Pyrazinamide: an Effective Agent for the Treatment of Leishmaniasis
Leishmaniasis is a disease that has been neglected by most of the developed world until now, despite the fact that it is the 2nd most prevalent parasitic disease after malaria in global disease burden. Formerly considered to be a tropical disease, infections are now emerging in general populations across Europe, North America and Austral-Asia. It’s becoming increasingly apparent that Leishmaniases are much more prevalent that previously suspected, with human migration and parasite carrier expansion dramatically affecting the spread of disease, dramatic outbreaks have occurred in locations with previously low levels of infection. The disease is transmitted by the bite of a sand-fly infected by parasites of the genus Leishmania. The disease can be characterized into several distinct syndromes ranging from the most common, Cutaneous Leishmaniasis which has symptoms of disfiguring ulcers, to the life threating form Visceral Leishmaniasis (VL), a systemic disease that if left untreated proves lethal. The various forms of this disease affect nearly 12 million people worldwide with estimates of one to two million new cases occurring annually. The disease claims the lives of approximately 60,000 people per year.
Although there are nearly 25 licensed compounds with anti-leishmanial effects only are few are used in humans and there are substantial drawbacks associated with these conventional treatment methods. These drugs often are highly toxic, have varying differences in strain sensitivity and resistance and moreover the expense of these drugs often precludes their use. With these limitations the need for safer, inexpensive and more widely available treatments continues to be one of the top research priorities for disease control.
Research has been performed whereby the antibacterial drug pyrazinamide traditionally used in the treatment of tuberculosis has a positive benefit in the treatment of leishmaniasis. The new use of a proven orally active drug would benefit both citizens of the developed world and at risk populations in endemic areas, where drug availability, delivery mode and price interfere with success of disease control programs.
- An agent for the treatment of Leishmaniases
- Lower cost and apparent toxicity as compared to traditional treatment methods for Leishmaniasis
- 50 years of clinical use for treatment of tuberculosis
- All aspects of pharmacodynamics, toxicity, and drug interactions are very well understood and documented
Pyrazinamide (PZA) has anti-leishmanial effect in vitro on both the promastigote and amastigote stages of development of Leishmania protozoa. More importantly through laboratory research it has been found that PZA dramatically decreases lesion development and parasite burden (number of parasites in host). PZA also works to increase the activation of infected macrophages and dendritic cells by increasing expression of co-stimulatory molecules and secretion of pro-inflammatory cytokines and nitric oxide, suggesting that PZA enhances effective immune responses against the parasite. These results not only show that PZA constitutes a very promising alternative therapy to Leishmaniasis but also suggests that the drug causes collateral immuno-stimulation.