Leishmaniasis: Possible New Strategies for Treatment (original) (raw)
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Visceral leishmaniasis: what are the needs for diagnosis, treatment and control
Nature Reviews Microbiology, 2007
Leishmaniasis, a vector-borne disease that is caused by obligate intra-macrophage protozoa, is endemic in large areas of the tropics, subtropics and the Mediterranean basin . This disease is characterized by both diversity and complexity 1 : it is caused by more than 20 leishmanial species and is transmitted to humans by ~30 different species of phlebotomine sandflies 2 .
Lancet Infectious Diseases, 2002
Visceral leishmaniasis is common in less developed countries, with an estimated 500 000 new cases each year. Because of the diversity of epidemiological situations, no single diagnosis, treatment, or control will be suitable for all. Control measures through case finding, treatment, and vector control are seldom used, even where they could be useful. There is a place for a vaccine, and new imaginative approaches are needed. HIV coinfection is changing the epidemiology and presents problems for diagnosis and case management. Field diagnosis is difficult; simpler, less invasive tests are needed. Current treatments require long courses and parenteral administration, and most are expensive. Resistance is making the mainstay of treatment, agents based on pentavalent antimony, useless in northeastern India, where disease incidence is highest. Second-line drugs (pentamidine and amphotericin B) are limited by toxicity and availability, and newer formulations of amphotericin B are not affordable. The first effective oral drug, miltefosine, has been licensed in India, but the development of other drugs in clinical phases (paromomycin and sitamaquine) is slow. No novel compound is in the pipeline. Drug combinations must be developed to prevent drug resistance. Despite these urgent needs, research and development has been neglected, because a disease that mainly affects the poor ranks as a low priority in the private sector, and the public sector currently struggles to undertake the development of drugs and diagnostics in the absence of adequate funds and infrastructure. This article reviews the current situation and perspectives for diagnosis, treatment, and control of visceral leishmaniasis, and lists some priorities for research and development.
New Strategies and Biomarkers for the Control of Visceral Leishmaniasis
Trends in Parasitology, 2019
Effective diagnosis and treatment of visceral leishmaniasis, together with the study of vectors and reservoirs, can lead to a better understanding of the parasite transmission dynamics and the development of more efficient control measures. Recent studies have applied new methodologies and biomarkers, and these have contributed to the early and rapid diagnosis of the disease; assessment of success of pharmacological treatments; efficient monitoring of immunosuppressed individuals; and to population screening for field trials of vaccine efficacy. This opinion article proposes an update to the diagnostic tools for visceral leishmaniasis and their rational and combined use to establish the real prevalence of infection or of exposure to Leishmania in endemic areas. Unveiling the Complexity of Visceral Leishmaniasis Leishmaniasis is a vector-borne infectious disease caused by parasites of the genus Leishmania. Globally distributed, it is poverty-related and is among the deadliest of the neglected tropical diseases (NTDs). Visceral leishmaniasis (VL), caused by Leishmania. donovani and Leishmania infantum, is the most severe clinical form. It affects internal organs and is fatal in 95% of cases if not successfully treated. On some occasions, after an episode of VL caused by L. donovani, the patient may develop a post-kala-azar dermal leishmaniasis (PKDL). So far, little is known about the mechanism by which a patient with VL develops PKDL [1]. The overall incidence of VL has declined in recent years, mainly because of the elimination efforts carried out in South Asia [2]. However, the incidence of VL has increased alarmingly in the Americas, where the recent report by the Pan American Health Organization (PAHO) and the World Health Organization (WHO) indicates that VL is expanding geographically: the number of cases has increased by 26.4%, while the fatality rate and number of deaths have grown progressively since 2014 [3]. In addition, epidemic outbreaks have appeared in Europe, the Indian subcontinent, and Eastern Africa [4-7]. The transmission dynamics (see Glossary) of Leishmania are complex and variable, and are dependent on environmental conditions, the distribution and biology of the vector, the reservoirs involved, and on the health, social, and economic aspects that affect the human host [2]. In the absence of an effective vaccine, the control of VL has been based on the prevention of sand fly bites, the elimination of animal reservoirs (if the VL is zoonotic), and the early detection and effective treatment of human cases [8]. Nevertheless, in regions endemic for VL, most infected individuals remain asymptomatic. Their possible role as 'parasite carriers' with capacity to infect sand flies has been suggested and is under active consideration [9]. Individuals who suffered previous VL infections for which treatment was not fully effective can also remain asymptomatic and subsequently relapse later. Additionally, immunosuppressed patients can remain asymptomatic after VL therapy, because they receive secondary prophylaxis; however, they can still act as reservoirs, as confirmed by xenodiagnoses [10]. This complex scenario for the transmission dynamics of VL makes it even more difficult to establish effective control measures, and highlights the clear need for improved tests that are able to distinguish between all the different conditions (Box 1). Diagnostic tests have to provide an immediate, reliable, confirmatory diagnosis of active VL cases independently of a central laboratory. Improved tests are also necessary to assess treatment success, a fundamental measure for predicting and avoiding relapses. This requires a specific test that goes beyond the clinical recovery of the patient, and the nondetection of the parasite, and confirms cure [11,12].
Review Recent updates and perspectives on leishmaniasis
Leishmaniasis is a neglected vector-borne tropical infection considered to be a disease of the poor. Concentrated in poverty-stricken countries within Southeast Asia, East Africa, and Latin America, it is also endemic in several Mediterranean countries. The management of the heterogeneous syndromes determined by parasites belonging to the genus Leishmania is particularly difficult in developed, non-endemic countries owing to the unfamiliarity of physicians with clinical symptoms, diagnostic possibilities, and available treatment options. Therefore, travelers and other people who may be exposed to sand flies in endemic areas should receive counseling regarding leishmaniasis and appropriate protective measures. Serological diagnosis is rarely used for cutaneous and mucocutaneous diseases, but it is the most commonly used technique for visceral leishmaniasis. The drugs used to treat this last disease are expensive and sometimes have toxic side effects. This review highlights the diagnostic, chemotherapeutic, and immunizing strategies to control leishmaniasis, though no human vaccine is commercially available currently owing to the complexity of the cellular immune response to this parasite.
Parasitology and Microbiology Research [Working Title]
Leishmaniasis is a vector-borne tropical/subtropical disease caused by an intracellular parasite transmitted to humans by sand fly bite. It is endemic in Asia, Africa, the Americas, and the Mediterranean region. Worldwide reports include 1.5-2 million new cases each year, more than 300 million at risk of acquiring the disease, and 70,000 deaths per year. Clinical features depend on the Leishmania species and immune response of the host, varying from localized cutaneous disease to visceral form with potentially fatal outcome; however, the common presentation is either cutaneous, mucocutaneous, or visceral leishmaniasis. Many therapeutic agents are being used in Leishmania treatment, but the only effective treatment is achieved with current pentavalent antimonials. WHO considers Leishmaniasis as one of the "Neglected Tropical Diseases" that continues to be prevalent despite international, national, and local efforts towards its control and elimination over the last decade. This chapter reviews the global perspective of Leishmaniasis with increasing recognition of emerging "Atypical forms" and new surge of disease across the world mainly due to increasing conflicts in endemic areas leading to forced migration among other causes. All these challenges related to environment, disease, and vector pose major implications on WHO's leishmaniasis control and elimination plan.
Expert Review of Anti-infective Therapy, 2013
Human visceral leishmaniasis (VL) continues to be a life-threatening neglected tropical disease, with close to 200 million people at risk of infection globally. Epidemics and resurgence of VL are associated with negligence by the policy makers, economic decline and population movements. Control of the disease is hampered by the lack of proficient vaccination, rapid diagnosis in a field setting and severe side effects of current drug therapies. The diagnosis of VL relied largely on invasive techniques of detecting parasites in splenic and bone marrow aspirates. rK39 and PCR, despite problems related to varying sensitivities and specificities and field adaptability, respectively, are considered the best options for VL diagnosis today. No single therapy of VL currently offers satisfactory efficacy along with safety. The field of VL research only recently shifted toward actively identifying new drugs for safe and affordable treatment. Oral miltefosine and safe AmBisome along with better use of amphotericin B have been rapidly implemented in the last decade. A combination therapy will substantially reduce the required dose and duration of drug administration and reduce the chance of the development of resistance. In addition, identification of asymptomatic cases, vector control and treatment of post-kala-azar dermal leishmaniasis would allow new perspectives in VL control and management.
Understanding Human Leishmaniasis:The Need for an Integrated Approach
Encyclopedia of Infectious Diseases
is 12 million people. Most of the affected countries are in the tropics and subtropics: more than 90% of the world's cases of visceral leishmaniasis are in India, Bangladesh, Nepal, Sudan, and Brazil (Fig. 6.2), 90% of all cases of mucocutaneous leishmaniasis (Fig. 6.3) occur in Bolivia, Brazil, and Peru, whereas 90% of all cases of cutaneous leishmaniasis (Fig. 6.3) occur in Afghanistan, Brazil, Iran, Peru, Saudi Arabia, and Syria (for further detail, see http://www.who.int/leishmaniasis/en/). 6.1.2 The Players in Leishmaniasis Leishmania parasites are responsible for cutaneous forms as well as visceral forms of the disease. Healing or progression of this infection is related to the genetic and immune status of the host, the virulence and pathogenicity of different species and strains of Leishmania, and the vector involved. The hosts can be humans but also rodents, dogs, and other mammals [16,307], and great diversity of immune response exists depending on the host considered (see Section 6.4 for details). Similarly, within 500 known phlebotomine species, only 31 have been positively identified as vectors of the Leishmania pathogenic species and 43 as probable vectors [181]. Among them, some vectors such as Phlebotomus Phlebotomus papatasi and P. Paraphlebotomus sergenti can only be 87