Smallpox host response

The host response to smallpox Analysis of the gene expression program in peripheral blood cells in a nonhuman primate model [pdf 897 kb] [248]... 

Rubins K, Whitney A, Jahrling P, et al. Genome-Wide Analysis of the Host Response to Variola Infection. Available http //www.who.int/csr/disease/smallpox/ genomewide/en/index.html. 

Three quarters of endemic cases of variola major fell into the classic, or ordinary, variety (see Figure 27-1). The fatality rate was 3% in vaccinated patients and 30% in unvaccinated. Other clinical forms of smallpox were associated with variola major, and it is likely that differences in both strain virulence and host response were responsible for these variations in clinical manifestations.68 Flat-type smallpox, noted in 2% to 5% of patients, was typified by (a) severe systemic toxicity and (b) the slow evolution of flat, soft, focal skin lesions (Figure 27-3). This syndrome caused 66% mortality in vaccinated patients and 95% mortality in unvaccinated. Hemorrhagic-type smallpox, seen in fewer than 3% of patients, was heralded by the appearance of extensive pete-chiae (Figure 27-4), mucosal hemorrhage, and intense toxemia death usually intervened before the development of typical pox lesions.69... 

The main portal of entry is the respiratory tract. Skin, conjunctival, and transplacental infection are less common. Once inoculation with the virus occurs, the smallpox virus survives and replicates successfully, despite the presence of an active host immune response. Infec-tivity rates are higher at the onset of the rash. The virus survives because of its ability to acquire and modulate host immune and inflammatory genes. Pox viruses are unique in their ability to replicate in the cytoplasm of infected cells. 

The virus that causes smallpox. Variola major, is a Category A biological threat agent (CDC 2007). It is a double-stranded DNA orthopoxvirus. It is a widely held opinion among infectious disease professionals that, historically, smallpox has been responsible for more deaths than all other infectious diseases combined. After aggressive efforts by the World Health Organization to immunize the world s population, and because the virus is unable to survive for more than a week outside of its only host, humans. Variola was declared eradicated in 1980 (Murray et al. 2005). The smallpox vaccine can prevent or lessen the severity of the disease if administered within 96 h of exposure. The duration of effectiveness of the vaccine used to eradicate smallpox is not known, and there are reported mild to life-threatening risks are associated with the vaccine. Once a victim is symptomatic, medications and intravenous fluid can be administered to make the patient more comfortable, but there are no antivirals available for unvaccinated infected individuals (Henderson et al. 1999). 

Undoubtedly, both cellular and humoral immune responses are important to recovery from smallpox. The inability of poxviruses to persist stably within the host cell accounts for their infections being relatively short-lived, without establishment of a latent infection. The importance of cellular immunity in recovery from infection has been demonstrated with other poxviruses,39 and the same is generally assumed with variola. Vaccination experiences demonstrated the rare but terrible consequence of vaccinia necrosum in persons with defects of cellular immunity. Early presentation on the host cell membrane of virus-encoded proteins provides means for immune recognition.40 It has been demonstrated that both antibody-dependent cellular cytotoxicity41 and heterogeneous cluster of differentiation (CD) 4+ cytotoxic T-lymphocyte clones42 are induced in response to vaccinia infection, and some immunodominant B-cell epitopes have been defined in both mice and vaccinated humans.43 The relatively large size of poxvirus polypeptides facilitates their rec-... 

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