Pentamidine Isethionate as Treatment and Secondary Prophylaxis for Disseminated Cutaneous Leishmaniasis During HIV Infection: Case Report

Calza, Leonardo; Marinacci, Ginevra; Manfredi, Roberto; Colangeli, Vincenzo; Fortunato, L; Chiodo, Francesco

doi:10.1179/joc.2001.13.6.653

Cited by 12 publications

(9 citation statements)

References 19 publications

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“…In such a situation, use of any of the few available VL treatment drugs for secondary prophylaxis carries the risk of emergence and spread of drug resistance. Pentamidine has been proposed for secondary prophylaxis in such a situation, since it exerts antileishmanial effect, is currently not used for VL treatment, and has been found to be relatively safe in a prophylactic dose [48]–[50]. An open-label multicentre clinical trial recruiting HIV coinfected adults at high risk of VL relapse is currently ongoing in Ethiopia to evaluate the feasibility, safety, and effectiveness of monthly intravenous administration of pentamidine (4 mg/kg) for a period of 12 to 18 months.…”

Section: Introductionmentioning

confidence: 99%

Visceral Leishmaniasis and HIV Coinfection in East Africa

et al. 2014

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Visceral Leishmaniasis (VL) is an important protozoan opportunistic disease in HIV patients in endemic areas. East Africa is second to the Indian subcontinent in the global VL caseload and first in VL-HIV coinfection rate. Because of the alteration in the disease course, the diagnostic challenges, and the poor treatment responses, VL with HIV coinfection has become a very serious challenge in East Africa today. Field experience with the use of liposomal amphotericin B in combination with miltefosine, followed by secondary prophylaxis and antiretroviral drugs, looks promising. However, this needs to be confirmed through clinical trials. Better diagnostic and follow-up methods for relapse and prediction of relapse should also be looked for. Basic research to understand the immunological interaction of the two infections may ultimately help to improve the management of the coinfection.

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Section: Introductionmentioning

confidence: 99%

Visceral Leishmaniasis and HIV Coinfection in East Africa

et al. 2014

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“…Studies have indicated that pentamidine is either similar in effectiveness (intravenous route) or less effective (aerosolized route) than TMP/SMX against PCP; however, pentamidine is better tolerated with fewer reported adverse events (Schneider et al 1992;May et al 1994;Nielsen et al 1995;Bellamy 2006). Pentamidine has also been studied as first-line treatment for other protozoal infections such as Old World cutaneous leishmaniasis (Hellier et al 2000;Nacher et al 2001;Lai A Fat et al 2002;Roussel et al 2006) and disseminated cutaneous leishmaniasis during HIV infection (Calza et al 2001). Because pentamidine isethionate is commonly used in the HIV population, it becomes difficult to discriminate between hearing loss that is secondary to disease progression versus hearing loss that is secondary to an occult ototoxic effect of disease treatment.…”

Section: Toxicity In Zebrafish Hair Cells Was Confirmed In the Mouse mentioning

confidence: 99%

Using the Zebrafish Lateral Line to Screen for Ototoxicity

Chiu

Cunningham

Raible

et al. 2008

JARO

177

128

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The zebrafish is a valuable model for studying hair cell development, structure, genetics, and behavior. Zebrafish and other aquatic vertebrates have hair cells on their body surface organized into a sensory system called the lateral line. These hair cells are highly accessible and easily visualized using fluorescent dyes. Morphological and functional similarities to mammalian hair cells of the inner ear make the zebrafish a powerful preparation for studying hair cell toxicity. The ototoxic potential of drugs has historically been uncovered by anecdotal reports that have led to more formal investigation. Currently, no standard screen for ototoxicity exists in drug development. Thus, for the vast majority of Food and Drug Association (FDA)-approved drugs, the ototoxic potential remains unknown. In this study, we used 5-day-old zebrafish larvae to screen a library of 1,040 FDA-approved drugs and bioactives (NINDS Custom Collection II) for ototoxic effects in hair cells of the lateral line. Hair cell nuclei were selectively labeled using a fluorescent vital dye. For the initial screen, fish were exposed to drugs from the library at a 100-μM concentration for 1 h in 96-well tissue culture plates. Hair cell viability was assessed in vivo using fluorescence microscopy. One thousand forty drugs were rapidly screened for ototoxic effects. Seven known ototoxic drugs included in the library, including neomycin and cisplatin, were positively identified using these methods, as proof of concept.Fourteen compounds without previously known ototoxicity were discovered to be selectively toxic to hair cells. Dose-response curves for all 21 ototoxic compounds were determined by quantifying hair cell survival as a function of drug concentration. Dose-response relationships in the mammalian inner ear for two of the compounds without known ototoxicity, pentamidine isethionate and propantheline bromide, were then examined using in vitro preparations of the adult mouse utricle. Significant dose-dependent hair cell loss in the mouse utricle was demonstrated for both compounds. This study represents an important step in validating the use of the zebrafish lateral line as a screening tool for the identification of potentially ototoxic drugs.

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“…Amphotericin B lipid complex has been used as first-line therapy for HIV-infected people [126]. Up to 30% of HIVinfected people with leishmaniasis experience relapse within 6 months after treatment, regardless of the treatment used; therefore, chronic suppressive therapy is recommended [127,128]. In HIV-infected people, treatment failure and resistance to standard medications are common, so combination therapy is often necessary [129].…”

Section: Leishmaniasismentioning

confidence: 99%

Parasitic Central Nervous System Infections in Immunocompromised Hosts: Malaria, Microsporidiosis, Leishmaniasis, and African Trypanosomiasis

Snydman¹,

Walker²,

Kublin³

et al. 2006

Clinical Infectious Diseases

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Immunosuppression associated with HIV infection or following transplantation increases susceptibility to central nervous system (CNS) infections. Because of increasing international travel, parasites that were previously limited to tropical regions pose an increasing infectious threat to populations at risk for acquiring opportunistic infection, especially people with HIV infection or individuals who have received a solid organ or bone marrow transplant. Although long-term immunosuppression caused by medications such as prednisone likely also increases the risk for acquiring infection and for developing CNS manifestations, little published information is available to support this hypothesis. In an earlier article published in Clinical Infectious Diseases, we described the neurologic manifestations of some of the more common parasitic CNS infections. This review will discuss the presentation, diagnosis, and treatment of the following additional parasitic CNS infections: malaria, microsporidiosis, leishmaniasis, and African trypanosomiasis.As detailed in our previous article [1], the risk of acquiring fungal, viral, bacterial or parasitic infection is increased in patients receiving immunosuppressive therapy after transplantation and in people with advanced HIV infection. CNS infection occurs in 5%-10% of transplant recipients and up to 19% of patients with AIDS [2]. Patients with advanced HIV infection (CD4 + cell count, <200 cells/mm 3 ) and patients who require high levels of immunosuppression because of graft rejection or graft-versus-host disease are at greater risk than others of developing opportunistic CNS infections. Although parasitic CNS infection can occur in any host, some infections are more common among patients undergoing specific types of transplantation (table 1). The clinical and radiographic manifestations of parasitic CNS infection are often similar in immunocompromised and immunocompetent hosts, but certain infections may blunt or enhance these manifestations in immunosuppressed hosts [3,4]. Although neurologic symptoms vary somewhat by infecting parasite, they are mainly determined by the location(s) of the infection within the CNS (table 2).Evaluation of the immunosuppressed host presenting with neurologic symptoms or signs of infection should be guided by (1) the degree of immunosuppression, type of transplant received,

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Pentamidine Isethionate as Treatment and Secondary Prophylaxis for Disseminated Cutaneous Leishmaniasis During HIV Infection: Case Report

Cited by 12 publications

References 19 publications

Visceral Leishmaniasis and HIV Coinfection in East Africa

Visceral Leishmaniasis and HIV Coinfection in East Africa

Using the Zebrafish Lateral Line to Screen for Ototoxicity

Parasitic Central Nervous System Infections in Immunocompromised Hosts: Malaria, Microsporidiosis, Leishmaniasis, and African Trypanosomiasis

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