Host-cell interaction of attenuated and wild-type strains of yellow fever virus can be differentiated at early stages of hepatocyte infection.

Yellow fever (YF) virus is currently found in tropical Africa and South America, and is responsible for a febrile to severe illness characterized by organ failure and shock. The attenuated YF 17D strain, used in YF vaccine, was derived from the wild-type strain Asibi. Although studies have been done on genetic markers of YF virulence, differentiation of the two strains in terms of host-cell interaction during infection remains elusive. As YF wild-type strains are hepatotropic, we chose a hepatic cell line (HepG2) to study YF virus-host cell interaction. HepG2 cells rapidly produced high titres of infectious viral particles for 17D and Asibi YF strains. However, HepG2 cells were more susceptible to the attenuated 17D virus infection, and only this virus strain induced early apoptosis in these cells. Molecular markers specific for the 17D virus were identified by microarray analysis and confirmed by quantitative RT-PCR analysis. As early as 1h postinfection, three genes, (IEX-1, IRF-1, DEC-1) all implicated in apoptosis pathways, were upregulated. Later in infection (48 h) two other genes (HSP70-1A and 1B), expressed in cases of cellular stress, were highly upregulated in 17D-infected HepG2 cells. The early specific upregulation of these cellular genes in HepG2 cells may be considered markers of the 17D virus. This study on the YF attenuated strain gives a new approach to the analysis of the factors involved in virus attenuation.

Control of mucocutaneous leishmaniasis, a neglected disease: results of a control programme in Satipo Province, Peru.

Mucocutaneous leishmaniasis (MCL) is an important health problem in many rural areas of Latin America, but there are few data on the results of programmatic approaches to control the disease. We report the results of a control programme in San Martin de Pangoa District, which reports one of the highest prevalences of MCL in Peru. For 2 years (2001--2002), the technicians at the health post were trained in patient case management, received medical support and were supplied with antimonials. An evaluation after 2 years showed the following main achievements: better diagnosis of patients, who were confirmed by microscopy in 34% (82/240) of the cases in 2001 and 60% of the cases (153/254) in 2002; improved follow-up during treatment: 237 of 263 (90%) patients who initiated an antimonial therapy ended the full treatment course; improved follow-up after treatment: 143 of 237 (60%) patients who ended their full treatment were correctly monitored during the required period of 6 (cutaneous cases) or 12 (mucosal cases) months after the end of treatment. These achievements were largely due to the human and logistical resources made available, the constant availability of medications and the close collaboration between the Ministry of Health, a national research institute and an international non-governmental organization. At the end of this period, the health authorities decided to register a generic brand of sodium stibogluconate, which is now in use. This should allow the treatment of a significant number of additional patients, while saving money to invest in other facets of the case management.