Induction of IL-10 and TGFß from CD4+CD25+FoxP3+ T Cells Correlates with Parasite Load in Indian Kala-azar Patients Infected with Leishmania donovani.

BACKGROUND: Visceral leishmaniasis (VL) is distinguished by a complex interplay of immune response and parasite multiplication inside host cells. However, the direct association between different immunological correlates and parasite numbers remains largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We examined the plasma levels of different disease promoting/protective as well as Th17 cytokines and found IL-10, TGFß and IL-17 to be significantly correlated with parasite load in VL patients (r = 0.52, 0.53 and 0.51 for IL-10, TGFß and IL-17, respectively). We then extended our investigation to a more antigen-specific response and found leishmanial antigen stimulated levels of both IL-10 and TGFß to be significantly associated with parasite load (r = 0.71 and 0.72 for IL-10 and TGFß respectively). In addition to cytokines we also looked for different cellular subtypes that could contribute to cytokine secretion and parasite persistence. Our observations manifested an association between different Treg cell markers and disease progression as absolute numbers of CD4+CD25+ (r = 0.55), CD4+CD25hi (r = 0.61) as well as percentages of CD4+CD25+FoxP3+ T cells (r = 0.68) all correlated with parasite load. Encouraged by these results, we investigated a link between these immunological components and interestingly found both CD4+CD25+ and CD4+CD25+FoxP3+ Treg cells to secrete significantly (p<0.05) higher amounts of not only IL-10 but also TGFß in comparison to corresponding CD25- T cells. CONCLUSIONS/SIGNIFICANCE: Our findings shed some light on source(s) of TGFß and suggest an association between these disease promoting cytokines and Treg cells with parasite load during active disease. Moreover, the direct evidence of CD4+CD25+FoxP3+ Treg cells as a source of IL-10 and TGFß during active VL could open new avenues for immunotherapy towards cure of this potentially fatal disease.

Situación de la leishmaniasis visceral americana en la ciudad de Corrientes, Argentina / Situation of American visceral leishmaniasis in the city of Corrientes, Argentina

INTRODUCCION: En 2009 se detectó por primera vez en la ciudad de Corrientes la presencia de Lutzomyia longipalpis, principal transmisor de la leishmaniasis visceral americana. En el pasado, esta zoonosis era considerada una endemia prevalente en las regiones tropicales y subtropicales del Viejo y del Nuevo Mundo. Actualmente, su distribución geográfica también incluye áreas suburbanas y urbanas debido a modificaciones del ecosistema de este insecto, ya sea por causas naturales y/o artificiales. A esta situación no es ajena la ciudad de Corrientes.OBJETIVO: Hacer un diagnóstico de situación que favorezca la vigilancia y el control integrado de la leishmaniasis.METODOS: Se realizó una encuesta entomológica. El estudio se llevó a cabo desde abril de 2010 a abril de 2011 en diez viviendas de diferentes barrios de la ciudad de Corrientes: en cinco de ellas se utilizaron trampas pegajosas y en las restantes, trampas CDC.RESULTADOS: En un domicilio ubicado en el casco céntrico de la ciudad se obtuvieron, mediante trampas CDC, 7.321 ejemplares: 80,9% (5.924) machos, 18,8% (1.375) hembras y 0,3% (22) sin identificación del sexo, por deterioro del material. El 83% se capturó en hábitats donde se encuentran palomas y conejos, mientras que el gallinero representó un 17%. En las demás viviendas no se obtuvieron flebótomos. La única especie identificada fue Lutzomyia longipalpis.CONCLUSIONES: Esta especie demostró gran capacidad de adaptación al ambiente urbano, poniendo en evidencia un aspecto epidemiológico importante. Además se la encontró activa durante las cuatro estaciones del año.

INTRODUCTION: The presence of Lutzomyia lingipalpis, primary vector of visceral leishmaniasis, was first detected in the city of Corrientes in 2009. This zoonosis used to be considered an endemic prevalent in tropical and subtropical regions of the Old and New World. Currently, its geographical distribution also includes suburban and urban areas, due to either natural or artificial changes in the ecosystem of this insect. The city of Corrientes is no stranger to this situation.OBJECTIVE: To make a situation analysis that promotes integrated monitoring and control of leishmaniasis.METHODS: An entomological survey was conducted. The study took place from April 2010 to April 2011 in the homes from different neighborhoods of the city of Corrientes - in five of them with sticky traps, in the remaining ones with CDC light traps.RESULTS: In a home located in the historic center of the city, 7.321 specimens were collected with CDC light traps: 80.9% (5.924) males, 18.8% (1.375) females and 0.3% (22) without gender identification due to material deterioration. The 83% was captured in habitats where there are pigeons and rabits, while the chicken coop represented 17%. In the other homes no sandflies were obtained. Lutzomyia longipalpis was the only species identified.CONCLUSIONS: This species showed a great capacity to adapt to urban environment, revealing an important epidemiological aspect. Besides, it was active during the four seasons.

Situación de la leishmaniasis visceral americana en la ciudad de Corrientes, Argentina / Situation of American visceral leishmaniasis in the city of Corrientes, Argentina

INTRODUCCION: En 2009 se detectó por primera vez en la ciudad de Corrientes la presencia de Lutzomyia longipalpis, principal transmisor de la leishmaniasis visceral americana. En el pasado, esta zoonosis era considerada una endemia prevalente en las regiones tropicales y subtropicales del Viejo y del Nuevo Mundo. Actualmente, su distribución geográfica también incluye áreas suburbanas y urbanas debido a modificaciones del ecosistema de este insecto, ya sea por causas naturales y/o artificiales. A esta situación no es ajena la ciudad de Corrientes.OBJETIVO: Hacer un diagnóstico de situación que favorezca la vigilancia y el control integrado de la leishmaniasis.METODOS: Se realizó una encuesta entomológica. El estudio se llevó a cabo desde abril de 2010 a abril de 2011 en diez viviendas de diferentes barrios de la ciudad de Corrientes: en cinco de ellas se utilizaron trampas pegajosas y en las restantes, trampas CDC.RESULTADOS: En un domicilio ubicado en el casco céntrico de la ciudad se obtuvieron, mediante trampas CDC, 7.321 ejemplares: 80,9% (5.924) machos, 18,8% (1.375) hembras y 0,3% (22) sin identificación del sexo, por deterioro del material. El 83% se capturó en hábitats donde se encuentran palomas y conejos, mientras que el gallinero representó un 17%. En las demás viviendas no se obtuvieron flebótomos. La única especie identificada fue Lutzomyia longipalpis.CONCLUSIONES: Esta especie demostró gran capacidad de adaptación al ambiente urbano, poniendo en evidencia un aspecto epidemiológico importante. Además se la encontró activa durante las cuatro estaciones del año.

INTRODUCTION: The presence of Lutzomyia lingipalpis, primary vector of visceral leishmaniasis, was first detected in the city of Corrientes in 2009. This zoonosis used to be considered an endemic prevalent in tropical and subtropical regions of the Old and New World. Currently, its geographical distribution also includes suburban and urban areas, due to either natural or artificial changes in the ecosystem of this insect. The city of Corrientes is no stranger to this situation.OBJECTIVE: To make a situation analysis that promotes integrated monitoring and control of leishmaniasis.METHODS: An entomological survey was conducted. The study took place from April 2010 to April 2011 in the homes from different neighborhoods of the city of Corrientes - in five of them with sticky traps, in the remaining ones with CDC light traps.RESULTS: In a home located in the historic center of the city, 7.321 specimens were collected with CDC light traps: 80.9% (5.924) males, 18.8% (1.375) females and 0.3% (22) without gender identification due to material deterioration. The 83% was captured in habitats where there are pigeons and rabits, while the chicken coop represented 17%. In the other homes no sandflies were obtained. Lutzomyia longipalpis was the only species identified.CONCLUSIONS: This species showed a great capacity to adapt to urban environment, revealing an important epidemiological aspect. Besides, it was active during the four seasons.

Genetic admixture in Brazilians exposed to infection with Leishmania chagasi.

Visceral leishmaniasis (VL) in northeast Brazil is a disease caused by infection with the protozoan Leishmania chagasi. Infection leads to variable clinical outcomes ranging from asymptomatic infection to potentially fatal disease. Prior studies suggest the genetic background of the host contributes to the development of different outcomes after infection, although it is not known if ancestral background itself influences outcomes. VL is endemic in peri-urban areas around the city of Natal in northeast Brazil. The population of northeast Brazil is a mixture of distinct racial and ethnic groups. We hypothesized that some sub-populations may be more susceptible than others to develop different clinical outcomes after L. chagasi infection. Using microsatellite markers, we examined whether admixture of the population as a whole, or markers likely inherited from a distinct ethnic background, differed between individuals with VL, individuals with an asymptomatic infection, or individuals with no infection. There was no apparent significant difference in overall population admixture proportions among the three clinical phenotype groups. However, one marker on Chr. 22 displayed evidence of excess ancestry from putative ancestral populations among different clinical phenotypes, suggesting this region may contain genes determining the course of L. chagasi infection.

[Visceral leishmaniasis with an unusually long incubation time]. / Viszerale Leishmaniose mit ungewöhnlich langer Inkubationszeit.

HISTORY: A 25-year-old woman of Yugoslavian origin came to Germany two years before and did not leave Germany since this time. She developed a phlebothrombosis during pregnancy which was treated surgically and with subsequent heparinisation. The pregnancy had to be terminated by section because of abnormal liver functions and increased blood pressure. These values returned to normal within two months. Further tests again showed raised liver function tests (GOT 57 U/l, GPT 71 U/l) and antibodies against smooth muscle and actin. Autoimmune hepatitis was diagnosed and prednisolone given (100 mg daily). In the subsequent 4 months the patient progressively lost more weight and a pancytopenia developed. Suspected of having a systemic haematological syndrome she was admitted to hospital. FINDINGS: Physical examination was unremarkable except for hepato- and splenomegaly (spleen 15.6 cm in diameter by sonography). Laboratory tests showed hypergammaglobulinaemia (50 g/l, 53%), increased WBC count, as well as decreased haemoglobin concentration and platelet count (900 WBC/microliter, Hb 10.9 g/l, 146,000 platelets/microliter). Bone marrow puncture unexpectedly revealed a large number of Leishmania donovani. TREATMENT AND COURSE: Five-valent antimony was administered (sodium stibogluconate 20 mg/kg daily intravenously as bolus for 14 days). She has been free of symptoms since then (follow-up period of one year). CONCLUSION: Visceral leishmaniasis is a rare disease in Europe. Incubation periods of several years have been reported and the infection can be easily mistaken for other chronic liver disease, in this case for an autoimmune hepatitis. Leishmaniasis should be included in the differential diagnosis of unclear liver disease if there is a suggestive history (country of origin or journey into an endemic area).

A kala-azar control programme for remote tribal communities.

Indigenous people have been trained to provide a culturally appropriate kala-azar control programme for the tribal population of Sahibganj, Bihar, India. Cultural resistance to modern medicine has been overcome and the influence of village witch-doctors has been countered.

PIP: In the district of Sahibganj, Bihar, India, there were 23,670 new cases of kala-azar between 1985 and 1990. The Social Development Centre, Dumka, drafted an emergency plan as a solution. 30 village health workers attended a 3-day training course regarding how to administer sodium stibogluconate intramuscularly, spray DDT, conduct door-to-door surveys, and refer affected persons to health centers. Kala-azar awareness programs in the villages imparted information on the treatment and control of the disease explaining that the disease could not be controlled by witch-doctors. DDT was sprayed during January/February and May/June on the inner walls of houses and covered cowsheds in order to eradicate sandfly prevalence. Persons who had had fever for more than 3 weeks underwent examinations for total and differential counts of white blood cells, haemoglobin concentration, aldehyde test, and thick and thin blood smears for the detection of malaria parasites. Treatment consisted of sodium stibogluconate given intramuscularly at 20 mg per kg body weight daily for 20 days in new cases and for 40 days in relapsed patients, with a maximum of 850 mg. Clinical cure was achieved if patients became afebrile and their spleens returned to normal size. If no relapse occurred in 6 months, the patients were regarded as definitively cured. Of the 1640 treated patients, 1592 were cured, and of the 48 patients who relapsed and were treated again with a 40-day course of sodium stibogluconate, 8 relapsed a second time. 44 patients became unresponsive to sodium stibogluconate and were sent to hospitals for treatment. The spraying performed by the village health workers reduced the incidence of kala-azar and malaria in 3 villages, while increased numbers of cases were recorded in 1 village. Remote tribal areas need educative, preventive, and curative programs backed up by mobile hospitals carrying diagnostic and spraying equipment.

Kala-azar in western Upper Nile province in the southern Sudan and its spread to a nomadic tribe from the north.

Since the start in 1988 of the present epidemic of kala-azar (visceral leishmaniasis) in western Upper Nile state in southern Sudan, the epidemiology of the disease in all parts of the Sudan where kala-azar has been reported was reassessed by the Leishmaniasis Research Group in Khartoum. In this paper, the spread of the epidemic is described among a nomadic tribe originating from southern Kordofan state, who migrate every year with their cattle to the Bentiu area in western Upper Nile state where the epidemic is still raging. 200 cases from this tribe were seen in Khartoum; another 56 cases were found during a field trip to the area. In addition, the Bentiu area was visited, where 301 cases were under treatment and another 52 of 1120 individuals screened were confirmed parasitologically. 20 cases of post-kala-azar dermal leishmaniasis were found. Parasites isolated from the nomadic tribe were of the same zymodeme as parasites isolated previously from the Nuer in western Upper Nile. The epidemiological findings in each state are discussed in relation to the tribes that were affected and the ecology of the area.