Malaria causes illness or death in unprotected travelers. Primaquine prevents malaria by attackin... more Malaria causes illness or death in unprotected travelers. Primaquine prevents malaria by attacking liver-stage parasites, a property distinguishing it from most chemoprophylactics and obviating 4-week postexposure dosing. A daily adult regimen of 30 mg primaquine prevented malaria caused by Plasmodium falciparum and P. vivax for 20 weeks in 95 of 97 glucose-6-phosphate dehydrogenase (G6PD)-normal Javanese transmigrants in Papua, Indonesia. In comparison, 37 of 149 subjects taking placebo in a parallel trial became parasitemic. The protective efficacy of primaquine against malaria was 93% (95% confidence interval [CI] 71%-98%); against P. falciparum it was 88% (95% CI 48%-97%), and >92% for P. vivax (95% CI >37%-99%). Primaquine was as well tolerated as placebo. Mild methemoglobinemia (mean of 3.4%) returned to normal within 2 weeks. Blood chemistry and hematological parameters revealed no evidence of toxicity. Good safety, tolerance, and efficacy, along with key advantages in dosing requirements, make primaquine an excellent drug for preventing malaria in nonpregnant, G6PD-normal travelers.
Background. Brucella endocarditis (BE) is a lethal complication of human brucellosis, which is ra... more Background. Brucella endocarditis (BE) is a lethal complication of human brucellosis, which is rarely seen and hardly described.
Annals of Tropical Medicine and Parasitology, 2003
The epidemiology of infection by Plasmodium falciparum and P. vivax was investigated among Javane... more The epidemiology of infection by Plasmodium falciparum and P. vivax was investigated among Javanese migrants to an endemic region of Papua, Indonesia. A cohort of 243 migrants from Java was followed for malaria in a new settlement village in the endemic Armopa area of north-eastern Papua, beginning on the day each migrant arrived in the village. The subjects were monitored during home visits (three/week) and by the twice-monthly production of bloodsmears that were checked for malarial parasites. At the end of 33 months, 159 (65%) of the subjects remained under follow-up. The prevalence of parasitaemia in the village declined from 16% among those already living there when the study began in August 1996, to 5% when the study finished in June 1999. Over this period, 596 infections by P. falciparum and 723 by P. vivax occurred in the cohort, 22 and 27 of the subjects each experiencing at least six infections by P. falciparum and P. vivax, respectively. The incidence of malarial infection was higher during the first and second years post-migration (3.2 and 2.7 infections/person-year) than during the third (1.2 infections/person-year). Although the geometric mean parasite counts for P. falciparum increased over time (1209, 1478, and 1830 parasites/microl in the first, second and third years, respectively), the corresponding values for P. vivax (497, 535 and 490 parasites/microl) showed no such trend. Only one of the nine subjects who developed severe malaria (requiring intravenous quinine therapy) was a child, giving an odds ratio for a case of severe malaria being in an adult of 6.1 (P=0.08).
Drug resistance has made malaria prevention difficult and the new agents are too expensive for wi... more Drug resistance has made malaria prevention difficult and the new agents are too expensive for widespread use. Primaquine, an established drug for treatment, is potentially useful for prevention. Malaria prophylaxis with primaquine was evaluated in Irian Jaya during one year in Javanese men who were not deficient in glucose-6phosphate dehydrogenase (G-6-PD). 126 volunteers were randomised to receive 0·5 mg/kg primaquine base or placebo daily (double-blinded), or 300 mg chloroquine base weekly (open).
New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria. The prophylacti... more New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria. The prophylactic efficacy of azithromycin against P. falciparum in malaria-immune Kenyans was 83%. We conducted a double-blind, placebo-controlled trial to determine the prophylactic efficacy of azithromycin against multidrug-resistant P. falciparum malaria and chloroquine-resistant Plasmodium vivax malaria in Indonesian adults with limited immunity. After radical cure therapy, 300 randomized subjects received azithromycin (148 subjects, 750-mg loading dose followed by 250 mg/d), placebo (77), or doxycycline (75, 100 mg/d). The end point was slide-proven parasitemia. There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks. Using incidence rates, the protective efficacy of azithromycin relative to placebo was 71.6% (95% confidence interval [CI], 50.3 -83.8) against P. falciparum malaria and 98.9% (95% CI, 93.1 -99.9) against P. vivax malaria. Corresponding figures for doxycycline were 96.3% (95% CI, 85.4 -99.6) and 98% (95% CI, 88.0 -99.9), respectively. Daily azithromycin offered excellent protection against P. vivax malaria but modest protection against P. falciparum malaria. Materiel Development Activity and the U.S. Naval Medical Research and Development Command (Department of Defense funding reference; 65807/ were coincidentally reduced [16]. In a malaria prophylaxis trial 849/QG). in Kenyan adults, 250 mg of azithromycin daily had a prophy-Reprints: Publications Office, US NAMRU-2, Box 3, Unit 8132, APO, AP lactic efficacy against P. falciparum malaria based on crude 96520-8132, USA. incidence of 83% (95% CI, 68 -91) [17]. Shropshire, SY1 3HS, United Kingdom ([email protected]). Azithromycin can be used by pregnant and breast-feeding Clinical Infectious Diseases 1999;28:74-81
Between January 1998 and December 2000, the Jayapura Provincial Public Hospital in northeastern I... more Between January 1998 and December 2000, the Jayapura Provincial Public Hospital in northeastern Indonesian New Guinea (Papua) admitted 5,936 patients with a diagnosis of malaria. The microscopic diagnosis at admission was Plasmodium falciparum (3,976, 67%), Plasmodium vivax (1,135, 19%), Plasmodium malariae (8, < 1%), and mixed species infections (817, 14%). Approximately 9% (367) of patients were classified as having severe malaria (277 P. falciparum, 36 P. vivax, 53 mixed infections, and 1 P. malariae) and 88 died (79 P. falciparum/mixed infections and 9 P. vivax). Risk of fatal outcomes among severe malaria patients was indistinguishable between those with falciparum versus vivax malaria (OR = 0.89; P = 0.771). Compared with non-pregnant women, pregnant women showed no higher risk of severe malaria (P = 0.643) or death caused by severe malaria (P = 0.748). This study compares admissions per population (based on census data), parasitemia, morbidity, and mortality among children versus adults, pregnant versus non-pregnant women, and urban/suburban versus rural residents.
Transactions of The Royal Society of Tropical Medicine and Hygiene, 1996
In February 1995 we surveyed resistance to chloroquine among patients with Plasmodium vivax malar... more In February 1995 we surveyed resistance to chloroquine among patients with Plasmodium vivax malaria at Nias Island, in the Indian Ocean near north-western Sumatra, Indonesa. The subjects, 21 indigenous males and females (6-50 years old) infected with >40 asexual blood stage parasites ofP. vivax per ~1 of blood, had mild symptoms or none at all. Seven of these patients had > 100 ng/mL whole blood chloroquine levels before the first supervised dose of chloroquine (3 doses of 10 mg/kg, 10 mg/kg, 5 mg/kg of base given at 24 h intervals). Whole blood chloroquine levels on the last day of dosing confirmed normal absorption (range 413-3248, mean 1141, SD 616 ng/mL). Blood films were examined on days 0,2,4,7,11,14,18,21 and 28 after initiating therapy. Three patients had recurrent asexual l? vivax parasitaemias between days 14 and 18, despite effective levels of chloroquine in whole blood (a100 ng/mL) at the time of recurrence. Resistance to standard chloroquine therapy by P. vivax appeared in 14% of infections among residents of Nias.
Combination therapy is one method of overcoming the global challenge of drug-resistant Plasmodium... more Combination therapy is one method of overcoming the global challenge of drug-resistant Plasmodium falciparum malaria. We conducted a hospital-based 28-day in vivo test comparing chloroquine/doxycycline to chloroquine or doxycycline alone for treating P. falciparum and Plasmodium vivax malaria in Irian Jaya, Indonesia. Eighty-nine patients with uncomplicated falciparum malaria were randomized to standard dose chloroquine (n ϭ 30), doxycycline (100 mg every 12 hours [7 days], n ϭ 20), or chloroquine with doxycycline (n ϭ 39); corresponding numbers for vivax malaria (n ϭ 63) were 23, 16, 24. Endpoints were parasite sensitivity (S) or resistance (RI/RII/ RIII). Of the 105 evaluable patients, chloroquine/doxycycline cured (S) 20/22 (90.9% [95% CI 78.9-100%]) patients with P. falciparum malaria; 2/22 (9.1% [0-21%]) were RIII resistant. Doxycycline cured 11/17 (64.7% [42.0-87.4%]) patients, and chloroquine 4/20 (20% [2.5-37.5%]). Against P. vivax, chloroquine/doxycycline cured (S) 12/17 (70.6% [48.9-92.2%]) patients, doxycycline 4/12 (33.3% [6.6-59.9%]), and chloroquine 5/17 (29.4% [7.7-51.1%]).
Malaria causes illness or death in unprotected travelers. Primaquine prevents malaria by attackin... more Malaria causes illness or death in unprotected travelers. Primaquine prevents malaria by attacking liver-stage parasites, a property distinguishing it from most chemoprophylactics and obviating 4-week postexposure dosing. A daily adult regimen of 30 mg primaquine prevented malaria caused by Plasmodium falciparum and P. vivax for 20 weeks in 95 of 97 glucose-6-phosphate dehydrogenase (G6PD)-normal Javanese transmigrants in Papua, Indonesia. In comparison, 37 of 149 subjects taking placebo in a parallel trial became parasitemic. The protective efficacy of primaquine against malaria was 93% (95% confidence interval [CI] 71%-98%); against P. falciparum it was 88% (95% CI 48%-97%), and >92% for P. vivax (95% CI >37%-99%). Primaquine was as well tolerated as placebo. Mild methemoglobinemia (mean of 3.4%) returned to normal within 2 weeks. Blood chemistry and hematological parameters revealed no evidence of toxicity. Good safety, tolerance, and efficacy, along with key advantages in dosing requirements, make primaquine an excellent drug for preventing malaria in nonpregnant, G6PD-normal travelers.
Background. Brucella endocarditis (BE) is a lethal complication of human brucellosis, which is ra... more Background. Brucella endocarditis (BE) is a lethal complication of human brucellosis, which is rarely seen and hardly described.
Annals of Tropical Medicine and Parasitology, 2003
The epidemiology of infection by Plasmodium falciparum and P. vivax was investigated among Javane... more The epidemiology of infection by Plasmodium falciparum and P. vivax was investigated among Javanese migrants to an endemic region of Papua, Indonesia. A cohort of 243 migrants from Java was followed for malaria in a new settlement village in the endemic Armopa area of north-eastern Papua, beginning on the day each migrant arrived in the village. The subjects were monitored during home visits (three/week) and by the twice-monthly production of bloodsmears that were checked for malarial parasites. At the end of 33 months, 159 (65%) of the subjects remained under follow-up. The prevalence of parasitaemia in the village declined from 16% among those already living there when the study began in August 1996, to 5% when the study finished in June 1999. Over this period, 596 infections by P. falciparum and 723 by P. vivax occurred in the cohort, 22 and 27 of the subjects each experiencing at least six infections by P. falciparum and P. vivax, respectively. The incidence of malarial infection was higher during the first and second years post-migration (3.2 and 2.7 infections/person-year) than during the third (1.2 infections/person-year). Although the geometric mean parasite counts for P. falciparum increased over time (1209, 1478, and 1830 parasites/microl in the first, second and third years, respectively), the corresponding values for P. vivax (497, 535 and 490 parasites/microl) showed no such trend. Only one of the nine subjects who developed severe malaria (requiring intravenous quinine therapy) was a child, giving an odds ratio for a case of severe malaria being in an adult of 6.1 (P=0.08).
Drug resistance has made malaria prevention difficult and the new agents are too expensive for wi... more Drug resistance has made malaria prevention difficult and the new agents are too expensive for widespread use. Primaquine, an established drug for treatment, is potentially useful for prevention. Malaria prophylaxis with primaquine was evaluated in Irian Jaya during one year in Javanese men who were not deficient in glucose-6phosphate dehydrogenase (G-6-PD). 126 volunteers were randomised to receive 0·5 mg/kg primaquine base or placebo daily (double-blinded), or 300 mg chloroquine base weekly (open).
New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria. The prophylacti... more New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria. The prophylactic efficacy of azithromycin against P. falciparum in malaria-immune Kenyans was 83%. We conducted a double-blind, placebo-controlled trial to determine the prophylactic efficacy of azithromycin against multidrug-resistant P. falciparum malaria and chloroquine-resistant Plasmodium vivax malaria in Indonesian adults with limited immunity. After radical cure therapy, 300 randomized subjects received azithromycin (148 subjects, 750-mg loading dose followed by 250 mg/d), placebo (77), or doxycycline (75, 100 mg/d). The end point was slide-proven parasitemia. There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks. Using incidence rates, the protective efficacy of azithromycin relative to placebo was 71.6% (95% confidence interval [CI], 50.3 -83.8) against P. falciparum malaria and 98.9% (95% CI, 93.1 -99.9) against P. vivax malaria. Corresponding figures for doxycycline were 96.3% (95% CI, 85.4 -99.6) and 98% (95% CI, 88.0 -99.9), respectively. Daily azithromycin offered excellent protection against P. vivax malaria but modest protection against P. falciparum malaria. Materiel Development Activity and the U.S. Naval Medical Research and Development Command (Department of Defense funding reference; 65807/ were coincidentally reduced [16]. In a malaria prophylaxis trial 849/QG). in Kenyan adults, 250 mg of azithromycin daily had a prophy-Reprints: Publications Office, US NAMRU-2, Box 3, Unit 8132, APO, AP lactic efficacy against P. falciparum malaria based on crude 96520-8132, USA. incidence of 83% (95% CI, 68 -91) [17]. Shropshire, SY1 3HS, United Kingdom ([email protected]). Azithromycin can be used by pregnant and breast-feeding Clinical Infectious Diseases 1999;28:74-81
Between January 1998 and December 2000, the Jayapura Provincial Public Hospital in northeastern I... more Between January 1998 and December 2000, the Jayapura Provincial Public Hospital in northeastern Indonesian New Guinea (Papua) admitted 5,936 patients with a diagnosis of malaria. The microscopic diagnosis at admission was Plasmodium falciparum (3,976, 67%), Plasmodium vivax (1,135, 19%), Plasmodium malariae (8, < 1%), and mixed species infections (817, 14%). Approximately 9% (367) of patients were classified as having severe malaria (277 P. falciparum, 36 P. vivax, 53 mixed infections, and 1 P. malariae) and 88 died (79 P. falciparum/mixed infections and 9 P. vivax). Risk of fatal outcomes among severe malaria patients was indistinguishable between those with falciparum versus vivax malaria (OR = 0.89; P = 0.771). Compared with non-pregnant women, pregnant women showed no higher risk of severe malaria (P = 0.643) or death caused by severe malaria (P = 0.748). This study compares admissions per population (based on census data), parasitemia, morbidity, and mortality among children versus adults, pregnant versus non-pregnant women, and urban/suburban versus rural residents.
Transactions of The Royal Society of Tropical Medicine and Hygiene, 1996
In February 1995 we surveyed resistance to chloroquine among patients with Plasmodium vivax malar... more In February 1995 we surveyed resistance to chloroquine among patients with Plasmodium vivax malaria at Nias Island, in the Indian Ocean near north-western Sumatra, Indonesa. The subjects, 21 indigenous males and females (6-50 years old) infected with >40 asexual blood stage parasites ofP. vivax per ~1 of blood, had mild symptoms or none at all. Seven of these patients had > 100 ng/mL whole blood chloroquine levels before the first supervised dose of chloroquine (3 doses of 10 mg/kg, 10 mg/kg, 5 mg/kg of base given at 24 h intervals). Whole blood chloroquine levels on the last day of dosing confirmed normal absorption (range 413-3248, mean 1141, SD 616 ng/mL). Blood films were examined on days 0,2,4,7,11,14,18,21 and 28 after initiating therapy. Three patients had recurrent asexual l? vivax parasitaemias between days 14 and 18, despite effective levels of chloroquine in whole blood (a100 ng/mL) at the time of recurrence. Resistance to standard chloroquine therapy by P. vivax appeared in 14% of infections among residents of Nias.
Combination therapy is one method of overcoming the global challenge of drug-resistant Plasmodium... more Combination therapy is one method of overcoming the global challenge of drug-resistant Plasmodium falciparum malaria. We conducted a hospital-based 28-day in vivo test comparing chloroquine/doxycycline to chloroquine or doxycycline alone for treating P. falciparum and Plasmodium vivax malaria in Irian Jaya, Indonesia. Eighty-nine patients with uncomplicated falciparum malaria were randomized to standard dose chloroquine (n ϭ 30), doxycycline (100 mg every 12 hours [7 days], n ϭ 20), or chloroquine with doxycycline (n ϭ 39); corresponding numbers for vivax malaria (n ϭ 63) were 23, 16, 24. Endpoints were parasite sensitivity (S) or resistance (RI/RII/ RIII). Of the 105 evaluable patients, chloroquine/doxycycline cured (S) 20/22 (90.9% [95% CI 78.9-100%]) patients with P. falciparum malaria; 2/22 (9.1% [0-21%]) were RIII resistant. Doxycycline cured 11/17 (64.7% [42.0-87.4%]) patients, and chloroquine 4/20 (20% [2.5-37.5%]). Against P. vivax, chloroquine/doxycycline cured (S) 12/17 (70.6% [48.9-92.2%]) patients, doxycycline 4/12 (33.3% [6.6-59.9%]), and chloroquine 5/17 (29.4% [7.7-51.1%]).
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