Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leishmania donovani causes visceral leishmaniasis (VL), which is typically fatal without treatment. There is substantial variation between individuals in rates of disease progression, response to treatment and incidence of post-treatment sequelae, specifically post-kala-azar dermal leishmaniasis (PKDL). Nevertheless, the majority of infected people are asymptomatic carriers. Hamsters and mice are commonly used as models of fatal and non-fatal VL, respectively. Host and parasite genetics are likely to be important factors, but in general the reasons for heterogeneous disease presentation in humans and animal models are poorly understood. Host microbiota has become established as a factor in cutaneous forms of leishmaniasis but this has not been studied in VL. We induced intestinal dysbiosis in mice and hamsters by long-term treatment with broad-spectrum antibiotics in their drinking water. There were no significant differences in disease presentation in dysbiotic mice. In contrast, dysbiotic hamsters infected with L. donovani had delayed onset and progression of weight loss. Half of control hamsters had a rapid progression phenotype compared with none of the ABX-treated animals and the nine-month survival rate was significantly improved compared to untreated controls (40% vs. 10%). Antibiotic-treated hamsters also had significantly less severe hepatosplenomegaly, which was accompanied by a distinct cytokine gene expression profile. The protective effect was not explained by differences in parasite loads or haematological profiles. We further found evidence that the gut-liver axis is a key aspect of fatal VL progression in hamsters, including intestinal parasitism, bacterial translocation to the liver, malakoplakia and iron sequestration, none of which occurred in non-progressing murine VL. Diverse bacterial genera were cultured from VL affected livers, of which Rodentibacter was specifically absent from ABX-treated hamsters, indicating this pathobiont may play a role in promoting disease progression. The results provide experimental support for antibiotic prophylaxis against secondary bacterial infections as an adjunct therapy in human VL patients.
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PMID:Fatal progression of experimental visceral leishmaniasis is associated with intestinal parasitism and secondary infection by commensal bacteria, and is delayed by antibiotic prophylaxis. 3228 50

The kingdom of Saudi Arabia (KSA) has succeeded in bringing the reported numbers of Visceral leishmaniasis (VL) cases from hundreds during the 1980s and 1990s to zero case in 2019. The endemicity of VL has been confined mainly to the Southwest regions, namely Jazan and Aseer regions. Leishmania donovani species have been identified as the causative species of VL, while L. infantum have been isolated only from dogs in the endemic areas. Many species of sand flies were caught in Southwest, but P. orientalis is the probable transmitter of the disease. The black rat (Rattus ratus) was found to be contributing to maintenance of the parasite life cycle. VL is primarily a disease of children, and 80% of cases were Saudi's, while cases from Yeminis nationality represent the majority of non- Saudi patients. The common clinical presentation consist of chronic fever, abdominal distention, weight loss, anemia and hepatosplenomegaly. Laboratory findings include: anemia, leukopenia, thrombocytopenia, hypoalbuminemia, hyperproteinaemia and hypergammaglobulinemia, low serum iron, and abnormal liver enzymes. Occurrence of jaundice has been identified as a bad prognostic sign. Diagnosis relying on direct smears from bone marrow aspirates was the commonest tool used, and also is advocated by the National Leishmaniasis Control Program (NLCP). Sodium stibogluconate (SSG) is the main drug used to treat VL cases, while Ambisome is preserved for complicated cases. Chemical control of sand flies using indoor residual spraying (IRS) with synthetic pyrethroids has been the most effective measure applied to prevent vector-human contact and disease transmission. The geographical overlap of VL and Malaria has facilitated the adoption and implementation of integrated vector control strategies. After reaching a zero case in 2019, the Ministry of Health (MoH) has a new commitment and facing a great challenge which are maintenance of current situation and elimination of VL. Through the support of stakeholders, encouragement of community participation, preparedness and readiness of leishmaniasis personnel, the new mission of the NLCP now is elimination of the scourge of VL from the country.
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PMID:Visceral leishmaniasis in Saudi Arabia: From hundreds of cases to zero. 3295 Apr 81


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