Jaime Carmona

Oxidative stress in patients with non-complicated malaria

AIM To compare oxidative stress in adults with non-complicated malaria and healthy controls. METHODOLOGY We measured malondialdehyde (MDA), total antioxidant status (TAS), catalase, superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). Oxidative stress was calculated based on MDA/TAS, MDA/GSH-PX and SOD/catalase indexes. RESULTS Mean MDA in patients was 3.9 micromol/L (controls = 1.3 micromol/L). Mean TAS was 0.9 mmol/L in patients and controls. Malaria patients had less catalase activity when compared to controls (209.4 vs. 320.4 k/gr), while SOD and GSH-PX activity was higher (79.4 U/mL, 11,884.2U/L vs. 54.3 U/mL, 9,672.6 U/L). MDA/TAS index was 3.5 fold more in patients than in controls, MDA/GSH-PX and SOD/catalase indexes were increased by 6 and 2.8 fold. MDA levels and MDA/TAS index showed no differences according to malarial history, parasitaemia, Plasmodium species, parasites stage, place of residence and drinking or smoking habits. CONCLUSIONS During acute non-complicated P. falciparum or P. vivax malaria, we observed high oxidative stress. This resulted from lipid peroxidation rather than from a reduced TAS. We propose MDA/TAS index as a useful marker of oxidative stress during malaria infection.

Clinical and laboratory findings of Plasmodium vivax malaria in Colombia, 2001

A descriptive study was carried out in 104 patients with Plasmodium vivax malaria, from the region of Turbo (Antioquia, Colombia). Clinical features and levels of hemoglobin, glycemia, serum bilirubin, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), creatinine and complete blood cell profile were established. 65% of the studied individuals were men and their mean age was 23. Of all individuals 59% had lived in the region for > 1 year and 91% were resident in the rural area. 42% were farmers and 35% had a history of malaria. The mean parasitaemia was 5865 parasites/mm3. The evolution of the disease was short (average of 4.0 days). Fever, headache and chills were observed simultaneously in 91% of the cases while the most frequent signs were palmar pallor (46%), jaundice (15%), hepatomegaly (17%), and spleen enlargement (12%). Anemia was found in 39% of the women and in 51% of the men, 8% of individuals had thrombocytopaenia and 41% had hypoglycemia.

Malaria en niños: relaciones entre nutrición e inmunidad

OBJECTIVE To explore some relationships among immunity, nutrition, and malaria in a group of children from a population with a high endemic incidence of malaria. METHODS This pilot descriptive prospective cross-sectional study was carried out in 1998 in the municipality of El Bagre, Antioquia, Colombia. Both boys and girls were studied in two groups: one group of 51 children had malaria and another group of 49 did not have malaria. The children with malaria had symptoms or signs of malaria and a positive thick blood film. The comparison group of 49 children without malaria (no signs or symptoms of malaria and a negative thick blood film) were chosen at random at government schools or childrens centers. For the study the following indices were calculated: weight-for-age, height-for-age, and weight-for-height. Also measured were the blood-serum concentrations of: albumin, prealbumin, apolipoprotein A1 (apoA1), transferrin, zinc, vitamin A, immunoglobulins G and M, interleukin-10 (IL-10), tumor necrosis factor-alpha, interferon-gamma, and lymphocyte populations. RESULTS Of the children studied, 69% presented some risk of malnutrition, and 63% had some risk of chronic malnutrition. With regard to the immunity and biochemical variables, the children with malaria had less apoA1 and albumin and more IL-10 than did the children without malaria. All the biochemical variables showed lower averages in the group with malaria, risk of malnutrition, and immune or biochemical changes, while all the immunity variables had higher averages in that same group of children. CONCLUSIONS 1) The high frequency of chronic malnutrition found clearly indicates the need for food supplementation measures. 2) The low values of prealbumin found could be due to the frequent bacterial or viral infections reported. 3) The serious vitamin A deficiency found calls for a supplementation program. 4) An association was found between low apoA1 values and the presence of malaria, but which one follows from the other is not known. 5) No relationship was observed between the anthropometric indicators of risk of malnutrition and the possible biochemical markers of malnutrition. 6) We found high levels of IL-10 in the children with malaria; this is the first time that this has been reported for Plasmodium vivax.

The Effect of Retinol Supplement on Blood Cytokine Concentrations in Children with Non-Severe Malaria Vivax

Malaria, malnutrition, low concentrations of retinol and intestinal parasitism coexist among the habitants of tropical regions of the world (Nacher, 2002). The Turbo municipality is one of the highly endemic malaria regions of Colombia. During 2006, 5.674 cases of malaria were reported in Turbo, corresponding to annual parasite index >10 (number of malaria cases per 1,000 persons per year). From these, 85% were caused by Plasmodium vivax (Eventos de interes en salud Publica, 2006). Also, the Uraba region, where Turbo is a major urban area, is one of the regions of Colombia with more cases of malnutrition in children under 15 years; 53.3% of children under 10 years presented chronic malnutrition risk (T/E 0.7 mmol/l (20 μg/dL) (WHO, 2009) once malaria receded. Within the children with malaria, 85% had anemia, and their haemoglobin values increased after one month of antimalarial treatment, although anemia persisted in 51% of them (Uscategui & Correa, 2007). During malaria, TH1 cytokines like interferon gamma (IFN ┛) and tumor necrosis factor alpha (TNF-┙), are required to control the primary parasitemia. Nevertheless antinflammatory cytokines or TH2 cytokines, such as interleukin 10 (IL-10) and transforming growth factor beta (TGF-┚), that modulate the proinflammatory effect, must be present along with those of the TH1 type, in order to prevent emergence of immune pathology (Schofield et al., 2005). Some in vitro studies revealed that retinol had an effect on the TH1/TH2 balance, as evidenced by reduction of IFN -┛ and TNF -┙ secretion by TH1 cells or by promoting TH2 cells growth and differentiation to produce larger quantities of the IL-10 (Cantorna et al., 1994; Iwata et al., 2003). Vitamin A deficiency has been associated with an increase in TH1 response, intestinal parasitism and malnutrition (Jason et al., 2002; Azevedo et al., 2005). Furthermore, the prevalence of TH1 cytokines in children with malaria has been associated with severe anemia (Kurtzhals et al., 1999).

Concentraciones sanguíneas de sulfadoxina y pirimetamina según la respuesta terapéutica antimalárica, en dos municipios de Antioquia, Colombia

PROBLEM There has been a constant increase in the level of therapeutic failure of the sulfadoxine-pyrimethamine (SP) combination for treating uncomplicated Plasmodium falciparum malaria. OBJECTIVE To use high-performance liquid chromatography to quantify blood levels of SP in patients with good clinical response and in patients who did not respond to treatment. METHODS This experimental study was carried out in 2002 in Turbo and Zaragoza, two municipalities in the department of Antioquia in Colombia. There were 79 patients (45 in Turbo and 34 in Zaragoza), including both men and women, who ranged in age from 1 year to 60 years. All the patients had uncomplicated Plasmodium falciparum malaria, with a parasite density of 500 to 50,000 parasites/microL. The patients were each randomly assigned to a treatment group. The treatment groups were not blinded; the physician who provided the medication also evaluated the therapeutic response. The treatment consisted of a single combination dose of sulfadoxine (25 mg/kg) and pyrimethamine (1.25 mg/kg) in tablets (500 mg of sulfadoxine and 25 mg of pyrimethamine). Clinical-parasitological follow-up was carried out for 21 days. Blood levels of sulfadoxine and pyrimethamine were measured two hours after the treatment was given and also the day of treatment failure, if that occurred. RESULTS Two hours after the treatment was given, the median blood level of sulfadoxine was 136.6 micromol/L in the patients who later showed a good clinical response, and it was 103.4 micromol/L among those who did not respond to treatment (P = 0.13). The medians for pyrimethamine were 848.4 nmol/L in patients with a good clinical response and 786.1 nmol/L in patients with treatment failure (P = 0.40). There were no significant differences in drug levels between the early-failure cases and the late-failure cases. The linear correlation between the blood levels of sulfadoxine and pyrimethamine was close to zero (r = 0.13). CONCLUSIONS Between 1998 and 2002, treatment failure with the SP combination increased from 13% to 22% in Turbo, and from 9% to 26% in Zaragoza. The lack of response in 2002 could not be explained by lower blood levels of the medications.