Topic
Visceral leishmaniasis
About: Visceral leishmaniasis is a research topic. Over the lifetime, 7486 publications have been published within this topic receiving 184865 citations. The topic is also known as: Kala-Azar & viscus leishmaniasis.
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TL;DR: It is indicated that miltefosine is as effective and well tolerated in Indian children with VL as in adults and that it can be recommended as the first choice for treatment of childhood VL in India.
Abstract: Miltefosine has previously been shown to cure 97% of cases of visceral leishmaniasis (VL) in Indian adults. Because approximately one-half of cases of VL occur in children, we evaluated use of the adult dosage of miltefosin (2.5 mg/kg per day for 28 days) in 80 Indian children (age, 2–11 years) with parasitologically confirmed infection in an open-label clinical trial. Clinical and parasitological parameters were reassessed at the end of treatment and 6 months later. One patient died of intercurrent pneumonia on day 6. The other 79 patients demonstrated no parasites after treatment, had marked clinical improvement, and were deemed initially cured. Three patients had relapse, and 1 patient was lost to follow-up. The final cure rate was 94% for all enrolled patients and 95% for evaluable patients. Side effects included mild-to-moderate vomiting or diarrhea (each in ∼25% of patients) and mild-to-moderate, transient elevations in the aspartate aminotransferase level during the early treatment phase (in 55%). This trial indicates that miltefosine is as effective and well tolerated in Indian children with VL as in adults and that it can be recommended as the first choice for treatment of childhood VL in India.
145 citations
TL;DR: The principle clinical and laboratory findings were weight loss, fever, hepato-splenomegaly, anaemia, leucopenia and hypergammaglobulinaemia, and Elevated transaminases and hyperbilirubinaemia were also observed.
Abstract: The epidemiological pattern of visceral leishmaniasis in north-eastern Brazil is changing. The disease was typically seen in rural, endemic areas, but is now occurring as an epidemic in the city of Natal where 316 cases have been reported since 1989; 49% were in children less than 5 years of age. The principle clinical and laboratory findings were weight loss, fever, hepato-splenomegaly, anaemia, leucopenia and hypergammaglobulinaemia. Elevated transaminases and hyperbilirubinaemia were also observed. The diagnosis was confirmed in 87% of cases by identifying amastigotes in aspirates from bone marrow or spleen. Five isolates were identified as Leishmania (L.) chagasi by isoenzyme analysis. The mortality rate was 9%; all deaths occurred during the first week in hospital. One person had concurrent human immunodeficiency virus infection. Among 210 household contacts and neighbours of patients from the endemic area examined for evidence of L. (L.) chagasi infection, 6 additional cases of visceral leishmaniasis were diagnosed. Thirtyeight percent of house-mates and neighbours gave a positive Montenegro skin test reaction, indicating prior subclinical infection.
144 citations
TL;DR: These findings indicate that MBL can modulate the clinical outcome of infection with L. chagasi and the function of infected macrophages.
Abstract: Levels of the serum opsonin mannan-binding lectin (MBL) were directly correlated with the probability of developing visceral leishmaniasis. Monocytes infected with MBL-opsonized Leishmania chagasi promastigotes secreted higher levels of tumor necrosis factor alpha and interleukin-6 than cells infected with nonopsonized parasites. Our findings indicate that MBL can modulate the clinical outcome of infection with L. chagasi and the function of infected macrophages.
144 citations
TL;DR: The clinical and histological features of 33 cases of diffuse cutaneous leishmaniasis seen in Ethiopia are described to show that, whereas the distribution of the lesions is a feature of the parasite, the appearance of the lesion and their histology is a features of the host's immune response.
Abstract: The clinical and histological features of 33 cases of diffuse cutaneous leishmaniasis (DCL) seen in Ethiopia are described. The disease starts as a nodule, usually on a limb. After a period of months or years, during which the initial lesion may rarely ulcerate, or even disappear, it starts to spread locally and distant metastases appear on the face, arms and legs; in appearance and distribution they bear some resemblance to leprosy. The disease spreads slowly, does not ulcerate, invade the viscera or heal. The patient remains remarkably well and there are no consistently abnormal findings in the blood or urine. Smears from the lesions show numerous amastigotes (L-D bodies). The histology is characterized by a thin epidermis and an intense dermal infiltration with macrophages, many of them vacuolated and stuffed with parasites; lymphocytes are absent or scanty. Under the influence of treatment the histology changes towards the tuberculoid. The leishmanin skin test is negative. Reasons are given why DCL in Ethiopia is not post kala-azar dermal leishmaniasis, and the features that distinguish it from simple oriental sore are presented. An attempt has been made to correlate the clinical and histological findings and to show that, whereas the distribution of the lesions is a feature of the parasite, the appearance of the lesions and their histology is a feature of the host's immune response. A histological classification, which indicates the state of the patient's cellular immune response, is given. In untreated DCL this response is absent. The state of reaction is not useful or protective. The frequency with which lymphatic damage was seen in these cases is considered as a possible cause, as opposed to effect, of the disease. The differential diagnosis is discussed.
144 citations
TL;DR: The results suggest that IFN-γ and IL-10 are the molecules most likely involved in determining fate of disease, and that simpler clinical evaluations, as a palpable spleen or liver, can be used.
Abstract: Leishmaniasis remains a serious public health problem in several parts of the developing world. Effective prophylactic measurements are hampered by imprecise comprehension of different aspects of the disease, including its immunoregulation. A better comprehension of immunoregulation in human VL may be useful both for designing and evaluating immunoprophylaxis. To explore immunoregulatory mechanisms, 20 visceral leishmaniasis (VL) patients were evaluated during active disease and at different periods up to one year after treatment determining their plasma cytokine levels, clinical parameters (palpable spleen and liver) and antibody levels. Elevated plasma levels of IFN-γ and of IL-12 p40 were observed during active disease, significantly decreasing after treatment whereas in vitro Leishmania antigen-stimulated IFN-γ production by PBMC exhibited an inverse pattern being low during disease and increasing steadily thereafter. Absence of IFN-γ activity is a hallmark of VL. The main candidate for blunting IFN-γ activity is IL-10, a cytokine highly elevated in plasma with sharp decrease after treatment. Activity of IL-10 is inferred by high levels of anti-Leishmania specific IgG1 and IgG3. TGF-β had elevated total, but not of active, levels lessening the likelihood of being the IFN-γ counterpart. Spleen or liver size presented a steady decrease but return to normal values at only 120 days after treatment. Anti-Leishmania IgG (total and subclasses) levels and DTH or Leishmania-stimulated lymphocyte proliferation conversion to positive also present a slow decrease after treatment. IL-6 plasma levels were elevated in only a few patients. Taken together our results suggest that IFN-γ and IL-10 are the molecules most likely involved in determining fate of disease. After treatment, there is a long delay before the immune profile returns to normal what precludes using plasma cytokine levels as criteria of cure as simpler clinical evaluations, as a palpable spleen or liver, can be used.
144 citations