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Leishmaniasis a disease caused by infection with the tropical parasitic organism leishmania (generally transmitted by sandfly bites), which can result in acute lesions of the lining (mucosa) of the nose and mouth. If untreated, this condition can cause progressive erosion of the nasal and oral mucosa leading to perforation of the nasal septum, narrowing of the oral canal, hoarseness, and suffocation. The World Health Organization (WHO) has recommended antimony (a metallic element) injections for the treatment of this disease, but little is known of the efficacy and toxicity of this regimen. To evaluate this, 29 consecutive and otherwise healthy patients referred to a Peruvian regional hospital for leishmaniasis infection were treated with daily intravenous infections of antimony for 28 days in the form of sodium stibogluconate. Immediately following therapy, 88 percent (63 of 72) lesions were healed or greatly improved, none of the lesions tested positive for parasitic infestation, and 18 of 29 patients showed complete clinical remission. At the 12-month follow-up visit, 37 lesions had reappeared, 8 new lesions had developed, and 8 of the patients remained symptom-free. Mildly afflicted patients responded better to the therapy than did severely afflicted ones. Side effects consisted of electrocardiographic abnormalities (T-wave inversion in four patients), abnormal liver function (10 patients), and muscular pain (24 patients). These acceptable levels of toxicity, and the limited efficacy of the WHO-recommended treatment regimen, suggests that either longer treatment periods or combining antimony treatment with other antileishmanial agents should be considered. (Consumer Summary produced by Reliance Medical Information, Inc.)

Malaria is a chronic disease caused by the infection of red blood cells with the parasite sporozoan Plasmodium, which is transmitted by mosquito bites or blood transfusion. The life cycle of Plasmodium can be divided into the asexual phase, which occurs in man, and the sexual phase, which occurs in the mosquito. The sporozoite form of Plasmodium enters man and invades tissue cells, such as liver cells. After 7 to 10 days, the sporozoites infect red blood cells and undergo schizogony, or several cell divisions, producing the merozoite form. The merozoites are released and invade other red blood cells, causing their destruction. This phase of the cycle is associated with symptoms of chills and fever. The merozoites are eventually transformed into microgametes or macrogametes, which are sucked up by the mosquito. The conventional treatment of malaria has proven inadequate, and efforts have focused on the development of a vaccine against the sporozoite stage of Plasmodium falciparum and Plasmodium vivax. The development of a vaccine for P. vivax is based on the presence of a surface protein on P. vivax sporozoites. However, recent studies have shown that the gene that codes for this surface protein varies in different forms of P. vivax. The DNA, or genetic material, of P. vivax was isolated and analyzed to determine the extent of variation in P. vivax forms from South America, the Indian subcontinent, and West Africa. Analyses showed that one genetic variant, or form that is slightly different from the predominant form, was detected in samples from all three geographic regions. In addition, five of six patients tested were shown to be infected by both the predominant and variant forms of P. vivax. These findings suggest that the development of a vaccine that is directed against a single component, such as the surface protein of P. vivax, may not be effective in controlling malaria. (Consumer Summary produced by Reliance Medical Information, Inc.)

ABSTRACTPrevious studies indicated that the Plasmodium yoeliicircumsporozoite protein (PyCSP) 57–70 region elicits T cells capable of eliminating infected hepatocytes in vitro. Herein, we report that the PyCSP58–67 sequence contains an H-2dbinding motif, which binds purified Kdmolecules in vitro with low affinity (3,267 nM) and encodes an H-2d-restricted cytotoxic T lymphocyte (CTL) epitope. Immunization of BALB/c mice with three doses of a multiple antigen peptide (MAP) construct containing four branches of amino acids 57 to 70 linked to a lysine-glycine core [MAP4(PyCSP57–70)] and Lipofectin as the adjuvant induced both T-cell proliferation and a peptide-specific CTL response that was PyCSP59–67 specific, H-2drestricted, and CD8+T cell dependent. Immunization with either DNA encoding the PyCSP or irradiated sporozoites demonstrated that this CTL epitope is subdominant since it is not recognized in the context of whole CSP immunization. The biological relevance of this CTL response was underlined by the demonstration that it could mediate genetically restricted, CD8+- and nitric-oxide-dependent elimination of infected hepatocytes in vitro, as well as partial protection of BALB/c mice against sporozoite challenge. These findings indicate that subdominant epitopes with low major histocompatibility complex affinity can be used to engineer epitope-based vaccines and have implications for the selection of epitopes for subunit-based vaccines.

Anopheles mosquitoes captured in Andoas, Peru, a Plasmodium vivaxendemic 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.

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.