Chemotherapy of leishmaniasis: present challenges

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

SUMMARY

Cutaneous and visceral leishmaniasis are amongst the most devastating infectious diseases of our time, affecting millions of people worldwide. The treatment of these serious diseases rely on a few chemotherapeutic agents, most of which are of parenteral use and induce severe side-effects. Furthermore, rates of treatment failure are high and have been linked to drug resistance in some areas. Here, we reviewed data on current chemotherapy practice in leishmaniasis. Drug resistance and mechanisms of resistance are described as well as the prospects for applying drug combinations for leishmaniasis chemotherapy. It is clear that efforts for discovering new drugs applicable to leishmaniasis chemotherapy are essential. The main aspects on the various steps of drug discovery in the field are discussed.

Related collections

Most cited references 185

Record: found
Abstract: found
Article: not found

The relationship between leishmaniasis and AIDS: the second 10 years.

Jorge Alvar, Pilar Aparicio, Abraham Aseffa … (2008)

To date, most Leishmania and human immunodeficiency virus (HIV) coinfection cases reported to WHO come from Southern Europe. Up to the year 2001, nearly 2,000 cases of coinfection were identified, of which 90% were from Spain, Italy, France, and Portugal. However, these figures are misleading because they do not account for the large proportion of cases in many African and Asian countries that are missed due to a lack of diagnostic facilities and poor reporting systems. Most cases of coinfection in the Americas are reported in Brazil, where the incidence of leishmaniasis has spread in recent years due to overlap with major areas of HIV transmission. In some areas of Africa, the number of coinfection cases has increased dramatically due to social phenomena such as mass migration and wars. In northwest Ethiopia, up to 30% of all visceral leishmaniasis patients are also infected with HIV. In Asia, coinfections are increasingly being reported in India, which also has the highest global burden of leishmaniasis and a high rate of resistance to antimonial drugs. Based on the previous experience of 20 years of coinfection in Europe, this review focuses on the management of Leishmania-HIV-coinfected patients in low-income countries where leishmaniasis is endemic.

0 comments Cited 271 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Oral miltefosine for Indian visceral leishmaniasis.

Shyam Sundar, T Jha, C P Thakur … (2002)

There are 500,000 cases per year of visceral leishmaniasis, which occurs primarily in the Indian subcontinent. Almost all untreated patients die, and all the effective agents have been parenteral. Miltefosine is an oral agent that has been shown in small numbers of patients to have a favorable therapeutic index for Indian visceral leishmaniasis. We performed a clinical trial in India comparing miltefosine with the most effective standard treatment, amphotericin B. The study was a randomized, open-label comparison, in which 299 patients 12 years of age or older received orally administered miltefosine (50 or 100 mg [approximately 2.5 mg per kilogram of body weight] daily for 28 days) and 99 patients received intravenously administered amphotericin B (1 mg per kilogram every other day for a total of 15 injections). The groups were well matched in terms of age, weight, proportion with previous failure of treatment for leishmaniasis, parasitologic grade of splenic aspirate, and splenomegaly. At the end of treatment, splenic aspirates were obtained from 293 patients in the miltefosine group and 98 patients in the amphotericin B group. No parasites were identified, for an initial cure rate of 100 percent. By six months after the completion of treatment, 282 of the 299 patients in the miltefosine group (94 percent [95 percent confidence interval, 91 to 97]) and 96 of the 99 patients in the amphotericin B group (97 percent) had not had a relapse; these patients were classified as cured. Vomiting and diarrhea, generally lasting one to two days, occurred in 38 percent and 20 percent of the patients in the miltefosine group, respectively. Oral miltefosine is an effective and safe treatment for Indian visceral leishmaniasis. Miltefosine may be particularly advantageous because it can be administered orally. It may also be helpful in regions where parasites are resistant to current agents. Copyright 2002 Massachusetts Medical Society

0 comments Cited 159 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance.

Murari Das, Bart Ostyn, Surendra Uranw … (2013)

Miltefosine (MIL), the only oral drug for visceral leishmaniasis (VL), is currently the first-line therapy in the VL elimination program of the Indian subcontinent. Given the paucity of anti-VL drugs and the looming threat of resistance, there is an obvious need for close monitoring of clinical efficacy of MIL. In a cohort study of 120 VL patients treated with MIL in Nepal, we monitored the clinical outcomes up to 12 months after completion of therapy and explored the potential role of drug compliance, parasite drug resistance, and reinfection. The initial cure rate was 95.8% (95% confidence interval [CI], 92.2-99.4) and the relapse rate at 6 and 12 months was 10.8% (95% CI, 5.2-16.4) and 20.0% (95% CI, 12.8-27.2) , respectively. No significant clinical risk factors of relapse apart from age <12 years were found. Parasite fingerprints of pretreatment and relapse bone marrow isolates within 8 patients were similar, suggesting that clinical relapses were not due to reinfection with a new strain. The mean promastigote MIL susceptibility (50% inhibitory concentration) of isolates from definite cures was similar to that of relapses. Although more tolerant strains were observed, parasite resistance, as currently measured, is thus not likely involved in MIL treatment failure. Moreover, MIL blood levels at the end of treatment were similar in cured and relapsed patients. Relapse in one-fifth of the MIL-treated patients observed in our study is an alarming signal for the VL elimination campaign, urging for further review and cohort monitoring.

0 comments Cited 124 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Title: Parasitology

Abbreviated Title: Parasitology

Publisher: Cambridge University Press (CUP)

ISSN (Print): 0031-1820

ISSN (Electronic): 1469-8161

Publication date Created: April 2018

Publication date (Electronic): January 20 2017

Publication date (Print): April 2018

Volume: 145

Issue: 4

Pages: 464-480

Article

DOI: 10.1017/S0031182016002523

PubMed ID: 29144211

SO-VID: 81c36c86-51cf-4b1c-a3da-5f0c45e02999

License:

https://www.cambridge.org/core/terms

History

Data availability:

Comments

Comment on this article

scite_

Cited by 46

See all cited by

Most referenced authors 2,764

See all reference authors

Chemotherapy of leishmaniasis: present challenges

Read this article at

SUMMARY

Related collections

Educational Challenges

Most cited references 185

The relationship between leishmaniasis and AIDS: the second 10 years.

Oral miltefosine for Indian visceral leishmaniasis.

Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance.

Author and article information

Journal

Article

History

Comments

Comment on this article

Similar content 505

Cited by 46

Most referenced authors 2,764