Clinical and serological follow-up in dogs with visceral leishmaniosis treated with allopurinol and sodium stibogluconate

Paşa, Serdar; Töz, Seray; Voyvoda, Hüseyin; Özbel, Yusuf

doi:10.1016/j.vetpar.2004.12.002

Cited by 24 publications

(14 citation statements)

References 20 publications

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“…Many studies have reported a significant decrease in levels of specific antibodies (mainly IgG) against crude Leishmania antigen in the follow-up of treated infected dogs. 15,16,21 This decrease in concentrations has been described in responsive and in nonresponsive dogs. 8,22 Therefore, seroreactivity against crude total parasite antigen cannot predict the outcome of treatment.…”

Section: Introductionmentioning

confidence: 65%

“…12 Successful chemotherapy has been correlated with a decrease in Leishmania -specific antibody levels, restoration of parasitespecific cell mediated immunity, and a reduction of parasite burden. 6,[13][14][15][16][17] However, drugs used to treat leishmaniasis have not been able to provide a sterile cure; although temporary clinical remission is normally achieved, relapses are frequent after use of the drug is stopped, 18 thus increasing the risk of parasitic resistance. 19,20 Research into a marker capable of predicting the success of therapy against Leishmania is required to develop a more rational therapy protocol, which must improve the probability of cure and reduce Leishmania resistance to drugs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dynamics and Predictive Potential of Antibodies against Insect-Derived Recombinant Leishmania infantum Proteins during Chemotherapy of Naturally Infected Dogs

Todolí

Galindo²,

Gómez-Sebastián³

et al. 2010

The American Journal of Tropical Medicine and Hygiene

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Section: Introductionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Dynamics and Predictive Potential of Antibodies against Insect-Derived Recombinant Leishmania infantum Proteins during Chemotherapy of Naturally Infected Dogs

Todolí

Galindo²,

Gómez-Sebastián³

et al. 2010

The American Journal of Tropical Medicine and Hygiene

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“…Current evidence indicates that purine analogues alone or in combination with other chemotherapeutic agents are very effective against almost any fast-growing cells (22,41). Allopurinol, a purine analogue, has been used to treat leishmaniasis alone (34,48) or combined with other drugs (21,35,36,39,47). It should be pointed out, however, that the efficacy of allopurinol monotherapy remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Purine Nucleobase Transport in Amastigotes of Leishmania mexicana : Involvement in Allopurinol Uptake

Al-Salabi

Koning

2005

Antimicrob Agents Chemother

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Nucleobase and nucleoside transporters play central roles in the biochemistry of parasitic protozoa, as they lack the ability to synthesize purines de novo and are absolutely reliant upon purine salvage from their hosts. Furthermore, such transporters are potentially critical to the pharmacology of these important human pathogens, because they mediate the uptake of purine analogues, as well as some nonpurine drugs, that can be selectively cytotoxic to the parasites. We here report the first identification and characterization of a purine nucleobase transporter in Leishmania amastigotes. Uptake of [ 3 H]hypoxanthine by Leishmania mexicana amastigotes was mediated by a single high-affinity transporter, LmexNBT1, with a K m of 1.6 ؎ 0.4 M and high affinity for adenine, guanine, and xanthine but low affinity for nucleosides and pyrimidine nucleobases. Allopurinol, an antileishmanial hypoxanthine analogue, was apparently taken up by the same transporter. Using Parasitic protozoa of the genus Leishmania are the etiological agents of leishmaniasis. Some 12 million people throughout the world suffer from leishmaniasis, ranging from the disfiguring cutaneous form to often-fatal visceral leishmaniasis. Leishmania species are sandfly-transmitted protozoan parasites. The life cycle is divided into promastigotes and metacyclics in the insect vectors and amastigotes in their mammalian hosts, which are responsible for all clinical manifestations.Most of the currently available antileishmanial drugs have been discovered empirically, as until recently insufficient information was known about the biochemistry, physiology, and molecular biology of these parasites and the interactions with their hosts (23). The limitations of the current treatment for leishmaniasis, as a result of drug resistance and the severe side effects of most of the existing therapeutic agents, and the urgent need for new therapeutic approaches, are well documented (12,56,60).The development of a rational therapeutic strategy for the treatment and prevention of parasitic disease depends on exploitation of fundamental biochemical disparities between parasite and host, such as the inability of protozoan parasites to synthesize purines de novo (5). Current antiprotozoal agents often derive selectivity from selective accumulation by the parasite rather than the host cell (15). The selectivity and the efficacy of purine antimetabolites can be achieved by the cell surface transporters that mediate access to the cell, as substrate recognition by nucleobase transporters is strikingly different in humans and kinetoplastids such as Trypanosoma brucei (58) and Leishmania major promastigotes (2). Purine and pyrimidine antimetabolites have been highly successful against many viral infections as well as malignancies (27) and show great promise against protozoal infections as well (reviewed in references 14, 17, and 23). Allopurinol, a purine nucleobase analogue, is clinically used against various manifestations of leishmaniasis (1,13,39).Whereas purine transporters in prom...

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“…Real-time polymerase chain reactivity (PCR) is considered to be the most sensitive molecular technique with lymph node, bone marrow, skin or spleen tissue preferable over blood, buffy coat or urine due to improved sensitivity (Maia et al, 2009). Clinical disease is usually associated with high serum antibody levels (Pasa et al, 2005). Seropositivity is found in 88-100% of dogs with clinical signs and/or clinicopathological abnormalities consistent with CanL (Solano-Gallego et al, 2009).…”

Section: Description Of the Diseasementioning

confidence: 99%

Data collection to characterise the impact of canine leishmaniosis and modelling of the role of animals in spreading Leishmania infantum within the European Union

Mattin

Brodbelt

Wylie

et al. 2014

EFSA Supporting Publications

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Canine leishmaniosis (CanL) is a major zoonosis transmitted by sand flies which can potentially cause severe fatal disease in humans and dogs. The disease is endemic in southern Europe and there are concerns about its introduction into the non-endemic areas of the European Union (EU). The objectives of this work were to investigate the efficacy of different control measures using a systematic review (SR), assess the role of dogs in the spread of Leishmania Infantum (L. infantum) in the EU and evaluate potential mitigation measures using simulation modelling, and evaluate the impact of the disease in endemic areas. The SR evaluated the effectiveness and safety of control measures for CanL using 23 clinical trials conducted on a total of 5861 dogs. Significant benefits were observed in the intervention groups for a number of vaccine types, deltamethrin collars, spot-ons, and prophylactic medication with domperidone. However, these results require confirmation in adequately powered well designed randomised controlled trials. The results of the stochastic simulation modelling suggest that there is a high risk of endemicity for disease-free EU regions with presence of a competent vector and where infected dogs are introduced. When evaluated individually and at a high level of implementation, the best mitigation measures in decreasing order of effectiveness were: repellent, vaccine, prophylactic medication and insecticide. Some combinations of mitigation measures showed a joint effect higher than the effect of individual measures. Test and exclusion of positive dogs moving into non-endemic areas was effective for low numbers of imports, but its benefits diminished as the number of imported dogs increased, given the low sensitivity of the diagnostic test used. The results of the impact assessment suggest clinical CanL is a common diagnosis in endemic parts of the EU. The estimated percentage of practice-attending dogs with a veterinary diagnosis of CanL by country was as follows: France 0.71%, Spain 3.71%, Portugal 2.92%, Italy 4.25% and Greece 7.80%. CanL can have a significant impact on the welfare of affected dogs and economic implications for owners, both for prevention and treatment. It is estimated that the use of preventative collars in these five countries cost dog owners €54 million in 2012 alone. The incidence of clinical human leishmaniosis is much lower than CanL, with reported data suggesting between 20 and 380 hospital admissions per country per year. Costs relating to hospital fees and time off work may amount to approximately €4.5million/year in Spain, Portugal, Italy and Greece. The current economic crisis is likely to have an adverse impact on the prevention and control of CanL.

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Clinical and serological follow-up in dogs with visceral leishmaniosis treated with allopurinol and sodium stibogluconate

Cited by 24 publications

References 20 publications

Dynamics and Predictive Potential of Antibodies against Insect-Derived Recombinant Leishmania infantum Proteins during Chemotherapy of Naturally Infected Dogs

Dynamics and Predictive Potential of Antibodies against Insect-Derived Recombinant Leishmania infantum Proteins during Chemotherapy of Naturally Infected Dogs

Purine Nucleobase Transport in Amastigotes of Leishmania mexicana : Involvement in Allopurinol Uptake

Data collection to characterise the impact of canine leishmaniosis and modelling of the role of animals in spreading Leishmania infantum within the European Union

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