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Biomedical subjects

J Kevin Baird

Publications and source records attributed to J Kevin Baird.

32 records · Page 2Linked to original sources

Very high risk of therapeutic failure with chloroquine for uncomplicated Plasmodium falciparum and P. vivax malaria in Indonesian Papua.

Chloroquine remains the first-line therapy for uncomplicated malaria in Indonesia. Among a series of trials of chloroquine for malaria on this archipelago conducted since 1990, we now report the highest risk of therapeutic failure yet observed. A clinical trial of standard chloroquine therapy for uncomplicated malaria at Arso PIR V in northeastern Indonesian Papua was conducted during 1995. We enrolled 104 non-immune subjects infected with Plasmodium falciparum (n = 55), P. vivax (n = 29), or P. falciparum plus P. vivax (n = 20) and administered supervised standard chloroquine therapy (10 + 10 + 5 mg/kg at 24-hour intervals). The 28-day cumulative incidence of therapeutic failure was 95% for P. falciparum, 84% for P. vivax, and 100% for mixed infections. Only one subject each for P. falciparum and P. vivax remained free of parasites at day 28. All recurrent parasitemias occurred with whole blood levels of chloroquine plus desethylchloroquine exceeding 100 ng/ml. These findings document almost complete failure of chloroquine against P. falciparum or P. vivax near the northeastern coast of Indonesian Papua.

Adolescent↗

Age-dependent impairment of IgG responses to glycosylphosphatidylinositol with equal exposure to Plasmodium falciparum among Javanese migrants to Papua, Indonesia.

Immune responses directed at glycosylphosphatidylinositol (GPI) anchors of Plasmodium falciparum may offer protection against symptomatic malaria. To independently explore the effect of age on generation of the anti-GPI IgG response, we measured serum anti-GPI IgGs in a longitudinal cohort of migrant Javanese children (6-12 years old) and adults (> or = 20 years old) with equivalent numbers of exposures to P. falciparum in Papua, Indonesia. While the peak response in adults was achieved after a single infection, comparable responses in children required > or = 3-4 infections. Significantly fewer children (16%) than adults (41%) showed a high (optical density > 0.44) anti-GPI IgG response (odds ratio [OR] = 3.8, 95% confidence interval [CI] = 2.3-6.3, P < 0.0001), and adults were more likely to show a persistently high response (OR = 5.5, 95% CI = 1.0-56.8, P = 0.03). However, the minority of children showing a strong response were significantly less likely to experience symptoms with subsequent parasitemia compared with those with a weak response (OR = 4.0, 95% CI = 1.1-13.8, P = 0.02). This effect was not seen among high- and low-responding adults (OR = 1.2, 95% CI = 0.5-2.8, P = 0.60). Host age, independent of cumulative exposure, apparently represents a key determinant of the quantitative and qualitative nature of the IgG response to P. falciparum GPI.

Adult↗

Identification of a polymorphic Plasmodium vivax microsatellite marker.

Microsatellite markers derived from simple sequence repeats have been useful in studying a number of human pathogens, including the human malaria parasite Plasmodium falciparum. Genetic markers for P. vivax would likewise help elucidate the genetics and population characteristics of this other important human malaria parasite. We have identified a locus in a P. vivax telomeric clone that contains simple sequence repeats. Primers were designed to amplify this region using a two-step semi-nested polymerase chain reaction protocol. The primers did not amplify template obtained from non-infected individuals, nor DNA from primates infected with the other human malaria parasites (P. ovale, P. malariae, or P. falciparum). The marker was polymorphic in P. vivax-infected field isolates obtained from Papua New Guinea, Indonesia and Guyana. This microsatellite marker may be useful in genetic and epidemiologic studies of P. vivax malaria.

Adult↗

Short report: in vivo sensitivity of Plasmodium falciparum to halofantrine in southern central Vietnam.

Drug-resistant Plasmodium falciparum is present in Vietnam. We assessed the in vivo sensitivity of P. falciparum to halofantrine in two villages in the southern part of central Vietnam. Halofantrine (8 mg/kg x 3 doses) was administered to 37 patients with either P. falciparum (n = 32) or mixed P. falciparum/P. vivax malaria (n = 5). End points were parasite sensitivity or resistance (RI/RII/RIII) determined by parasite clearance, persistence, or recurrence during 28 days of follow-up. By day 28, 31 (93.9%) of 33 (95% confidence interval = 79.8-99.2%) patients were sensitive. Two patients had recurrent P. falciparum parasitemia on days 14 and 21. Halofantrine effectively treated uncomplicated P. falciparum malaria in these Vietnamese patients.

Adolescent↗

Atovaquone/proguanil therapy for Plasmodium falciparum and Plasmodium vivax malaria in Indonesians who lack clinical immunity.

Thirty-eight of 295 subjects participating in a randomized, double-blind, placebo-controlled trial of the efficacy of daily administration of atovaquone/proguanil for malaria prevention developed malaria at some time during the 20-week prophylaxis period. These subjects (3 atovaquone/proguanil recipients and 35 placebo recipients) were treated with 4 tablets of atovaquone/proguanil per day for 3 days. Atovaquone/proguanil provided safe, well-tolerated, and effective therapy for uncomplicated malaria in nonimmune Indonesians.

Adolescent↗

Randomized, placebo-controlled trial of atovaquone/proguanil for the prevention of Plasmodium falciparum or Plasmodium vivax malaria among migrants to Papua, Indonesia.

The increasing prevalence of resistance to antimalarial drugs reduces options for malaria prophylaxis. Atovaquone/proguanil (Malarone; GlaxoSmithKline) has been >95% effective in preventing Plasmodium falciparum malaria in lifelong residents of areas of holoendemicity, but data from persons without clinical immunity or who are at risk for Plasmodium vivax malaria have not been described. We conducted a randomized, double-blinded study involving 297 people from areas of nonendemicity in Indonesia who migrated to Papua (where malaria is endemic) < or =26 months before the study period. Subjects received prophylaxis with 1 Malarone tablet (250 mg of atovaquone and 100 mg of proguanil hydrochloride; n=148) or placebo (n=149) per day for 20 weeks. Hematologic and clinical chemistry values did not change significantly. The protective efficacy of atovaquone/proguanil was 84% (95% confidence interval [CI], 44%-95%) for P. vivax malaria, 96% (95% CI, 72%-99%) for P. falciparum malaria, and 93% (95% CI, 77%-98%) overall. Atovaquone/proguanil was well tolerated, safe, and effective for the prevention of drug-resistant P. vivax and P. falciparum malaria in individuals without prior malaria exposure who migrated to Papua, Indonesia.

Adolescent↗

Chloroquine-resistant Plasmodium malariae in south Sumatra, Indonesia.

Oral chloroquine is the treatment of choice for uncomplicated Plasmodium malariae infections worldwide. We did a prospective 28-day in-vivo assessment of the efficacy of chloroquine for treatment of P malariae on Legundi Island in Lampung Bay, Sumatra, Indonesia. Of 28 patients, one had recurrent parasitaemia on day 28, and two had persistent parasitaemia to day 8. Whole-blood chloroquine and desethylchloroquine concentrations were at ordinarily effective levels (> or = 100 microg/L) on day 8 in both cases of persistent parasitaemia. These findings suggest that clinical resistance to chloroquine by P malariae occurs in the Indonesian archipelago of southeast Asia.

Adolescent↗

Short report: hepatitis b infection and severe Plasmodium falciparum malaria in Vietnamese adults.

We investigated the prevalence of infection with hepatitis B virus among adult Vietnamese patients hospitalized for severe Plasmodiumfalciparum malaria. Sera from patients admitted with severe malaria in Ho Chi Minh City, Vietnam, between May 1991 and January 1996 were assayed for hepatitis B surface antigen (HB(s)Ag) by a commercial enzyme-linked immunosorbent assay kit. The overall prevalence of HB(s)Ag was 23.77% (77 of 324). This was higher than reported estimates of prevalence in the general catchment population for the study hospital (mean, 9.8%; range, 9-16%). No association was found between risk of death caused by severe malaria and HB(s)Ag. Patients admitted with cerebral malaria had a slightly greater risk of registering positive for HB(s)Ag (relative risk, 1.28; 95% confidence interval, 1.04-1.58) relative to other manifestations of severe malaria. Chronic infection with hepatitis B virus may be a risk factor for severe malaria.

Adolescent↗

Seasonal malaria attack rates in infants and young children in northern Ghana.

The incidence density of infection and disease caused by Plasmodium falciparum in children aged six to 24 months living in the holoendemic Sahel of northern Ghana was measured during the wet and dry seasons of 1996 and 1997. At the beginning of each season, a cohort composed of 259 and 277 randomly selected children received supervised curative therapy with quinine and Fansidar and primaquine for those with normal glucose-6-phosphate dehydrogenase activity. The 20 weeks of post-therapy follow-up consisted of three home visits weekly and examination of Giemsa-stained blood films once every two weeks. Blood films were also taken from children brought to clinic with illness. The incidence density of parasitemia after radical cure was 4.7 infections/person-year during the dry season and 7.1 during the wet season (relative risk = 1.51, 95% confidence interval [CI] = 1.25-1.81; P = 0.00001). Although the mean parasitemia count at time of reinfection in the dry season (3,310/microl) roughly equaled that in the wet season (3,056/microl; P = 0.737), the risk ratio for parasitemia > 20,000/microl during the wet season was 1.71 (95% CI = 1.2-2.4; P = 0.0025). The risk ratio for parasitemia > 20,000/microl with fever during the wet season was 2.45 (95% CI = 1.5-4.1; P = 0.0002). The risk ratio for anemia (hemoglobin < 8 g/dl) at first post-radical cure parasitemia showed no difference between seasons (1.0; 95% CI = 0.73-1.4; P = 0.9915). We did not see seasonal differences in anemia known to exist in this region, probably because the longitudinal cohort design using first parasitemia as an end point prevented the subjects from developing the repeated or chronic infections required for anemia induction. These findings bear upon the design of malaria drug and vaccine trials in holoendemic areas.

Anemia↗

Epidemic malaria in the Menoreh Hills of Central Java.

After more than 50 years of effective management, resurgent malaria threatens residents in the Menoreh Hills and the foothills of the Dieng Plateau of Central Java, Indonesia. The Dieng Plateau dominates the highland center of Central Java. The steep Menoreh Hills, surrounded by rice paddy habitats, cover approximately 500 km2 with no peaks greater than 1,000 m. We studied epidemic malaria in Purworejo district, one of the three districts containing the Menoreh Hills. Between 1986 and 1995, the annual parasite incidence (API) in Purworejo ranged from 2 to 11 cases per 1,000 residents per year and was typically approximately 5 per 1,000. In 2000 the API was 44.5. This sharp increase was confined to subdistricts in and around the Menoreh Hills and Dieng Plateau foothills. The primary vectors of malaria, those favoring steep, forested hillsides on Java, were Anopheles maculatus and Anopheles balabacensis. Deterioration of vector control activity, followed by a severe economic downturn in 1997, may explain the epidemic. Malaria in the Menoreh Hills and lower Dieng Plateau threatens surrounding areas of rice paddy inhabited by Anopheles aconitus as well as a nearby coastal habitat where the even more efficient vector Anopheles sundaicus occurs in abundance. Most of the 130 million people living on Java never experienced the hyper- and holoendemic malaria that occurred throughout most of the island before the effective DDT spraying and chloroquine treatment campaigns of the 1950s. Reintroduced endemic malaria threatens the island of Java.

Adult↗

Short report: therapeutic efficacy of chloroquine combined with primaquine against Plasmodium falciparum in northeastern Papua, Indonesia.

Chloroquine combined with primaquine was evaluated for therapy of uncomplicated malaria caused by Plasmodium falciparum in nonimmune Javanese migrants to northeastern Papua, Indonesia. Subjects were randomized to treatment with standard chloroquine therapy (25 mg/kg in 3 doses over the course of 48 hours) with 30 mg primaquine administered daily for 28 days (n = 25) or a placebo of primaquine (n = 28). The 14-day cumulative incidence of therapeutic failure was 56% with primaquine and 79% with placebo (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.1-1.3; P = 0.08). Primaquine administered daily created a marginally significant improvement in therapeutic efficacy at day 14, but not at day 7 (20% versus 36%; OR, 0.2; 95% CI, 0.1-1.8; P = 0.2) or day 28 (82% versus 93%; OR, 0.31; 95% Cl, 0.04-2.1; P = 0.23). This report corroborates studies suggesting that therapeutic doses of primaquine exert no discernible effect on parasitemia by P. falciparum.

Antimalarials↗

A biologic basis for integrated malaria control.

In a series of models of Plasmodium falciparum dynamics, spontaneous local extinctions of the parasite sometimes occurred under steady, perennial-transmission conditions. These extinctions occurred only with extremely low mosquito densities or when the parameter describing the duration of human infection-blocking immunity was at its maximum value, and, simultaneously, those describing vector survivorship and the duration of human infectivity were at their minimum values. The range and frequency of extinctions increased with seasonal transmission, and decreased with the emergence of recombinant genotypes. Here we extend the immunity parameter up to levels that would describe a successful vaccine, and examine the combined influences of seasonality, genotype cross-reactivity, meiotic recombination, and human population turnover on parasite persistence. As Ross did 90 years ago, we conclude that malaria control programs that encompass several methods and targets of intervention are the most likely to succeed. Success is more likely if programs are cognizant of local circumstances of transmission, and, within that context, aim to reduce vector survivorship and human infectivity as well as augment human immunity.

Animals↗