Upregulation of ICAM-1, IL-1 and reactive oxygen intermediates (ROI) by exogenous antigens from Plasmodium falciparum parasites in vitro, and of sICAM-1 in the acute phase of malaria.

After 4 hours of stimulation of human mononuclear leukocytes in the presence of 300 ng/ml exogenous Plasmodium falciparum antigens, the ICAM-1 expression increased variably from 15% to 375%. Simultaneously, an increase of IL-1 mRNA production could be observed in Northern blot hybridizations with a specific cDNA gene probe for human IL-1 alpha labelled with digoxigenin. Furthermore, the reactive oxygen intermediates (ROI) production was also found to be enhanced in similar conditions. Additionally, when the levels of soluble ICAM-1 (sICAM-1) in plasma of 122 patients with P. falciparum or Plasmodium vivax malaria were analyzed in an enzyme immunoassay (EIA), significant sICAM-1 increases were found, more pronounced in patients with P. falciparum malaria, in comparison with healthy controls and with the same patients 4 weeks after chemotherapy. The presented results indicate that the expression of ICAM-1 may also be upregulated by exogenous Plasmodium antigens besides cytokines like IL-1 during the acute phase of malaria, with subsequently elevated sICAM-1 concentrations in blood.

Circulating anodic and cathodic antigen in serum and urine from Schistosoma haematobium-infected Cameroonian children receiving praziquantel: a longitudinal study.

A cohort of 148 Cameroonian children infected with Schistosoma haematobium was followed before praziquantel therapy and 1, 2, 3, 5, and 12 months thereafter. Egg output, the reagent strip index (RSI, a pathological marker), and circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) in serum and urine were quantified. At enrollment, the median level of egg output was 365/10 mL of urine; 97% of children had a positive RSI; CAA was detected in serum from 76% of children and in urine from 64%; and CCA was detected in serum from 55% of children and in urine from 87%. Two months after chemotherapy, egg output and RSI had decreased significantly; reinfection later developed in parallel with increases in the serum and urine concentrations of CAA and the urine concentrations of CCA. The measurement of CAA and CCA is useful for diagnosis, evaluation of disease severity, and follow-up of chemotherapy in individuals infected with S. haematobium.

Serum protein concentrations in Plasmodium falciparum malaria.

In patients with uncomplicated Plasmodium falciparum infection cytokine-mediated serum protein levels of C-reactive protein (CRP), coeruloplasmin (COE), beta 2-microglobulin (B2M), alpha 1-acid glycoprotein (AAG), alpha 1-antitrypsin (AAT), haptoglobin (HPT), prealbumin (PRE), retinol binding protein (RBP), albumin (ALB) and transferrin (TRF) were measured in an endemic area of the Amazonian rain forest. Semi-immune (SI) and nonimmune (NI) patients were investigated. In both patient groups the serum concentrations of CRP, COE and B2M were elevated on admission. In addition AAG and AAT concentrations were increased in NI patients compared to control subjects. Significantly lower serum concentrations of HPT, PRE, RBP, ALB and TRF were seen in both patient groups during the acute phase of the disease, and were more pronounced in NI patients. After a 28-day follow-up, AAT and B2M were normal in SI patients but HPT, AAT and B2M were still significantly altered in NI patients.

Prevalence and level of antibodies to the circumsporozoite proteins of human malaria parasites, including a variant of Plasmodium vivax, in the population of two epidemiologically distinct areas in the state of Acre, Brazil.

A seroepidemiological study of the prevalence of antibodies against the repeating epitopes of circumsporozoite (CS) proteins of human malaria parasites was conducted in 2 different areas in the state of Acre, Brazil in 1987 and 1990. In 1987 antibodies against the CS protein of the VK 247 variant Plasmodium vivax as well as antibodies against the CS proteins of P. falciparum and the classic P. vivax were found at relatively high rates in the 2 areas, but significant microepidemiological differences were observed. In 1990, when large scale migration in Amazonia had ceased and control measures were applied in the study areas, the malaria endemicity decreased, as determined by the declining prevalence of anti-sporozoite antibodies against all Plasmodium species, and the small number of individuals with positive blood smears. Antibodies against sporozoites of the variant P. vivax did not cross-react with the CS proteins of the classic P. vivax, nor with antibodies against sporozoites of P. falciparum and P. malariae. Sera containing antibodies against the CS protein of P. malariae were found at a very low frequency, and only in 1987. The anti-CS protein antibody response to all Plasmodium species was age-related.

Immune response in patients during and after Plasmodium falciparum infection.

The kinetics of indicators of lymphocyte activation were determined in non- and semiimmune patients with uncomplicated Plasmodium falciparum infection and in control subjects in Acre, Brazil. Delayed type hypersensitivity (DTH) to seven recall antigens was weakest in nonimmune patients. Both patient groups differed significantly from controls on admission (P less than .001 for both) and improved considerably after clindamycin therapy. Total serum IgG and IgM, but not antimalarial antibodies, were highest in nonimmune patients compared with semiimmune patients and controls during acute malaria. Immunoglobulin levels normalized after chemotherapy. A striking decrease of CD4+ peripheral blood lymphocytes, normalizing after chemotherapy, was seen in both patient groups, and was more pronounced in nonimmune patients. A slight increase in interleukin-2 receptor (IL-2R)-bearing cells was found in nonimmune patients. In addition, soluble plasma IL-2R was significantly elevated in them (P less than .001) and to a lesser extent in semiimmune patients. These findings were paralleled by significantly decreased IL-2 concentrations in plasma (P less than .001) during the acute phase of malaria, suggesting pronounced general immunosuppression in nonimmune malaria patients.

Immunological alterations in uncomplicated Plasmodium falciparum malaria. Relationship between parasitaemia and indicators of macrophage activation.

Numerical alterations of circulating lymphocytes were investigated in 37 Brazilian patients with uncomplicated Plasmodium falciparum malaria and in a group of 15 healthy controls. The number of CD4+ T helper/inducer cells was significantly lower in patients than controls, whereas absolute numbers of CD8+ suppressor/cytotoxic T cells did not differ between the groups. TNF and neopterin levels were markedly increased in the plasma of patients and remained slightly elevated after chemotherapy with clindamycin. Neopterin, but not TNF levels, were significantly correlated with parasitaemia. TNF was inversely related to monocyte counts. Interferon gamma could not be detected in the plasma of control subjects and was observed in only one patient. We conclude that in uncomplicated falciparum malaria the distribution of phenotypes of circulating lymphocytes are altered slightly and that the high plasma levels of TNF and neopterin indicate excessive release of these molecules by activated macrophages and the activation of cellular immune mechanisms during the infection.

Differences in drug response of Plasmodium falciparum within an area of the Amazon region.

Clinical characteristics of patients with falciparum malaria, as well as sensitivity of Plasmodium falciparum to chloroquine and mefloquine, were investigated in 2 distinct strata within the same geographical area of the Amazon Basin. One stratum was the population living along the road, the other that living along the river, both near Rio Branco, capital of Acre State, Brazil. The clinical features did not differ between the 2 strata. Full in vitro sensitivity of P. falciparum to mefloquine was observed in both areas. However, significant differences in chloroquine sensitivity were observed between the 2 strata. EC50 values for chloroquine were 0.8484 mumol/litre for parasite isolates from the road stratum (E) and 0.4638 mumol/litre for parasite isolates from the river stratum (R). EC90 values were 2.8095 and 1.2549 mumol/litre in strata 'E' and 'R', respectively. Continuous drug pressure over years in area 'E' and relatively low drug pressure in area 'R' were presumably responsible for these differences.

Clindamycin treatment of falciparum malaria in Brazil.

Oral treatment with clindamycin (5 mg/kg twice a day, for five consecutive days) was studied in patients with uncomplicated falciparum malaria in Acre, Brazil, an area with multiresistant Plasmodium falciparum. Parasitaemia ranged between 12 and 79560/microliters of blood admission. Thirty-five out of 44 patients admitted to the study could be followed up for 28 days. Only two patients showed parasitaemia six days after admission, and no asexual parasites were observed by day seven. Twenty-eight days after admission all patients were cured. Of the nine patients withdrawn from the study, five were lost during follow up and four needed different treatment (quinine 15 mg/kg twice a day, for ten days) because clinical symptoms did not improve within 60 h after admission. These patients had experienced their first attack by P. falciparum. In individual cases oral clindamycin can be used as an alternative treatment in semi-immune patients with uncomplicated falciparum malaria from an area where multiresistant parasites frequently occur. However, because of the slow response in all cases described here, and the risk of development of resistance if clindamycin is used alone it cannot be recommended as monotherapy in non-immune patients.

In vitro drug sensitivity of Plasmodium falciparum in Acre, Brazil.

In Acre, the westernmost state of Brazil in the Amazon region, the sensitivity of Plasmodium falciparum to chloroquine, amodiaquine, mefloquine, quinine and sulfadoxine/pyrimethamine was determined in vitro by the Rieckmann microtechnique. The study was performed between January and June 1987; the in vitro parasite responses to all antimalarial drugs were determined according to the recommendations of WHO. Of 83 isolates of P. falciparum, all were sensitive to mefloquine and of 87 isolates of P. falciparum, 84 (97%) were sensitive to quinine. The EC50 for mefloquine was 0.27 mumol/l and for quinine 4.60 mumol/l. In contrast, 65 of 89 (73%) and 70 of 83 (84%) isolates were resistant to amodiaquine and chloroquine, respectively; 11 isolates even grew at 6.4 mumol chloroquine/l. The EC50 for amodiaquine was 0.34 mumol/l and for chloroquine 0.73 mumol/l. Sulfadoxine/pyrimethamine resistance was seen in 23 of 25 (92%) cases. These data clearly indicate that in the western part of the Amazon region the 4-aminoquinolines, as well as sulfadoxine/pyrimethamine, can no longer be recommended for the treatment of P. falciparum infections.

In vitro drug sensitivity of Plasmodium falciparum in Acre, Brazil

In Acre, the westernmost state of Brazil in the Amazon ragion, the sensitivity of Plasmodium falciparum to chloroquine, amodiaquine, mefloquine, quinine and uslfadozine/pyrimethamine was determined in vitro by the Rieckmann microtechnique. The study was performed between January and June 1987; the in vitro parasite responses to all antimalarial drugs were determined according to the recommendations of WHO. Of 83 isolates of P. falciparum, all were sensitive to mefloquine and of 87 isolated of P. falciparum, 84 (97 per cent) were sensitive to quinine. The EC50 for mefloquine was 0.27 umol/1 and for quinine 4.60 umol/1. In contrast, 65 of 89 (73 per cent) and 70 of 83 (84 per cent) isolates were resistant to amodiaquine was 0.34 umol/1 and for chloroquine 0.73 umol/1. Sulfadoxine /pyrimethamine resistance was seen in 23 of 25 (92 per cent) cases

These data clearly indicate that in the western part of the Amazon region the 4-aminoquinolines, as well as sulfadoxine/pyrimethamine, can no longer be recommended for the treatment of P. falciparum infections(AU)