RESUMEN
We present 3 children with massive pulmonary embolism and review 17 recent pediatric reports. Malignancies were a frequent cause (40%), and sudden death was common (60%). Compared with adults, diagnosis was more likely to be made at autopsy (P < .0001), more children were treated with embolectomy/thrombectomy (P = .0006), and mortality was greater (P = .03).
Asunto(s)
Embolia Pulmonar/complicaciones , Adolescente , Niño , Preescolar , Resultado Fatal , Femenino , Enfermedad de la Hemoglobina SC/complicaciones , Hemosiderosis/complicaciones , Humanos , Síndrome de Klippel-Trenaunay-Weber/complicaciones , Masculino , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapiaRESUMEN
Mutations in the chloroquine resistance (CQR) transporter gene of Plasmodium falciparum (Pfcrt; chromosome 7) play a key role in CQR, while mutations in the multidrug resistance gene (Pfmdr1; chromosome 5) play a significant role in the parasite's resistance to a variety of antimalarials and also modulate CQR. To compare patterns of genetic variation at Pfcrt and Pfmdr1 loci, we investigated 460 blood samples from P. falciparum-infected patients from four Asian, three African, and three South American countries, analyzing microsatellite (MS) loci flanking Pfcrt (five loci [approximately 40 kb]) and Pfmdr1 (either two loci [approximately 5 kb] or four loci [approximately 10 kb]). CQR Pfmdr1 allele-associated MS haplotypes showed considerably higher genetic diversity and higher levels of subdivision than CQR Pfcrt allele-associated MS haplotypes in both Asian and African parasite populations. However, both Pfcrt and Pfmdr1 MS haplotypes showed similar levels of low diversity in South American parasite populations. Median-joining network analyses showed that the Pfcrt MS haplotypes correlated well with geography and CQR Pfcrt alleles, whereas there was no distinct Pfmdr1 MS haplotype that correlated with geography and/or CQR Pfmdr1 alleles. Furthermore, multiple independent origins of CQR Pfmdr1 alleles in Asia and Africa were inferred. These results suggest that variation at Pfcrt and Pfmdr1 loci in both Asian and African parasite populations is generated and/or maintained via substantially different mechanisms. Since Pfmdr1 mutations may be associated with resistance to artemisinin combination therapies that are replacing CQ, particularly in Africa, it is important to determine if, and how, the genetic characteristics of this locus change over time.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Antimaláricos/farmacología , Cloroquina/farmacología , Resistencia a Medicamentos/genética , Variación Genética , Proteínas de Transporte de Membrana/genética , Plasmodium falciparum/efectos de los fármacos , Proteínas Protozoarias/genética , África/epidemiología , Animales , Asia/epidemiología , Haplotipos , Humanos , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Plasmodium falciparum/clasificación , Plasmodium falciparum/genética , Prevalencia , América del Sur/epidemiologíaRESUMEN
We describe here the sequence of the Plasmodium vivax mdr1 gene from 10 different isolates differing in chloroquine sensitivity. The deduced amino acid sequence of PvMDR1 shares more than 70% similarity with other malarial MDR proteins and it displays consensus motifs of an ABC family transporter including two transmembrane domains and two ATP binding cassettes. Similarity and dendrogram analyses revealed that sequences could be grouped according to their geographical origin. Within each geographical group however, no correlation was found between chloroquine resistance and specific mutations.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Antimaláricos/farmacología , Cloroquina/farmacología , Genes MDR/genética , Plasmodium vivax/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/química , Alelos , Secuencia de Aminoácidos , Animales , Brasil , Secuencia de Consenso , Secuencia Conservada , Resistencia a Medicamentos/genética , Variación Genética/genética , Haplorrinos , Humanos , Datos de Secuencia Molecular , Papúa Nueva Guinea , Filogenia , Plasmodium vivax/clasificación , Plasmodium vivax/efectos de los fármacos , Mutación Puntual , Alineación de SecuenciaRESUMEN
Primaquine is the only available drug for preventing relapse of malaria, and confusion surrounds its use. This review examines the wide range of clinical applications of primaquine described in the medical literature between 1946 and 2004. The risk of relapse of Plasmodium vivax malaria without primaquine therapy ranged from 5% to 80% or more, depending largely upon geographic location. Supervision of therapy profoundly impacts the risk of relapse, and almost all reports of malaria resistant to primaquine are associated with lack of such supervision. We nonetheless suspect that there is widespread resistance to the standard course of primaquine therapy, which is 15 mg primaquine base daily for 14 days. Clinical evidence confirms that a course of 15 mg daily for just 5 days, a regimen widely used in areas where malaria is endemic, has no discernible efficacy. This review supports a recommendation for a regimen of 0.5 mg/kg primaquine daily for 14 days, on the basis of superior efficacy and good tolerability and safety in nonpregnant persons without glucose-6-phosphate dehydrogenase deficiency.
Asunto(s)
Antimaláricos/uso terapéutico , Malaria/tratamiento farmacológico , Primaquina/uso terapéutico , Animales , Antimaláricos/efectos adversos , Resistencia a Medicamentos , Humanos , Malaria/parasitología , Plasmodium/efectos de los fármacos , Plasmodium/fisiología , Primaquina/efectos adversosRESUMEN
An expanding risk and range of endemic malaria threatens travelers. Primaquine is an old drug recently demonstrated to offer effective prophylaxis. Clinical trials conducted in Indonesia, Kenya, and Colombia showed that a primaquine base (30 mg per day) had protective efficacy against Plasmodium falciparum and Plasmodium vivax of 85%-93%. Among 339 children (age, >8 years) and adults taking this regimen for 12-52 weeks, there was no greater risk of adverse symptomatic events among primaquine users than among recipients of placebo in double-blind studies. Among 151 subjects evaluated after 20 or 52 weeks of daily primaquine therapy, methemoglobinemia was found to be mild (<13%; typically <6%) and transient (duration, <2 weeks). We consider primaquine base (0.5 mg/kg per day consumed with food) to be safe, well-tolerated, and effective prophylaxis against malaria for nonpregnant persons and those with normal glucose-6-phosphate dehydrogenase levels. Primaquine's major advantage over most drugs for chemoprophylaxis is that it does not have to be taken before entering or beyond 3 days after leaving a malarious area.
Asunto(s)
Antimaláricos/uso terapéutico , Malaria Falciparum/prevención & control , Malaria Vivax/prevención & control , Primaquina/uso terapéutico , Adulto , Animales , Antimaláricos/efectos adversos , Quimioprevención , Ensayos Clínicos como Asunto , Tolerancia a Medicamentos , Humanos , Plasmodium falciparum/efectos de los fármacos , Plasmodium vivax/efectos de los fármacos , Primaquina/efectos adversos , ViajeRESUMEN
At a public hospital in Georgetown, Guyana, 44 patients seeking treatment for symptomatic, slide-confirmed malaria were given standard chloroquine (CQ) therapy and followed for 28 days. The patients apparently had pure infections with Plasmodium falciparum (14), P. vivax (13) or P. malariae (one), or mixed infections either of P. falciparum and P. vivax (17) or of P. falciparum, P. malariae and P. vivax (two). Each received supervised treatment with 10 mg CQ base/kg on each of days 0 and 1, and 5 mg/kg on day 2. On the day of enrollment (day 0), the patients complained of fever (100%), headache (100%), malaise (94%), myalgia (79%), nausea (67%), vertigo (49%) and vomiting (33%). Many (39%) were ill enough to confine themselves to bed. On day 4, fewer of the subjects complained of fever (15%), headache (15%), malaise (6%), myalgia (21%), nausea (6%), vertigo (24%) or vomiting (0%) despite the relatively high (>48%) risk of therapeutic failure. The cumulative incidence of parasitological failure against P. falciparum was 15% at day 4, 33% at day 7 and 48% at day 14. All of the P. vivax and P. malariae infections cleared before day 4 and none recurred by day 7. Two infections with P. vivax recurred later (on day 14 or 28) but in the presence of less than adequate, whole-blood concentrations of CQ plus desethyl-chloroquine (i.e. <100 ng/ml). Taken together, the results indicate a high risk of therapeutic failure of CQ against P. falciparum but also indicate that resistance to CQ in P. vivax occurs infrequently in Guyana.
Asunto(s)
Antimaláricos/uso terapéutico , Cloroquina/uso terapéutico , Malaria/tratamiento farmacológico , Adolescente , Adulto , Animales , Antimaláricos/efectos adversos , Niño , Cloroquina/efectos adversos , Resistencia a Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Tablas de Vida , Malaria/diagnóstico , Malaria Falciparum/diagnóstico , Malaria Falciparum/tratamiento farmacológico , Malaria Vivax/diagnóstico , Malaria Vivax/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Plasmodium malariae , Recurrencia , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: Akathisia is a common side effect of traditional neuroleptic drugs and is associated with medication refusal and impulsive behavior. While our previous experience indicates that clozapine is effective in treating persistent akathisia, two controlled studies indicate vastly different prevalence rates of akathisia (7% vs. 40%) in patients receiving clozapine. METHOD: We used the Barnes Rating Scale for Drug-Induced Akathisia to estimate the prevalence of akathisia in patients receiving stable doses of clozapine alone (N = 29) in a state hospital. Measurements were also made of manifest psychopathology (Brief Psychiatric Rating Scale) and tardive dyskinesia (Abnormal Involuntary Movement Scale). RESULTS: Two patients (6.8%) receiving clozapine were rated as having akathisia. Only 4 (28.6%) of the 14 subjects with a history of moderate-to-severe tardive dyskinesia on traditional neuroleptic drugs continued to show current evidence of tardive dyskinesia, and in 10 patients (71.4%) there was no evidence of the syndrome (p < .002). In the 4 subjects with tardive dyskinesia there was amelioration to a milder form of the syndrome. There were no new cases of tardive dyskinesia among clozapine-treated subjects. CONCLUSION: These data support the low prevalence of akathisia in patients receiving stable doses of clozapine monotherapy. There is further support that clozapine has an ameliorating effect on tardive dyskinesia associated with traditional neuroleptic drugs. These and other data indicate the need for a controlled trial of clozapine in patients experiencing persistent and disabling akathisia on traditional neuroleptic drugs.
Asunto(s)
Acatisia Inducida por Medicamentos/epidemiología , Clozapina/efectos adversos , Adulto , Acatisia Inducida por Medicamentos/etiología , Acatisia Inducida por Medicamentos/prevención & control , Antipsicóticos/efectos adversos , Clozapina/uso terapéutico , Discinesia Inducida por Medicamentos/epidemiología , Discinesia Inducida por Medicamentos/etiología , Discinesia Inducida por Medicamentos/prevención & control , Femenino , Humanos , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/tratamiento farmacológico , Prevalencia , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológicoRESUMEN
A 27-year-old white woman from New York City acquired an infection by a Brugia species while she camped in the Amazon basin of Peru. She was infected by at least one adult male worm and one gravid female worm. Both worms were intact and in a lymphatic vessel of a right cervical lymph node. The lymph node and surrounding fibroadipose tissue contained many microfilariae. The male worm was 50 micron wide and the female, 100 micron. Both worms had thin (1 micron) cuticles with fine transverse striations. There were 3 to 4 somatic muscle cells per quadrant. Microfilariae had tails characteristic of the genus Brugia. Although specific identification was not possible from the available material, the worm closely resembled Brugia guyanensis, a parasite of the coatimundi (Nasua nasua) and the only species of Brugia known in South America.