proguanil is an efficacious, easily administered, safe regimen for the treatment of uncomplicated, multidrug-resistant falciparum malaria in Brazil.

Adolescent↗

Failure of doxycycline as a causal prophylactic agent against Plasmodium falciparum malaria in healthy nonimmune volunteers.

OBJECTIVE: To determine whether doxycycline, 100 mg administered as a single daily oral dose, is effective as a causal prophylactic agent, an agent active against the pre-erythrocytic liver stage of Plasmodium falciparum malaria parasites, in healthy nonimmune persons. If effective, the recommendation by the Centers for Disease Control and Prevention (CDC) that doxycycline be continued for 4 weeks after returning from malaria-endemic areas could be shortened to 1 week. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Medical ward at the U.S. Army Research Institute of Infectious Diseases, Fort Detrick, Maryland. PARTICIPANTS: 18 nonimmune, healthy, adult male volunteers, age 21.7 +/- 2.9 (SD) years, were enrolled in two groups, one of 8 persons and one of 10 persons. Six participants in the first group and 7 in the second group received doxycycline. The remaining participants received placebo. Two volunteers were dropped from the study, leaving 16 participants for analysis. INTERVENTION: Each participant received doxycycline, 100 mg, or placebo in a single daily oral dose starting 3 days before exposure to P. falciparum-infected mosquitoes and ending 6 days after exposure. MEASUREMENTS: Monitoring for parasitemia, plasma doxycycline concentrations, and mosquitoes' salivary-gland sporozoite grade. RESULTS: 6 of 6 (100% [95% Cl, 54% to 100%]) participants on doxycycline in the first group and 2 of 6 (33% [Cl, 4% to 78%]) in the second group were protected from malaria. No differences were found between protected and nonprotected participants in the doxycycline elimination half-life (T1/2) (20.8 +/- 5.0 h compared with 21.9 +/- 5.2 h), the steady-state average plasma concentration (1626 +/- 469 ng/mL compared with 1698 +/- 651 ng/mL), or other pharmacokinetic parameter estimates. The mean mosquito salivary-gland sporozoite grade was significantly higher (P = 0.02) in protected (3.5 +/- 0.3) than in nonprotected persons (3.1 +/- 0.1). Overall, 8 of 12 persons on doxycycline were protected from malaria, yielding a causal prophylactic efficacy rate of 67% (Cl, 35% to 90%). CONCLUSIONS: A dosing regimen of doxycycline, 100 mg once daily, administered as a causal prophylactic agent against P. falciparum malaria in healthy, nonimmune volunteers, had an unacceptably high failure rate. Therefore, the CDC recommendation that doxycycline should be taken daily starting 1 to 2 days before travel, during travel, and for 4 weeks after travel should still be followed.

Administration, Oral↗

Vaccine-preventable disease susceptibility in a young adult Micronesian population.

Current US military recruit vaccination policy presumes that recruits have had a complete childhood immunization series. This assumption may not be appropriate for recruits from Micronesia, who may have had limited access to modern health care, including immunization programs. During 1988 and 1990, a cross-sectional serosurvey was conducted among 66 US military recruits, 56 from the Federated States of Micronesia and 10 from the Republic of the Marshall Islands, collectively referred to as Micronesia. Antibody seronegativity levels for 12 vaccine-preventable (or potentially so) diseases were: measles (52%), mumps (14%), rubella (21%), varicella (38%), diphtheria (39%) tetanus (0%), polio type 1 (4%), polio type 2 (0%), polio type 3 (14%), hepatitis A (9%), hepatitis B (17%), and hepatitis C (98%). Compared with Army recruits in general, Micronesian recruits were significantly more likely to be seronegative for measles and varicella and seropositive for hepatitis types A and B. Personal histories of disease were felt to be inadequate in predicting antibody status.

Adult↗

Comparison of mefloquine, chloroquine plus pyrimethamine-sulfadoxine (Fansidar), and chloroquine as malarial prophylaxis in eastern Thailand.

From July 1983 to March 1984 a randomized double blind prophylactic trial in Thai gem miners working across the border in Cambodia was conducted to determine the prophylactic efficacy of 3 drug regimens against P. falciparum and P. vivax malaria along the Thai-Cambodian border. Gem miners have a high incidence of malaria. Maximum duration of individual participation was 14 weeks. Of 334 participants in this study who were seen every 2 weeks, 145 received mefloquine 500 mg fortnightly, 112 received chloroquine 300 mg base weekly plus Fansidar (1000 mg sulfadoxine and 50 mg pyrimethamine) fortnightly and 77 received chloroquine as 300 mg base weekly. The significant reduction of vivax malaria in study subjects (compared to background incidence) implied good compliance with self administration of chloroquine in the intervening weeks between scheduled appointments. The attack rate in each prophylactic regimen was 2188 cases/1000/year with mefloquine, 8338 cases/1000/year with chloroquine-Fansidar and 10,207 cases/1000/year receiving chloroquine alone. There was a 79% prophylactic efficacy for mefloquine and 18% efficacy for the chloroquine plus Fansidar regimen compared to chloroquine. Using life table analysis, 56% of the mefloquine group, 6% of the chloroquine-Fansidar group and 4% of the chloroquine group were malaria free at the end of the 14 weeks study. The chloroquine plus sulfadoxine-pyrimethamine regimen prescribed for prophylaxis is no longer effective for multidrug resistant strains of P. falciparum in the study area. This study also seriously questions the efficacy of mefloquine prophylaxis.

Adolescent↗

Mefloquine kinetics in cured and recrudescent patients with acute falciparum malaria and in healthy volunteers.

Mefloquine pharmacokinetics were compared in a randomized clinical trial in Thailand among patients with malaria and healthy volunteers. A single oral dose of 1500 mg mefloquine hydrochloride was administered to 11 patients and 5 volunteers and 750 mg was given to 16 patients and 5 volunteers. Efficacy was 82% for 1500 mg and 63% for 750 mg. In cured patients taking 750 mg mefloquine, peak plasma drug concentration (Cmax) and area under the plasma concentration-time curve (AUC) were significantly greater than in the patients for whom treatment failed (p less than 0.0005 and p less than 0.01, respectively), and plasma mefloquine levels were significantly higher from 8 hours to 18 days after treatment. Mefloquine AUC was reduced and variable in the presence of diarrhea. Compared with noninfected volunteers, clinically ill patients displayed a delayed time to reach peak concentration (p less than 0.01) and significantly higher mefloquine plasma levels in the first 2 days after administration of either the 750 mg or the 1500 mg dose. Mefloquine AUC was similar in patients with malaria and healthy volunteers. Because plasma levels increased in temporal relationship with clinical illness, mefloquine volume of distribution or clearance (or both) was reduced during the acute phase of illness.

Acute Disease↗

Plasmodium berghei: malaria infection causes increased cardiac output in rats, Rattus rattus.

Thirty-two 4-week-old male Wistar rats were infected with Plasmodium berghei malaria. On Days 12 through 14, blood volume, arterial blood pressure, right ventricular pressure, heart rate, cardiac output, stroke volume, hematocrit, and vascular resistances were determined. All of the cardiovascular parameters measured, with the exception of calculated pulmonary vascular resistance, changed progressively as the peripheral blood parasitemia increased. With a rising parasitemia, cardiac output increased, despite a reduced heart rate. The highest parasitemia of 63% was accompanied by a doubling of the normal cardiac output. The relationship between parasitemia and cardiac output can be described by the equation, cardiac output = (6.14) x % parasitemia + 452 ml/min/kg. The mean arterial blood pressure was lower than controls when parasitemia exceeded 20%, whereas systolic right ventricular pressure was elevated only at the highest parasitemias. When noninfected control rats were compared with those animals having parasitemias greater than 40%, in the infected animals, mean arterial pressure was 28% lower (P less than 0.01) and systolic right ventricular pressure rose by 21% (P less than 0.02). A 50% decline was observed in the total peripheral vascular resistance (P less than 0.01), although the pulmonary resistance was apparently unchanged. With P. berghei infection, there is also a marked anemia, an increase in plasma volume, and a 16% increase in blood volume (% body weight). It is concluded from these results that although the hemodynamic changes previously reported in the literature indicate that infection with malaria may result in focal blockages in microvessels and poor tissue perfusion, the total systemic effect, in the rat, is an increase in cardiac output secondary to a reduced peripheral resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗