RESUMO
Studies were conducted from 1986 through 1993 to further define the geographic distribution and relative importance of different species of Leishmania as a cause of leishmaniasis in Peru. Patients with a clinical diagnosis of cutaneous and/or mucosal or diffuse cutaneous leishmaniasis were enrolled at the Naval Medical Research Institute Detachment (NAMRID) Laboratory in Lima, the Tropical Disease Clinic at San Marcos University Daniel A. Carrión, the Central Military Hospital, and a Ministry of Health hospital in Cusco, Peru. Clinical features, lesion aspirates, and biopsy tissue were obtained from each patient. All specimens were collected and assayed separately, including multiple specimens from some of the same patients for Leishmania parasites by inoculating aliquots of either aspirates or biopsy tissue suspensions onto Senekji's blood agar medium. Stocks of Leishmania isolates were used to prepare promastigotes to produce extracts for identifying the Leishmania species by the cellulose acetate electrophoresis enzyme technique. A total of 351 isolates of Leishmania were obtained from 350 patients who were infected primarily in the low and high jungle of at least 15 different Departments of Peru. Of the 351 isolates, 79% were identified as L. (V.) braziliensis, 7% as L. (V.) guyanensis, 10% as L. (V.) peruviana, 2% as L. (V.) lainsoni, and 1.7% as L. (L.) amazonensis. The clinical form of disease varied depending on the species of Leishmania, with L. (V.) braziliensis being associated most frequently with cutaneous, mucosal ulcers and mixed cutaneous and mucosal disease, and L. (V) peruviana, L. (V.) guyanensis, L. (V.) lainsoni with cutaneous lesions. Leishmania (L.) amazonensis was isolated from six patients, three with cutaneous lesions, one with mucosal lesions, and two with diffuse cutaneous lesions. Among all of the leishmaniasis cases, males were affected more frequently, and cases occurred among patients less than 10 to more than 51 years of age. These data further defined the geographic distribution and the relative frequency of Leishmania species associated with different clinical forms of leishmaniasis in Peru.
Assuntos
Leishmania/classificação , Leishmaniose/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Animais , Criança , Pré-Escolar , Eletroforese em Acetato de Celulose , Feminino , Geografia , Humanos , Lactente , Isoenzimas/análise , Leishmania/enzimologia , Leishmaniose/parasitologia , Masculino , Pessoa de Meia-Idade , Peru/epidemiologia , Distribuição por SexoRESUMO
A randomized, open, controlled clinical trial was designed to evaluate the efficacy, tolerance, and safety of sodium stibogluconate plus allopurinol and sodium stibogluconate alone as treatment of patients with mucocutaneous leishmaniasis. In phase 1 of the study, all 22 patients with severe disease had improvement of their lesions, but only two had clinical cure (both of these patients received sodium stibogluconate alone). In phase 2, which included 59 patients with moderate disease, the cure rate among sodium stibogluconate recipients was 75% (21 of 28) compared with 63.6% (14 of 22) among the sodium stibogluconate plus allopurinol recipients. The rates of clinical adverse events were similar among both groups. Thrombocytopenia was more frequent in the sodium stibogluconate plus allopurinol recipients, but the difference was not statistically significant. Eight patients (two sodium stibogluconate recipients and six sodium stibogluconate plus allopurinol recipients) withdrew from the study because of severe thrombocytopenia. In this study, the addition of allopurinol to sodium stibogluconate provided no clinical benefit as treatment of mucocutaneous leishmaniasis.
Assuntos
Alopurinol/administração & dosagem , Gluconato de Antimônio e Sódio/administração & dosagem , Antiprotozoários/administração & dosagem , Leishmaniose Mucocutânea/tratamento farmacológico , Adulto , Alopurinol/efeitos adversos , Gluconato de Antimônio e Sódio/efeitos adversos , Antiprotozoários/efeitos adversos , Quimioterapia Combinada , Tolerância a Medicamentos , Humanos , Masculino , SegurançaRESUMO
Surveys were conducted from 1986 through 1992 to define the etiology and geographic distribution of human leishmaniasis in Peru. Lesion aspirates and skin biopsies were obtained from clinically diagnosed cases of leishmaniasis and tested for promastigotes by standard culture techniques. The isozyme profile of the isolates was determined by the cellulose acetate electrophoresis technique. Data indicated that the isozyme profiles for Leishmania isolates from six patients were similar to that of reference strains of L. lainsoni. These results are the first reported evidence of L. lainsoni and the first association of this parasite with human cases of cutaneous leishmaniasis in Peru.
Assuntos
Leishmania/isolamento & purificação , Leishmaniose Cutânea/parasitologia , Adolescente , Adulto , Animais , Biópsia , Eletroforese em Acetato de Celulose , Humanos , Isoenzimas/análise , Leishmania/classificação , Leishmania/enzimologia , Leishmaniose Cutânea/epidemiologia , Masculino , Peru/epidemiologia , Pele/parasitologiaRESUMO
The efficacy and toxicity of two regimens of antimony, 28 and 40 days of 20 mg of antimony/kg/day, were compared in the treatment of culture-positive mucosal leishmaniasis involving more than one anatomic site. Forty consecutive eligible Peruvians with infiltrative or ulcerative mucosal disease of the lips, nose, palate-uvula-pharynx, or larynx-epiglottis were randomized to receive either 28 days (P28) or 40 days (P40) of sodium stibogluconate (Pentostam). Treatment was prematurely terminated due to thrombocytopenia in three patients and two patients did not complete six months of follow-up. At one month post-treatment, 13% (2 of 16) of the P28 patients and 16% (3 of 19) of the P40 patients no longer had infiltrates or ulcers and were initially considered cured. During a further 11 months of follow-up, infiltrated lesions healed in eight more P28 patients and in 10 more P40 patients. The cure rate after 12 months of follow-up was therefore 63% for both groups (10 of 16 in the P28 group and 12 of 19 in the P40 group). The total of 13 patients who had infiltrates or ulcers at the 9-12-month follow-up were considered failures. All seven patients (three in the P28 group and four in the P40 group) whose lesions were culture-positive for Leishmania at some point in the 12 months after treatment, and who were thereby parasitologic failures, were also clinical failures.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Gluconato de Antimônio e Sódio/uso terapêutico , Leishmaniose Mucocutânea/tratamento farmacológico , Doenças Profissionais/tratamento farmacológico , Adulto , Gluconato de Antimônio e Sódio/administração & dosagem , Gluconato de Antimônio e Sódio/efeitos adversos , Esquema de Medicação , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Peru , Resultado do TratamentoRESUMO
Pentavalent antimony (Sbv), formulated as sodium stibogluconate or meglumine antimoniate, is the standard treatment for the leishmaniases. In 16 of 17 consecutive, prospectively observed patients in Washington D.C., serum levels of amylase and lipase rose to abnormal values after therapy with sodium stibogluconate was started; 12 of 17 had symptoms of pancreatitis. Sbv therapy was continued to completion in 7 of 17 patients and interrupted in 10 of 17. Pancreatitis improved in every patient after Sbv therapy was stopped. Sbv treatment was resumed after brief interruptions in 6 of 10 patients. All six of these patients had flares of pancreatitis, but each completed therapy. Subsequently, we measured amylase and lipase levels in stored sera from 32 patients treated in Peru with either sodium stibogluconate or meglumine antimoniate for mucosal leishmaniasis. In all 32 Peruvian patients, serum amylase and lipase rose to abnormal levels during Sbv therapy; 11 of 32 had symptoms of pancreatitis. Standard Sbv regimens induce pancreatitis in almost all patients, but continued therapy is often tolerated; pancreatitis subsides when therapy is stopped, and rechallenge may be tolerated after a brief halt in treatment.
Assuntos
Gluconato de Antimônio e Sódio/efeitos adversos , Pancreatite/induzido quimicamente , Adulto , Amilases/sangue , Gluconato de Antimônio e Sódio/administração & dosagem , Antiprotozoários/administração & dosagem , Antiprotozoários/efeitos adversos , District of Columbia , Humanos , Leishmaniose Mucocutânea/tratamento farmacológico , Leishmaniose Visceral/tratamento farmacológico , Lipase/sangue , Masculino , Meglumina/administração & dosagem , Meglumina/efeitos adversos , Antimoniato de Meglumina , Pessoa de Meia-Idade , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/efeitos adversos , Pancreatite/enzimologia , Peru , Estudos ProspectivosRESUMO
Anopheles mosquitoes captured in Andoas, Peru, a Plasmodium vivax-endemic area in the Peruvian Amazon region, contained both VK210 and VK247 P. vivax circumsporozoite (CS) proteins. Approximately 0.9% of the 4,403 mosquitoes tested by enzyme-linked immunosorbent assay were positive; 28% and 72% of the positive mosquitoes contained VK210 and VK247 CS proteins, respectively. These findings correlate strongly with a recent report of the presence of antibodies in residents of this area that recognize the VK210 and VK247 repeats, clearly indicating that both P. vivax CS protein polymorphs are common in the region.
Assuntos
Anopheles/parasitologia , Plasmodium vivax/química , Proteínas de Protozoários/análise , Animais , Peru , Plasmodium vivax/isolamento & purificaçãoRESUMO
Individuals living in a malaria-endemic area in northern Peru were found to have antibodies to the variant repeat sequence of the circumsporozoite (CS) protein of Plasmodium vivax. The presence of IgG antibody to the predominant repeat sequence GDRAA/DGPA represented by the recombinant protein NS1(81) V20 (V20), and the variant repeat sequence ANGAGNQPG contained in the synthetic peptide Pvk247, was determined by enzyme-linked immunosorbent assay. IgG antibodies to the repeats were present in 78 (26%) of 298 serum samples; 56% of the positive serum samples had antibodies to V20 and 60% had antibodies to Pvk247. These findings stress the importance of considering the variant epitope in designing a vaccine based on the repeat region of the vivax CS protein. In a malaria-endemic area such as the one in this study, in which exposure to the variant repeat epitope may be as frequent as exposure to the predominant repeat, a vaccine based solely on the predominant repeat epitope may be ineffective against the variant form.
Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Malária Vivax/epidemiologia , Plasmodium vivax/imunologia , Proteínas de Protozoários , Adolescente , Adulto , Fatores Etários , Sequência de Aminoácidos , Animais , Antígenos de Protozoários/química , Antígenos de Protozoários/genética , Criança , Pré-Escolar , Humanos , Imunoglobulina G/sangue , Lactente , Malária Vivax/imunologia , Dados de Sequência Molecular , Peru/epidemiologia , Plasmodium vivax/genética , PrevalênciaRESUMO
The presence in the New World of a variant strain of Plasmodium vivax (VK247) containing a unique circumsporozoite (CS) repeat domain was determined by the detection of antibodies to the variant CS protein and by genetic analysis of the CS gene from field isolates. Whole blood specimens were collected on filter paper from patients infected with P. vivax in Mexico and Peru. Plasmodium vivax DNA was eluted from filter paper samples and the CS gene was amplified by the polymerase chain reaction (PCR) and analyzed for the presence of VK247 or VK210 DNA by oligoprobe hybridization. Sera eluted from a companion filter paper sample were screened for antibodies reactive with the predominant and variant repeat peptides by enzyme-linked immunosorbent assays (ELISA) and with sporozoites by the immunofluorescent antibody (IFA) test. All 24 patients were positive by PCR and oligoprobe hybridization for either VK210 (16 of 24), VK247 (3 of 24), or both (5 of 24). Mixed infections were common (5 of 7) in Peru, but were not observed in the Mexican isolates (0 of 17). All three VK247 infections from Mexico occurred in residents of the foothills above Tapachula (P = 0.02). Of patients with smear-positive P. vivax infection, 42% (10 of 24) had detectable antibodies eluted from dried blood dots that were reactive with the CS protein by IFA or ELISA. These findings establish the widespread distribution of the P. vivax variant CS protein in the New World and indicate that dried blood filter paper samples represent a valuable source of material for the serologic and molecular analysis of plasmodial infections.
Assuntos
Anticorpos Antiprotozoários/biossíntese , Antígenos de Protozoários/genética , Variação Genética , Malária Vivax/parasitologia , Plasmodium vivax/imunologia , Proteínas de Protozoários , Animais , Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Sequência de Bases , DNA de Protozoário/análise , DNA de Protozoário/química , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Amplificação de Genes , Humanos , México , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Sondas de Oligonucleotídeos/química , Peru , Plasmodium vivax/genética , Reação em Cadeia da PolimeraseRESUMO
The circumsporozoite (CS) protein of Plasmodium vivax consists of a central repeat region flanked by highly conserved non-repeat regions. Serum samples from 33 individuals with naturally acquired infections of P. vivax were tested for antibodies to four antigens representing the vivax CS protein. Three recombinant proteins containing different overlapping sequences in the non-repeat regions and either the entire central repeat region (vivax-1 and vivax-2) or two of the repeat sequences (vivax-3) were used as antigens in an enzyme-linked immunosorbent assay (ELISA). Antibodies to two other proteins, one (NS1(81)V20) containing the entire predominant repeat region (GDRAA/DGQPA) and the other (Pvk247) containing the variant repeat sequence (ANGAGNQPG) that was recently reported from Thailand were also measured by ELISA. Immunoglobulin G antibodies to the antigen representing the predominant repeat were present in 15% of the patients on the first day of treatment (day 0) and in 24% of the patients two weeks later (post-treatment). Six and 12% of the patients had IgG antibodies to the antigen containing the variant repeat on day 0 and post-treatment, respectively. A larger proportion of the sera had antibodies to the three antigens containing the non-repeat sequences; on the first day of treatment and two weeks later, 79 and 97% of the patients, respectively, had antibodies to vivax-1, vivax-2, and vivax-3. In this sample of Peruvians naturally infected with P. vivax, the most prevalent antibody responses were targeted to epitopes in the non-repeat region of the CS protein rather than to epitopes in the repeat region.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Anticorpos Antiprotozoários/biossíntese , Antígenos de Protozoários/imunologia , Malária Vivax/imunologia , Plasmodium vivax/imunologia , Proteínas de Protozoários , Adulto , Animais , Anticorpos Antiprotozoários/sangue , Especificidade de Anticorpos , Ligação Competitiva , Ensaio de Imunoadsorção Enzimática , Epitopos/imunologia , Humanos , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Imunoglobulina M/biossíntese , Imunoglobulina M/sangue , Proteínas Recombinantes/imunologia , Sequências Repetitivas de Ácido Nucleico/imunologiaRESUMO
We studied the interaction of sera from residents of an area in northern Peru where vivax malaria is endemic with four recombinant DNA-derived circumsporozoite (CS) proteins of Plasmodium vivax. The antigens used in the enzyme-linked immunosorbent assay included one Escherichia coli-produced and three Saccharomyces cerevisiae-produced recombinant proteins. Three of the proteins (NS1(81)V20, Vivax-1, and Vivax-2) contain the entire central repeat region of the P. vivax CS protein, and one protein (Vivax-3) contains only two repeat sequences. Vivax-1, Vivax-2, and Vivax-3 contain different lengths of sequences flanking the repeats. A higher percentage of the sera had antibodies to Vivax-2 and Vivax-3, the two proteins containing the longest nonrepeat sequences, than to NS1(81)V20 or Vivax-1. Children less than 5 years of age did not have immunoglobulin G antibodies to NS1(81)V20; however, they had antibodies to Vivax-1, Vivax-2, and Vivax-3. The finding that individuals living in a malaria-endemic area produce antibodies to peptides containing nonrepeat regions of the CS protein emphasizes the need to characterize the immune response to these regions in naturally exposed and experimentally immunized humans.