It is important to realize that leishmaniasis guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The IDSA and ASTMH consider adherence to these guidelines to be voluntary, with the ultimate determinations regarding their application to be made by the physician in the light of each patient's individual circumstances.

Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH)

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Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH)*

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.

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Chemotherapy of leishmaniasis: present challenges

Limited therapeutic options in visceral leishmaniasis (VL) make the treatment of this neglected disease very challenging. In addition to this, long treatment duration and toxic adverse effects make it even more difficult. With no effective vaccine available to date, treatment of VL is based only on chemotherapy. In the Indian subcontinent, a single dose of liposomal amphotericin B (L-AmB) and multidrug therapy (L-AmB + miltefosine, L-AmB + paromomycin [PM], or miltefosine + PM) are the treatments of choice for VL. In East Africa, however, combination therapy of pentavalent antimonials (Sbv) and PM remains the treatment of choice, and in the Mediterranean region and South America, L-AmB is the recommended drug. Fexinidazole and PA-824 are new promising drugs which have shown encouraging results in preclinical studies.

https://journals.sagepub.com/doi/pdf/10.1177/2049936116646063

Recent developments and future prospects in the treatment of visceral leishmaniasis

Introduction: Leishmaniasis is a vector-borne neglected tropical disease which manifests as visceral leishmaniasis (VL), cutaneous leishmaniasis (CL), and mucocutaneous leishmaniasis (MCL)....

Current and emerging medications for the treatment of leishmaniasis

Visceral leishmaniasis (VL; Kala-azar) is a vector-borne disease caused by Leishmania donovani parasites. VL is endemic in the Indian state of Bihar, which accounts for 40% of the worldwide burden of VL [1]. Although the prevalence of human immunodeficiency virus (HIV) in Bihar is considered low (0.2%–0.3%), it is one of the few states where prevalence is increasing [2]. A recent study from India has suggested that 2.4% of all patients ≥14 years of age presenting with VL were unknowingly coinfected with HIV [3].

HIV-infected patients are more likely to develop symptomatic VL due to reactivation of dormant Leishmania infection acquired prior to being infected with HIV or due to a much higher rate of clinical manifestation following primary Leishmania infection after acquiring HIV. Therefore, VL is generally considered an opportunistic infection in patients with HIV and often presents with atypical clinical features [4]. Coinfected patients are at higher risk of relapse and death, and this risk appears inversely correlated with CD4 counts. Furthermore, VL adversely affects the response to antiretroviral treatment [4, 5]. Worse outcomes and the treatment challenges faced by coinfected patients as compared to immunocompetent patients are well documented in the literature [6].

There are currently no evidence-based treatment recommendations for coinfected patients in Asia. Moreover, observational studies by Medecins Sans Frontieres (MSF) in India have shown that outcomes for HIV coinfected patients receiving 20 mg/kg AmBisome (Gilead Pharmaceuticals, Foster City, California) were substantially worse than in VL patients not known to be HIV coinfected [7–9], whereas a recent study in Ethiopia showed that 32% of coinfected patients demonstrated parasitological failure following treatment with 30 mg/kg AmBisome despite clinical improvement [10]. Therefore, the MSF VL treatment program in Bihar, in collaboration with the Rajendra Memorial Research Institute (RMRI), chose to treat HIV-VL coinfected patients on a compassionate basis using a combination of 30 mg/kg AmBisome and 14 days of miltefosine (Impavido, Paladin, Canada). This combination was adopted after consultation of experts, taking into account the synergistic properties of AmBisome and miltefosine [6, 11] and has been used in another center with promising results [12]. Additionally, the compassionate use of miltefosine in combination with liposomal amphotericin B (at 30 mg/kg total dose) in 111 HIV coinfected VL patients in east Africa seems to suggest substantially higher cure rates and lower failure rates both in primary VL and VL relapse than high-dose AmBisome monotherapy[12]. In this report, we describe the outcomes up to 18 months following treatment with this combination therapy under routine program conditions in Bihar, India.

Deepak Kumar

Papers

Combination Treatment for Visceral Leishmaniasis Patients Coinfected with Human Immunodeficiency Virus in India