The purpose of this study was to compare an experimental regimen of atovaquone plus proguanil wit... more 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/mL). 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.
Background: Co-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is n... more Background: Co-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is not infrequent as both share same route of exposure. The risk of developing chronic hepatitis B virus is 6%, in general population but can reach 10-20% in HBV/HIV co-infected patients. When compared to general population, the response rate to HBV vaccine in HIV-infected patients is diminished, so previous studies have tried to improve this response using variety of schedules, doses and co-administration of immunomodulators. The purpose of this study was to evaluate two doses of recombinant HBV vaccine (10 or 40 µg), IM at 0, 1 and 6 months. Vaccination response was measured 30-50 days after last dose; titers of >9.9 IU/L were considered positive. Results: Seventy-nine patients were included, 48 patients (60.7%) serconverted. Thirty-nine patients (49.3%) received 10 µg vaccine dose, 24 patients (61.5%) seroconverted. Forty patients (50.7%) received 40 µg vaccine dose, 24 (60%) seroconverted. There were no differences between two doses. A statistically significant higher seroconversion rate was found for patients with CD4 cell counts at vaccination ≥ 200 cel/mm3 (33 of 38 patients, 86.8%), compared with those with CD4 < 200 cel/mm3 (15 of 41, 36.6%), [OR 11.44,, p = 0.003], there were no differences between two vaccine doses. Using the logistic regression model, CD 4 count <200 cel/ mm 3 were significantly associated with non serologic response (p = 0.003). None other variables such as gender, age, risk exposure for HIV, viral load, type or duration of HAART or AIDS-defining illness, were asociated with seroconversion. In this study, an increase dose of HBV vaccine did not show to increase the rate of response in HIV infected subjects. The only significant findings associated to the response rate was that a CD4 count ≥ 200 cel/mm 3 , we suggest this threshold at which HIV patients should be vaccinated.
The American Journal of Tropical Medicine and Hygiene, 2001
This study evaluated the cure rate of the standard recommended regimen for Plasmodium vivax malar... more 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 ϭ 1.5 g over a three-day period plus primaquine: total dose ϭ 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 personmonths) between 33 and 137 days after treatment initiation. Risk factors for relapses (P Յ 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.
Hawai'i journal of medicine & public health : a journal of Asia Pacific Medicine & Public Health, 2013
Falls are the leading cause of injury among older adults in the United States, with the instituti... more Falls are the leading cause of injury among older adults in the United States, with the institutionalized elderly at elevated risk for injury and death. Physical weakness and mental frailty, prevalent in institutionalized elderly, are major risk factors for falls. The purpose of this study was to evaluate a program that addresses both the physical and mental aspects of exercise to reduce falls in institutionalized elderly. Twenty-seven volunteer subjects residing in an assisted living facility participated in the 24 week randomized crossover study. After demographic, fall history, and mental status examinations, subjects were randomly assigned first to ten weeks of either an exercise class or a control group, followed by a four week "washout period" of no activity, then cross assigned to ten weeks as either a control group or exercise class, respectively. Falls as well as mental status changes were monitored during the study. After adjusting for differences in baseline ris...
BACKGROUND Falls in the elderly represent a public health crisis. Effective prevention programs n... more BACKGROUND Falls in the elderly represent a public health crisis. Effective prevention programs need to conduct economic analyses. The Move With Balance program showed a 65% reduction in falls in institutionalized elderly. METHODS We evaluated the return on investment (ROI) of Move With Balance. We calculated the ROI for 2 situations: first, using data from the current study (N = 27); second, extrapolating the data to an "intended" annual program (N = 45) where training costs can be spread over 6 years. RESULTS The program costs for the current study was $11,143. Based on an efficacy rate of 65%, we estimated that 13 falls were averted among the 21 participants in the treatment group. At a cost of $1440/fall, total averted cost of falls was $18,720. The ROI was 1.7:1 for a 10-week period. Program effects persisted for at least 6 months. Extrapolating the current program costs and fall rates to include classes for 45 people twice a year, the annual program costs would be $27,217. Total annual averted cost of falls would be $208,594. The annual ROI in this group would be 7.6:1. CONCLUSIONS Move With Balance not only is efficacious in reducing falls in institutionalized elderly but also has a positive ROI.
The American Journal of Tropical Medicine and Hygiene
In the Brazilian Amazon, travel costs to centralized malaria clinics for diagnosis and treatment ... more 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.
The American Journal of Tropical Medicine and Hygiene
This study characterizes a Plasmodium berghei white rat model of P. falciparum malaria in the pre... more This study characterizes a Plasmodium berghei white rat model of P. falciparum malaria in the pregnant human. Seventy-day-old and 114-day-old female rats, given an infecting inoculum at time of mating, had higher parasitemias and a more severe anemia than age- and sex-matched controls. Under these experimental conditions, the parasitemia went to crisis in all animals and there were no fatal infections. In contrast, all animals died when the infection was initiated 7 days after conception, a timing that brought a coincidence of peak parasitemia and term. Pregnancy during the post-crisis subpatent period did not cause recrudescence. At the time of delivery, the parasitemia was consistently higher in the placental (crush smear) blood than in the peripheral (tail) blood. This difference was greatest in animals giving birth shortly before or 1-2 days after the parasitemic crisis. Very young, compact parasite forms predominated in the placental blood, whereas trophozoites predominated in the peripheral blood.
The American Journal of Tropical Medicine and Hygiene
A series of isolates of Plasmodium falciparum from eastern Thailand was collected prior to and af... more A series of isolates of Plasmodium falciparum from eastern Thailand was collected prior to and after treatment failure with mefloquine. Patterns of drug sensitivity to standard and new antimalarials were characterized by using an in vitro assay based on the inhibition of schizont maturation. In vitro levels of mefloquine sensitivity of isolates were correlated with clinical treatment failures. In vitro parasite resistance to mefloquine is defined as an inhibitory dose-50 value greater than 20 nM. For isolates collected prior to treatment, there was no significant difference in mefloquine sensitivity patterns between subsequent successes and failures, suggesting that mefloquine treatment failures could not be predicted based on in vitro sensitivity of pretreatment isolates. A series of paired isolates were collected both prior to treatment with mefloquine and after recrudescence. Recrudescent isolates showed significant decreases in sensitivity to mefloquine, WR 194965, enpiroline, and halofantrine; no significant changes in sensitivity to amodiaquine, qinghaosu, and pyrimethamine; and an increase in sensitivity to chloroquine.
The American Journal of Tropical Medicine and Hygiene
A clinic-hospital-based leptospirosis surveillance program was conducted to determine the morbidi... more A clinic-hospital-based leptospirosis surveillance program was conducted to determine the morbidity and risk factors in nonepidemic settings. The study was conducted on two islands, Kauai and Hawaii (Big Island), in the state of Hawaii for one year during 1988 and 1989. An active, more comprehensive case detection system was used on the Big Island that enabled us to determine the incidence of clinical disease. Subjects from both islands were used to conduct a case-control study for risk factors. One hundred seventy-two subjects from the Big Island (who presented with any two of the following symptoms: fever, headache, myalgia, or nausea/vomiting) were enrolled in the study. Twenty cases were diagnosed by culture, serology, or fluorescent antibody tissue staining at autopsy. Six cases required hospitalization and two succumbed to fatal infections. We estimated that these cases represented an annual incidence rate of 128 per 100,000 person-years in our target population. For 33 cases, 77 controls were matched for island, age, sex, and time of onset of illness. Interviews were conducted retrospectively in a double-blinded fashion with cases and controls and evaluated approximately 30 risk factors. Factors that were associated most strongly with development of leptospirosis were household use of rainwater catchment systems (P = 0.003), presence of skin cuts during the incubation period (P = 0.008), contact with cattle or the urine of cattle (P = 0.05 and P = 0.03, respectively), and handling of animal tissues (P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
The American Journal of Tropical Medicine and Hygiene
We studied the effects of daily proguanil compared to weekly chloroquine as malaria prophylaxis i... more 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.
In vitro drug susceptibility profiles were assessed in 75 Plasmodium falciparum isolates from 4 s... more 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% (IC 50) and 90% (IC 90) 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 IC 50 and IC 90 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 clinicalparasitological 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.
The community of Hana, Hawai&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more The community of Hana, Hawai&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;i began a program of home modifications to help their elderly prevent falls. We estimated the cost benefit of these modifications from construction costs and published reports of effectiveness and cost of treating falls. We interviewed clients to determine risk of falling. The average cost of home modifications was $800. The average annual averted medical cost of falling was $1728.
Background: Sugar cane harvesting by burning on Maui island is an environmental health issue due ... more Background: Sugar cane harvesting by burning on Maui island is an environmental health issue due to respiratory effects of smoke. Volcanic smog ("vog") from an active volcano on a neighboring island periodically blankets Maui and could confound a study of cane smoke's effects since cane burning is not allowed on vog days. This study examines the association between cane burning and emergency department (ED) visits, hospital admissions, and prescription fills for acute respiratory illnesses. Methods: This retrospective study controlled for confounders that could increase respiratory distress on non-burn days by matching each burn day with a non-burn day and then comparing the ratio of patients with respiratory distress residing in the path of sugar burn smoke to those residing elsewhere on Maui on burn versus non-burn days. Patients with acute respiratory distress were defined as those with one or more acute respiratory diagnoses at one of the hospitals or emergency departments on Maui. Separately, patients with acute respiratory illness were identified through prescription records from four community pharmacies, specifically defined as those who filled prescriptions for acute respiratory distress. Results: There were 1,256 reports of respiratory distress prescriptions and 686 hospital/ED diagnoses of acute respiratory illness. The ratio of cases within to outside of smoke exposure was higher on burn days for both the ED/hospital data and the pharmacy, though not statistically significant. In post-hoc analyses of the pharmacy data based on the number of acres burned as a proxy for volume of smoke, there was a dose response trend for acreage burned such that the highest quartile showed a statistically significant higher proportion of acute respiratory distress in the exposed versus non-exposed regions (P = 0.015, OR 2.4, 95 % CI [1.2-4.8]). Conclusions: After adjusting for confounders on non-burn days, there was a significantly higher incidence of respiratory distress in smoke-exposed regions when greater amounts of acres were burned. Health officials should consider actions to reduce the negative health outcomes associated with sugar cane burning practices.
The elderly consume a disproportionate amount of health care resources, and the recent trend in o... more The elderly consume a disproportionate amount of health care resources, and the recent trend in obesity will only escalate costs. EnhanceFitness® (EF) is an exercise program designed to increase the strength, flexibility, and balance of older adults. A comprehensive controlled study in Washington state of an elderly population has shown that participants who attend at least one EF class per week reduce healthcare costs by 20% per year. The present study reports the costs and potential benefits of replicating EF on Kaua'i. For Kaua'i the annual cost of an EF pilot program for 132 clients would be $204,735. Attendance records of the Kaua'i program showed that 96 (73%) of those enrolled attended at least weekly. Based on national reports of healthcare costs for the elderly, averting 20% of the costs for these 96 elderly would save $344,256 per year. The expected investment to return ratio, I-R ratio, for EF on Kaua'i is about 1-1.8. On economic grounds, a case can be ma...
The community of Hana, Hawai 'i began a program of home modifications to help their elderly p... more The community of Hana, Hawai 'i began a program of home modifications to help their elderly prevent falls. We estimated the cost benefit of these modifications from construction costs and published reports of effectiveness and cost of treating falls. We ...
Mefloquine pharmacokinetics were compared in a randomized clinical trial in Thailand among patien... more 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 < 0.0005 and p < 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 < 0.01) and significantly higher mefloquine plasma levels in the first 2 days after administration of eithe...
Transfusion-transmitted malaria is a severe disease with high fatality rate. Most Brazilian blood... more Transfusion-transmitted malaria is a severe disease with high fatality rate. Most Brazilian blood banks in the Amazon region perform malaria screening using microscopic examination (thick smears). Since low parasite concentrations are expected in asymptomatic blood donors a high sensitivity test should be used for donor screening. This study determined the sensitivity of a nested-PCR for plasmodium detection in pooled samples. We performed a one-stage criterion validation study with 21 positive samples pooled with samples from ten negative volunteer until three different concentrations were reached (0.33; 0.25; 0.20 parasites/μL - p/μL). Nested PCR was performed as described by Snounou et al. (1993). Sensitivities (and confidence intervals) were determined by stratum of final parasite concentration on the pooled samples. All samples with parasitemia values of 0.33 and 0.25 p/μL had 100% sensitivity (95%CI=86.3-100). One negative result was obtained from a sample with 0.20 p/μL sensitivity=95.2% (95%CI=76.2-99.9). Compared to parasitemia detectable under ideal conditions of thick smear, this nested-PCR in pooled sample was able to detect 40 times more parasites per microliter. Nested-PCR in pooled samples should be considered as a high sensitive alternative to thick smear for donor screening in blood banks at endemic regions. Local authorities need to assess cost:benefit advantages of this method compared to alternatives.
Transactions of the Royal Society of Tropical Medicine and Hygiene, 2000
Of 184 volunteers tested by 3 different EIAs for anti-HIV antibodies in Peixoto de Azevedo, Mato ... more Of 184 volunteers tested by 3 different EIAs for anti-HIV antibodies in Peixoto de Azevedo, Mato Grosso, Brazil, 21 were reactive for at least one of the EIA tests, and none exhibited clinical AIDS. Of the 21, only 1 was positive by anti-HIV-1 Western blotting, 6 were negative and 14 ...
The purpose of this study was to compare an experimental regimen of atovaquone plus proguanil wit... more 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/mL). 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.
Background: Co-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is n... more Background: Co-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is not infrequent as both share same route of exposure. The risk of developing chronic hepatitis B virus is 6%, in general population but can reach 10-20% in HBV/HIV co-infected patients. When compared to general population, the response rate to HBV vaccine in HIV-infected patients is diminished, so previous studies have tried to improve this response using variety of schedules, doses and co-administration of immunomodulators. The purpose of this study was to evaluate two doses of recombinant HBV vaccine (10 or 40 µg), IM at 0, 1 and 6 months. Vaccination response was measured 30-50 days after last dose; titers of >9.9 IU/L were considered positive. Results: Seventy-nine patients were included, 48 patients (60.7%) serconverted. Thirty-nine patients (49.3%) received 10 µg vaccine dose, 24 patients (61.5%) seroconverted. Forty patients (50.7%) received 40 µg vaccine dose, 24 (60%) seroconverted. There were no differences between two doses. A statistically significant higher seroconversion rate was found for patients with CD4 cell counts at vaccination ≥ 200 cel/mm3 (33 of 38 patients, 86.8%), compared with those with CD4 < 200 cel/mm3 (15 of 41, 36.6%), [OR 11.44,, p = 0.003], there were no differences between two vaccine doses. Using the logistic regression model, CD 4 count <200 cel/ mm 3 were significantly associated with non serologic response (p = 0.003). None other variables such as gender, age, risk exposure for HIV, viral load, type or duration of HAART or AIDS-defining illness, were asociated with seroconversion. In this study, an increase dose of HBV vaccine did not show to increase the rate of response in HIV infected subjects. The only significant findings associated to the response rate was that a CD4 count ≥ 200 cel/mm 3 , we suggest this threshold at which HIV patients should be vaccinated.
The American Journal of Tropical Medicine and Hygiene, 2001
This study evaluated the cure rate of the standard recommended regimen for Plasmodium vivax malar... more 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 ϭ 1.5 g over a three-day period plus primaquine: total dose ϭ 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 personmonths) between 33 and 137 days after treatment initiation. Risk factors for relapses (P Յ 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.
Hawai'i journal of medicine & public health : a journal of Asia Pacific Medicine & Public Health, 2013
Falls are the leading cause of injury among older adults in the United States, with the instituti... more Falls are the leading cause of injury among older adults in the United States, with the institutionalized elderly at elevated risk for injury and death. Physical weakness and mental frailty, prevalent in institutionalized elderly, are major risk factors for falls. The purpose of this study was to evaluate a program that addresses both the physical and mental aspects of exercise to reduce falls in institutionalized elderly. Twenty-seven volunteer subjects residing in an assisted living facility participated in the 24 week randomized crossover study. After demographic, fall history, and mental status examinations, subjects were randomly assigned first to ten weeks of either an exercise class or a control group, followed by a four week "washout period" of no activity, then cross assigned to ten weeks as either a control group or exercise class, respectively. Falls as well as mental status changes were monitored during the study. After adjusting for differences in baseline ris...
BACKGROUND Falls in the elderly represent a public health crisis. Effective prevention programs n... more BACKGROUND Falls in the elderly represent a public health crisis. Effective prevention programs need to conduct economic analyses. The Move With Balance program showed a 65% reduction in falls in institutionalized elderly. METHODS We evaluated the return on investment (ROI) of Move With Balance. We calculated the ROI for 2 situations: first, using data from the current study (N = 27); second, extrapolating the data to an "intended" annual program (N = 45) where training costs can be spread over 6 years. RESULTS The program costs for the current study was $11,143. Based on an efficacy rate of 65%, we estimated that 13 falls were averted among the 21 participants in the treatment group. At a cost of $1440/fall, total averted cost of falls was $18,720. The ROI was 1.7:1 for a 10-week period. Program effects persisted for at least 6 months. Extrapolating the current program costs and fall rates to include classes for 45 people twice a year, the annual program costs would be $27,217. Total annual averted cost of falls would be $208,594. The annual ROI in this group would be 7.6:1. CONCLUSIONS Move With Balance not only is efficacious in reducing falls in institutionalized elderly but also has a positive ROI.
The American Journal of Tropical Medicine and Hygiene
In the Brazilian Amazon, travel costs to centralized malaria clinics for diagnosis and treatment ... more 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.
The American Journal of Tropical Medicine and Hygiene
This study characterizes a Plasmodium berghei white rat model of P. falciparum malaria in the pre... more This study characterizes a Plasmodium berghei white rat model of P. falciparum malaria in the pregnant human. Seventy-day-old and 114-day-old female rats, given an infecting inoculum at time of mating, had higher parasitemias and a more severe anemia than age- and sex-matched controls. Under these experimental conditions, the parasitemia went to crisis in all animals and there were no fatal infections. In contrast, all animals died when the infection was initiated 7 days after conception, a timing that brought a coincidence of peak parasitemia and term. Pregnancy during the post-crisis subpatent period did not cause recrudescence. At the time of delivery, the parasitemia was consistently higher in the placental (crush smear) blood than in the peripheral (tail) blood. This difference was greatest in animals giving birth shortly before or 1-2 days after the parasitemic crisis. Very young, compact parasite forms predominated in the placental blood, whereas trophozoites predominated in the peripheral blood.
The American Journal of Tropical Medicine and Hygiene
A series of isolates of Plasmodium falciparum from eastern Thailand was collected prior to and af... more A series of isolates of Plasmodium falciparum from eastern Thailand was collected prior to and after treatment failure with mefloquine. Patterns of drug sensitivity to standard and new antimalarials were characterized by using an in vitro assay based on the inhibition of schizont maturation. In vitro levels of mefloquine sensitivity of isolates were correlated with clinical treatment failures. In vitro parasite resistance to mefloquine is defined as an inhibitory dose-50 value greater than 20 nM. For isolates collected prior to treatment, there was no significant difference in mefloquine sensitivity patterns between subsequent successes and failures, suggesting that mefloquine treatment failures could not be predicted based on in vitro sensitivity of pretreatment isolates. A series of paired isolates were collected both prior to treatment with mefloquine and after recrudescence. Recrudescent isolates showed significant decreases in sensitivity to mefloquine, WR 194965, enpiroline, and halofantrine; no significant changes in sensitivity to amodiaquine, qinghaosu, and pyrimethamine; and an increase in sensitivity to chloroquine.
The American Journal of Tropical Medicine and Hygiene
A clinic-hospital-based leptospirosis surveillance program was conducted to determine the morbidi... more A clinic-hospital-based leptospirosis surveillance program was conducted to determine the morbidity and risk factors in nonepidemic settings. The study was conducted on two islands, Kauai and Hawaii (Big Island), in the state of Hawaii for one year during 1988 and 1989. An active, more comprehensive case detection system was used on the Big Island that enabled us to determine the incidence of clinical disease. Subjects from both islands were used to conduct a case-control study for risk factors. One hundred seventy-two subjects from the Big Island (who presented with any two of the following symptoms: fever, headache, myalgia, or nausea/vomiting) were enrolled in the study. Twenty cases were diagnosed by culture, serology, or fluorescent antibody tissue staining at autopsy. Six cases required hospitalization and two succumbed to fatal infections. We estimated that these cases represented an annual incidence rate of 128 per 100,000 person-years in our target population. For 33 cases, 77 controls were matched for island, age, sex, and time of onset of illness. Interviews were conducted retrospectively in a double-blinded fashion with cases and controls and evaluated approximately 30 risk factors. Factors that were associated most strongly with development of leptospirosis were household use of rainwater catchment systems (P = 0.003), presence of skin cuts during the incubation period (P = 0.008), contact with cattle or the urine of cattle (P = 0.05 and P = 0.03, respectively), and handling of animal tissues (P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
The American Journal of Tropical Medicine and Hygiene
We studied the effects of daily proguanil compared to weekly chloroquine as malaria prophylaxis i... more 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.
In vitro drug susceptibility profiles were assessed in 75 Plasmodium falciparum isolates from 4 s... more 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% (IC 50) and 90% (IC 90) 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 IC 50 and IC 90 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 clinicalparasitological 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.
The community of Hana, Hawai&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more The community of Hana, Hawai&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;i began a program of home modifications to help their elderly prevent falls. We estimated the cost benefit of these modifications from construction costs and published reports of effectiveness and cost of treating falls. We interviewed clients to determine risk of falling. The average cost of home modifications was $800. The average annual averted medical cost of falling was $1728.
Background: Sugar cane harvesting by burning on Maui island is an environmental health issue due ... more Background: Sugar cane harvesting by burning on Maui island is an environmental health issue due to respiratory effects of smoke. Volcanic smog ("vog") from an active volcano on a neighboring island periodically blankets Maui and could confound a study of cane smoke's effects since cane burning is not allowed on vog days. This study examines the association between cane burning and emergency department (ED) visits, hospital admissions, and prescription fills for acute respiratory illnesses. Methods: This retrospective study controlled for confounders that could increase respiratory distress on non-burn days by matching each burn day with a non-burn day and then comparing the ratio of patients with respiratory distress residing in the path of sugar burn smoke to those residing elsewhere on Maui on burn versus non-burn days. Patients with acute respiratory distress were defined as those with one or more acute respiratory diagnoses at one of the hospitals or emergency departments on Maui. Separately, patients with acute respiratory illness were identified through prescription records from four community pharmacies, specifically defined as those who filled prescriptions for acute respiratory distress. Results: There were 1,256 reports of respiratory distress prescriptions and 686 hospital/ED diagnoses of acute respiratory illness. The ratio of cases within to outside of smoke exposure was higher on burn days for both the ED/hospital data and the pharmacy, though not statistically significant. In post-hoc analyses of the pharmacy data based on the number of acres burned as a proxy for volume of smoke, there was a dose response trend for acreage burned such that the highest quartile showed a statistically significant higher proportion of acute respiratory distress in the exposed versus non-exposed regions (P = 0.015, OR 2.4, 95 % CI [1.2-4.8]). Conclusions: After adjusting for confounders on non-burn days, there was a significantly higher incidence of respiratory distress in smoke-exposed regions when greater amounts of acres were burned. Health officials should consider actions to reduce the negative health outcomes associated with sugar cane burning practices.
The elderly consume a disproportionate amount of health care resources, and the recent trend in o... more The elderly consume a disproportionate amount of health care resources, and the recent trend in obesity will only escalate costs. EnhanceFitness® (EF) is an exercise program designed to increase the strength, flexibility, and balance of older adults. A comprehensive controlled study in Washington state of an elderly population has shown that participants who attend at least one EF class per week reduce healthcare costs by 20% per year. The present study reports the costs and potential benefits of replicating EF on Kaua'i. For Kaua'i the annual cost of an EF pilot program for 132 clients would be $204,735. Attendance records of the Kaua'i program showed that 96 (73%) of those enrolled attended at least weekly. Based on national reports of healthcare costs for the elderly, averting 20% of the costs for these 96 elderly would save $344,256 per year. The expected investment to return ratio, I-R ratio, for EF on Kaua'i is about 1-1.8. On economic grounds, a case can be ma...
The community of Hana, Hawai 'i began a program of home modifications to help their elderly p... more The community of Hana, Hawai 'i began a program of home modifications to help their elderly prevent falls. We estimated the cost benefit of these modifications from construction costs and published reports of effectiveness and cost of treating falls. We ...
Mefloquine pharmacokinetics were compared in a randomized clinical trial in Thailand among patien... more 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 < 0.0005 and p < 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 < 0.01) and significantly higher mefloquine plasma levels in the first 2 days after administration of eithe...
Transfusion-transmitted malaria is a severe disease with high fatality rate. Most Brazilian blood... more Transfusion-transmitted malaria is a severe disease with high fatality rate. Most Brazilian blood banks in the Amazon region perform malaria screening using microscopic examination (thick smears). Since low parasite concentrations are expected in asymptomatic blood donors a high sensitivity test should be used for donor screening. This study determined the sensitivity of a nested-PCR for plasmodium detection in pooled samples. We performed a one-stage criterion validation study with 21 positive samples pooled with samples from ten negative volunteer until three different concentrations were reached (0.33; 0.25; 0.20 parasites/μL - p/μL). Nested PCR was performed as described by Snounou et al. (1993). Sensitivities (and confidence intervals) were determined by stratum of final parasite concentration on the pooled samples. All samples with parasitemia values of 0.33 and 0.25 p/μL had 100% sensitivity (95%CI=86.3-100). One negative result was obtained from a sample with 0.20 p/μL sensitivity=95.2% (95%CI=76.2-99.9). Compared to parasitemia detectable under ideal conditions of thick smear, this nested-PCR in pooled sample was able to detect 40 times more parasites per microliter. Nested-PCR in pooled samples should be considered as a high sensitive alternative to thick smear for donor screening in blood banks at endemic regions. Local authorities need to assess cost:benefit advantages of this method compared to alternatives.
Transactions of the Royal Society of Tropical Medicine and Hygiene, 2000
Of 184 volunteers tested by 3 different EIAs for anti-HIV antibodies in Peixoto de Azevedo, Mato ... more Of 184 volunteers tested by 3 different EIAs for anti-HIV antibodies in Peixoto de Azevedo, Mato Grosso, Brazil, 21 were reactive for at least one of the EIA tests, and none exhibited clinical AIDS. Of the 21, only 1 was positive by anti-HIV-1 Western blotting, 6 were negative and 14 ...
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