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Jason D Maguire

Publications and source records attributed to Jason D Maguire.

17 recordsLinked to original sources
PubMed2006

Reader technique as a source of variability in determining malaria parasite density by microscopy.

BACKGROUND: Accurate identification and quantification of malaria parasites are critical for measuring clinical trial outcomes. Positive and negative diagnosis is usually sufficient for the assessment of therapeutic outcome, but vaccine or prophylactic drug trials require measuring density of infection as a primary endpoint. Microscopy is the most established and widely-used technique for quantifying parasite densities in the blood. METHODS: Results obtained by 24-27 expert malaria microscopists, who had independently read 895 slides from 35 donors, were analysed to understand how reader technique contributes to discrepancy in measurements of parasite density over a wide range of densities. RESULTS: Among these 35 donations, standard deviations ranged from 30% to 250% of the mean parasite density and the percent discrepancy was inversely correlated with the mean parasite density. The number of white blood cells indexed and whether parasites were counted in the thick film or thin film were shown to significantly contribute to discrepancy amongst microscopists. CONCLUSION: Errors in microscopy measurements are not widely appreciated or addressed but have serious consequences for efficacy trials, including possibly abandoning promising vaccine candidates.

Animals↗
PubMed2006

Combined chloroquine, sulfadoxine/pyrimethamine and primaquine against Plasmodium falciparum in Central Java, Indonesia.

BACKGROUND: Chloroquine (CQ) or sulfadoxine-pyrimethamine (SP) monotherapy for Plasmodium falciparum often leads to therapeutic failure in Indonesia. Combining CQ with other drugs, like SP, may provide an affordable, available and effective option where artemisinin-combined therapies (ACT) are not licensed or are unavailable. METHODS: This study compared CQ (n = 29 subjects) versus CQ + SP (with or without primaquine; n = 88) for clinical and parasitological cure of uncomplicated falciparum malaria in the Menoreh Hills region of southern Central Java, Indonesia. Gametocyte clearance rates were measured with (n = 56 subjects) and without (n = 61) a single 45 mg dose of primaquine (PQ). RESULTS: After 28 days, 58% of subjects receiving CQ had cleared parasitaemia and remained aparasitaemic, compared to 94% receiving CQ combined with SP (p < 0.001). Msp-2 genotyping permitted reinfection-adjusted cure rates for CQ and CQ combined with SP, 70% and 99%, respectively (p = 0.0006). CONCLUSION: Primaquine exerted no apparent affect on cure of asexual stage parasitaemia, but clearly accelerated clearance of gametocytes. CQ combined with SP was safe and well-tolerated with superior efficacy over CQ for P. falciparum parasitaemia in this study.

Adolescent↗
PubMed2006

Production and validation of durable, high quality standardized malaria microscopy slides for teaching, testing and quality assurance during an era of declining diagnostic proficiency.

BACKGROUND: Sets of Giemsa-stained, blood smear slides with systematically verified composite diagnoses would contribute substantially to development of externally validated quality assurance systems for the microscopic diagnosis of malaria. METHODS: whole blood from Plasmodium-positive donors in Cambodia and Indonesia and individuals with no history of risk for malaria was collected. Using standard operating procedures, technicians prepared Giemsa-stained thick and thin smears from each donor. One slide from each of the first 35 donations was distributed to each of 28 individuals acknowledged by reputation as having expertise in the microscopic diagnosis of malaria. These reference readers recorded presence or absence of Plasmodium species and parasite density. A composite diagnosis for each donation was determined based on microscopic findings and species-specific small subunit ribosomal RNA (ssrRNA) DNA polymerase chain reaction (PCR) amplification. RESULTS: More than 12,000 slides were generated from 124 donations. Reference readers correctly identified presence of parasites on 85% of slides with densities <100 parasites/microl, which improved to 100% for densities >350 parasites/microl. Percentages of agreement with composite diagnoses were highest for Plasmodium falciparum (99%), followed by Plasmodium vivax (86%). CONCLUSION: Herein, a standardized method for producing large numbers of consistently high quality, durable Giemsa-stained blood smears and validating composite diagnoses for the purpose of creating a malaria slide repository in support of initiatives to improve training and competency assessment amidst a background of variability in diagnosis is described.

Animals↗
PubMed2006

Mefloquine is highly efficacious against chloroquine-resistant Plasmodium vivax malaria and Plasmodium falciparum malaria in Papua, Indonesia.

BACKGROUND: During the period of 1996-1999, we prospectively monitored 243 Javanese adults and children after arriving in Papua, Indonesia, and microscopically documented each new case of malaria by active surveillance. METHODS: In a randomized, open-label, comparative malaria treatment trial, 72 adults and 50 children received chloroquine for each incident case of malaria, and 74 adults and 47 children received mefloquine. RESULTS: Among 975 primary treatment courses, the cumulative 28-day curative efficacies were 26% and 82% for chloroquine against Plasmodium falciparum malaria and Plasmodium vivax malaria, respectively. Mefloquine cure rates were far superior (96% against P. falciparum malaria and 99.6% against P. vivax malaria). CONCLUSIONS: Mefloquine is a useful alternative treatment for P. vivax malaria and P. falciparum malaria in areas such as Papua, where chloroquine is still recommended as the first-line therapeutic agent.

Adult↗
PubMed2006

Rapid onset of transmission-reducing antibodies in javanese migrants exposed to malaria in papua, indonesia.

Transmission of Plasmodium falciparum malaria is initiated by sexual stages in the mosquito. Anti-Pfs48/45 and anti-Pfs230 sexual stage antibodies that are ingested together with parasites can reduce parasite development and subsequently malaria transmission. Acquisition of sexual stage immunity was studied in a cohort of 102 non-immune Javanese individuals migrating to hyperendemic Papua Indonesia. Seroprevalence of antibodies against Pfs48/45 and Pfs230 and functional transmission-reducing activity (TRA) were measured upon arrival and at 6, 12, and 24 months. Asexual parasitemia and gametocytemia were assessed every two weeks. The TRA and seroreactivity increased with the number of P. falciparum infections. The longitudinally sustained association between TRA and antibodies against Pfs48/45 (odds ratio [OR] = 3.74, 95% confidence interval [CI] = 1.51-9.29) and Pfs230 (OR = 3.72, 95% CI = 1.36-10.17) suggests that functional transmission reducing immunity is acquired after limited exposure to infection.

Adult↗
PubMed2006

Strongyloidiasis with gastric mucosal invasion presenting with acute interstitial nephritis.

We report an atypical occurrence of invasive Strongyloides stercoralis infection of the stomach mucosa in an elderly female patient from Bangka Island, northwestern Indonesia. The patient presented with severe epigastric pain, edema of the legs, proteinuria and severe hypoalbuminemia. Gastric and duodenal biopsies found eggs, larval and adult forms present in the superficial mucosa with mild inflammation. The Harada-Mori filter paper culture technique revealed S. stercoralis filariform larvae and free-living adult worms, corroborating the diagnosis. The infection was associated with acute interstitial nephritis. The patient showed rapid and dramatic improvement after treatment with mebendazole.

Aged↗
PubMed2005

Endemic coastal malaria in the Thousand Islands District, near Jakarta, Indonesia.

OBJECTIVES: To conduct malaria surveillance near Jakarta where only imported malaria has been described over the past two decades and to characterize endemicity and risk to heavily populated peri-urban locations. METHODS: Standard cross-sectional malariometric surveys and mosquito collections at the Thousand Islands District and developing peri-urban areas of Jakarta. RESULTS: During October 2000 outbreak investigations in the Tidung Island group, the slide positive rate was 47% (38%Plasmodium falciparum, 7%P. vivax, and 2% mixed infections) among 733 persons screened. Very few parasitemic inhabitants were symptomatic (<1%), and native residents were more commonly infected than immigrants (odds ratio 1.72), consistent with endemic autochthonous transmission. Adult and larval mosquito collections detected Anopheles sundaicus. In June 2001, prevalence of parasitemia at Pari Island, where sampling was adequate for comparison, remained high, 32%vs. 43% previously. Among 1377 individuals screened at nearby Tangerang District, a heavily populated mainland suburb dominated by fishponds through which many islanders travel to Jakarta, only 19 malaria infections were identified, all imported from Pari Island. Entomological surveillance in Tangerang identified An. subpictus, An. vagus, and An. barbirostris, all considered minor malaria vectors on Java. CONCLUSIONS: Malaria is endemic in the Tidung Island group. Imported malaria occurs in the heavily populated Tangerang District where coastal development is increasing and vector breeding sites and demographic patterns lend increasingly to malaria importation and risk of emergent malaria. Careful attention to the impact of coastal development activities on vector populations and efforts to prevent introduction of An. sundaicus are warranted.

Adolescent↗
PubMed2005

Novel Plasmodium vivax dhfr alleles from the Indonesian Archipelago and Papua New Guinea: association with pyrimethamine resistance determined by a Saccharomyces cerevisiae expression system.

In plasmodia, the dihydrofolate reductase (DHFR) enzyme is the target of the pyrimethamine component of sulfadoxine-pyrimethamine (S/P). Plasmodium vivax infections are not treated intentionally with antifolates. However, outside Africa, coinfections with Plasmodium falciparum and P. vivax are common, and P. vivax infections are often exposed to S/P. Cloning of the P. vivax dhfr gene has allowed molecular comparisons of dhfr alleles from different regions. Examination of the dhfr locus from a few locations has identified a very diverse set of alleles and showed that mutant alleles of the vivax dhfr gene are prevalent in Southeast Asia where S/P has been used extensively. We have surveyed patient isolates from six locations in Indonesia and two locations in Papua New Guinea. We sequenced P. vivax dhfr alleles from 114 patient samples and identified 24 different alleles that differed from the wild type by synonymous and nonsynonymous point mutations, insertions, or deletions. Most importantly, five alleles that carried four or more nonsynonymous mutations were identified. Only one of these highly mutant alleles had been previously observed, and all carried the 57L and 117T mutations. P. vivax cannot be cultured continuously, so we used a yeast assay system to determine in vitro sensitivity to pyrimethamine for a subset of the alleles. Alleles with four nonsynonymous mutations conferred very high levels of resistance to pyrimethamine. This study expands significantly the total number of novel dhfr alleles now identified from P. vivax and provides a foundation for understanding how antifolate resistance arises and spreads in natural P. vivax populations.

Alleles↗
PubMed2005

Bartonella species in rodents and shrews in the greater Jakarta area.

In February 2004, we captured 221 rodents and shrews in the Greater Jakarta area as part of a study to determine the prevalence of rodent-associated vector-borne infections. Microscopic examination of blood smears revealed 6% (13/218) to be positive for Bartonella spp. The corresponding DNA samples, either from blood blots or frozen spleen pieces and from fleas collected on these animals, were tested for evidence of Bartonella infection by PCR, targeting the portions: 378bp and 930bp of the citrate synthase gene (g/tA). The sequences from our sample clusters with a Peruvian entity, B. phoceensis, B. rattimassiliensis and B. elizabethae, the latter species has been associated with endocarditis and neuroretinitis in humans. As previous analyses have shown, there appears to be little geographic or host consistency with phylogenetic placement. The public health significance of these findings remains to be determined.

Animals↗
PubMed2004

Dihydrofolate reductase mutations in Plasmodium vivax from Indonesia and therapeutic response to sulfadoxine plus pyrimethamine.

BACKGROUND: The target enzyme of pyrimethamine is dihydrofolate reductase (DHFR), but little is known about allelic variants of dhfr in Plasmodium vivax populations. Still less is known about associations between specific alleles and the failure of sulfadoxine/pyrimethamine (S/P) to clear the erythrocytic stages of P. vivax in vivo. METHODS: We studied P. vivax dhfr mutations in 24 patients who received S/P therapy in Papua or Central Java, Indonesia, and we measured the resistance of the alleles in vitro in a dhfr yeast expression assay. RESULTS: Fourteen (58%) of 24 patients had an inadequate therapeutic response. Two of 6 alleles that were identified were novel. One allele that expressed 4 point mutations (57L+58R+61M+117T) correlated with a high risk of therapeutic failure. The 9 patients infected by P. vivax carrying this allele proved 23 times more likely to experience early therapeutic failure, compared with patients infected by P. vivax carrying other alleles (P=.003; 95% confidence interval, 2-450). This allele also conferred high levels of pyrimethamine resistance in vitro. The experimental antifolate WR99210 inhibited the allele in this system. CONCLUSIONS: The present study identified a strong correlation between specific mutations in P. vivax dhfr and S/P treatment failure. Our results suggest that WR99210 could provide effective therapy for S/P-resistant P. vivax.

Animals↗
PubMed2004

Comparative efficacy of chloroquine and sulfadoxine-pyrimethamine for uncomplicated Plasmodium falciparum malaria and impact on gametocyte carriage rates in the East Nusatenggara province of Indonesia.

The efficacy of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) was evaluated in 89 subjects greater than one year of age with uncomplicated P. falciparum malaria in the East Nusatenggara Province of Indonesia. Fever clearance time was longer in the SP group than in the CQ group. However, parasite clearance time was extended in subjects who received CQ compared with those who received SP. Major adverse events were not observed in either group, and no hospitalizations were required during the study. Treatment failure rates at day 28 were 69% for CQ and 8.5% for SP. In both treatment groups, gametocytemia developed during the follow-up period, but was more pronounced in the SP group, peaking at 94% on day 7. Regardless of treatment group, children < 10 years of age had significantly higher treatment failure rates than subjects >/=10 years of age (relative risk = 2.49), suggesting that acquired immunity influenced treatment outcomes in the presence of parasite drug resistance. Although a highly effective alternative to CQ for clearing infection, SP treatment also presented some potential drawbacks (e.g., increased and persistent gametocytemia). Replacement of CQ with SP as a first-line therapy, either alone or in combination with CQ, in those areas of Indonesia with high levels of CQ resistance should significantly improve treatment outcomes, particularly in vulnerable populations lacking clinical immunity. More efficacious and rapidly acting asexual stage treatments are generally associated with increased gametocyte clearance and combination therapy in areas where drug resistance is high or emerging may provide an additional means for reducing transmission.

Adolescent↗
PubMed2003

New haplotypes of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene among chloroquine-resistant parasite isolates.

Mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene were examined to assess their associations with chloroquine resistance in clinical samples from Armopa (Papua) and Papua New Guinea. In Papua, two of the five pfcrt haplotypes found were new: SVIET from Armopa and CVIKT from an isolate in Timika. There was also a strong association (P < 0.0001) between the pfcrt 76T allele and chloroquine resistance in 50 samples. In Papua New Guinea, mutations in the pfcrt gene were observed in 15 isolates with chloroquine minimum inhibitory concentrations (MICs) of 16-64 pmol, while the remaining six isolates, which had a wild-type pfcrt gene at codon 76, had MICs of 2-8 pmol. These observations confirm that mutations at codon 76 in the pfcrt gene are present in both in vivo and in vitro cases of chloroquine resistance, and that detection of the pfcrt 76T allele could predict potential chloroquine treatment failures.

Animals↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMedDate not supplied

Imported malaria in Jakarta, Indonesia: passive surveillance of returned travelers and military members postdeployment.

BACKGROUND: Autochthonous malaria does not currently occur in Jakarta, the most populous city in Indonesia. Military, forestry, mining, and tourist activities draw Jakarta residents to distant parts of the archipelago with high rates of malaria. Although malaria is a reportable disease in Jakarta, little has been published. METHODS: We collected demographic and travel information from patients in Jakarta with microscopically confirmed malaria from January 2004 to February 2005, using a standardized data collection form. These results were compared to regional rainfall statistics and transit patterns of Jakarta residents to and from rural areas. RESULTS: Data from 240 patients were collected. Aceh Province was the travel destination most commonly recorded for military members, while Papua and Bangka Island were the most frequently cited by civilians. Plasmodium falciparum accounted for 53% of cases, of which 15% had detectable gametocytemia. The most common admission diagnoses were malaria (39%), febrile illness not otherwise specified (23%), viral hepatitis (19%), and dengue (11%). The median time from admission to microscopic diagnosis was 2 days for civilian patients and 2.5 days for military patients. The highest number of cases occurred in May, July, and December with the nadir in October. CONCLUSIONS: The diagnosis of malaria may be overlooked and therefore delayed, in nonendemic areas such as Jakarta. Travel destinations associated with contracting malaria vary significantly for civilian and military populations. The factors affecting the peak months of importation likely include rainfall, holiday transit, military flight availability, and referral center locations.

Adult↗