Current concepts in parasitology. Leishmaniasis.
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Biomedical subjects
Publications and source records attributed to P D Marsden.
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Two stocks of Trypanosoma cruzi isolated from patients with advanced megaoesophagus produced megastomach in chronically infected mice. The mice showed evidence of stomach dilatation and a delay in intestinal transit time. These findings are discussed in the light of the hypothesis that regional variations in T. cruzi determines mega formation in man.
In patients serologically positive for Trypanosoma cruzi infection the three bug species/instar combinations used in xenodiagnosis showed third-instar Dipetalogaster maximus to be more efficient in detecting circulating trypanosomes than the first instar of the same species which, in turn, is more sensitive than third-instar Triatoma infestans. The sensitivity of the pool technique of faecal examination compared with individual dissection was investigated. Four pool examinations (the product of 20 bugs) were equivalent to 10 individual bug dissections. Because of the ease of providing large numbers of bugs for mass xenodiagnosis, first-instar D. maximus has replaced third-instar T. infestans in our routine work. The value of third-instar D. maximus as a xenodiagnostic agent needs further investigation.
In five rhesus monkeys surviving 'Peru strain' or 'strain 7' Trypanosoma cruzi infection for six to eight years, positive xenodiagnosis results and high indirect fluorescent antibody titres (4096 - 65536) persisted until the animals were killed. Abnormal electrocardiograph patterns in two monkeys (H and K) were possibly compatible with myocardial damage. Histopathological changes attributable to T. cruzi infection were minor in four monkeys but severe in one (R). In this animal, infected with what was judged previously to be the less virulent of the two T. cruzi stocks used ('strain 7'), there was severe myocarditis, with myofibre degeneration, and lesions of the oesophagus. Elevated serum levels of five enzymes were not detected in any of the chronically infected monkeys.
A trial of Nifurtimox (Lampit) in 26 patients with mucocutaneous leishmaniasis is reported. 13 patients with cutaneous lesions and 13 patients with mucosal disease were treated with a daily oral divided dose of 10 mg/kg body-weight for 30 days. 46% of the cutaneous cases and only 15% of the mucosal cases apparently responded to this regimen during at least one year of follow up. The difficulties of assessing cure in this disease are briefly discussed. We consider that Nifurtimox remains an investigational drug. While possibly exhibiting some anti-leishmanial activity it cannot be recommended for routine use in either form of the disease.
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First instar Dipetalogaster maximus proved as effective as third instar Triatoma infestans in detecting circulating Trypanosoma cruzi in patients with chronic infections examined in a routine xenodiagnostic laboratory. Since rearing costs are diminished, D. maximus has now replaced T. infestans as the xenodiagnostic agent in our laboratory. However, further work is needed to define the optimal conditions necessary when using this species in xenodiagnosis.
Investigations into the viability time of T. cruzi in dead bugs experimentally infected with "Peru" strain showed a maximum of 9 days for Dipetalogaster maximus and 8 for Triatoma infestans maintained at ambient temperature (26 degrees C). On refrigeration survival was increased to 60 days. In routine xenodiagnosis in the refrigerator 90 day survival was noted of both T. cruzi and the vector bug.
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Information on the acute and early chronic phases of infection with Trypanosoma cruzi in eight rhesus monkeys is reported with particular reference to the pattern of subpatent parasitaemia and serology. Xenodiagnosis was superior to animal inoculation and blood culture in its capacity to detect subpatent parasitaemia. Each monkey showed an individual, relatively constant pattern of this not related to the nature of the inoculum. Levels of indirect fluorescent and indirect haemagglutinating antibodies remained elevated during a year of observations. One monkey died with a megaoesophagus. Another monkey after challenge with a heterologous strain by orbital inoculation failed to develop Romana's sign and showed no change in serum antibody levels or degree of xenopositivity.
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Fifth instar Rhodnius prolixus, Triatoma infestans and Panstrongylus megistus were fed on a rhesus monkey (Macaca mullatta) with a chronic infection of Peru strain Trypanosoma cruzi and examined 30 days later for the presence of trypanosomes in the rectum. No correlation could be demonstrated between either blood meal size or sex and the subsequent development of a rectal infection with T. cruzi. As T. infestans and P. megistus were more highly infected than R. prolixus in terms of both percentage infected and degree of infection, the two former species can be regarded as more suitable for the xenodiagnosis of this particular strain of T. cruzi in M. Mullatta.
Cerebral malaria is an acute diffuse encephalopathy associated only with Plasmodium falciparum. It is probably a consequence of the rapid proliferation of the parasites in the body of man in relation to red cell invasion, and results in stagnation of blood flow in cerebralcapillaries with thromobotic occlusion of large numbers of cerebral capillaries. The subsequent cerebral pathology is cerebral infarction with haemorrhage and cerebral oedema. The wide prevalence of P. falciparum in highly endemic areas results in daily challenges to patients from several infected mosquitoes. It is thus important to understand the characteristics of P. falciparum, since this is one of the most important protozoan parasites of man and severe infection from it constitutes one of the few real clinical emergencies in tropical medicine. One of the more important aspects of the practice of medicine in the tropics is to establish a good understanding of the pattern of medical practice in that area. This applies to malaria as well as to other diseases. The neophyte might be somewhat surprised to learn, for example that an experienced colleague who lives in a holoendemic malarious area such as West Africa, sees no cerebral malaria. But the explanation is simple when the doctor concerned has a practice which involves treating adults only. Cerebral malaria is rare in adults, because in highly endemic areas, by the age of 1 year most of the infants in a group under study have already experienced their first falciparum infection. By the time they reach adult life, they have a solid immunity against severe falciparum infections. In fact, "clinical malaria" could occur in such a group under only two circumstances: 1) in pregnancy, a patent infection with P. falciparum might develop, probably due to an IgG drain across the placenta to the foetus;2) in an individual who has constantly taken antimalarials and who may have an immunity at such a low level that when antimalarial therapy is interrupted, clinical malaria might ensue. The above examples emphasise the paramount importance of the clinician dealing with malaria having some insight into the complex immunity processes operative in the human host; these have been reviewed by McGregor.
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