allopurinol and Parasitemia

The review discusses the roles of serum xanthine oxidase, serum catalase and trypanosome-specific immune responses in the regulation of the level of trypanosome parasitaemic waves in Cape buffalo.

Topics: Animals; Antibodies, Protozoan; Antibody Specificity; Buffaloes; Catalase; Parasitemia; Trypanosoma; Trypanosomiasis, African; Variant Surface Glycoproteins, Trypanosoma; Xanthine Oxidase

Leishmaniasis is among the world's most neglected diseases. Dogs are the main reservoirs/hosts of Leishmania infantum, causative agent of both canine and human visceral leishmaniosis. Canine leishmaniasis (CanL) represents a public health problem as one of the most prevalent zoonotic diseases worldwide. Current therapeutics present drawbacks; thus, there is a need for more effective, safer, and cheaper drugs. The aim of this study was to evaluate and to compare the efficacy of oral administration of artesunate or meglumine antimoniate/allopurinol in dogs with clinical leishmaniasis. Forty-two dogs with naturally occurring clinical leishmaniasis were included in this open-label, simple randomized positive-control clinical field trial with 6 months of follow-up. Dogs received meglumine antimoniate 100 mg/kg/day and allopurinol 30 mg/kg/day for 28 days (control group, n = 26) or artesunate 25 mg/kg/day for 6 days (test group, n = 16). The animals were evaluated for their clinical evolution, parasite load (by qPCR) and humoral response at different time points: 0, 30, 90, and 180 days after treatment. Data analyses showed a significant improvement in both groups in clinical scores, parasitemia and antibody titers after treatment. Compared to the control group, the artesunate group showed significantly lower clinical score (P = 0.0001), lower parasitemia (P = 0.0001) and antibody titers after 6 months of follow-up. Compared to baseline values, a rapid, significant reduction (P < 0.012) in antibody levels, 2.28- versus 3.04-fold for the control versus artesunate groups, respectively, was observed 30 days after treatment. Antibody levels continued to decrease further in the artesunate group, where 58% of cases became seronegative at the 6-month follow-up. All qPCR-positive dogs were negative after treatment with artesunate, while 14.3% remained positive with the appearance of two new cases in the control group. Artesunate was well tolerated, and no side effects were recorded. Treatment failures were similar in both groups with 27.27% (6/22), including 18.18% (4/22) mortality in the control group, versus 26.66% (4/15), including 13.33% (2/15) mortality in the artesunate group. This is the first report showing the potential of artesunate in the treatment of dogs with clinical leishmaniasis. Artesunate showed higher efficacy than the current first-line treatment for CanL without any adverse effects. It could be a good alternative chemotherapy for CanL, and may be c

Topics: Allopurinol; Animals; Antiprotozoal Agents; Artesunate; Dog Diseases; Dogs; Female; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine Antimoniate; Parasite Load; Parasitemia; Zoonoses

The emergence of chloroquine resistance, and a world-wide scarcity of quinine, have resulted in a search for newer antimalarial drugs directed against falciparum malaria. Allopurinol causes virtually complete inhibition of purine biosynthesis of malaria parasites, which may prove lethal to the parasites. This study was designed to examine if allopurinol is additive to quinine in the treatment of acute falciparum malaria. Forty-seven Asian-Indian adults with acute complicated falciparum malaria were assigned to a treatment period of five days. They were randomly assigned to receive either oral allopurinol (12 mg/kg in three divided doses for five days) plus quinine (600 mg intravenously every 8 hr for two days, followed by 600 mg orally every 8 hr for three days ) (n = 24), or quinine alone (600 mg intravenously every 8 hr for two days, followed by 600 mg orally every 8 hr for three days) (n = 23). The responses were assessed by parasite clearance time, defervescence time, splenomegaly disappearance time, and cure rate. In the allopurinol-quinine (ALLQUIN)-treated group, all the durations were significantly shorter than those in the quinine alone (QUIN)-treated group. They were ALLQUIN versus QUIN (mean +/- SD = 65.33 +/- 11.47 hr versus 76.78 +/- 18.20 hr; P = 0.0214; 57.66 +/- 13.01 hr versus 82.52 +/- 23.55 hr, P = 0.0002; 10 +/- 1.64 days versus 14.65 +/- 2.4 days; P = 0.0002), respectively. The cure rate was higher in the ALLQUIN group (91.7%) than in the QUIN group (87%). However, this difference was not statistically significant. Therefore, this study indicates that allopurinol can be an additive to quinine to bring about both faster eradication of Plasmodium falciparum and clinical remission than with quinine alone.

Topics: Acute Disease; Acute Kidney Injury; Adolescent; Adult; Aged; Allopurinol; Anemia; Antimalarials; Antimetabolites; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Malaria, Cerebral; Malaria, Falciparum; Male; Middle Aged; Parasitemia; Quinine; Splenomegaly

Topics: Allopurinol; Animals; Antibodies, Protozoan; Antiprotozoal Agents; Dog Diseases; Dogs; Female; Follow-Up Studies; Leishmania infantum; Leishmaniasis; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Parasite Load; Parasitemia; Toll-Like Receptor 2; Toll-Like Receptor 4; Up-Regulation

In order to determine the in vivo activity against the protozoan Trypanosoma cruzi, two doses (50 and 75 mg/kg) of a chloroform extract of Carica papaya seeds were evaluated compared with a control group of allopurinol. The activity of a mixture of the three main compounds (oleic, palmitic and stearic acids in a proportion of 45.9% of oleic acid, 24.1% of palmitic and 8.52% of stearic acid previously identified in the crude extract of C. papaya was evaluated at doses of 100, 200 and 300 mg/kg. Both doses of the extracts were orally administered for 28 days. A significant reduction (p < 0.05) in the number of blood trypomastigotes was observed in animals treated with the evaluated doses of the C. papaya extract in comparison with the positive control group (allopurinol 8.5 mg/kg). Parasitemia in animals treated with the fatty acids mixture was also significantly reduced (p < 0.05), compared to negative control animals. These results demonstrate that the fatty acids identified in the seed extracts of C. papaya (from ripe fruit) are able to reduce the number of parasites from both parasite stages, blood trypomastigote and amastigote (intracellular stage).

Topics: Allopurinol; Animals; Carica; Chagas Disease; Drug Evaluation, Preclinical; Mice; Mice, Inbred BALB C; Myocarditis; Myocardium; Parasitemia; Plant Extracts; Seeds; Trypanocidal Agents; Trypanosoma cruzi

We have previously shown that clomipramine and allopurinol used separately are effective in preventing chronic chagasic cardiomyopathy. The aim of the present study was to evaluate the effect of the association of clomipramine (Clo--5 mg/kg/day/90 days) and allopurinol (Allo--5, 10, or 15 mg/kg/day/90 days) for the treatment of experimental Chagas disease in the acute stage. Treatment effectiveness was evaluated through parasitemia, survival, electrocardiography, serology, and cardiac histopathology. Groups treated showed no electrocardiographic abnormalities, in contrast to those untreated which presented 25% of mice with conduction alterations. The myocardium of treated mice (Clo, Allo10+Clo, and Allo15+Clo) presented no structural alterations. Cardiac b-receptor affinity was preserved in mice treated with Clo or Clo+Allo at the different doses; receptor density of the Clo and Allo15+Clo groups did not differ from the non-infected group. Anti-cruzipain antibody levels were similar in treated and untreated groups. Survival was significantly increased in the treated groups (p < 0.05), with Clo and all the Clo+Allo groups presenting the highest rates. These results show that the association of clomipramine + allopurinol is effective for Chagas disease treatment and has the same effect as clomipramine alone.

Topics: Allopurinol; Animals; Antibodies, Protozoan; Antigens, Protozoan; Antiprotozoal Agents; Chagas Disease; Clomipramine; Cysteine Endopeptidases; Disease Models, Animal; Drug Therapy, Combination; Electrocardiography; Male; Mice; Myocardium; Parasitemia; Protozoan Proteins; Survival Analysis; Treatment Outcome; Trypanosoma cruzi

There is a real need for new and less toxic drugs for the treatment of Chagas disease, as nifurtimox and benznidazole are effective but toxic and provoke unpleasant side effects, especially in adult patients. Allopurinol, commonly used to treat the hiperuricemia, is also used by the Trypanosoma cruzi's hypoxantine guanine fosforyltransferase as an alternative substrate incorporating it into the parasite's ribonucleic acid, provoking the death of the parasite. However, the results of using allopurinol as chemotherapy for Chagas disease are not clear. For that, we investigated the evolution of the T. cruzi infection in mice treated with allopurinol (5, 10 or 15 mg/kg for 90 days) obtaining a reduction in the parasitaemia (p<0.05), no electrocardiographic alterations (p<0.05) and a conserved myocardial and cardiac beta-receptors' affinity values with the highest dose of the drug, compared to those of the uninfected mice. Cruzipain immunoglobulin G levels remained high in all the groups as well as the survival (70%, 90 days post-infection). Allopurinol prevented the acute phase evolving into the chronic cardiac disease.

Topics: Allopurinol; Animals; Antibodies, Protozoan; Chagas Disease; Cysteine Endopeptidases; Electrocardiography; Male; Mice; Myocardium; Parasitemia; Protozoan Proteins; Survival Analysis; Trypanosoma cruzi

The introduction of PCR has efficiently improved diagnosis of canine leishmaniasis. In order to provide a robust, efficient and reliable diagnostic method, a duplex PCR assay targeting the Leishmania infantum kDNA minicircle and the canine GAPDH gene as inner control was designed. Sensitivity of the assay reached 0.15 parasites/ml blood. Development, testing and application of this system on a group of 10 dogs during therapy administration (60 days) are also described. Six dogs (out of eight that have been showing a positive PCR result on peripheral blood during the study) were tested negative at day 62, indicating a reduction of parasitaemia at the end of the treatment period. All the animals had a positive PCR on lymph node aspirate both at the beginning and at the end of treatment. These findings seem to suggest that, in order to test therapy efficacy, PCR on whole blood could be a useful assay in dogs that have a positive PCR at the beginning of the treatment, while PCR positivity on lymph nodes lasts longer than the observation period during therapy administration. The presence of the GAPDH inner control band efficiently contributed to prevent false negatives, by highlighting samples affected by haemoglobin inhibition or inappropriate DNA isolation.

Topics: Allopurinol; Animals; Antiprotozoal Agents; DNA, Kinetoplast; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Leishmania infantum; Leishmaniasis, Visceral; Lymph Nodes; Lymphadenitis; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Parasitemia; Phosphoric Monoester Hydrolases; Polymerase Chain Reaction; Predictive Value of Tests; Sensitivity and Specificity

Elevated plasma levels of xanthine oxidase and liver function parameters have been associated with inflammatory events in several human diseases. While xanthine oxidase provides in vitro protection against malaria, its pathophysiological functions in vivo and interactions with liver function parameters remain unclear. This study examined the interactions and plasma levels of xanthine oxidase (XO) and uric acid (UA), catalase (CAT) and liver function parameters GOT, GPT and bilirubin in asymptomatic (n=20), uncomplicated (n=32), and severe (n=18) falciparum malaria children aged 3-13 years. Compared to age-matched control (n=16), significant (p<0.05) elevation in xanthine oxidase by 100-550%, uric acid by 15.4-153.8%, GOT and GPT by 22.1-102.2%, and total bilirubin by 2.3-86% according to parasitaemia (geometric mean parasite density (GMPD)=850-87100 parasites/microL) was observed in the malarial children. Further comparison with control revealed higher CAT level (16.2+/-0.5 vs 14.6+/-0.4 U/L; p<0.05) lacking significant (p>0.05) correlation with XO, but lower CAT level (13.4-5.4 U/L) with improved correlations (r=-0.53 to -0.91; p<0.05) with XO among the asymptomatic and symptomatic malaria children studied. 75% of control, 45% of asymptomatic, 21.9% of uncomplicated, and none of severe malaria children had Hb level>11.0 g/dL. Multivariate analyses further revealed significant (p<0.05) correlations between liver function parameters and xanthine oxidase (r=0.57-0.64) only in the severe malaria group. We conclude that elevated levels of XO and liver enzymes are biochemical features of Plasmodium falciparum parasitaemia in Nigerian children, with both parameters interacting differently to modulate the catalase response in asymptomatic and symptomatic falciparum malaria.

Topics: Adolescent; Alanine Transaminase; Animals; Aspartate Aminotransferase, Mitochondrial; Bilirubin; Catalase; Child; Child, Preschool; Female; Hemoglobins; Humans; Liver; Liver Function Tests; Malaria, Falciparum; Male; Multivariate Analysis; Nigeria; Parasitemia; Plasmodium falciparum; Uric Acid; Xanthine Oxidase

The killing of blood-stage malaria parasites in vivo has been attributed to reactive intermediates of oxygen (ROI) and of nitrogen (RNI). However, in the case of the latter, this contention is challenged by recent observations that parasitemia was not exacerbated in nitric oxide synthase (NOS) knockout (KO) (NOS2-/- or NOS3-/-) mice or in mice treated with NOS inhibitors. We now report that the time course shows that Plasmodium chabaudi parasitemia in NADPH oxidase KO (p47phox-/-) mice also was not exacerbated, suggesting a minimal role for ROI-mediated killing of blood-stage parasites. It is possible that the production of protective antibodies during malaria may mask the function of ROI and/or RNI. However, parasitemia in B-cell-deficient JH-/- x NOS2-/- or JH-/- x p47phox-/- mice was not exacerbated. In contrast, the magnitude of peak parasitemia was significantly enhanced in p47phox-/- mice treated with the xanthine oxidase inhibitor allopurinol, but the duration of patent parasitemia was not prolonged. Whereas the time course of parasitemia in NOS2-/- x p47phox-/- mice was nearly identical to that seen in normal control mice, allopurinol treatment of these double-KO mice also enhanced the magnitude of peak parasitemia. Thus, ROI generated via the xanthine oxidase pathway contribute to the control of ascending P. chabaudi parasitemia during acute malaria but alone are insufficient to suppress parasitemia to subpatent levels. Together, these results indicate that ROI or RNI can contribute to, but are not essential for, the suppression of parasitemia during blood-stage malaria.

Topics: Allopurinol; Animals; Enzyme Inhibitors; Guanidines; Malaria; Mice; Mice, Inbred C57BL; Mice, Knockout; NADPH Oxidases; Nitric Oxide; Nitric Oxide Synthase; Parasitemia; Plasmodium chabaudi; Reactive Oxygen Species