Urinary schistosomiasis among school children in Ile-Ife, Nigeria.

A study of urinary schistosomiasis among 553 randomly selected primary and secondary school children in Ile-Ife township in 1988 shows that nearly half (48.5%) of the school children were infected. There was a sharp increase in both the prevalence and intensity of the infection up to age 13 years which then declined slightly by age 14. About 50% of the infected school children had gross hematuria. There was an association between the intensity of the infection and the presence of hematuria. The main strategies recommended for the control of the infection were regular disinfection of ponds and streams in the town and adequate treatment of infected school children, backed up with school health education programme.

Socio-cultural problems in the execution of a Guinea worm control programme. A case report.

It is a known fact that dracunculiasis (guinea worm infection) can be controlled through the provision of clean water. This case report elucidates some of the problems militating against the effectiveness of such a control method in a rural and illiterate community. These problems are borne from inappropriate equipment, health education and cultural prejudices. Solutions to these problems are suggested.

Cations in body fluids of Trypanosoma brucei in infected rabbits.

Serum copper, magnesium, zinc, calcium and ionized calcium (Ca++) concentrations were compared in 6 rabbits infected with Trypanosoma brucei brucei and 5 uninfected rabbits. There was a significant depletion of Mg and Zn and a significant increase in Cu from about day 10 of infection to the end. There was no change in plasma total calcium or free diffusible calcium. There was a development of kidney damage as shown clinically by proteinuria and urinary loss of magnesium and zinc, and histologically by the observation of hypercellularity in the glomeruli and tubular degeneration. Our findings thus indicate that trypanosomiasis causes kidney damage which may be responsible for the depletion of the cations seen in the study. Some of the clinical manifestations associated with African trypanosomiasis such as convulsions, anaemia, electrocardiographic changes and splenomegaly may therefore be related to these cation changes.

Neurochemical measurements in the brains of mice infected with Trypanosoma brucei brucei (TREU 667).

Trypanosoma brucei brucei (TREU 667) infected mice were used as a model of African trypanosomiasis, a disease in which neuropsychiatric manifestations occur. To study the possible neurochemical basis of these abnormalities, we measured brain acetylcholine receptor numbers, activities of the cholinergic enzymes, choline acetyltransferase (CAT), and acetylcholinesterase (AChE), and regional concentrations of the monoamines, dopamine (DA), serotonin (5-HT), and norepinephrine (NE), and their acid metabolites, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) in mice infected with T. b. brucei. There were no significant changes in CAT or AChE activities or acetylcholine receptor numbers at either 35 or 50 days post-infection (PI). At day 35 PI, the only significant finding was a decrease in 5-HIAA concentration in the brain stem, a change which did not persist to day 50 PI. At day 50 PI there were, however, significant increases in DA concentration in the brain stem and NE concentrations in the hippocampus, cerebellum, brain stem and striatum. To establish a chronic relapsing murine model, mice were treated with diminazene aceturate (Berenil) at day 60 PI and killed 60 days later (120 days PI). In these mice, 5-HT concentrations were significantly increased in the hypothalamus and decreased in the cortex. In addition, 5-HIAA concentrations were increased in the striatum and hypothalamus and HVA concentrations were increased in the striatum and hippocampus. Our data, taken together with that of others, suggests that there are alterations in the monoaminergic, but not in the cholinergic, neuronal system, in African trypanosomiasis. These data may form the basis for the neuropsychiatric abnormalities that are associated with this disease.

Trypanosoma cruzi infection in diabetic mice.

The course of infection due to Trypanosoma cruzi (Brazil strain) was examined in mutant and streptozotocin (STZ)-induced diabetic mice. Mutant diabetic mice (+db/+db) are obese, have elevated blood glucose levels, normal insulin levels and impaired cell mediated immunity (CMI). Their littermates (m+/m+, m+/+db) are of normal weight, normoglycaemic and immunocompetent. Infected +db/+db mice died within 20-25 d after infection (AI) with a mean peak parasitaemia of 6 X 10(6) trypomastigotes/ml accompanied by heavy tissue parasitism. The nondiabetic littermates had low, transient, parasitaemia, no tissue parasitism, and 100% survival. Immune mouse serum (IMS) was given to infected +db/+db mice thrice weekly beginning on day 1 AI. During IMS treatment, parasitaemia remained significantly lower than in untreated mice. However, when IMS treatment was discontinued parasitaemia rose and mortality ensued. To examine the effects of hyperglycaemia in the absence of other variables such as genetics or CMI, T. cruzi infection was studied in STZ-induced diabetic mice. Normal C57BL/6 mice, resistant to infection with the Brazil strain, exhibited low transient parasitaemia and no mortality. In contrast, STZ-induced hyperglycaemic C57BL/6 mice developed high parasitaemia and 100% mortality by day 40 AI. When these hyperglycaemic mice were treated with insulin continuously by pump, their blood glucose levels returned to normal but parasitaemia and mortality were unchanged. These data indicate that hyperglycaemia significantly increases parasitaemia and mortality in mice infected with T. cruzi.

Protection against fatal murine Chagas' disease with a Leishmania braziliensis panamensis stock.

Past attempts to immunize mice against a fatal Trypanosoma cruzi infection utilizing related hemoflagellates have been unsuccessful. In the present study, C57BL/6 mice received a footpad inoculation of 10(7) promastigotes of Leishmania braziliensis panamensis. Six and 9 weeks subsequent to this inoculation mice were infected intraperitoneally with the Tulahuen strain of T. cruzi. All immunized mice survived infection over the 6-month period of observation whereas control mice regularly died. There was an early transient T. cruzi parasitemia in the immunized mice. Culture of blood and organs as well as histopathological examination of various organs 6 months post-challenge failed to yield any evidence of T. cruzi. Heat-killed and freeze-thawed extracts of promastigotes did not confer any protection. These observations raise the possibility that certain leishmanial species might confer natural protection against a T. cruzi infection and that this information could be useful in the development of a vaccine.

Trypanosoma brucei: infection in murine diabetes.

The course of infection due to Trypanosoma brucei infection was observed in genetically diabetic and streptozotocin-induced diabetic mice. A strain of T. brucei, TREU 667, was used which produces a chronic infection in C57BL/6(B6) mice lasting greater than 60 days. Genetic diabetic mice (+db/+db) are obese, and have elevated blood glucose levels, normal levels of insulin, and impaired cell-mediated immunity. Their littermates (m+/m+, m+/+db) are of normal weight, and are normoglycemic and immunocompetent. The infected +db/+db mice lived significantly longer than the nondiabetic littermates. In contrast to this finding, streptozotocin-induced diabetic B6 mice developed higher parasitemia and had shorter survival times than control B6 mice. Continuous treatment with insulin of these streptozotocin-induced diabetic mice led to normalization of blood glucose and a significant reduction of parasitemia. While hyperglycemia may be associated with higher parasitemia and death in streptozotozin-induced diabetes, genetic factors may play an additional role in the genetic models.

Pathogenesis of anemia in Trypanosoma brucei-infected mice.

The pathogenesis of anemia was studied in trypanosome-infected mice. A strain of Trypanosoma brucei, TREU 667, was used which first produces an acute phase marked by waves of parasitemia. Erythrocytes from infected animals were coated with immunoglobulin M during or just before the waves of anemia and parasitological crises. Erythrocytes from normal animals could be sensitized with "precrisis" sera presumably containing antigen and antibody. These data suggest that anemia during the acute phase is due to sensitization of erythrocytes with immunoglobulin M-antigen complexes. The anemia is partially compensated by a strong erythropoietic response. The acute phase is followed by a chronic phase marked by a constant high parasitemia and immunosuppression. The less marked anemia occurring during this latter phase is due to hemodilution and perhaps a low but significant immune response to the parasites, which causes continuing erythrocyte sensitization by immunoglobulin M-antigen complexes.

Role of calcium in trypanocidal drug action.

The synergistic effect of serum on the drug combination of salicylhydroxamic acid plus glycerol, which is active against Trypanosoma brucei, is due to diffusible calcium ions. The synergistic activity can be removed by dialysis of the serum or by addition of calcium chelating agents. A buffer containing calcium can mimic the synergistic activity of serum. This finding may have important implications in the clinical management of African trypanosomiasis in humans. Calcium also has a synergistic effect on melarsoprol, the only drug available for treating sleeping sickness patients with central nervous system involvement, and the concentration of calcium has been reported to be depressed inthe serum of experimentally infected animals.

Further studies on difluoromethylornithine in African trypanosomes.

DL-alpha-Difluoromethylornithine (DFMO), a specific enzyme-activated irreversible inhibitor of ornithine decarboxylase (ODC) was previously shown to cure mice infected with Trypanosoma brucei brucei, a parasite of game and cattle in Africa and Trypanosoma brucei rhodesiense, a human African Sleeping Sickness pathogen. Our studies now indicate that DFMO blocks ornithine decarboxylase and lowers trypanosome polyamine levels in vivo. Polyamine uptake in T.b. brucei also resembles that previously described for mammalian cells. The therapeutic potential of DFMO can now also be extended to another human pathogen, Trypanosoma brucei gambiense. Finally, DFMO acts synergistically with another drug, bleomycin, to cure acute trypanosome infections, and furthermore, this same drug combination provides a new approach to the treatment of trypanosomal infections of the central nervous system.