Assuntos
Leishmaniose/diagnóstico , Leishmaniose/tratamento farmacológico , Antiprotozoários/uso terapêutico , América Central , Infecções por HIV/complicações , Infecções por HIV/parasitologia , Humanos , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Mucocutânea/diagnóstico , Leishmaniose Mucocutânea/tratamento farmacológico , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/tratamento farmacológico , América do Norte , América do SulRESUMO
After 6 months of a trip to Haiti, a 25-year-old healthy man presented with a 6-week history of a very slow progressive intermittent bilateral testicular pain and swelling. The biopsies in both testicles revealed the presence of a dead filarial parasite. Polymerase chain reaction products of the DNA from the biopsy were shown to have a 100% identity to Wuchereria bancrofti. Despite being uncommon in travelers, this presentation of W. bancrofti highlights the possibility of acquiring W. bancrofti during short-term trips to highly endemic regions of the world (i.e., Haiti).
Assuntos
Filariose Linfática/parasitologia , Testículo/parasitologia , Wuchereria bancrofti/fisiologia , Adulto , Animais , Filariose Linfática/diagnóstico , Filariose Linfática/patologia , Haiti , Humanos , Masculino , Testículo/patologia , Viagem , Wuchereria bancrofti/patogenicidadeRESUMO
The majority of malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), encoded by the pfhrp2 gene. Recently, P. falciparum isolates from Peru were found to lack pfhrp2 leading to false-negative RDT results. We hypothesized that pfhrp2-deleted parasites in Peru derived from a single genetic event. We evaluated the parasite population structure and pfhrp2 haplotype of samples collected between 1998 and 2005 using seven neutral and seven chromosome 8 microsatellite markers, respectively. Five distinct pfhrp2 haplotypes, corresponding to five neutral microsatellite-based clonal lineages, were detected in 1998-2001; pfhrp2 deletions occurred within four haplotypes. In 2003-2005, outcrossing among the parasite lineages resulted in eight population clusters that inherited the five pfhrp2 haplotypes seen previously and a new haplotype; pfhrp2 deletions occurred within four of these haplotypes. These findings indicate that the genetic origin of pfhrp2 deletion in Peru was not a single event, but likely occurred multiple times.
Assuntos
Antígenos de Protozoários/genética , Deleção de Genes , Parasitos/genética , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Animais , Teorema de Bayes , Análise por Conglomerados , Haplótipos/genética , Humanos , Repetições de Microssatélites/genética , Peru , Fenótipo , PrevalênciaRESUMO
BACKGROUND: Sulfadoxine-pyrimethamine was a common first line drug therapy to treat uncomplicated falciparum malaria, but increasing therapeutic failures associated with the development of significant levels of resistance worldwide has prompted change to alternative treatment regimes in many national malaria control programs. METHODOLOGY AND FINDING: We conducted an in vivo therapeutic efficacy trial of sulfadoxine-pyrimethamine at two locations in the Peruvian Amazon enrolling 99 patients of which, 86 patients completed the protocol specified 28 day follow up. Our objective was to correlate the presence of polymorphisms in P. falciparum dihydrofolate reductase and dihydropteroate synthase to in vitro parasite susceptibility to sulfadoxine and pyrimethamine and to in vivo treatment outcomes. Inhibitory concentration 50 values of isolates increased with numbers of mutations (single [108N], sextuplet [BR/51I/108N/164L and 437G/581G]) and septuplet (BR/51I/108N/164L and 437G/540E/581G) with geometric means of 76 nM (35-166 nM), 582 nM (49-6890- nM) and 4909 (3575-6741 nM) nM for sulfadoxine and 33 nM (22-51 nM), 81 nM (19-345 nM), and 215 nM (176-262 nM) for pyrimethamine. A single mutation present in the isolate obtained at the time of enrollment from either dihydrofolate reductase (164L) or dihydropteroate synthase (540E) predicted treatment failure as well as any other single gene alone or in combination. Patients with the dihydrofolate reductase 164L mutation were 3.6 times as likely to be treatment failures [failures 85.4% (164L) vs 23.7% (I164); relative risk = 3.61; 95% CI: 2.14 - 6.64] while patients with the dihydropteroate synthase 540E were 2.6 times as likely to fail treatment (96.7% (540E) vs 37.5% (K540); relative risk = 2.58; 95% CI: 1.88 - 3.73). Patients with both dihydrofolate reductase 164L and dihydropteroate synthase 540E mutations were 4.1 times as likely to be treatment failures [96.7% vs 23.7%; RR = 4.08; 95% CI: 2.45 - 7.46] compared to patients having both wild forms (I164 and K540). CONCLUSIONS: In this part of the Amazon basin, it may be possible to predict treatment failure with sulfadoxine-pyrimethamine equally well by determination of either of the single mutations dihydrofolate reductase 164L or dihydropteroate synthase 540E. TRIAL REGISTRATION: ClinicalTrials.gov NCT00951106.
Assuntos
Antimaláricos/farmacologia , Di-Hidropteroato Sintase/genética , Plasmodium falciparum/enzimologia , Mutação Puntual , Pirimetamina/farmacologia , Sulfadoxina/farmacologia , Tetra-Hidrofolato Desidrogenase/genética , Animais , Plasmodium falciparum/efeitos dos fármacosRESUMO
To determine whether antibodies to the 19-kDa fragment of merozoite surface protein 1 (MSP1(19)) help to control blood-stage Plasmodium falciparum infection, we performed a rechallenge experiment of previously infected Aotus monkeys. Monkeys previously exposed to the FVO strain of P. falciparum that did or did not develop high antibody titers to MSP1(19) and malaria-naïve monkeys were challenged with erythrocytes infected with the same strain. Prepatent periods were prolonged in previously infected monkeys compared with malaria-naïve monkeys. Previously infected monkeys with preexisting anti-MSP1(19) antibodies showed low peak parasitemias that cleared spontaneously. Previously infected monkeys that had no or low levels of pre-existing anti-MSP1(19) antibodies also showed low peak parasitemias, but because of low hematocrits, all of these animals required treatment with mefloquine. All previously malaria-naïve animals were treated because of high parasitemias. The results of this study suggest that antibody to the 19-kDa carboxy-terminal fragment of MSP1 plays a role in preventing the development of anemia, an important complication often associated with malaria.
Assuntos
Anemia/imunologia , Anticorpos Antiprotozoários/imunologia , Malária Falciparum/imunologia , Proteína 1 de Superfície de Merozoito/imunologia , Doenças dos Macacos/parasitologia , Plasmodium falciparum/imunologia , Anemia/parasitologia , Anemia/patologia , Animais , Anticorpos Antiprotozoários/sangue , Antimaláricos/uso terapêutico , Aotidae , Modelos Animais de Doenças , Eritrócitos/parasitologia , Malária Falciparum/complicações , Malária Falciparum/patologia , Mefloquina/uso terapêutico , Proteína 1 de Superfície de Merozoito/administração & dosagem , Doenças dos Macacos/imunologia , Doenças dos Macacos/patologia , Parasitemia/tratamento farmacológico , Parasitemia/imunologia , Plasmodium falciparum/crescimento & desenvolvimentoRESUMO
A retrospective surveillance study was conducted to examine the micro-geographic variation of malaria incidence in three malaria-endemic communities in the Northern Peruvian Amazon. The annual malaria risk rate (per 100) ranged from 38% to 47% for Plasmodium vivax and from 15% to 18% for P. falciparum. Spatial clusters were found for P. vivax in Padre Cocha, Manacamiri, and Zungaro Cocha, and for P. falciparum only in Padre Cocha. Spatial-temporal clusters showed that the highest monthly number of P. vivax cases varied every year from December to March in 1996-1997 and from February to June in 1998-1999, and for P. falciparum from November to April in 1996-1997 and from January to April in 1998-1999. Our results suggest a constant presence of high-risk areas (hot spots) for malaria infection in periods with high or low malaria incidence. Modest targeted control efforts directed at identified high-risk areas may have significant impact on malaria transmission in this region.
Assuntos
Habitação , Malária/epidemiologia , Análise por Conglomerados , Feminino , Geografia , Humanos , Incidência , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Masculino , Peru/epidemiologia , Estudos Retrospectivos , Estações do Ano , Clima TropicalRESUMO
Two expert research microscopists, each blinded to the other's reports, diagnosed single-species malaria infections in 2,141 adults presenting at outpatient malaria clinics in Tak Province, Thailand, and Iquitos, Peru, in May-August 1998, May-July 1999, and May-June 2001. Plasmodium vivax patients with gametocytemia had higher fever and higher parasitemia than those without gametocytemia; temperature correlated with parasitemia in the patients with gametocytemia. Plasmodium falciparum patients with gametocytemia had lower fever than those without gametocytemia, but similar parasitemia; temperature correlated with parasitemia in the patients without gametocytemia. Hematologic data in Thailand in 2001 showed lower platelet counts in P. vivax patients with gametocytemia than in the P. vivax patients without gametocytemia, whereas P. falciparum patients with gametocytemia had similar platelet counts but lower red blood cell counts, hemoglobin levels, hematocrit levels, and higher lymphocyte counts than patients without gametocytemia.
Assuntos
Doenças Endêmicas , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Parasitemia/epidemiologia , Adulto , Fatores Etários , Animais , Estudos Transversais , Contagem de Eritrócitos , Feminino , Febre , Hematócrito , Hemoglobinas/análise , Humanos , Contagem de Leucócitos , Malária Falciparum/parasitologia , Malária Vivax/parasitologia , Masculino , Parasitemia/parasitologia , Peru/epidemiologia , Tailândia/epidemiologiaRESUMO
Enumeration of parasites by microscopic examination of blood smears is the only method available for quantifying parasitemia in infected blood. However, the sources and scale of error inherent in this technique have not been systematically investigated. Here we use data collected in outpatient clinics in Peru and Thailand to elucidate important sources of variation in parasite density measurements. We show that discrepancies between readings from two independent microscopists and multiple readings from a single microscopist are inversely related to the density of the infection. We present an example of how differences in reader technique, specifically the number of white blood cells counted, can contribute to the differences between readings. We discuss the implications of this analysis for field studies and clinical trials.
Assuntos
Malária Falciparum/diagnóstico , Malária Falciparum/epidemiologia , Malária Vivax/diagnóstico , Malária Vivax/epidemiologia , Microscopia/métodos , Animais , Humanos , Leucócitos/parasitologia , Variações Dependentes do Observador , Peru , TailândiaRESUMO
White blood cells (WBCs) were counted in 4697 individuals who presented to outpatient malaria clinics in Maesod, Tak Province, Thailand, and Iquitos, Peru, between 28 May and 28 August 1998 and between 17 May and 9 July 1999. At each site and in each year, WBC counts in the Plasmodium falciparum-infected patients were lower than those in the Plasmodium vivax-infected patients, which, in turn, were lower than those in the uninfected patients. In Thailand, one-sixth of the P. falciparum-infected patients had WBC counts of <4000 cells/microL. Leukopenia may confound population studies that estimate parasite densities on the basis of an assumed WBC count of 8000 cells/microL. For instance, in the present study, use of this conventional approach would have overestimated average asexual parasite densities in the P. falciparum-infected patients in Thailand by nearly one-third.
Assuntos
Contagem de Leucócitos , Leucopenia/parasitologia , Malária Falciparum/sangue , Malária Vivax/sangue , Adolescente , Adulto , Distribuição por Idade , Humanos , Leucopenia/epidemiologia , Peru , TailândiaRESUMO
We conducted a randomized, double-blind, phase III yellow fever (YF) vaccine trial among 1,107 healthy children in Sullana in northern Peru. The safety and efficacy (by measurement of geometric mean neutralizing antibody titer responses) were determined for two YF vaccines, ARILVAX (n = 738) and YF-VAX(R) (n = 369). Serocon-version rates were higher (94.9%) in ARILVAX than in YF-VAX (90.6%) recipients. The two-sided 95% confidence interval (YF-VAX-ARILVAX) was (-12.8% to -2.5%), indicating that the higher seroconversion rate for Arilvax was significant. Post-vaccination (30-day) mean log(10) neutralization indices were found to be similar for both products: 1.32 for ARILVAX and 1.26 for YF-VAX (P = 0.1404, by analysis of variance). A similar number of subjects in each group reported at least one adverse event (AE); 441 (59.8%) for ARILVAX versus 211 (59.9%) for YF-VAX. Most (591; 96.7%) of these were of a mild nature and resolved without treatment. There were no treatment-related serious AEs. This is the first randomized, double-blind comparison of two YF vaccines in a pediatric population; both vaccines were shown to be highly immunogenic and well-tolerated.