Therapeutic Efficacy of Allopurinol in Patients with Chronic Chagas' Disease

Gallerano, R; Marr, J. Joseph; Sosa, R

doi:10.4269/ajtmh.1990.43.159

Cited by 81 publications

(55 citation statements)

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“…After the introduction of nifurtimox and benznidazole, few compounds were assayed in chagasic patients. The results obtained with allopurinol (ALLO) [4-hydroxypyrazolo (3,4-d) pyrimidine HPP] in experimental animals and the knowledge about its mode of action led to clinical assays for the treatment of Chagas disease (Lauria-Pires et al 1988, Galleano et al 1990.…”

Section: Limitations For the Use Of Specific Therapy In Chagas Diseasementioning

confidence: 99%

Usefulness of PCR-based assays to assess drug efficacy in Chagas disease chemotherapy: value and limitations

Britto¹

2009

Mem. Inst. Oswaldo Cruz

100

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Section: Limitations For the Use Of Specific Therapy In Chagas Diseasementioning

confidence: 99%

Usefulness of PCR-based assays to assess drug efficacy in Chagas disease chemotherapy: value and limitations

Britto¹

2009

Mem. Inst. Oswaldo Cruz

100

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“…The trypanosomatid HGPRT also initiates the intracellular metabolism of allopurinol (HPP, 4-hydroxypyrazolo [3,4]pyrimidine), an effective antileishmanial and antitrypanosomal agent (7,8) that is nontoxic to humans and widely used in the treatment of hyperuricemia and gout (9). Indeed, HPP has demonstrated significant therapeutic efficacy in patients with either cutaneous leishmaniasis (10) or chronic Chagas disease (11).…”

mentioning

confidence: 99%

Localization and Targeting of the Leishmania donovaniHypoxanthine-Guanine Phosphoribosyltransferase to the Glycosome

Shih¹,

Hwang²,

Carter³

et al. 1998

Journal of Biological Chemistry

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Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme in the purine salvage pathway of many protozoan parasites. The predicted amino acid sequences of certain HGPRT proteins from parasites of the Trypanosomatidae family reveal a COOH-terminal tripeptide signal that is consistent with the degenerate topogenic signal targeting proteins to the glycosome, a fuel-metabolizing microbody unique to these parasites. To determine definitively the intracellular milieu of HG-PRT in these pathogens, polyclonal antiserum to the purified recombinant HGPRT from Leishmania donovani was generated in rabbits, and confocal and immunoelectron microscopy were employed to establish that the L. donovani HGPRT is localized exclusively to the glycosome. No HGPRT protein was detected in ⌬hgprt null mutants in which both alleles of the HGPRT locus had been replaced by a drug-resistance cassette. Transfectants of the ⌬hgprt knockout strain in which a wildtype HGPRT was amplified on an expression plasmid contained augmented amounts of HGPRT, all of which was localized to the glycosome. ⌬hgprt transfectants containing amplified copies of a mutated HGPRT construct in which the Ser-Lys-Val COOH-terminal targeting signal had been deleted expressed HGPRT throughout the parasite, including subcellular organelles such as the nucleus and flagellum. These data demonstrate that the L. donovani HGPRT is compartmentalized exclusively within the glycosome and that the COOH-terminal tripeptide of the protein is necessary to achieve targeting to this organelle.

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“…Otra fuente de heterogeneidad entre los estudios se explicaría por los años de seguimiento, los cuales varían entre seis meses (Solari 1998) y 24 años (Streiger 2004); esto se suma a la diversidad de métodos diagnósticos utilizados, RPC (Solari 1998 y 2001), ELISA (Streiger 2004, Fabbro 2007, IFI (Gallerano 1990, Coura 1997) y xenodiagnóstico (Cerisola 1977). Se describe en la literatura médica que existe directa relación entre los métodos diagnósticos utilizados y la probabilidad de detectar la infección por T. cruzi, debido a que la conversión seroló-gica (no detección de anticuerpos contra T. cruzi) demora años o décadas en ocurrir luego del tratamiento 7 , como también por la disminución progresiva de la parasitemia haciéndose prácticamente indetectable para los métodos directos en fase indeterminada.…”

Section: Discussionunclassified

“…Además, las reacciones adversas a medicamentos serían un factor importante en el abandono del tratamiento, hecho descrito en ocho de los 27 pacientes en el estudio de Coura (1997). En dos estudios se describe una prevalencia de efectos adversos entre 31 y 32% (Gallerano 1990 y Fabbro 2007), lo que concuerda con los valores aproximados de 30 a 40% reportados en la literatura científi ca 2,18 . Lamentablemente no se describen las características de los participantes que abandonaron el estudio, específi camente en sus hallazgos clínicos y serológicos.…”

Section: Discussionunclassified

Eficacia de nifurtimox para el tratamiento de pacientes con enfermedad de Chagas crónica

Fuentes

2012

Rev. chil. infectol.

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Background: Most Chagas patients belong to the chronic indeterminate stage, in which pharmacological treatment has an inconclusive outcome. Objective: To evaluate the effi cacy of nifurtimox treatment in chronic asymptomatic Trypanosoma cruzi infection. Methods: We performed a systematic review and meta-analysis of electronically published literature, with no language, type of study, age or gender restrictions, until September 2010. Studies of chronic asymptomatic Chagas disease patients treated exclusively with nifurtimox were included in the analysis. Treatment effi cacy was evaluated using parasitological or serological parameters. Results: Of 463 identifi ed studies, 7 were fi nally selected: 6 observational studies and 1 randomized clinical trial; 4 of the studies were in adults, 3 in children < 14 years. In 6 studies, outcomes were defi ned by serological techniques. Summary estimate (log odds) was 0.37 (CI 95% -1.32 -2.07). Conclusions: The analyzed studies gave discordant results. Those might be explained by differences in the populations studied, follow-up periods, diagnostic techniques, and sample size. More studies are necessary to obtain conclusive results about treatment effi cacy of nifurtimox in this clinical phase of T. cruzi infection.

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Therapeutic Efficacy of Allopurinol in Patients with Chronic Chagas' Disease

Cited by 81 publications

References 0 publications

Usefulness of PCR-based assays to assess drug efficacy in Chagas disease chemotherapy: value and limitations

Usefulness of PCR-based assays to assess drug efficacy in Chagas disease chemotherapy: value and limitations

Localization and Targeting of the Leishmania donovaniHypoxanthine-Guanine Phosphoribosyltransferase to the Glycosome

Eficacia de nifurtimox para el tratamiento de pacientes con enfermedad de Chagas crónica

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