Poor response to azithromycin in cutaneous leishmaniasis leading to a premature interruption of a multicentric phase III clinical trial in Brazil

Introduction Parenteral antimony-based compounds are still the standard of care for cutaneous leishmaniasis (CL) treatment in many countries, despite their high toxicity. Previous studies showed that oral azithromycin could be an option for CL treatment. The aim of this study was to evaluate efficacy and safety of oral azithromycin (AZ) for CL treatment compared with injectable meglumine antimoniate (MA). Methods This was a randomized, open-label, 2-arm, non-inferiority clinical trial. Treatment-naïve patients with localized CL were treated with MA (15mg/kg/day up to 1,215mg) or AZ (500mg/day) during 20 consecutive days. The primary efficacy end point was a CL cure 90 days after treatment completion. The analysis was performed with intention-to-treat (ITT) and per protocol (PP) analyses. After an anticipated interim analysis, the study was interrupted due to the high failure rate in the azithromycin group. Results Twenty-four volunteers were included in each group. The MA group had a higher cure rate than the AZ group with the ITT and PP analyses, which were 54.2% versus 20.8% [relative risk (RR) 1.97; 95% confidence intervals (95%CI) 1.13-3.42] and 72.2% versus 23.8% (RR 3.03; 95%CI 1.34-6.87), respectively. No unexpected adverse events were observed. Conclusions Azithromycin is ineffective for CL treatment and does not seem to have a role in the therapeutic arsenal for CL.

Phlebotominae sand flies (Diptera: Psychodidae): potential vectors of American cutaneous leishmaniasis agents in the area associated with the Santo Antônio Hydroelectric System in Western Amazonian Brazil

INTRODUCTION: An entomological study was conducted as part of a vector-monitoring program in the area associated with the Santo Antônio hydroelectric system in State of Rondônia, Western Amazonian Brazil. METHODS: Fourteen sampling sites were surveyed to obtain data on the potential vectors of Leishmania spp. in the area. Sand flies were collected from 2011 to 2014 during the months of January/February (rainy season), May/June (dry season), and September/October (intermediary season) using light traps arranged in three vertical strata (0.5, 1, and 20m). RESULTS : A total of 7,575 individuals belonging to 62 species/subspecies were collected. The five most frequently collected sand flies were Psychodopygus davisi (Root) (36.67%), Trichophoromyia ubiquitalis (Mangabeira) (8.51%), Nyssomyia umbratilis (Ward & Fraiha) (6.14%), Bichromomyia flaviscutellata (Mangabeira) (5.74%), and Psychodopygus complexus (Mangabeira) (5.25%). These species have been implicated in the transmission of American cutaneous leishmaniasis agents in the Brazilian Amazon region and described as potential vectors of this disease in the study area. CONCLUSIONS: Additional surveillance is needed, especially in areas where these five species of sand fly are found.

Detection of Leishmania (Viannia) DNA in leucocytes from the blood of patients with cutaneous leishmaniasis

ABSTRACTINTRODUCTION:Cutaneous leishmaniasis (CL) is a serious and global public health issue, with the potential of developing a mucosal form, occurring as subclinical cases, and showing recurrence despite previous treatment.METHODS:Polymorphonuclear and mononuclear DNA obtained from 49 patients was subjected to polymerase chain reaction for detection of Leishmania (Viannia).RESULTS:DNA was detected in mononuclear cells from two patients with active primary lesions positive for CL, with infection periods of 3 and 6 months, respectively.CONCLUSIONS:The DNA of Leishmania (Viannia) indicates probable parasite dissemination possibly explaining subclinical case emergence, lesion recurrence, and mucosal lesion appearance.

New method for evaluation of cutaneous sensibility in diabetic feet: preliminary report

Diabetic neuropathy is an important complication of the disease, responsible for ulceration and amputation of the foot. Prevention of these problems is difficult mainly because there is no method to correctly access sensibility on the skin of the foot. The introduction of the Pressure-Specified Sensory Device (PSSD TM) in the last decade made possible the measurement of pressure thresholds sensed by the patient, such as touch, both static and in movement, on a continuous scale. This paper is the first in Brazil to report the use of this device to measure cutaneous sensibility in 3 areas of the foot: the hallux pulp, the calcaneus, and the dorsum, which are territories of the tibial and fibular nerves. METHOD: Non-diabetic patients were measured as controls, and 2 groups of diabetic patients - with and without ulcers - were compared. The PSSD TM was used to test the 3 areas described above. The following were evaluated: 1 PS (1-point static), 1 PD (1-point dynamic), 2 PS (2-points static), 2 PD (2-points dynamic). RESULTS: The diabetic group had poorer sensibility compared to controls and diabetics with ulcers had poorer sensibility when compared to diabetics without ulcers. The differences were statistically significant (P <.001). CONCLUSION: Due to the small number of patients compared, the results should be taken as a preliminary report.

Cutaneous allergic reactions to Triatoma infestans after xenodiagnosis

We determined the frequency of cutaneous allergic reactions to bites of Triatoma infestans during xenodiagnosis in a rural community where Panstrongylus megistrus is the only domestic vector of Trypanosoma cruzi. Localized urticaria or more intense cutaneous allergic reactions at 48 and 72 hours were observed in 86.7% and 82.1% respectively of the individuals in our study. Urticaria was more severe in children and older adults and in women than in men. The high frequency of reactions suggests either cutaneous reactivity to T. infestans without prior sensitization or cross reactivity between P. megistus and T. infestans. A single application of topical corticosteroid or antihistamine medication did not reduce the cutaneous reactions.

The principal reservoir host of cutaneous leishmaniasis in the urban areas of Manaus, Central Amazon of Brazil

Twenty one opossums (Didelphis marsupialis) from disturbed primary forest in the vicinity of Manaus, and seven from an isolated island of secondary vegetation within the city of Manaus, were examined for the presence of Leishmania. Of the opossums from the primary forests, 13 (61.9%) were found to be positive for Leishmania braziliensis guyanenesis. One additional opossum was found to be positive for Le. mexicana amazonensis. A simple and economical trapping technique for opossums is presented here, and a control method in special cases is suggested.

Study of an outbreak of cutaneous leishmaniasis in Venezuela: the role of domestic animals

During an outbreak of cutaneous leishmaniasis in a locality (Las Rosas, Cojedes State, venezuela) previously non-endemic, 12.9% of humans, 7% of dogs and 21.4% of donkeys (Equus asinus) had lesions with paraites. The agent in the three hosts was identified as Leishmania braziliensis, subspecies braziliensis at least in man and donkey. The probable vector was Lutzomyia panamensis. No infection was found in a small sample of wild mammals examined. The outbreak was apparently linked with the importation of donkeys with ulcers, from endemic areas. The Authors call attention to the fact that not only in the foci of "uta", but also in areas of the other forms of American cutaneous leishmaniasis, dogs are frequently found infected. They emphasize the necessity of searching for the infection in donkeys and of performing hemocultures and xenodiagnosis with sandflies in human, canine and equine cases, to verify their possible role as sources of infection, and not merely as dead ends in the epidemiological chain of the disease.

Experimental infection of Lutzomyia longipalpis fed on a patient with cutaneous leishmaniasis due to Leishmania mexicana amazonensis

The authors were able to infect phlebotomine sandflies on a human case of American Cutaneous Leishmaniasis by feeding females of Lutzomyia longipalpis on a patient with a lesion due to Leishmania mexicana amazonensis.

Active cutaneous leishmaniasis in Brazil, induced by Leishmania donovani chagasi

L.d. chagasi was isolated from active cutaneous leishmaniasis in both human and canine infections in an endemic area in Rio de Janeiro, Brazil. Both isolates were identified by molecular and immunological characterization of the parasite using three different methods: electrophoretic mobility of isoenzymes; restriction endonuclease fragment analysis of kDNA and serodeme analysis using monoclonal antibodies. This seems to be the first well documented case in the New World of a "viscerotropic" Leishmania inducing a case of cutaneous leishmaniasis. This observation emphasizes that the diagnosis of the etiologic agent of human or canine visceral leishmaniasis based solely upon clinical and epidemiological critwria may lead to erroneous conclusions.

Cutaneous leishmaniasis in frequent in equines from an endemic area in Rio de Janeiro, Brazil

In an endemic area of cutaneous leishmaniasis in Rio de Janeiro State where a mule had been found infected, a systematic search among equines was performed, resulting in the detection of Leishmania parasites in skin lesions of 30.8% of the animals, which included horses and mules. The eventual role of equines in the epidemiology of the human disease is being investigated.

Ecology of sandflies (Diptera: Psychodidae) in a restricted focus of cutaneous leishmaniasis en Northern Venezuela: I. Description of the study area, catching methods and species composition

A study on the ecology of phlebotomine sandfly fauna in a restricted focus of cutaneous leishmaniasis in northern Venezuela was undertaken in order to investigate the species responsible for the transmission. The study area and catching methods for phlebotomine sandflies are described. A total of 9,061 females and 1,662 males were collected during a year-term study. 12 species of Lutzomya and 1 species of Brumptomya sp. were identified. Absolute and relative abundance and ocurrence for each species were determined. The rel ative occurrence allowed to distinguish the common species, viz. L. panamensis, L. ovallesi, L. gomezi, L. tinidadensis, L. atroclavata, L. cayennensis, L. shannoni and L. olmeca bicolor from the rare species vis., L. punctigeniculata, L. rangeliana, L. evansi and L. dubitans. General comments on the species composition of the sandfly fauna in this locality are made.

Ecology of sandflies (Diptera: Psychodidae) in a restricted focus of cutaneous leishmaniasis in Northern Venezuela: II. Species composition in relation to habitat, catching method and hour of catching

The ecology of phlebotomine sandflies in an endemic focus of cutaneous leishmaniasis in Northern Venezuela (San Esteban, Carabobo State) was investigated through a year-term study. Three different habitats: viz. a house, a pridomestic area and a sylvatic area, were covered and the species composition, the abundance and occurrence of each species were analyzed in relation to the habitats, catching methods and hour of catching. L. panamensis, L. gomezi and L. ovallesi are the species which bite man, although almost exclusively at night. All of them hide by day and are common in the sylvatic area. Moreover, L. panamensis and L. gomezi successfully approach the house and seem to settle in the peridomestic area. L. shannoni and L. olmeca bicolor also approach and accidentally bite man. L. trinidadensis, L. atroclavata and L. cayennensis are the common non-antrhopophilic species in the area.

Ecology of sandflies (Diptera: Psychodidae) in a restricted focus of cutaneous leishmaniasis in Northern Venezuela: III. Seasonal fluctuation

A one year-long study (March 1979-March 1980) was carried out at San Esteban, an endemic focus of cutaneous leishmaniasis in Northern Venezuela, with the aim of observing the seasonal fluctuation of the local phlebotomine sandflies species. The influence of climatic factors (temperature, relative humidity and rainfall) on population dynamics was analyzed in three collecting sites - a house, a peridomestic area and a sylvatic region. Among anthropophilic species, L. panamensis behaved as a wetseason species, the mean minimum relative humidity being the critical factor influencing the total number of individuals. When the population density of this fly decreased, it was successfully replaced by L. ovallesi, a dry-season species. On the other hand, seasonal variations of L. gomezi were more strongly affected by the temperature.

Ecology of sandflies Diptera: Psychodidae) in a restricted focus of cutaneous leishmaniasis in Northern Venezuela: IV. Sandfly monthly fluctuation and leishmaniasis incidence relationship

An attempt has been made to correlate the monthly incidence of human leishmaniasis with the temporal distribution of sandfly species at San Esteban, Northern Venezuela. Upon statistical analysis, the seasonal fluctuation of L. ovallesi population correlated strongly with the human disease, while the dynamics of L. panamensis, generally believed to be the vector in the Central area of the country, showed only a very weak correlation. These findings support the hypothesis that L. panamensis might not be the main or unique species responsible for the transmission in this area and that L. ovallesi and additionally L. olmeca bicolor might be involved in the epidemiology of the disease.