RESUMEN
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
Aotus monkeys are good models for erythrocyte-induced Plasmodium falciparum and P. vivax infections and have been extensively used in malarial drug and vaccine development. Recently, it has been shown that certain species of Aotus can be infected with sporozoites, and that the degree of susceptibility varies among species. We demonstrate here that Panamanian Aotus lemurinus lemurinus are susceptible to a sporozoite-induced infection, opening the possibility that this species of Aotus could be used as models for testing the efficacy of pre-erythrocytic P. falciparum vaccines and drug candidates directed at the pre-erythrocytic stages of P. falciparum and P. vivax malaria. In this species, we compared sporozoite infection rates. Two of four animals splenectomized prior to infection with sporozoites developed patent parasitemias. Seven of eight animals splenectomized either 7 or 35 days after infection became parasitemic. Additionally, we used a P. falciparum-specific polymerase chain reaction (PCR) method to detect the early appearance of parasitized erythrocytes in the blood prior to detection by conventional microscopy, and found that the parasitemia was detected first in five animals by the PCR method, first in three animals by blood film, with one parasitemia detected simultaneously. We also demonstrated the feasibility of infecting monkeys located in Panama with sporozoites isolated at an insectary in Atlanta, thus documenting the feasibility of similar studies where the insectary and monkey colony are not in the same location. A subsequent attempt to infect these monkeys using sporozoites was not successful, suggesting that this model of human malaria is not yet ready for routine use in vaccine or drug efficacy screening. This model merits further study because of the importance of testing pre-erythrocytic P. falciparum malaria vaccines and drugs in animals.
Asunto(s)
Aotus trivirgatus/inmunología , Modelos Animales de Enfermedad , Malaria Falciparum/veterinaria , Plasmodium falciparum/patogenicidad , Animales , Anopheles/parasitología , ADN Protozoario/química , Ensayo de Inmunoadsorción Enzimática/veterinaria , Femenino , Malaria Falciparum/inmunología , Masculino , Hibridación de Ácido Nucleico , Panamá , Parasitemia/sangre , Reacción en Cadena de la Polimerasa/veterinaria , Esplenectomía/veterinariaRESUMEN
We examined envelope protein profiles, chromosomal restriction endonuclease digest patterns, and immune responses to envelope proteins for collections of Salmonella typhi strains isolated in Peru and Indonesia. Only minor differences in envelope protein patterns were apparent among strains. Strains from 7 of 20 Indonesian patients had a distinct chromosomal digest pattern compared with patterns of Peruvian and other Indonesian strains. Strains with this pattern carried the gene for the j flagellar antigen (H1-j); differences in response to envelope proteins of j and d strains were noted on immunoblot analysis. Our data suggest that there are genotypic and phenotypic differences among S. typhi strains. The clinical importance of these differences remains to be fully evaluated; however, in this study it was not possible to show a clear correlation between strain characteristics and disease severity.