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Biomedical subjects

G D Shanks

Publications and source records attributed to G D Shanks.

At least 19 recordsLinked to original sources
PubMed2005

Travel as a risk factor for uncomplicated Plasmodium falciparum malaria in the highlands of western Kenya.

In the 1980s, highland malaria returned to the tea estates of western Kenya after an absence of nearly a generation. In order to determine the importance of travel for the spread of malaria in this region, we prospectively collected blood films and travel, demographic and geographic information on well persons and outpatients on tea estates near the western rim of the Rift Valley. Risk factors for malaria asexual parasitaemia included: tribal/ethnic group, home province and home district malaria endemicity. Travel away from the Kericho tea estates within the previous two months showed an odds ratio (OR) for parasitaemia of 1.59 for well persons and 2.38 for outpatients. Sexual stages of malaria parasites (gametocytes) had an OR of 3.14 (well persons) and 2.22 (outpatients) for those who had travelled. Increased risk of malaria parasitaemia with travel was concentrated in children aged <5 years. An increase in population gametocytaemia is possibly due to increased chloroquine resistance and suppressed infections contracted outside of the tea estates.

Animals↗
PubMed2003

Epidemiology of highland malaria in western Kenya.

OBJECTIVES: To investigate the epidemiology of falciparum malaria in workers from a highland tea plantation in western Kenya with very seasonally limited malaria transmission to determine what factors are associated with increased risk of malaria transmission in the Kenyan highlands. DESIGN: A cross-sectional study with rolling, random subject enrollment from April 1998 through October 1999. SETTING: Highland tea plantation located at 0 degrees 22' south and 35' 17' east in the Rift Valley highlands of western Kenya, an area with seasonally limited malaria transmission. SUBJECTS: The data for the study were obtained from enrollment of outpatients from the healthcare system of a major tea company, which has 18 estates with 22,000 workers and approximately 50,000 persons eligible for health care. Of the 2796 patients evaluated during the study period, 798 cases of malaria were confirmed by positive peripheral blood smear; 1998 smear-negative patients were pressured to be non-infected and served as controls (Ratio: 2.52: 1). INTERVENTIONS: Tea estate workers do not receive malaria chemoprophylaxis, but were given easily available free treatment for any symptomatic infections. MAIN OUTCOME MEASURES: Smear-positive cases were compared with smear-negative patients for multiple demographic and disease variables, including sex, age, travel history, ethnic origin, home district transmission risk index and length of residence. Disease characteristics, including parasite types, counts and clinical symptoms, and treatments administered were described. RESULTS: Malaria was predominantly P. falciparum (>99%); asexual parasite counts ranged from 1-10,440 per mm3, with a mean of 803.6 (95% confidence interval: 695.2, 912.0). Gametocytemia was present in 7.5% of smear-positive malaria cases, but was rare in the absence of blood asexual forms (0.5%). Prior use of a variety of antimalarial drugs was extremely common and negatively predictive of parasitemia in patients presenting for clinical treatment (Pearson Chi-square 50.81, p < 0.001), as was a subjective history of previous malaria infection in the past year (F = 26.65, 14 df, p < 0.001; univariate ANOVA). Amodiaquine was the most commonly used drug to treat cases of either smear-proven or clinically suspected malaria, accounting for 56% of therapy; pyrimethamine/sulfadoxine was used to treat 27%, artemesinin 8% and chloroquine was administered to only 3%, while combination therapy was used in 5% of cases, and only a single treatment (0.1 %) was recorded using quinine. Subjects with a prior history of treatment for malaria were statistically less likely to be infected again (Pearson Chi-square 50.81, p < 0.001). Presenting with symptoms suggestive of malaria was statistically associated with parasitemia, particularly fever, headache and dizziness, (p <0.001 for all, univariate ANOVA), but in general, clinical symptoms were not an effective discriminator of malarial disease. Ethnic group predicted malaria infection with groups traditionally from the Lake Victoria lowland regions having a greater prevalence of parasitemia (F = 2.04, 4. df, p = 0.002, univariate ANOVA). Parasitemia was significantly associated with age less than ten years (Pearson Chi-Square 145.99, p < 0.001), with a history of travel more than twenty kilometers from site within six weeks (Pearson Chi-square 58.28, p < 0.001) and with time since arrival on the plantation of one year or less (Pearson Chi-square 185.12, p <0.001) CONCLUSION: Lower infection rates in persons with a history of prior infection implies a protective effect; the predilection of malaria for young and immunologically naive victims was confirmed. The proclivity in some ethnic groups for travel to holoendemic areas also accounts for the strong associations between recent travel, lowland ethnic group and infection. These findings taken together suggest that importation of malaria to the highlands, as well as travel away from the highlands, are important sources of new infections among persons living and working there.

Adolescent↗
PubMed2001

A new primaquine analogue, tafenoquine (WR 238605), for prophylaxis against Plasmodium falciparum malaria.

We tested tafenoquine (WR 238605), a new long-acting 8-aminoquinoline, for its ability to prevent malaria in an area that is holoendemic for Plasmodium falciparum. In a double-blinded, placebo-controlled, randomized clinical trial in western Kenya, adult volunteers received a treatment course of 250 mg halofantrine per day for 3 days, to effect clearance of preexisting parasites. The volunteers were then assigned to 1 of 4 drug regimens: placebo throughout; 3 days of 400 mg (base) of tafenoquine per day, followed by placebo weekly; 3 days of 200 mg of tafenoquine per day, followed by 200 mg per week; and 3 days of 400 mg of tafenoquine per day, followed by 400 mg per week. Prophylaxis was continued for up to 13 weeks. Of the evaluable subjects (223 of 249 randomized subjects), volunteers who received 400 mg tafenoquine for only 3 days had a protective efficacy of 68% (95% confidence interval [CI], 53%-79%), as compared with placebo recipients; those who received 200 mg per day for 3 days followed by 200 mg per week had a protective efficacy of 86% (95% CI, 73%-93%); and those who received 400 mg for 3 days followed by 400 mg per week had a protective efficacy of 89% (95% CI, 77%-95%). A similar number of volunteers in the 4 treatment groups reported adverse events. Prophylactic regimens of 200 mg or 400 mg of tafenoquine, taken weekly for < or =13 weeks, are highly efficacious in preventing falciparum malaria and are well tolerated.

Adolescent↗
PubMed2001

Malaria chemoprophylaxis in the age of drug resistance. II. Drugs that may be available in the future.

All current regimens of malaria chemoprophylaxis have serious drawbacks as a result of either suboptimal efficacy, difficulty with medication compliance, or adverse events. Two 8-aminoquinolines may be approaching registration, with primaquine having completed its prophylactic field testing and tafenoquine having begun advanced field testing at the end of 2000. Primaquine has long been used for management of relapses of malaria, but in the past decade, it has been reexamined for use in malaria prevention in order to stop infection in the liver. In field trials performed in Indonesia and Colombia, the efficacy of primaquine for malaria prevention was approximately 90%, compared with that of placebo. Because of its short half-life, primaquine requires daily administration. For adults, the prevention regimen is 30 mg base daily (0.5 mg base/kg/day), and it can probably be discontinued soon after departure from an area where malaria is endemic. To kill parasites that already exist in the liver, terminal prophylaxis is given after exposure to relapses of malaria infection; for adults, such prophylaxis usually consists of 15 mg base (0.3 mg base/kg/day) given daily for 2 weeks. Primaquine-induced gastrointestinal disturbances can be minimized if the drug is taken with food. Neither primaquine nor tafenoquine should be given to persons with glucose-6-phosphate dehydrogenase deficiency, to avoid the development of potentially severe drug-induced hemolysis. Tafenoquine is an analogue of primaquine that is more potent than the parent drug. Field trials in Kenya, Ghana, Gabon, and Southeast Asia have demonstrated an efficacy rate of approximately 90% for tafenoquine. Its long half-life allows for infrequent dosing (currently tested at 200 mg base/week), and its effect on parasites at the liver stage may allow for drug discontinuation at the time of departure from the area of endemicity.

Aminoquinolines↗
PubMed2001

Malaria chemoprophylaxis in the age of drug resistance. I. Currently recommended drug regimens.

As international travel becomes increasingly common and resistance to antimalarial drugs escalates, a growing number of travelers are at risk for contracting malaria. Parasite resistance to chloroquine and proguanil and real or perceived intolerance among patients to standard prophylactic agents such as mefloquine have highlighted the need for new antimalarial drugs. Promising new regimens include atovaquone and proguanil, in combination; primaquine; and a related 8-aminoquinoline, tafenoquine. These agents are active against the liver stage of the malaria parasite and therefore can be discontinued shortly after the traveler leaves an area where malaria is endemic, which encourages adherence to the treatment regimen. Part 1 of this series reviews currently recommended chemoprophylactic drug regimens, and part 2 will focus on 8-aminoquinoline drugs.

Animals↗
PubMed2001

Malaria early warning in Kenya.

Kenya displays large spatiotemporal diversity in its climate and ecology. It follows that malaria transmission will reflect this environmental heterogeneity in both space and time. In this article, we discuss how such heterogeneity, and its epidemiological consequences, should be considered in the development of early warning systems for malaria epidemics.

Disease Outbreaks↗
PubMed2000

Etiology of interepidemic periods of mosquito-borne disease.

Dengue viruses and malaria protozoa are of increasing global concern in public health. The diseases caused by these pathogens often show regular seasonal patterns in incidence because of the sensitivity of their mosquito vectors to climate. Between years in endemic areas, however, there can be further significant variation in case numbers for which public health systems are generally unprepared. There is an acute need for reliable predictions of within-year and between-year epidemic events. The prerequisite for developing any system of early warning is a detailed understanding of the factors involved in epidemic genesis. In this report we discuss the potential causes of the interepidemic periods in dengue hemorrhagic fever in Bangkok and of Plasmodium falciparum malaria in a highland area of western Kenya. The alternative causes are distinguished by a retrospective analysis of two unique and contemporaneous 33-year time series of epidemiological and associated meteorological data recorded at these two sites. We conclude that intrinsic population dynamics offer the most parsimonious explanation for the observed interepidemic periods of disease in these locations.

Animals↗
PubMed1998

Efficacy and safety of atovaquone/proguanil as suppressive prophylaxis for Plasmodium falciparum malaria.

Currently recommended prophylactic regimens for Plasmodium falciparum malaria are associated with a high incidence of adverse events and/or suboptimal efficacy. In a double-blind, placebo-controlled, randomized clinical trial in western Kenya, adult volunteers received a treatment course of atovaquone/proguanil hydrochloride (250 mg/100 mg per tablet) to eliminate preexisting infection. Immediately thereafter, subjects were randomized to one of the three prophylactic regimens to receive one atovaquone/proguanil tablet daily (n = 68), two atovaquone/proguanil tablets daily (n = 65), or placebo (n = 65) for 10 weeks. The study endpoint for any subject was the development of parasitemia, evident on blood smear, during prophylaxis. Of the evaluable subjects, all in the low-dose (54 of 54) and high-dose (54 of 54) atovaquone/proguanil groups remained malaria-free during the 10-week prophylaxis period, in contrast to only 48% (26 of 54) in the placebo group (P < .001). Both atovaquone/proguanil prophylactic regimens were as well tolerated as placebo. Thus, atovaquone/proguanil appears to be highly efficacious and safe as prophylaxis for P. falciparum malaria.

Adolescent↗
PubMed1998

Successful double-blinded, randomized, placebo-controlled field trial of azithromycin and doxycycline as prophylaxis for malaria in western Kenya.

Azithromycin prevents malaria in animal models and early clinical trials. We determined the prophylactic efficacy of three antibiotic regimens given for 10 weeks (azithromycin, 250 mg daily; azithromycin, 1,000 mg weekly; and doxycycline, 100 mg daily) relative to that of placebo for 232 adult volunteers residing in an area of intense malaria transmission. Any confirmed parasitemia during the study was considered a prophylactic failure. Two hundred thirteen volunteers (92%) completed the study. The prophylactic efficacies were as follows: daily azithromycin, 82.7% (95% confidence interval [CI], 68.5%-91.1%); weekly azithromycin, 64.2% (95% CI, 47.1%-77.1%); and daily doxycycline, 92.6% (95% CI, 79.9%-97.5%). All regimens were well tolerated. We concluded that both 100 mg of doxycycline and 250 mg of azithromycin, given daily, were effective as prophylaxis for malaria in this setting. If studies with nonimmune volunteers confirm these results for semi-immune volunteers, a daily azithromycin regimen may have special utility for individuals with contraindications to treatment with doxycycline or other antimalarial agents.

Adolescent↗
PubMed1997

Ex vivo antimalarial activity of proguanil combined with dapsone against cycloguanil-resistant Plasmodium falciparum isolates.

The ex vivo antimalarial activity of plasma samples obtained from 20 healthy Caucasian volunteers following daily proguanil (200 mg) plus dapsone (8 mg) for malaria chemoprophylaxis inhibited five cycloguanil-resistant Thai isolates of Plasmodium falciparum. All volunteers were phenotyped as extensive metabolisers (EMs) of proguanil. Three of the five isolates were obtained from Thai soldiers who had failed malaria prophylaxis on daily proguanil (200 mg) plus dapsone (4.0 or 12.5 mg). The Thai soldiers were also classified as EMs, but had relatively lower plasma cycloguanil concentrations compared to values reported in the literature for Caucasians and black Kenyans. Although the high level of parasite resistance to cycloguanil was the most likely explanation for the Thai soldiers failing prophylaxis on proguanil plus dapsone, their low cycloguanil concentrations may have also contributed to their lack of protection. However, in areas where parasites are more susceptible to cycloguanil, such as in certain regions of Africa, proguanil plus dapsone may still be an effective chemoprophylactic drug combination.

Animals↗
PubMed1997

Mefloquine compared with doxycycline for the prophylaxis of malaria in Indonesian soldiers. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Mefloquine and doxycycline are the two drugs recommended for prophylaxis of malaria for visitors to areas where Plasmodium falciparum is resistant to chloroquine. OBJECTIVE: To compare the efficacy and tolerability of mefloquine with those of doxycycline as prophylaxis for malaria. DESIGN: Randomized, double-blind, placebo-controlled field trial of chemoprophylaxis of malaria. SETTING: Northeastern Irian Jaya, Indonesia. PARTICIPANTS: 204 Indonesian soldiers. INTERVENTION: After radical curative treatment, participants were randomly assigned to receive 100 mg of doxycycline per day and mefloquine placebo; 250 mg of mefloquine per week (preceded by a loading dose of 250 mg/d for 3 days) and doxycycline placebo; or placebos for both drugs. Prophylaxis lasted approximately 13 weeks. MEASUREMENTS: The primary end point for efficacy was the first occurrence of malaria, as documented by a positive malaria smear. Malaria smears were obtained weekly and when patients had symptoms suggesting malaria. Reported symptoms were recorded daily, and an exit study questionnaire was conducted. RESULTS: In the placebo group, 53 of 69 soldiers developed malaria (9.1 person-years), resulting in an attack rate of 5.8 cases per person-year (95% CI, 4.3 to 7.7 cases per person-year). Plasmodium falciparum accounted for 57% of cases, and P. vivax accounted for 43% of cases. No malaria occurred in the 68 soldiers (16.9 person-years) in the mefloquine group; thus, the protective efficacy of mefloquine was 100% (CI, 96% to 100%). In the doxycycline group, P. falciparum malaria occurred in 1 of 67 soldiers (16.0 person-years), yielding a protective efficacy of 99% (CI, 94% to 100%). Both drugs were very well tolerated. CONCLUSIONS: Mefloquine and doxycycline were both highly efficacious and well tolerated as prophylaxis of malaria in Indonesian soldiers.

Adult↗
PubMed1997

Potentiation of the antimalarial activity of atovaquone by doxycycline against Plasmodium falciparum in vitro.

The effect of doxycycline, obtained from human volunteers administered doxycycline, on the minimum inhibitory concentration (MIC) of atovaquone was determined against the K1 and FC27 isolates of Plasmodium falciparum in vitro. Doxycycline concentrations ranging from 0.10-1.18 microg/ml added to atovaquone produced MIC ratios [atovaquone + doxycycline/atovaquone alone] ranging from 0.38 to 0.70. These results suggest that the antimalarial activity of atovaquone is potentiated by doxycycline. Additionally, these drugs may be rational partners for the treatment and prophylaxis of falciparum malaria.

Animals↗
PubMed1997

In vitro activities of the biguanide PS-15 and its metabolite, WR99210, against cycloguanil-resistant Plasmodium falciparum isolates from Thailand.

The in vitro activities of the new biguanide PS-15 and its putative active metabolite, WR99210, were determined against seven different isolates or clones of Plasmodium falciparum. The mean 50% inhibitory concentrations of PS-15 and WR99210 were 1,015 and 0.06 ng/ml, respectively. WR99210 was up to 363 times more potent than cycloguanil, the active metabolite of proguanil, against cycloguanil-resistant parasites. The pronounced activity of WR99210 against multidrug-resistant P. falciparum indicates that further studies are required to determine the value of the prodrug, PS-15, as an antimalarial agent.

Animals↗
PubMed1997

WR 238605, chloroquine, and their combinations as blood schizonticides against a chloroquine-resistant strain of Plasmodium vivax in Aotus monkeys.

The compound WR 238605 is a primaquine analog being developed by the U.S. Army as an antimalarial drug. Currently, there is no established treatment for Plasmodium vivax parasitemias that are not cured by chloroquine. This study tested WR 238605, chloroquine, and their combinations against a chloroquine-resistant strain of P. vivax (AMRU 1) in Aotus monkeys. A total dose of 3 mg/kg of WR 238605 given at a dosage of 1 mg/kg/day for three days cleared patent parasites in all eight monkeys but recrudescence of parasitemia occurred 15-25 days after initiation of treatment. A total dose of 9 mg/kg of WR 238605 over a three-day period cured all three monkeys of their infections. A total dose of 30 mg/kg of chloroquine did not clear patent infections in three monkeys, whereas a total dose of 60 mg/kg generally (two of three) cleared patent parasitemia but did not cure. Whereas total doses of 30 mg/kg of chloroquine or 3 mg/kg of WR 238605 given alone failed to cure, both drugs given in combination at these dosages cured two of three infections. These results indicate that WR 238605 may be an alternative treatment for chloroquine-resistant vivax malaria.

Aminoquinolines↗
PubMed1995

Effectiveness of doxycycline combined with primaquine for malaria prophylaxis.

OBJECTIVE: To assess the causal prophylactic activity (activity against the pre-erythrocytic liver stage) of a daily regimen of doxycycline combined with low dose primaquine against malaria in Australian Defence Force personnel deployed to Papua New Guinea (PNG). PARTICIPANTS AND SETTING: A 53-strong Australian Army engineer detachment deployed to the north coast of PNG for 42 days starting in July 1993. INTERVENTIONS: The soldiers took doxycycline (100 mg) and primaquine (7.5 mg) daily, starting at least two days before they entered the endemic area and continuing for three days after their return to Australia. No primaquine eradication course was given at that time. MAIN OUTCOME MEASURES: The number of soldiers who developed malaria, plasma drug concentrations and drug side effects. RESULTS: None of the 53 men developed malaria while in PNG. Three developed falciparum malaria two to three weeks after leaving the endemic area, although one of them had taken doxycycline alone because of glucose-6-phosphate dehydrogenase deficiency. Nine men developed vivax malaria between three and 40 weeks after leaving PNG, and three had relapses. Doxycycline was generally well tolerated, with only three of the men requiring a change of medication to mefloquine because of adverse gastrointestinal symptoms. CONCLUSIONS: Although doxycycline generally provides good protection against malaria infection, it cannot be relied on for causal prophylaxis, even when combined with low dose primaquine. Because the malaria infections occurred only after return to Australia, doxycycline appears to be effective in suppressing malaria while the drug is being taken. Intense, repeated exposure to malaria may require an extended period of chemoprophylaxis on return from an endemic area.

Australia↗
PubMed1995

Doxycycline for malaria prophylaxis in Australian soldiers deployed to United Nations missions in Somalia and Cambodia.

The operational effectiveness of daily doxycycline alone or combined with weekly chloroquine were assessed during deployments of Australian Defence Force personnel to malaria-endemic countries. Doxycycline was given as part of mandated disease prevention measures during United Nations missions to Somalia (900 men for 4 months) and Cambodia (600 men for 12 months over two annual rotations). In Somalia the soldiers were in an area of low endemicity and experienced only three malaria cases (one Plasmodium falciparum, two P. vivax), all occurring after returning to Australia. In Cambodia the level of malaria exposure varied greatly, resulting in eight malaria cases during the entire 2-year mission (two P. falciparum, six P. vivax). Doxycycline was generally well tolerated, with 1.7% (Somalia) and 0.6% (Cambodia) of the men requiring a change of medication to mefloquine due to adverse effects. Doxycycline is an effective chemoprophylactic agent during operational deployments when soldiers truly take it every day.

Animals↗
PubMed1994

A statistical analysis of the antimalarial activity of proguanil and cycloguanil in human volunteers.

Proguanil, an orally administered antimalarial drug, was given to 36 individuals (200 mg daily for 3 days). The antimalarial activity in plasma samples collected after the drug administration was then determined by bioassay. Concentrations of proguanil and cycloguanil (the principal active metabolite) in these samples were also measured by high performance liquid chromatography. A regression analysis was then performed on these variables to determine if the antimalarial activity of the samples was due to proguanil alone or to proguanil and cycloguanil together. The analysis indicated that cycloguanil is the main determinant of antimalarial activity after proguanil administration and that the activity of cycloguanil is not influenced by the presence of proguanil.

Adolescent↗