Leishmaniasis, Mucocutaneous

American cutaneous leishmaniasis (ACL) is the most prevalent form of leishmaniasis, associated with an ulcerative and stigmatizing mucocutaneous pathology. This study assessed the incidence of Leishmania (Viannia) braziliensis in members of the Argentine Army who were exposed to sandfly bites in Iguazú National Park (INP), northeastern Argentina, during an outbreak of ACL in 2019, and the presence of Leishmania in rodents, opossums and phlebotomine sandflies collected in the area of exposure. Samples from military personnel, wild animals and phlebotomine sandflies were analysed. A total of 20 (40%) patients among the Army personnel and two Akodon montensis rodents (11%) were positive for the presence of Leishmania sp. genes by PCR, while Nyssomyia whitmani and Migonemyia migonei, competent vectors of Leishmania, were also found at the same site. Sequences of hsp70 DNA fragments obtained from human samples confirmed the identity of L. (V.) braziliensis. The risk to which military personnel carrying out activities in the forest are exposed is highlighted, and this risk extends to any worker and visitor who circulates without protection in the INP, coming into contact with transmission "hot spots" due to the concentration of vectors, reservoirs and/or parasites.

Leishmania, a protozoan parasite, is responsible for the occurrence of leishmaniasis, a disease that is prevalent in tropical regions. Visceral Leishmaniasis (VL), also known as kala-azar in Asian countries, is one of the most significant forms of VL, along with Cutaneous Leishmaniasis (CL) and Mucocutaneous Leishmaniasis (ML). Management of this condition typically entails the use of chemotherapy as the sole therapeutic option. The current treatments for leishmaniasis present several drawbacks, including a multitude of side effects, prolonged treatment duration, disparate efficacy across different regions, and the emergence of resistance. To address this urgent need, it is imperative to identify alternative treatments that are both safer and more effective. The identification of appropriate pharmacological targets in conjunction with biological pathways constitutes the initial stage of drug discovery. In this review, we have addressed the key metabolic pathways that represent potential pharmacological targets as well as prominent treatment options for leishmaniasis.

American Tegumentary Leishmaniasis (ATL) treatment is based on pentavalent antimonials (Sb5+), but these drugs have been associated to several adverse effects. Hearing loss and tinnitus during treatment with meglumine antimoniate (MA) have already been reported. This study aimed to describe the usefulness of self-reporting of hearing loss and tinnitus in diagnosing MA-induced ototoxicity.

A prospective longitudinal study was conducted with 102 patients with parasitological diagnosis of ATL, treated with different MA schemes. The presence of clinical auditory toxicity was defined as the emergence or worsening of self-reporting hearing loss and/or tinnitus during monitoring. Measures of sensitivity, specificity, and the positive and negative predictive value of the patient's self-reporting of hearing loss and tinnitus in relation to the result of the audiometric test (considered the gold standard) were calculated.

The age of the evaluated patients ranged from 15 to 81 years, with a median of 41 years, and most were male (73.5%). Seventy-five patients (73.5%) had cutaneous leishmaniasis and 27 (26.5%) mucosal leishmaniasis. Eighty-six patients (84.3%) received intramuscular (IM) treatment and 16 (15.7%) were treated with intralesional MA. During treatment, 18 (17,6%) had tinnitus and 7 (6,9%) had complaint of hearing loss. 53 (52%) patients had cochlear toxicity confirmed by tone threshold audiometry and high frequency audiometry, from which 60% received a dose of 20 mg Sb5+/kg/day (p = 0.015) and 96.2% were treated with IM MA (p = 0.001). Tinnitus has greater specificity and positive predictive value than hearing loss, with a low number of false positives, but with a high false negative value.

Although the large number of false negatives suggests that self-report of hearing loss or tinnitus cannot be considered a good screening test for referring the patient to an audiometry, the low number of false positives suggests the need to value the patient's complaint for referral. Otherwise, this study reinforces the importance of audiological monitoring during treatment with MA, especially in those patients with self-reporting of hearing loss or tinnitus when treated with 20 mg Sb5+/kg/day via IM.