RESUMO
Malaria is one of the most prevalent infectious diseases worldwide; it is transmitted in over 100 countries, and it is a major cause of serious morbidity and mortality in travelers. Clinicians should inform travelers of their risk, teach them the principles of personal protection, and offer individualized chemoprophylaxis regimens. The increasing prevalence of multiple drug-resistant Plasmodium falciparum in many parts of the world makes nonpharmacologic methods of malaria prevention important.
Assuntos
Anopheles , Antimaláricos/uso terapêutico , Mordeduras e Picadas de Insetos/prevenção & controle , Malária/prevenção & controle , Viagem , Animais , Saúde Global , Humanos , Insetos Vetores , Malária/epidemiologia , Fatores de RiscoRESUMO
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited disorder of red blood cell metabolism. Affected individuals may suffer a severe hemolytic crisis when treated with primaquine, an antimalarial. A survey of 966 male Southeast Asian refugees determined that 50 (5.2%) were G6PD-deficient. This prevalence suggests that a G6PD assay should be performed prior to primaquine therapy in this high-risk population.
Assuntos
Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Refugiados , Adulto , Sudeste Asiático/etnologia , Humanos , Malária/tratamento farmacológico , Masculino , Primaquina/efeitos adversos , Primaquina/uso terapêutico , Estados UnidosRESUMO
Amodiaquine, a 4-aminoquinoline which has been shown to be effective in treating infections with chloroquine-resistant strains of Plasmodium falciparum, was evaluated against chloroquine-resistant infections in children in Zanzibar, Tanzania, during July 1982. A 25-mg base/kg dosage of amodiaquine produced parasite clearance in 34 of 38 (89%) children in a mean of 2.8 days. When followed for 28 days, 15 of 38 (39%) children were completely cured of their infection as judged by the absence of renewed parasitemia. The parasite clearance rates produced by amodiaquine were significantly higher than those observed in a comparison group of children treated with 25 mg base/kg chloroquine. There was, however, no difference in the cure rates in the chloroquine and amodiaquine groups. Despite the enhanced parasite clearance rate, amodiaquine is not sufficiently more effective against Zanzibari strains of P. falciparum to replace chloroquine. Other alternative drugs must be evaluated to define the optimal malaria therapy regimen on Zanzibar.
Assuntos
Amodiaquina/uso terapêutico , Cloroquina/uso terapêutico , Malária/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Criança , Pré-Escolar , Cloroquina/farmacologia , Avaliação de Medicamentos , Resistência a Medicamentos , Humanos , Lactente , TanzâniaRESUMO
The presence of antibody to the repeating epitope of the circumsporozoite protein of Plasmodium falciparum was determined in children 1 month to 10 years old from three villages in western Kenya using the synthetic peptide (PNAN)5 in an enzyme-linked immunosorbent assay. The percentage of antibody-positive children increased with age and differed in the three villages. The village with the lowest percentage of antibody-positive children had the lowest percentage of infections as determined by detection of blood stage parasites. The villages also differed in the age at which antibody first appeared. In one village, only 12% of the children had antibody by the age of 5; while in the other two villages, 60% and 73% had antibody by 4 years of age.
Assuntos
Anticorpos Antiprotozoários/análise , Antígenos de Protozoários/imunologia , Antígenos de Superfície/imunologia , Malária/imunologia , Plasmodium falciparum/imunologia , Proteínas de Protozoários , Fatores Etários , Animais , Anopheles/parasitologia , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Humanos , Lactente , Quênia , Malária/epidemiologiaRESUMO
Enzyme-linked immunosorbent assays (ELISAs) for the circumsporozoite (CS) antigens of Plasmodium falciparum, P. malariae, and P. ovale were used to identify species of sporozoite and oocyst infections detected by dissection in Anopheles gambiae s.1. and An. funestus collected in western Kenya. ELISAs identified 92.5% of 1,113 salivary gland infections; Plasmodium species infections included 79.4% P. falciparum, 3.2% P. malariae, 1.7% P. ovale, and 2 or more Plasmodium species were detected in 15.7% of the Anopheles in which the species of parasite was identified. Identification was more likely with greater numbers of sporozoites observed in dissections, increasing from 65% ELISA positivity in mosquitoes with 1-10 sporozoites in their salivary glands to 96% in mosquitoes with over 1,000 sporozoites. ELISAs detected CS antigen in 66% of 294 Anopheles that by dissection had oocysts but uninfected salivary glands. Of 112 Anopheles with a single species of Plasmodium detected in the salivary glands, 29 (25.9%) had 1 or more additional species detected in the midgut, indicating a high potential for multiple infections. Similar proportions of Plasmodium species were found in An. gambiae s.1. and An. funestus.
Assuntos
Anopheles/parasitologia , Antígenos de Protozoários/análise , Antígenos de Superfície/análise , Ensaio de Imunoadsorção Enzimática , Plasmodium/isolamento & purificação , Proteínas de Protozoários , Animais , Quênia , Plasmodium/imunologia , Plasmodium falciparum/imunologia , Plasmodium falciparum/isolamento & purificação , Plasmodium malariae/imunologia , Plasmodium malariae/isolamento & purificação , Valor Preditivo dos Testes , Especificidade da EspécieRESUMO
Two cross-sectional surveys of 954 persons in Asembo Bay and Got Nyabondo, western Kenya, were performed in August-September 1986, after long rains, and in February-March 1987, after a comparatively dry season. Serologic testing was performed using an ELISA with synthetic peptides representing repeat amino acid sequences of the Plasmodium falciparum ring-infected erythrocyte surface antigen (RESA), (EENV)5, (EENVEHDA)4, and (DDEHVEEPTVA)2 and repeat sequences (PNAN)5 and (NAAG)5 of the P. falciparum and P. malariae circumsporozoite proteins. In 1986, 45%, 73%, 72%, 85%, and 59% of the persons in Asembo Bay had antibodies to the respective peptides. In Got Nyabondo, the rates were 44%, 67%, 56%, 36%, and 41%, respectively. All positivity rates increased with age. When next determined in 1987, the positivity rates and levels of reactivity were generally unchanged in Asembo Bay, but were decreased in Got Nyabondo.
Assuntos
Envelhecimento/imunologia , Eritrócitos/parasitologia , Malária/imunologia , Adolescente , Animais , Anticorpos Antiprotozoários/imunologia , Antígenos de Superfície/imunologia , Criança , Pré-Escolar , Estudos Transversais , Eritrócitos/imunologia , Humanos , Lactente , Malária/epidemiologia , Plasmodium falciparum/imunologia , Plasmodium malariae/imunologia , Estações do Ano , Estudos SoroepidemiológicosRESUMO
Synthetic DNA oligomers homologous to 21-base long repetitive sequences of Plasmodium falciparum DNA were labeled with 32P using T4 kinase, and were hybridized with purified DNA and with processed blood samples from Africa. The sequence PFR1, its antiparallel oligomer PFR1R, and PFR1 covalently attached to biotin hybridized similarly to P. falciparum DNA. One-microliter aliquots of blood from Zaire spotted on prewet nylon filters and hybridized with PFR1 gave detectable autoradiogram signals from samples with parasitemias as low as 1,000 parasites/mm3. Blood lysis and protein digestion followed by alkylation allowed dot-blot processing of larger aliquots of blood. After hybridization with PFR 1 and autoradiography, 26 samples were scored positive visually, compared with 34 scored positive by microscopy. The effective sensitivity for processed 10-microliter samples was about 500 parasites/mm3. Signals from hybridized probes were quantitated by liquid scintillation counting and densitometry, and were proportional to the amounts of purified P. falciparum DNA applied to the filter. Autoradiogram signals also were roughly proportional (correlation coefficient, r = 0.77) to the number of parasites/mm3 of blood from field samples as determined by microscopic examination.
Assuntos
DNA/análise , Malária/diagnóstico , Plasmodium falciparum/isolamento & purificação , Animais , Autorradiografia , República Democrática do Congo , Humanos , Quênia , Hibridização de Ácido Nucleico , Oligodesoxirribonucleotídeos , Plasmodium falciparum/genética , Sequências Repetitivas de Ácido NucleicoRESUMO
Recombinant sporozoite vaccine or placebo were administered once to 25 volunteers from an area endemic for malaria. Antibody to R32tet32 rose in 9 of 15 receiving vaccine and remained elevated in 6 for 6 months. Mean absorbance increase was 0.43 +/- 0.40 with vaccine, 0.01 +/- 0.23 with placebo, and 0.72 +/- 0.19 in responders. Six non-responders had significantly lower pre-immunization levels (0.07 +/- 0.05) than responders (0.39 +/- 0.25). There was an association between an increase in immunofluorescence (n = 4) and an increase in absorbance (n = 9) among vaccine recipients (n = 15). Vaccine-induced increase in antibody to natural circumsporozoite antigen was indicated by increases in immunofluorescence and by increases in circumsporozoite precipitation score in 2 of the 5 responders with highest antibody increase measured by enzyme-linked immunosorbent assay. Response to subunit sporozoite vaccine paralleled response to prior natural sporozoite exposure and was significant and prolonged in a population with prior natural exposure to malaria.
Assuntos
Anticorpos Antiprotozoários/biossíntese , Malária/prevenção & controle , Plasmodium falciparum/imunologia , Vacinas Protozoárias/imunologia , Adulto , Animais , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Humanos , Imunidade Inata , Quênia , Malária/imunologia , Masculino , Proteínas Recombinantes/imunologia , Fatores de TempoRESUMO
Existing analytical methods for assaying the 4-aminoquinoline antimalarial amodiaquine in body fluids are nonspecific and obscure the fact that little or no amodiaquine is present in the blood of dosed persons. We have isolated four metabolites of amodiaquine. The two major metabolites have been identified; one is desethylamodiaquine, and the other has been tentatively identified on the basis of proton nuclear magnetic resonance spectroscopy as 2-hydroxydesethylamodiaquine. We developed a reverse-phase high-performance liquid chromatographic (HPLC) method that separates the two major metabolites from each other and from amodiaquine, allowing separate quantification. The impact of these findings on in vitro sensitivity testing and blood analysis of persons dosed with amodiaquine is discussed.
Assuntos
Amodiaquina/metabolismo , Amodiaquina/uso terapêutico , Biotransformação , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de MassasRESUMO
A strain of Plasmodium vivax from Indonesia was adapted to splenectomized Aotus and Saimiri monkeys and tested for its susceptibility to chloroquine. Animals were infected by intravenous inoculation of heparinized parasitized blood and subsequently treated with 8 or 15 mg (base) of chloroquine by oral intubation. Recrudescence of infection occurred in 4 of 4 Aotus and 5 of 6 Saimiri monkeys treated with 15 mg base of chloroquine, indicating a level of resistance between that of the standard Chesson strain of P. vivax and the recently reported resistant strains from Papua New Guinea.
Assuntos
Cloroquina/uso terapêutico , Malária Vivax/tratamento farmacológico , Plasmodium vivax/efeitos dos fármacos , Animais , Aotus trivirgatus , Cloroquina/farmacologia , Indonésia , SaimiriRESUMO
A strain of Plasmodium malariae (Uganda I/CDC) was isolated from an infant who had been infected via blood transfusion from a donor who had entered the United States 8 yr previously. After passage through a splenectomized chimpanzee, the parasite was studied in 29 splenectomized Aotus azarae boliviensis monkeys. Maximum parasitemias were higher in Aotus monkeys without previous Plasmodium infection than in Aotus monkeys with a history of P. vivax infection. Animals with a history of infection with both P. vivax and P. falciparum had lower maximum parasitemias than did monkeys in either of the 2 preceding groups. The highest rates of mosquito infection were most often obtained during the 10-day period just after the parasite count rose above 500/mm3 of blood. The most susceptible mosquito was Anopheles freeborni followed by An. stephensi, An. gambiae, An. dirus, and An. maculatus. Two attempts to transmit the Uganda I/CDC strain of P. malariae to other monkeys by sporozoite inoculation were unsuccessful.
Assuntos
Anopheles/parasitologia , Cebidae/parasitologia , Plasmodium malariae/patogenicidade , Animais , Bolívia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Plasmodium malariae/crescimento & desenvolvimento , Plasmodium malariae/isolamento & purificação , Especificidade da Espécie , UgandaAssuntos
Infecções por Enterobacteriaceae/diagnóstico , Doenças do Recém-Nascido/diagnóstico , Osteomielite/diagnóstico , Cefamandol/uso terapêutico , Citrobacter , Quimioterapia Combinada , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Feminino , Gentamicinas/uso terapêutico , Humanos , Recém-Nascido , Doenças do Recém-Nascido/tratamento farmacológico , Doenças do Recém-Nascido/microbiologia , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , TíbiaRESUMO
This article is a report of the authors' experience with a series of forty-six patients with Crohn's disease seen in psychiatric consultation over a nine year period. We treated twenty-two of these patients in either long term or short term psychotherapy in addition to the initial psychiatric evaluation. A brief literature review of previous studies on the psychiatric aspects of Crohn's disease is also presented. The most common reason that psychiatric consultation was requested was depression, followed by pain and narcotic-related problems. Factors which appeared to contribute to psychiatric morbidity were the following: duration of Crohn's disease, frequent hospitalizations and surgical procedures, presence of an ostomy, history of proctocolectomy, current psychosocial stress unrelated to Crohn's disease and a history of traumatic childhood experiences. Four suggestions regarding psychiatric management of this group of patients are presented and discussed.
Assuntos
Doença de Crohn/psicologia , Transtornos Mentais/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta , Estudos Retrospectivos , Papel do Doente , Estresse Psicológico/psicologiaRESUMO
We have determined the time course of radiometric detection of microbial growth in 2348 positive blood culture specimens obtained at Wyler Children's Hospital during a 5-year interval. Overall 72 and 88% of isolates were detected within 48 and 72 hours after sampling, respectively. For pathogenic organisms aerobic detection was generally more rapid and more inclusive than anaerobic detection. At 48 hours of incubation the detection of six potential pathogens (Salmonella sp., Haemophilus influenzae, Group D streptococci, Neisseria meningitidis, coagulase-negative staphylococci, Candida sp.) was significantly delayed compared with detection of other pathogenic organisms recovered from blood. At 72 hours of incubation the detection rates remained less than 95% for H. influenzae, Staphylococcus aureus, Klebsiella sp., coagulase-negative staphylococci, Group D streptococci and Candida sp. These data should assist clinical decisions regarding duration of antibiotic therapy for the presumptive diagnosis of bacteremia in children.
Assuntos
Bactérias/classificação , Sangue/microbiologia , Radioisótopos de Carbono , Sepse/diagnóstico , Antibacterianos/uso terapêutico , Candida/classificação , Dióxido de Carbono/metabolismo , Humanos , Técnicas Microbiológicas , Radiometria , Fatores de TempoRESUMO
Tandem fused-silica capillary gas chromatographic methods for the determination of chloroquine and its major metabolite, desethylchloroquine, are described. Method A employs a single extraction step and internal standardization to permit rapid, precise analyses for chloroquine in whole blood. Method B, employing derivatization with pentafluoropropionic anhydride, can then be applied to the extract to allow qualitative and quantitative confirmation of chloroquine and sensitive, precise quantification for desethylchloroquine. The detection limit for chloroquine in blood is 5 ng/ml by both methods; the limit for desethylchloroquine is 15 ng/ml. Excellent precision is achieved by the methodology, partly due to the use of separate internal standards for the two analytes, each internal standard being a close analogue of the corresponding analyte. Data are presented which demonstrate the increase over time of metabolite relative to unchanged chloroquine found in the blood of a volunteer undergoing a chemoprophylactic regimen of chloroquine.
Assuntos
Cloroquina/análogos & derivados , Cloroquina/metabolismo , Cloroquina/sangue , Cloroquina/isolamento & purificação , Cloroquina/uso terapêutico , Cromatografia Gasosa , Resistência Microbiana a Medicamentos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Malária/tratamento farmacológico , Métodos , Fatores de TempoRESUMO
National malaria surveillance data were reviewed in an analysis of the epidemiological impact of the transmission of chloroquine-resistant Plasmodium falciparum in Africa on malaria in the United States. Between 1975 and 1983, P. falciparum infections acquired by U.S. citizens who visited East Africa, especially Kenya, increased 21-fold. Estimated attack rates for P. falciparum per 100,000 U.S. travelers to Kenya rose from 21.2 cases in 1977 to 83.3 cases in 1982, a rise suggesting that the increase in imported malaria was not due to increased travel. The percentage of reported cases in U.S. citizens with P. falciparum infections acquired in East Africa who indicated having used chloroquine prophylaxis increased from 22.2% in 1978 to 75.8% in 1983; in contrast, no change in the reported use of chloroquine prophylaxis was observed in those infected in West Africa during the same period. These results suggest that chloroquine can no longer be considered a highly effective drug for prevention of malaria caused by P. falciparum in U.S. travelers to East Africa.
Assuntos
Malária/epidemiologia , África Oriental , África Ocidental , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Resistência a Medicamentos , Humanos , Malária/parasitologia , Malária/prevenção & controle , Malária/transmissão , Plasmodium falciparum/efeitos dos fármacos , Risco , Estados Unidos/etnologiaRESUMO
Methodology has been developed to facilitate the collection, transport, and analysis of blood samples in studies of chloroquine absorption and metabolism. The method utilizes high-performance liquid chromatography (HPLC) with fluorescence detection to quantify chloroquine and its major metabolite, desethylchloroquine, in 100-microliters quantities of blood collected on filter paper. Detection limits are 5 ng/ml for both analytes. No loss of either analyte occurred from filter-paper-collected blood spots stored over a twelve-weeks' period at room temperature. Filter-paper-collected, finger-stick blood spots give values for each analyte comparable to corresponding determinations on venous, whole-blood samples. The HPLC mobile phase selected has general applicability to the separation of antimalarial drugs. The methodology permits effective assessment of chloroquine prophylaxis compliance and parasite drug resistance in remote, malaria-endemic regions.
Assuntos
Cloroquina/sangue , Coleta de Amostras Sanguíneas/métodos , Cloroquina/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Filtração , Humanos , Masculino , Espectrometria de Fluorescência/métodos , Fatores de TempoRESUMO
A population-based field study was conducted in Zanzibar Town, Zanzibar, Tanzania, to assess the in-vivo and in-vitro susceptibility to chloroquine of Plasmodium falciparum. Single-dose therapy with chloroquine (10 mg base/kg) failed to clear parasitaemia in 11 of 22 (50%) treated subjects, and a standard therapeutic regimen of chloroquine (25 mg base/kg) failed to clear parasitaemia in 11 of 32 (34%) treated subjects. Concurrent in-vitro testing by the Rieckmann micromethod showed that 8 of 12 (66%) isolates were chloroquine-resistant.
Assuntos
Cloroquina/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Adolescente , Criança , Pré-Escolar , Cloroquina/administração & dosagem , Cloroquina/uso terapêutico , Resistência Microbiana a Medicamentos , Humanos , Lactente , Malária/tratamento farmacológico , TanzâniaRESUMO
Chemoprophylaxis using chloroquine (CQ) in suppressive doses has been recommended to protect pregnant women in malarious areas from the adverse effects of malaria during pregnancy. In a malaria-endemic area of western Kenya with CQ-resistant Plasmodium falciparum, we determined the prevalence and density of falciparum infection in gravid and nulligravid women and compared the in-vivo parasite response to CQ using two regimens: 25 mg/kg body weight (CQ25) divided over a period of three days (for high-density parasitaemias) and 5 mg/kg body weight (CQ5) weekly for 4 weeks (for low-density parasitaemias). P. falciparum infections were present in 102 (42%) of 244 pregnant women. A greater proportion of primigravidae were parasitaemic (68%) than nulligravidae (50%, P=0.02) or multigravidae (33%, P <10(-6)). Primigravidae showed a higher geometric mean parasite density. In the CQ25 treatment group, failure to clear parasites by day 7 was more common in primigravidae than nulligravidae (P=0.008) or multigravidae (P=0.15). In the CQ5 treatment group, primigravidae were more likely to show increasing parasite density than nulligravidae or multigravidae.In this area of Kenya, virtually all women in their first pregnancy are exposed to malaria and are at greatest risk for malaria infection; compared with other women, they show higher parasite densities and are least likely to respond to chloroquine treatment in areas of chloroquine resistance. Malaria control strategies might be targeted to this group of women, but we are pessimistic about the efficacy of weekly CQ5 where there is chloroquine resistance.
Assuntos
Cloroquina/administração & dosagem , Malária/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Complicações Infecciosas na Gravidez/parasitologia , Animais , Feminino , Humanos , Quênia , Malária/prevenção & controle , Paridade , GravidezRESUMO
A high-performance liquid chromatographic method using oxidative electrochemical detection has been developed for selective and sensitive quantification of the antimalarial drug amodiaquine and three of its metabolites in the blood of dosed individuals. The method requires only one extraction step and has detection limits of 1 ng/ml for amodiaquine and its metabolites desethylamodiaquine and bisdesethylamodiaquine and 3 ng/ml for 2-hydroxydesethylamodiaquine. Minor modification of the mobile phase preserves the chromatographic separation and allows ultraviolet spectroscopic detection, which, although appreciably less sensitive, permits monitoring of levels of amodiaquine and the three metabolites in blood and urine samples if an electrochemical detector is unavailable. Levels of amodiaquine and the three metabolites were determined for two volunteers undergoing a nine-week chemoprophylactic regimen in connection with travel to a malarious area. Data are included to compare the in vitro antimalarial activities against three strains of Plasmodium falciparum of amodiaquine and the three metabolites considered.