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Clinical and epidemiologic profile of visceral leishmaniasis in Trujillo state, Venezuela (1975-2007)
Abstract
The objective of this study was to consolidate and analyze information in reference to clinical and epidemiological aspects of patients with Visceral Leshismaniasis in Trujillo State, Venezuela through a retrospective study which included interned patients from 1975-2007. 82 clinical records were reviewed: 55 children and teenagers between 0- 17 years, and 27 adults between 18 and 60 years. 53.7% of them were children between 0 and 5 years. Among adults, the male sex was dominant (P=0. 002). In reference to the signs and symptoms, a significant difference was found between children/teenagers and adults in the variables of astenia (P=0.001) and loss of weight (P=0.001) which were more frequent among adults. The average ingression to the hospital was 31.17 ±14 days and the rate of mortality was 4.9%. In conclusion the LVA in Trujillo state is persistently endemic with a low and sporadic cases, which must be discarded in adult patients who come from endemic areas with weight loss and asthenia.
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Previous studies have shown that variation in the distribution of vectors associated to the transmission of Leishmania species may be related to climatic changes. However, the potential implications of these ecological changes in human health need to be further defined in various endemic populations where leishmaniasis carries a substantial burden of disease such as in Northeastern Colombia. Herein, we report the impact of El Niño Southern Oscillation climatic fluctuations during 1985-2002 in the occurrence of cases of leishmaniasis in two northeastern provinces of Colombia. During this period, we identified that during El Niño, cases of leishmaniasis increased, whereas during La Niña phases, leishmaniasis cases decreased. This preliminary data show how climatic changes influence the occurrence of leishmaniasis in northeastern Colombia and contributes to the growing body of evidence that shows that the incidence of vector-borne diseases is associated with annual changes in weather conditions
Visceral leishmaniasis (VL) is a protozoa disease caused by parasites of the leishmania donovani complex, whose clinical symptoms include prolonged fever, hepatomegaly, splenomegaly, anemia and gradual weight loss, and could be life threatening, especially in children, if not diagnosed early. Between most serological tests used for diagnosing VL is the enzyme linked immuno-absorbent assay (ELISA). At the present time antigens increase the specificity of serological tests, which has been achieved by the use of recombinant antigens, such as recombinant K39 antigen (rK39). In this study rK39 antigen was assessed, using ELISA for the serological diagnosis of visceral leishmaniasis. 100 confirmed positive serum samples for VL were used, having any three of the following criteria: clinical signs, epidemiology, serological confirmation or demonstration of parasite (bone marrow aspiration). Controls were 100 confirmed negative serum samples for VL and 30 sera infected with other pathologies: tuberculosis (5), trypanosomiasis (5), toxoplasmosis (5), leprosy (5), cutaneous leismaniasis (5), malaria (2), HIV/AIDS (3). The rK39 ELISA obtained a sensitivity of 92% and a specificity of 100%. The positive predicted value was 100% and the negative predicted value was 92.56%. No cross reaction was observed with the sera infected with other pathologies. The rK39 ELISA has a high sensitivity and specificity for the serological diagnosis of VL, and the use of this test for the VL diagnostic protocol is recommended.
The kala-azar epidemic in the State of Piauí 1980-1986 is analyzed on the basis of the data collected by SUCAM Piauí. The outbreak began in towns of central and northern Piauí in 1980. In contrast what has happened in endemic periods in which the disease occurred in areas of higher altitude and semi-arid climate, the epidemic developed in humid tropical river valleys in rural zones. The epidemic was worst in the towns. The state capital, Teresina, hit in 1981, reached the epidemic peak in 1984 and accounted, for more than 60% of the 1,509 cases in the state. The epidemic was not substantial in those regions sprayed to combat malaria and Chagas' disease. While control in Teresina was attempted through intensive use of insecticides, the outbreak gave way spontaneously in rural areas. Neither the number of cases nor the phlebotomine population of Teresina presented significant seasonal variations but were moderately correlated. There was greater prevalence in children of 5 years of age or less, especially during the peak epidemic years, and much lesser prevalence in adults over 40 years of age. The geographical distribution of the epidemic process and its beginning, concommitant with a prolonged drought with its accompanying migration of people and domestic animals from endemic to epidemic regions, suggests that migration unleashed the epidemic. The fact that the epidemic process spontaneously relinquished its hold in areas where no control was attempted, indicates that the end of the epidemic cannot be attributed solely to measures of control. An analysis of the coefficients of specific incidence within age groups sparks the discussion about the possibility that progressive reduction of susceptibility (determined by the great number of assymptomatic infections as well as by long-lasting immunity) contributed to the extinction of the epidemic.
Apresenta-se o resultado de um estudo de campo sobre a leishmaniose visceral autóctone da Ilha de São Luís. Com início em 2004 e término em 2006, a pesquisa visou conhecer aspectos epidemiológicos e clínicos determinantes da endemia. Foram analisados 299 casos autóctones, sendo 83,6% em menores de 9 anos e 54,1% do sexo masculino. O agravo ocorreu em todos os meses do ano com pico em junho. O coeficiente de incidência foi reduzido de 46,1 para 35,2 casos por 100.000 habitantes nos anos estudados. O diagnóstico teve confirmação laboratorial em 93,3% dos casos. O tratamento de escolha foi à base de N-metilglucamina com percentual de cura de 96,1%. A letalidade média foi de 3,7%. Em função da inexistência de ações mais sistemáticas de controle, propõe-se a criação de um programa a ser desenvolvido pelos municípios sob a coordenação da Secretaria de Estado da Saúde.
Descreve-se o perfil epidemiológico da leishmaniose visceralentre índios no estado de Roraima, Brasil, baseado na ocorrência de casos humanos observados e nos inquéritos caninos e entomológicos realizados no período de 1989 a 1993. Foram registrados 82 casos humanos de leishmaniose visceral em seis dos oito municípios então existentes no estado; houve predomínio de 69,5% para o sexo masculino entre os casos observados. A maioria (52,4%) dos casos foi entre crianças de zero a dez anos de idade. Registrou-se o índice de 10,3% de infecção canina natural, entre 3.773 cães examinados em 74 localidades pesquisadas. A Lutzomyia longipalpis foi encontrada nas áreas de maior prevalência da doença, em 31 localidades diferentes. Os casos humanos, caninos e vetores estão concentrados em regiões onde predominam serras e lavrados, áreas características de ocorrência da leishmaniose visceral americana. A introdução e intensificação das atividades garimpeiras na região podem ter contribuído para a introdução da doença.
Evaluation of recombinant K39 antigen for the serological diagnosis of visceral leishmaniasis with enzyme linked immuno-absorbent assay (ELISA). Visceral leishmaniasis (VL) is a protozoa disease caused by parasites of the leishmania donovani complex, whose clinical symptoms include prolonged fever, hepatomegaly, splenomegaly, anemia and gradual weight loss, and could be life threatening, especially in children, if not diagnosed early. Between most serological tests used for diagnosing VL is the enzyme linked immuno-absorbent assay (ELISA). At the present time antigens increase the specifi city of serological tests, which has been achieved by the use of recombinant antigens, such as recombinant K39 antigen (rK39). In this study rK39 antigen was assessed, using ELISA for the serological diagnosis of visceral leishmaniasis. 100 confi rmed positive serum samples for VL were used, having any three of the following criteria: clinical signs, epidemiology, serological confi rmation or demonstration of parasite (bone marrow aspiration). Controls were 100 confi rmed negative serum samples for VL and 30 sera infected with other pathologies: tuberculosis (5), trypanosomiasis (5), toxoplasmosis (5), leprosy (5), cutaneous leismaniasis (5), malaria (2), HIV/AIDS (3). The rK39 ELISA obtained a sensitivity of 92% and a specifi city of 100%. The positive predicted value was 100% and the negative predicted value was 92.56%. No cross reaction was observed with the sera infected with other pathologies. The rK39 ELISA has a high sensitivity and specifi city for the serological diagnosis of VL, and the use of this test for the VL diagnostic protocol is recommended.
Leishmaniasis emergence in Europe is reviewed, based on a search of literature up to and including 2009. Topics covered are the disease, its relevance, transmission and epidemiology, diagnostic methods, treatment, prevention, current geographical distribution, potential factors triggering changes in distribution, and risk prediction. Potential factors triggering distribution changes include vectorial competence, importation or dispersal of vectors and reservoir hosts, travel, and climatic/environmental change. The risk of introducing leishmaniasis into the European Union (EU) and its spread among Member States was assessed for the short (2-3 years) and long term (15-20 years). There is only a low risk of introducing exotic Leishmania species because of the absence of proven vectors and/or reservoir hosts. The main threat comes from the spread of the two parasites endemic in the EU, namely Leishmania infantum, which causes zoonotic visceral and cutaneous leishmaniasis in humans and the domestic dog (the reservoir host), and L. tropica, which causes anthroponotic cutaneous leishmaniasis. The natural vector of L. tropica occurs in southern Europe, but periodic disease outbreaks in Greece (and potentially elsewhere) should be easily contained by surveillance and prompt treatment, unless dogs or other synanthropic mammals prove to be reservoir hosts. The northward spread of L. infantum from the Mediterranean region will depend on whether climate and land cover permit the vectors to establish seasonal biting rates that match those of southern Europe. Increasing dog travel poses a significant risk of introducing L. infantum into northern Europe, and the threat posed by non-vectorial dog-to-dog transmission should be investigated.
Background:
Climate change is increasingly being implicated in species' range shifts throughout the world, including those of important vector and reservoir species for infectious diseases. In North America (México, United States, and Canada), leishmaniasis is a vector-borne disease that is autochthonous in México and Texas and has begun to expand its range northward. Further expansion to the north may be facilitated by climate change as more habitat becomes suitable for vector and reservoir species for leishmaniasis.
Methods and findings:
The analysis began with the construction of ecological niche models using a maximum entropy algorithm for the distribution of two sand fly vector species (Lutzomyia anthophora and L. diabolica), three confirmed rodent reservoir species (Neotoma albigula, N. floridana, and N. micropus), and one potential rodent reservoir species (N. mexicana) for leishmaniasis in northern México and the United States. As input, these models used species' occurrence records with topographic and climatic parameters as explanatory variables. Models were tested for their ability to predict correctly both a specified fraction of occurrence points set aside for this purpose and occurrence points from an independently derived data set. These models were refined to obtain predicted species' geographical distributions under increasingly strict assumptions about the ability of a species to disperse to suitable habitat and to persist in it, as modulated by its ecological suitability. Models successful at predictions were fitted to the extreme A2 and relatively conservative B2 projected climate scenarios for 2020, 2050, and 2080 using publicly available interpolated climate data from the Third Intergovernmental Panel on Climate Change Assessment Report. Further analyses included estimation of the projected human population that could potentially be exposed to leishmaniasis in 2020, 2050, and 2080 under the A2 and B2 scenarios. All confirmed vector and reservoir species will see an expansion of their potential range towards the north. Thus, leishmaniasis has the potential to expand northwards from México and the southern United States. In the eastern United States its spread is predicted to be limited by the range of L. diabolica; further west, L. anthophora may play the same role. In the east it may even reach the southern boundary of Canada. The risk of spread is greater for the A2 scenario than for the B2 scenario. Even in the latter case, with restrictive (contiguous) models for dispersal of vector and reservoir species, and limiting vector and reservoir species occupancy to only the top 10% of their potential suitable habitat, the expected number of human individuals exposed to leishmaniasis by 2080 will at least double its present value.
Conclusions:
These models predict that climate change will exacerbate the ecological risk of human exposure to leishmaniasis in areas outside its present range in the United States and, possibly, in parts of southern Canada. This prediction suggests the adoption of measures such as surveillance for leishmaniasis north of Texas as disease cases spread northwards. Potential vector and reservoir control strategies-besides direct intervention in disease cases-should also be further investigated.
OBJETIVO: Descrever as características clínico-epidemiológicas, o tratamento e a letalidade das crianças internadas com leishmaniose visceral em um hospital pediátrico de referência. MÉTODOS: Análise retrospectiva dos dados biológicos, demográficos, clínicos e laboratoriais das crianças internadas no Instituto Materno-Infantil de Pernambuco, em Recife, no período compreendido entre 1996 e 2001. RESULTADOS: Foram incluídas 431 crianças, de 4 meses a 13,7 anos de idade, sendo que 50,3% eram do sexo feminino, e 82,5% eram do interior do estado de Pernambuco. Cerca de 70% dos domicílios eram de alvenaria, 70% não dispunham de água encanada ou sistema de esgoto sanitário, e o tempo médio de permanência das mães na escola foi de 3 anos. Esplenomegalia e febre estavam presentes em 97% e 95,6% dos casos, respectivamente, e 44,5% dos pacientes eram subnutridos. Em 47 (10,9%) dos pacientes foi detectada infecção na admissão. O nível médio de hemoglobina foi de 6 g/dl, de leucócitos 3.516/mm³ e de plaquetas 118.641/mm³. O tratamento de escolha foi o glucantime (98% dos casos), e em sete pacientes, a anfotericina B foi utilizada. A letalidade foi de 10,2%, sendo que as principais causas imediatas de óbito foram atribuídas a infecções associadas, hemorragias e insuficiência hepática. CONCLUSÕES: Os autores destacam as características clínicas, epidemiológicas e laboratoriais da leishmaniose visceral em área endêmica, além do diagnóstico tardio e alta letalidade, sugerindo a capacitação de profissionais de saúde para o reconhecimento precoce e tratamento adequado da doença e suas complicações.
Objetivo: comparar os dados clínicos e laboratoriais no pré e pós-tratamento de pacientes portadores de leishmaniose visceral (LV), admitidos em hospital pediátrico localizado em área não-endêmica, destacando a importância do reconhecimento da LV na faixa etária pediátrica. Métodos: avaliação dos dados clínicos, laboratoriais e de tratamento de pacientes portadores de LV no período compreendido entre 1981 e 1992, comparando-se os valores médios de hemoglobina, leucócitos, neutrófilos, plaquetas, albumina, gamaglobulina, classes e subclasses de imunoglobulinas, tamanho do fígado e baço antes e após o tratamento, utilizando-se o teste "t" para amostras pareadas. Resultados: foram incluídos 78 pacientes, com idade variando entre 8 meses e 13,5 anos, sendo 44 casos do sexo masculino e 61 provenientes da Bahia. Febre e esplenomegalia estavam presentes em 96,1% e 100% dos casos, respectivamente. O diagnóstico parasitológico foi obtido em 74/78 pacientes, com positividade pelo mielograma e/ou mielocultura em 67 casos (85,7%), 5 pela biópsia hepática e 2 pela punção esplênica. Os valores hematológicos e a albumina sérica apresentaram melhora significante ao término do tratamento (p
Background:
Malaria remains a serious problem in Colombia. The number of malaria cases is governed by multiple climatic and non-climatic factors. Malaria control policies, and climate controls such as rainfall and temperature variations associated with the El Niño/Southern Oscillation (ENSO), have been associated with malaria case numbers. Using historical climate data and annual malaria case number data from 1960 to 2006, statistical models are developed to isolate the effects of climate in each of Colombia's five contrasting geographical regions.
Methods:
Because year to year climate variability associated with ENSO causes interannual variability in malaria case numbers, while changes in population and institutional control policy result in more gradual trends, the chosen predictors in the models are annual indices of the ENSO state (sea surface temperature [SST] in the tropical Pacific Ocean) and time reference indices keyed to two major malaria trends during the study period. Two models were used: a Poisson and a Negative Binomial regression model. Two ENSO indices, two time reference indices, and one dummy variable are chosen as candidate predictors. The analysis was conducted using the five geographical regions to match the similar aggregation used by the National Institute of Health for its official reports.
Results:
The Negative Binomial regression model is found better suited to the malaria cases in Colombia. Both the trend variables and the ENSO measures are significant predictors of malaria case numbers in Colombia as a whole, and in two of the five regions. A one degree Celsius change in SST (indicating a weak to moderate ENSO event) is seen to translate to an approximate 20% increase in malaria cases, holding other variables constant.
Conclusion:
Regional differentiation in the role of ENSO in understanding changes in Colombia's annual malaria burden during 1960-2006 was found, constituting a new approach to use ENSO as a significant predictor of the malaria cases in Colombia. These results naturally point to additional needed work: (1) refining the regional and seasonal dependence of climate on the ENSO state, and of malaria on the climate variables; (2) incorporating ENSO-related climate variability into dynamic malaria models.
The urbanization of visceral leishmaniasis in Brazil has been related to environmental changes, migration, interaction and spread of sylvatic reservoirs and infected dogs to areas with no transmission, and adaptation of the vector Lutzomyia longipalpis to the peridomiciliary environment. From 1980 to 2005, Brazil recorded 59,129 cases of visceral leishmaniasis, 82.5% of which in the Northeast region. Visceral leishmaniasis gradually spread to other regions of the country: in 1998 these other regions reported 15% of all cases, but by 2005 this proportion had increased to 44%. From 1998 to 2005, indigenous cases were reported in 1,904 different municipalities of the country (34.2%). Reservoir and vector control pose major challenges for disease control, since there is a need for better knowledge of vector behavior in urban areas, and control activities involve high operational costs. In recent years the Brazilian Ministry of Health has supported research on the laboratory diagnosis of infection and disease in humans and dogs, treatment of patients, evaluation of the effectiveness of control strategies, and development of new technologies that could contribute to the surveillance and control of visceral leishmaniasis in the country.
Visceral leishmaniasis is an endemic disease caused by various species of Leishmania. We made a retrospective study of 57 consecutive patients with visceral leishmaniasis in Brazil. Patients with visceral leishmaniasis were identified using the registries of the São José Infectious Diseases Hospital. The sample was divided into two groups: patients with serum creatinine (Scr) <1.3mg/dL and Scr > or = 1.3mg/dL. We compared these two groups for differences in clinical manifestations and laboratory features. Patients' mean age was 28 +/- 18 years old; 74% were male. The main clinical symptoms and signs presented in the initial evaluation were: fever (97%), splenomegaly (96.4%), weight loss (95.5%), pallor (93.6%), cough (89.7%), hepatomegaly (87.2%), asthenia (83.3%), anorexia (82.9%) and vomiting (73.9%). Acute renal failure was found in 15 patients (26.3%) and eight of these patients had ARF before amphotericin B administration. The mean age was higher in the group with Scr > or =1.3mg/dL. Death occurred in three cases; all deaths occurred with Scr > or =1.3mg/dL. There were no significant differences in the frequencies of the clinical symptoms and signs between the two groups. The laboratory data and demographic characteristics were significantly worse in the Scr > or =1.3mg/dL group. Renal dysfunction is an important feature of this disease; it is associated with important morbidity and can increase mortality.
The laboratory and field observations summarized in this paper on visceral leishmaniasis ecology in the State of Bahia, Brazil are based on the author's observations over the past 35 years in a number of state's foci, public health records and literature citations. The disease is endemic with epidemic outbreaks occurring every ten years and its geographical distribution is expanding rapidly in the last years. Leishmania chagasi is the main ethiologic agent of the visceral leishmaniasis but Le. amazonensis s. lato was the only leishmania isolated by other authors from some visceral leishmaniasis human cases in the state. Lutzomyia longipalpis (with one or two spots on tergites III and IV and two sized different populations) was epidemiologically incriminated as the main vector. It was found naturally infected with promastigotes, and it was infected with four species of leishmanias in the laboratory. Although the experimental transmission of Le. amazonensis by the bite of Lu. longipalpis to hamsters was performed, the author was not successful in transmitting Le. chagasi in the same way. The dog is the most important domestic source for infection of the vector, however it is not a primary reservoir. The opossum Didelphis albiventris was found naturally infected with Le. chagasi but its role as reservoir is unknown. Foxes and rodents were not found infected with leishmanias in Bahia.
As part of an epidemiological study in an old focus of American Visceral Leishmaniasis (AVL) in Venezuela (Guayabita, Aragua State), a longitudinal entomological survey (January 1993-June 1994) was carried out. A total of 3,239 males and 6,043 females belonging to 11 phlebotomine sandfly species were collected. The two recognised vectors of AVL in the New World, Lutzomyia evansi and Lu. longipalpis were found to be sympatric. Lutzomyia evansi was the dominant species (86.4%), almost ten fold times more abundant than Lu. longipalpis (10.6%). The two species alternated seasonally: Lu evansi peaked at the end of the rainy season while Lu. longipalpis, almost virtually absent during such period, increased in the dry season. This species seems more greatly influenced by the temperature. Seven of 4,559 Lutzomyia evansi (0.15%) and one of 353 Lu. longipalpis (0.28%) were found positive for suprapyloric promastigotes. Using the polymerase chain reaction (PCR) with universal primers, all isolates were identified as Leishmania spp. Two cultures from Lu. evansi, IEVA/VE/93/UCNA-2 and IEVA/VE/93/UCNA-3, were established. k-DNA restriction analysis showed high homologies between these isolates and Leishmania chagasi. High hybridization signal with L. chagasi specific kDNA confirmed these results. These findings suggest that Lu. evansi may play a role as vector of visceral leishmaniasis in this area. The identity of the parasite carried by Lu. longipalpis needs to be confirmed.
This paper reviews the current knowledge of leishmaniasis epidemiology in Venezuela, Colombia, Ecuador, Peru, and Bolivia. In all 5 countries leishmaniasis is endemic in both the Andean highlands and the Amazon basin. The sandfly vectors belong to subgenera Helcocyrtomyia, Nyssomiya, Lutzomyia, and Psychodopygus, and the Verrucarum group. Most human infections are caused by Leishmania in the Viannia subgenus. Human Leishmania infections cause cutaneous lesions, with a minority of L. (Viannia) infections leading to mucocutaneous leishmaniasis. Visceral leishmaniasis and diffuse cutaneous leishmaniasis are both rare. In each country a significant proportion of Leishmania transmission is in or around houses, often close to coffee or cacao plantations. Reservoir hosts for domestic transmission cycles are uncertain. The paper first addresses the burden of disease caused by leishmaniasis, focusing on both incidence rates and on the variability in symptoms. Such information should provide a rational basis for prioritizing control resources, and for selecting therapy regimes. Secondly, we describe the variation in transmission ecology, outlining those variables which might affect the prevention strategies. Finally, we look at the current control strategies and review the recent studies on control.
An increase in the incidence of human visceral leishmaniasis (HVL) has been detected in recent years on Margarita Island, located off the NE coast of Venezuela. Recent studies have revealed reactivity to rK39 antigen (Leishmania chagasi) in 20% of 541 sera from domestic dogs in endemic communities; PCR reactions were positive using primers for the L. donovani complex. Here we report that isolates from human and canine infection, identified by isoenzyme analysis, correspond to L. infantum, zymodeme MON-1. This appears to be the first isolation and identification of an isolate from HVL on Margarita Island and demonstrates the presence of this zymodeme in the canine population.
Lutzomyia pseudolongipalpis, the first new sand fly species within the longipalpis complex, is described based on females and males from La Rinconada, Curarigua, Lara State, Venezuela. Similar to Lutzomyia longipalpis sensu lato, females of the new species show spermathecae with 8-10 annulations and cibarial armature with 8-12 horizontal teeth. However, L. pseudolongipalpis females show conspicuous vertical cibarial teeth, large stipites and wing vein sections, round cerci, and short and broad valvifers that separate them from L. longipalpis s. l. females. L. pseudolongipalpis and L. longipalpis s. l. males are isomorphic, both having parameres with two curved setae on a simple tubercle. The analysis of morphometric characters and their diagnostic value is in progress.
Lutzomyia pseudolongipalpis Arrivillaga & Feliciangeli is the first new sand fly species in the L. longipalpis species complex that has been formally described since it was separated by genetic as well as by morphological characters. It is the putative vector of the American visceral leishmaniasis in La Rinconada, Curarigua, a restricted focus in central western Venezuela. We investigated the feeding behavior of this species. The blood meals from 210 of 429 (48.9%) engorged females caught by CDC light traps were identified by a dot enzyme-linked immuno-absorbent assay using antisera against humans and common domestic animals. We propose a new index, the host selectivity index, which is the number of sand flies fed on a given host relative to the available biomass of that host, as an indicator of the feeding behavior of this phlebotomine sand fly. The host selectivity index is compared with the forage ratio, which is the percentage of sand flies fed on a given host by the percentage which that host represented in the total census of available animals and humans. The most attractive animal for L. pseudolongipalpis in Curarigua was the dog, whereas humans were shown to be relatively unattractive. However, not only selectivity or biomass, but also the accessibility to this host may have influenced these results. The low population density of dogs and the low accessibility of L. pseudolongipalpis to humans in relation to domestic animals might help to explain the sporadic transmission of visceral leishmaniasis in this focus.
A thorough understanding of the transmission mechanism of any infectious agent is crucial to implementing an effective intervention strategy. Here, our current understanding of the mechanisms that Leishmania parasites use to ensure their transmission from sand fly vectors by bite is reviewed. The most important mechanism is the creation of a "blocked fly" resulting from the secretion of promastigote secretory gel (PSG) by the parasites in the anterior midgut. This forces the sand fly to regurgitate PSG before it can bloodfeed, thereby depositing both PSG and infective metacyclic promastigotes in the skin of a mammalian host. Other possible factors in transmission are considered: damage to the stomodeal valve; occurrence of parasites in the salivary glands; and excretion of parasites from the anus of infected sand flies. Differences in the transmission mechanisms employed by parasites in the three subgenera, Leishmania, Viannia and Sauroleishmania are also addressed.
To compare the clinical and laboratorial data before and after the treatment of patients with visceral leishmaniasis admitted to a pediatric hospital in a nonendemic area, highlighting the importance of recognizing visceral leishmaniasis in pediatric patients.
Clinical, laboratorial and treatment data of 78 patients with visceral leishmaniasis were evaluated from 1981 to 1992. We analyzed the average level of hemoglobin, leukocyte, neutrophil, platelet, albumin, gammaglobulin, class and subclass of immunoglobulin, size of the liver and spleen during the pre- and post-treatment using the paired t test.
We included 78 patients with visceral leishmaniasis, 44 males, with age ranging from 8 months to 13.5 years. Sixty-one patients were from Bahia. Fever and splenomegaly were present in 96.1% and 100% of the cases, respectively. The parasitological diagnosis was obtained in 74/78 patients: 67 patients through smear and/or culture of bone marrow (85.7%), five through liver biopsy and two through spleen puncture. The hematological findings and serum albumin presented significant improvement at the end of treatment (P<0.001), differently from serum gammaglobulin levels (P=0.087). There was predominance of IgG1 subclass, with two patients presenting low levels of IgG2. Initial treatment used antimoniate in 67 cases and amphotericin B in five. Eleven patients (15.7%) needed a second treatment, and were considered cured after it. There was significant improvement in the liver and spleen size at the end of the treatment (P<0.001). One patient presented spontaneous remission and five died due to bleeding.
In order to obtain accurate diagnosis and treatment, especially regarding health services of areas with low-incidence of visceral leishmaniasis, the diagnosis of patients with fever and visceromegaly, who come from endemic areas, should include visceral leishmaniasis.
Background:
There are few reports describing the epidemiology of visceral leishmaniasis (VL) in Somalia. Over the years 2002 to 2005, a yearly average of 140 patients were reported from the Huddur centre in Bakool region, whereas in 2006, this number rose to 1002 patients. Given the limited amount of information on VL and the opportunity to compare features with the studies done in 2000 in this part of Somalia, we describe the epidemiologic and clinical features of patients who presented to the Huddur treatment centre of Bakool region, Somalia, using data routinely collected over a five-year observation period (2002-2006).
Methodology:
Methods used included the analysis of routine data on VL cases treated in the Huddur treatment centre, a retrospective study of records of patients admitted between 2004 and 2006, community leaders interviews, and analysis of blood specimens taken for parasite species identification in Antwerp Institute of Tropical Medicine.
Principal findings:
A total of 1671 VL patients were admitted to the Huddur centre from January 2002 until December 2006. Nearly all patients presented spontaneously to the health centre. Since 2002, the average patient load was stable, with an average of 140 admissions per year. By the end of 2005, the number of admissions dramatically increased to reach a 7-fold increase in 2006. The genotype of L. donovani identified in 2006 was similar to the one reported in 2002. 82% of total patients treated for VL originated from two districts of Bakool region, Huddur and Tijelow districts. Clinical recovery rate was 93.2% and case fatality rate 3.9%.
Conclusions:
After four years of low but constant VL case findings, a major increase in VL was observed over a 16-month period in the Huddur VL centre. The profile of the patients was pediatric and mortality relatively low. Decentralized treatment centers, targeted active screening, and community sensitization will help decrease morbidity and mortality from VL in this endemic area. The true magnitude of VL in Somalia remains unknown. Further documentation to better understand transmission dynamics and thus define appropriate control measures will depend on the stability of the context and safe access to the Somali population.
Infantile visceral leishmaniasis (IVL), or Kala Azar, is a parasitic disease caused by the proliferation of a protozoan parasite Leishmania in the reticulo-histiocyte system. It is characterized by its geographical distribution most frequently in the Mediterranean area, India, East Africa and South America. In Morocco, during these last years, we are witnessing a significant recrudescence mainly in young child. The authors performed a retrospective study of 209 cases of visceral leishmaniasis admitted to the service of pediatrics at the University Hospital of Fez (CHU Hassan II) during a six-year period from January 1998 to December 2004. The average age of our patients is 3.7 years and boys are more affected (sex-ratio=1.45) 90% of the cases come from the suburbs of Fez, primarily from Taounate. The average time of consultation is 2.26 months. The main reasons are abdominal distension (68%), fever (94.5%) and the paleness (50%); rarely a hemorrhagic syndrome (8.5%). The clinical examination shows anaemia in 90% of the cases, fever in 92.6% of the cases and splenomegaly in 97.66% of the cases. The diagnosis is confirmed by the myelogram and the serology of leishmaniasis in 91.3% of the cases. Average diagnosis time is eight days. The identification of the parasite is achieved in collaboration with the Pasteur Institute of Casablanca and Leishmania infantum zymodeme-1 is detected in 100% of the cases. The treatment is based on glucantime at the dose of 80 to 100 mg/kg per day during 21 to 30 days and is efficient in 95.57% of the cases. We deplored six deaths which occurred due to malnutrition and probably in association with a macrophage activation syndrome. Infantile visceral leishmaniasis is the most frequent zoonosis in Morocco. Fez and its suburbs are an area of high endemicity. Its eradication must initially be based on improving socioeconomic conditions as well as fighting against malnutrition, which is a risk factor.
Hypothesis-testing methods for multivariate data are needed to make rigorous probability statements about the effects of factors and their interactions in experiments. Analysis of variance is particularly powerful for the analysis of univariate data. The traditional multivariate analogues, however, are too stringent in their assumptions for most ecological multivariate data sets. Non-parametric methods, based on permutation tests, are preferable. This paper describes a new non-parametric method for multivariate analysis of variance, after McArdle and Anderson (in press). It is given here, with several applications in ecology, to provide an alternative and perhaps more intuitive formulation for ANOVA (based on sums of squared distances) to complement the description provided by McArdle and Anderson (in press) for the analysis of any linear model. It is an improvement on previous non-parametric methods because it allows a direct additive partitioning of variation for complex models. It does this while maintaining the flexibility and lack of formal assumptions of other non-parametric methods. The test-statistic is a multivariate analogue to Fisher’s F-ratio and is calculated directly from any symmetric distance or dissimilarity matrix. P-values are then obtained using permutations. Some examples of the method are given for tests involving several factors, including factorial and hierarchical (nested) designs and tests of interactions.
Malaria has been increasing globally, and epidemics tend to occur when weather conditions favor this vector-borne disease. Long-term meteorologic forecasting using El Niño Southern Oscillation (ENSO) may assist in anticipating epidemics and targeting scarce resources.
To determine whether malaria epidemics in Venezuela are related to ENSO and rainfall and to determine whether such a relationship could be used to predict outbreaks.
Retrospective analysis of national malaria morbidity (1975-1995) and mortality (1910-1935) data in the coastal zone and interior of Venezuela in relation to El Niño events and rainfall.
Correlation between malaria mortality and morbidity and sea surface temperatures (SSTs) in the Eastern Tropical Pacific, a parameter of ENSO.
Malaria mortality and morbidity have increased by an average of 36.5% (95% confidence interval, 3.7%-69.3%; P=.004) in years following recognized El Niño events. A moderate correlation was found between Pacific tropical SST during a Niño event and malaria 1 year later (r=0.50, P<.001). Malaria mortality is more strongly related to drought in the year preceding outbreaks than to rainfall during epidemic years.
Historic and recent data from Venezuela demonstrate that malaria increases by an average of about one third in the year following a Nino event; change in malaria risk can be predicted from Pacific SSTs in the previous year. Therefore, the occurrence of an El Niño event may help predict malaria epidemics in this part of South America.
The interannual variation in malaria cases in Colombia between 1960 and 1992 shows a close association with a periodic climatic phenomenon known as El Niño Southern Oscillation (ENSO). Compared with other years, malaria cases increased by 17.3% during a Niño year and by 35.1% in the post-Niño year. The annual total number of malaria cases is also strongly correlated (r = 0.62, P < 0.001) with sea surface temperature (SST) anomalies in the eastern equatorial Pacific, a principal parameter of ENSO. The strong relation between malaria and ENSO in Colombia can be used to predict high and low-risk years for malaria with sufficient time to mobilize resources to reduce the impact of epidemics. In view of the current El Niño conditions, we anticipate an increase in malaria cases in Colombia in 1998. Further studies to elucidate the mechanisms which underlie the association are required. As Colombia has a wide range of climatic conditions, regional studies relating climate and vector ecology to malaria incidence may further improve an ENSO-based early warning system. Predicting malaria risk associated with ENSO and related climate variables may also serve as a short-term analogue for predicting longer-term effects posed by global climate change.
The infection rates and development of Leishmania chagasi in two sandfly species, Lutzomyia evansi and Lutzomyia longipalpis, were evaluated under natural and experimental conditions. Natural infection rates of Lu. evansi in San Andrés de Sotavento (Colombia) and Montañas de Peraza (Venezuela) (0.05 and 0.2%, respectively) were similar to those previously recorded for this species in Colombia and Venezuela and for Lu. longipalpis in many foci of American Visceral Leishmaniasis (AVL). Both sand fly species were able to support the development of two Colombian strains of L. chagasi experimentally acquired from dogs, hamsters or membrane feeders. However, the experimental infection rates and the sequence of parasite development in the guts of these sand flies revealed that parasite colonisation, differentiation, migration and attachment were more frequent and uniform in Lu. longipalpis than in Lu. evansi. This is consistent with a more recent association between L. chagasi and Lu. evansi, and these results might help to explain the irregularity of AVL outbreaks in foci where Lu. evansi has been reported as the sole vector.
Objective:
To report recent data on the distribution of human and canine visceral leishmaniasis (VL) in Venezuela, and to highlight problems associated with effective control measures.
Methods:
We report the number of cases, incidence rate, age and sex distribution, and mortality rates for human VL (HVL) for the period of 1995 through 2000, based on National Registry of Leishmaniasis data. We carried out serological studies on a total of 3 025 domestic dogs from the 12 states in Venezuela reporting cases of human VL in this 1995-2000 period and also from the state of Yaracuy, where cases were reported earlier during the decade of the 1990s.
Results:
From 1995 through 2000, 242 cases of HVL were reported from 12 states, in various sections of Venezuela. There was a relatively stable national incidence rate of 0.2 cases per 100 000 persons per year. Of the 242 cases, 26.0% were from Margarita Island, one of the three islands that make up the state of Nueva Esparta (Margarita Island was the only one of the Nueva Esparta islands that had HVL cases). Over the 1995-2000 period, the annual incidence rates for Nueva Esparta ranged from 1.7 to 3.8 cases per 100 000 population. Males in Venezuela were more frequently affected (59.5%) than were females (40.5%). In terms of age, 67.7% of the VL patients were </= 4 years of age, and 80.6% were younger than 15 years. The mortality rate among the persons with VL was 7.85% during the 1995-2000 period. Serological screening with rK39 antigen of 1 217 dogs from Margarita Island found a 28.5% positivity rate (testing of dogs was not done on the two other islands of Nueva Esparta). In contrast, the rate was 2.8% in the 1 808 samples from dogs from 12 states on the mainland.
Conclusions:
Human and canine VL are unevenly distributed in Venezuela. The distribution may reflect such factors as differences among the states in human population density, vector density, and the presence or absence of other trypanosomatidae. Particularly high infection rates in very young children as well as in domestic dogs occur in semiurban communities of Nueva Esparta, where other human-infecting trypanosomatidae have not been reported. Control measures related to limiting canine infection might contribute to disease control where VL infections are frequent. Reducing VL mortality requires increased awareness among medical professionals of the possibility of VL in the differential diagnosis of hepato-splenic syndromes, particularly in children.
Leishmaniasis represents a complex of diseases with an important clinical and epidemiological diversity. Visceral leishmaniasis (VL) is of higher priority than cutaneous leishmaniasis (CL) as it is a fatal disease in the absence of treatment. Anthroponotic VL foci are of special concern as they are at the origin of frequent and deathly epidemics (e.g. Sudan). Leishmaniasis burden remains important: 88 countries, 350 million people at risk, 500,000 new cases of VL per year, 1-1.5 million for CL and DALYs: 2.4 millions. Most of the burden is concentrated on few countries which allows clear geographic priorities. Leishmaniasis is still an important public health problem due to not only environmental risk factors such as massive migrations, urbanisation, deforestation, new irrigation schemes, but also to individual risk factors: HIV, malnutrition, genetic, etc em leader Leishmaniasis is part of those diseases which still requires improved control tools. Consequently WHO/TDR research for leishmaniasis has been more and more focusing on the development of new tools such as diagnostic tests, drugs and vaccines. The ongoing effort has already produced significant results. The newly available control tools should allow a scaling up of control activities in priority areas. In anthroponotic foci, the feasibility of getting a strong impact on mortality, morbidity and transmission, is high.
Visceral leishmoniosis has recently become established in the peri-urban areas of the city of Rio de Janeiro. Mauro Marzochi, Keyla Marzochi and Raimundo Carvalho here discuss its incidence, and consider the factors involved in its establishment and propagation, as well as environmental, human, social, economic and historical factors.
From a hospital-based surveillance carried out in Rajendra Memorial Research Institute of Medical Sciences, Patna, Bihar, India, the socio-economic, demographic and treatment response information of 737 patients admitted with visceral leishmaniasis (VL) during January 2001-December 2003, were analysed. The disease was two times higher in males than in females because of several factors including clothing pattern, sleeping habits and occupation. In Bihar, the second poorest state in India, poverty plays a major role in perpetuation of the disease, contributing to malnutrition, illiteracy (60%), and poor housing (82%). Further, presences of peri-domestic animal shelters around houses (63%) and vegetations (77%) facilitate breeding of sand fly vector. Clinical and laboratory characteristics were similar in the age groups <12 years and >12 years. The increasing unresponsiveness of VL patients to conventional anti-leishmanial drugs, e.g. sodium antimony gluconate (SAG) and pentamidine, has definitely posed a major therapeutic challenge in combating the disease. Amphotericin B, though costly, is highly effective. Miltefosine is a highly promising new oral drug for VL.
The state of Bihar in India carries the largest share of the world's burden of antimony-resistant visceral leishmaniasis. We analysed clinical studies done in Bihar with different treatments between 1980 and 2004. Overall, 53 studies were included (all but one published), of which 15 were comparative (randomised, quasi-randomised, or non-randomised), 23 dose-finding, and 15 non-comparative. Data from comparative studies were pooled when appropriate for meta-analysis. Overall, these studies enrolled 7263 patients in 123 treatment arms. Adequacy of methods used to do the studies and report on them varied. Unresponsiveness to antimony has developed steadily in the past to such an extent that antimony must now be replaced, despite attempts to stop its progression by increasing dose and duration of therapy. The classic second-line treatments are unsuited: pentamidine is toxic and its efficacy has also declined, and amphotericin B deoxycholate is effective but requires hospitalisation for long periods and toxicity is common. Liposomal amphotericin B is very effective and safe but currently unaffordable because of its high price. Miltefosine-the first oral drug for visceral leishmaniasis-is now registered and marketed in India and is effective, but should be used under supervision to prevent misuse. Paromomycin (or aminosidine) is effective and safe, and although not yet available, a regulatory submission is due soon. To preserve the limited armamentarium of drugs to treat visceral leishmaniasis, drugs should not be deployed unprotected; combinations can make drugs last longer, improve treatment, and reduce costs to households and health systems. India, Bangladesh, and Nepal agreed recently to undertake measures towards the elimination of visceral leishmaniasis. The lessons learnt in Bihar could help inform policy decisions both regionally and elsewhere.
A prospective study on 23 patients with American visceral leishmaniasis (VL), comparing clinical and laboratory parameters of 14 children (mean age of 3.85+/-3.39 years) to nine adults (27.4+/-10.90 years) was performed in São Luís, Maranhão, Brazil, between August 2000 and July 2002. Data were collected at entrance (day 0), end of treatment, as well as 120 and 210 days after treatment using a protocol chart containing patient identification, clinical and laboratory data. N-Methylglucamine antimonate administered at the dose of 20mg/Sb5+/kg/day for 20-30 days was successfully used in all patients. Patients were followed for 1 year after treatment, and no relapses were observed. A prolonged duration of the disease, lymphadenopathy and bleeding predominated in adult patients, while hepatomegaly and skin-mucosal pallor were more frequent in children. Disease was longer and more severe in adults than in children. Although both groups exhibited a trend toward normalization of hematological and biochemical parameters, more children returned sooner to normal values than adults. Difference in clinical or laboratory parameters between children and adults did not indicate the need for different clinical or therapeutic approaches.
To relate entomological, epidemiological and geographical data to understand the transmission dynamics of visceral leishmaniasis (VL) in a closed focus in western Venezuela.
Spatial and temporal patterns of Lutzomyia pseudolongipalpis, the most prevalent phlebotomine sand fly species (99.7%), were studied in El Brasilar, Curarigua, Lara State, Venezuela, a small rural community of 20 dwellings and 118 inhabitants. The sand fly population was monitored using Centers for Disease Control light traps monthly throughout 1 year in the domestic and sylvatic habitats and for 3 months in all inhabited houses.
Temporal variation followed the yearly bimodal pattern of precipitation with the highest population densities in April and December. Infection with flagellates suggestive of Leishmania spp. was detected in 0.01% of 10,026 dissected females of L. pseudolongipalpis, which proved to be highly endophilic. Prevalence of Leishmania infection in people, as measured by the leishmanin skin test, was correlated with distance of the houses from the woodland and with sand fly abundance. A logistic regression model showed that for people who live in the village, the proximity to the woodland (linear) should be considered a risk factor for Leishmania infection (binary) (z = -2.02, P = 0.04, OR = 0.98, 95% CI = 0.97-0.99). This was consistent with the association between the proportion of VL infection and the log of sand fly abundance, which was negatively correlated with distance from the woodland.
We discuss strategies that might be useful in controlling VL transmission in this endemic focus.
Visceral leishmaniasis (VL) is a parasitic infection that uncommonly affects renal transplantation recipients, even in endemic areas. It may be associated with other infections, or masked by these, and may present subclinically and/or atypically for extended periods. The evolution may be particularly severe and diagnosis is often delayed. If not adequately diagnosed and treated, VL can be fatal and so should be suspected in renal transplantation recipients presenting unexplained fever, splenomegaly, and pancytopenia. The authors report 8 cases of VL out of a total of 800 renal transplant recipients from two transplant hospitals centers in Brazil. The clinical, diagnostic, and therapeutic features are reviewed.
The aim of this study was to determine the epidemiology of patients hospitalized for leishmaniasis during the period 1999 to 2003.
This is a retrospective study using the Minimum Data Set for Hospital Discharge (CMBD, Conjunto Mínimo Básico de Datos al alta hospitalaria), a national surveillance system database.
There were 1,180 hospital admissions with a primary diagnosis of leishmaniasis, 34% of which were readmissions, yielding a total of 786 new cases of leishmaniasis and an incidence rate of 0.4 per 100,000 population/year. The disease mainly affected children under five years of age and adults between 25 and 44. The most frequent form of presentation was visceral leishmaniasis, which was documented in 83.6% of hospitalizations. Among the autonomous communities of Spain, Madrid and Castilla-La Mancha showed the highest incidence rates, whereas Galicia and Extremadura presented the lowest rates. Patients coinfected with HIV accounted for 42% of hospital admissions for leishmaniasis. Nonetheless, between 2000 and 2003, a decrease was observed in the number of hospitalizations in this subgroup and an increase of patients without HIV coinfection.
The increase in hospitalization rates for leishmaniasis in Spain indicates that this avoidable zoonosis remains a considerable public health problem in our country.
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