Cutaneous leishmaniasis in the Peruvian Andes: risk factors identified from a village cohort study.

Risk factors for cutaneous leishmaniasis were identified from a comparative study of transmission rates in 27 villages in the Departments of Lima, Ancash, and Piura in Peru. To evaluate regression analysis as a tool for the incrimination of sand fly vectors in the absence of other biologic evidence, univariate and multivariate logistic regression analyses were used to identify which of 14 variables (the abundance of nine sand fly species, four social factors, and region) predicted transmission rates in villages (incidence, active prevalence, or cumulative prevalence). In general, suspected or proven vectors (e.g., Lutzomyia peruensis) had the strongest associations with transmission rate, indicating that regression is a useful supplementary method of incriminating vectors. Regression was then used to quantify the importance of suspected risk factors. Transmission rate increased with the abundance of Lu. peruensis, Lu. ayacuchensis, Lu. noguchii, and, to a lesser extent, Lu. verrucarum and transmission was higher among villagers who slept more frequently in temporary shelters in crop areas. There were also weak effects of the number of dogs/ person (negative) and the number of persons/household (positive). Linear regressions failed to detect a threshold sand fly density below which transmission ceases. The minimal adequate multiple regression model explained 82% of the variance in village incidence rates. This model was used to predict the effect on incidence of reducing each of the four suspected vectors in northern and southern Peru. The results indicate that vector control programs in the south should aim at Lu. peruensis, Lu. verrucarum, and Lu. noguchii, but focus on Lu. ayacuchensis in the north.

High continuous antimony therapy in two patients with unresponsive mucosal leishmaniasis.

The treatment of two patients with severe mucosal leishmaniasis due to Leishmania braziliensis braziliensis is described. Both patients had received much prior antimonial therapy and one had relapsed after a total dose of 2.5 g of Amphotericin B. Both patients responded to prolonged continuous Pentostam therapy at a daily dose of 20 mg Sbv/kg/day for 62 days in one case and for 85 days in the other. Pentavalent antimonials can be curative in such protracted courses in selected patients unresponsive to standard chemotherapy.

Spraying houses in the Peruvian Andes with lambda-cyhalothrin protects residents against cutaneous leishmaniasis.

A household vector control trial was carried out in the Peruvian Andes to measure the effect of spraying inside walls and ceilings with lambda-cyhalothrin on the risk for residents of cutaneous leishmaniasis caused by Leishmania peruviana. The mortality rates of Lutzomyia verrucarum measured with WHO contact bioassay cones set on adobe walls characteristic of the endemic region indicated an LD95 for lambda-cyhalothrin of about 20 mg/m2, and no reduction in effectiveness for at least 6 months on indoor adobe walls sprayed with 25 mg/m2. A random selection of 112 houses were sprayed (starting in 1992/93) at 6-monthly intervals with a mean dose of 34 mg/m2, leaving 154 control houses (with closely matched pre-intervention measurements of incidence and sandfly abundance). Comparisons of pre- and post-intervention sandfly indoor abundance, measured at regular intervals for up to 2 years using CDC light traps, in 22 sprayed and 21 control houses demonstrated that spraying significantly reduced the indoor abundance of Lu. verrucarum by an average of 78% and of Lu. (Helcocyrtomyia) peruensis by 83%. Spraying was also associated with a significant reduction of 77% in the proportion of bloodfed sandflies collected in light traps. The proportion of susceptible householders acquiring leishmaniasis during the trial was significantly reduced by 54% as a result of spraying. The observed impact of spraying was greatest, 81% (95% confidence intervals 20-95%), when the cases detected during the first 6 months after the intervention were excluded from the analysis, suggesting a significant pre-patent period.

Natural infections of Leishmania peruviana in animals in the Peruvian Andes.

Evidence that domestic dogs may act as reservoir hosts for cutaneous leishmaniasis in the Peruvian Andes is provided by the isolation, for the first time, from naturally infected dogs of parasites identified (by isoenzymes) as Leishmania peruviana. Leishmania parasites were isolated from nasal aspirates or biopsies from 5 (1.8%) of 279 asymptomatic dogs samples in endemic villages of the Peruvian Andes. In addition, Leishmania (Viannia) infections were identified in 15 (5.4%) of 276 nasal samples by the polymerase chain reaction (PCR) using subgenus-specific primers. Further circumstantial evidence for a reservoir role for dogs comes from the finding of a relatively high dog blood index among the sandfly vectors collected inside houses (29% for Lutzomyia peruensis and 17% for Lu. verrucarum). Possible wild mammal reservoir hosts for Andean cutaneous leishmaniasis were also detected in endemic villages. At least 8 species were identified among the 1266 small mammals trapped. Leishmania parasites were isolated from blood or skin biopsies taken from 2 (2.6%) of 78 Didelphis albiventris and 6 (1.2%) of 511 Phyllotis andinum. Three isolates were identified by isoenzymes as L. peruviana, and the other 5 were identified by PCR as Leishmania (Viannia) species. Leishmania (Viannia) infections were also identified by PCR directly on skin biopsies taken from 2 (2.8%) of 72 D. albiventris, 1 (0.2%) of 499 P. andinum, and 4 (2.6%) of 153 Akodon sp.

Long-term follow-up of patients with Leishmania (Viannia) braziliensis infection and treated with Glucantime.

Seventy-nine patients with cutaneous (62) or mucosal (17) infection with Leishmania (Viannia) braziliensis in Três Braços, Bahia, Brazil, were followed for at least 4 years after initiating treatment with antimony. Cutaneous relapses occurred in 6/62 (10%), mucosal relapse after cutaneous infection in 2/62 (3%), and mucosal relapse after mucosal disease in 2/17 (17%). It is concluded that relapse (cutaneous and mucosal) is rare after adequate antimony therapy and that no definite prediction of relapse (clinical, serological or by skin reaction) is possible.

Human genetic susceptibility and infection with Leishmania peruviana.

Racial differences, familial clustering, and murine studies are suggestive of host genetic control of Leishmania infections. Complex segregation analysis has been carried out by use of the programs POINTER and COMDS and data from a total population survey, comprising 636 nuclear families, from an L. peruviana endemic area. The data support genetic components controlling susceptibility to clinical leishmaniasis, influencing severity of disease and resistance to disease among healthy individuals. A multifactorial model is favored over a sporadic model. Two-locus models provided the best fit to the data, the optimal model being a recessive gene (frequency .57) plus a modifier locus. Individuals infected at an early age and with recurrent lesions are genetically more susceptible than those infected with a single episode of disease at a later age. Among people with no lesions, those with a positive skin-test response are genetically less susceptible than those with a negative response. The possibility of the involvement of more than one gene together with environmental effects has implications for the design of future linkage studies.

Cutaneous leishmaniasis in the Peruvian Andes: an epidemiological study of infection and immunity.

A prospective longitudinal survey of cutaneous leishmaniasis (Leishmania peruviana) was carried out in Peru on a study population of 4716 persons living in 38 villages (Departments of Lima, Ancash and Piura). Demographic and clinical data were collected from all individuals, and a Montenegro skin test (MST) was carried out on 72% (3418) of the study population. Each household was revisited at 3-monthly intervals for up to 2 years to detect new leishmaniasis cases; 497 people received a second MST at the end of the study. Analysis of the epidemiological data indicated that (i) 17% (16/94) of all infections were subclinical, (ii) this percentage increased significantly with age, (iii) clinical infections led to 73.9% protective immunity (95% C.I. 53.0-85.5%) and relatively permanent MST responsiveness (recovery rate = 0.0098/year; 95% C.I. 0.000-0.020/year), (iv) sub-clinical infections led to protective immunity, which was positively correlated with their MST induration size (increasing by 17.9% per mm; P < 0.0001), and a mean MST recovery rate of 0.114/year (4/421 man-months), and (v) recurrent leishmaniasis was dominated by reactivations, not by reinfections.

Cutaneous leishmaniasis in the Peruvian Andes: factors associated with variability in clinical symptoms, response to treatment, and parasite isolation rate.

The severity of cutaneous leishmaniasis may be determined by host immunity, parasite virulence, and host or vector behavior. We performed a multivariate analysis to identify the main causes of the variability in clinical symptoms, response to treatment, and parasite isolation rate among Peruvian patients. The effect of host immunity was demonstrated first by the finding that secondary infections induced smaller lesions associated with a lower parasite isolation rate than did primary infections and, second, by the finding of fewer lesions in older patients. Phenotypic differences between parasite populations were suggested by the observation that the mean scar size and number varied between villages: patients had more scars in villages where the transmission rates were higher. Human behavior probably determined the site of lesions on the body, since most lesions in the cooler South were on the head, whereas in the North, lesions were equally frequent on the extremities. In addition, older patients, who were more likely infected through occupational exposure, had fewer head lesions. Geographic variation in the pattern of exposure to sandflies indicates that uta control strategies should be region specific.

Disseminated cutaneous leishmaniasis in a field clinic in Bahia, Brazil: a report of eight cases.

Eight Bahian patients with cutaneous leishmaniasis who had 20 or more ulcerative lesions of short duration are described. Of five identifications of isolated parasites, four were Leishmania braziliensis braziliensis and one was L. mexicana amazonensis. All but one had positive Montenegro tests initially, and all did after treatment. All had circulating anti-leishmanial antibodies and five responded well to glucantime therapy suggesting a functioning immune response. This is quite different to the anergic hansenoid leishmaniasis seen with L. mexicana amazonensis infections in Brazil. Possible reasons for the occurrence of this type of leishmaniasis are briefly discussed.

Attempts using cryotherapy to achieve more rapid healing in patients with cutaneous leishmaniasis due to L.braziliensis braziliensis.

O uso da crioterapia associada ao Glucantime na terapia da leishmaniose tegumentar foi estudado em 17 pacientes com um total de 23 lesoes de pele por leishmaniose, em uma area onde Leishmania braziliensis braziliensis e a especie em circulacao. A crioterapia nao influenciou a rapidez da cicatrizacao. Ela foi abandonada como metodo de terapia auxiliar em nossa pratica, embora possa ser util para especies de Leishmania causando lesoes mais superficiais e limitads no homem, sem o perigo de metastase

Estudo clínico evolutivo da leishmaniose em area endemica de leishmania brasiliensis brasiliensis / Evolutivo clinical study of leishmaniasis in endemic area of leishmania brasiliensis brasiliensis

Foram estudadas as características clínicas evolutivas de 239 pacientes portadores de leishmaniose tegumentar que vivem em Três Braços, Bahia, área endêmica da doença. 1- 182 (76 por cento) dos pacientes apresenta-ram lesoes exclusivamente cutâneas (LC) e 57 (24 por cento) acometimento mucoso (LM). Nestas duas categorias as lesoes foram divididas como únicas e múltiplas. 96,7 por cento das cepas isoladas dos pacientes da área foram identificadas como L.b. braziliensis. Verificou-se somente duas infecçoes humanas comprovadas por L. mexicana. 2- Demonstrou-se o parasito em 71 por cento dos casos na LC e em 48 por cento dos casos na LM, com o uso combinado de vários métodos (esfregaço e/ou histologia e/ou cultura e/ou inoculaçao ou hamster)