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Herpesviruses

The herpesvirus group of the family Herpesviridae comprises large, enveloped, double-stranded DNA viruses found in both animals and humans. They are ubiquitous and produce infections ranging from painful skin ulcers to chickenpox to encephalitis. The major members of the group to infect humans are the two herpes simplex viruses (HSV-1 and -2), cytomegalovirus (CMV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), herpesvirus 6, and the recently discovered human herpesvirus types 7 and 8. Occasionally, the simian herpesvirus, herpes B virus, has caused human disease.

Human Herpesvirus Type 6

In 1986 a human herpesvirus, now called human herpesvirus type 6 (HHV-6), was identified in cultures of peripheral blood lymphocytes from patients with lymphoproliferative diseases (Box 2). The virus, which is genetically distinct but morphologically similar to other herpesviruses, replicates in lymphoid tissue, especially CD4+ T lymphocytes, and has two distinct variants, A and B. Initially it was thought that HHV-6 would grow only in freshly isolated B-lymphocytes, and the virus was referred to as the human B-lymphotropic virus (HBLV); now it is clear that the virus is preferentially tropic for CD4+ T lymphocytes. HHV-6 establishes a latent infection in T cells but may be activated to a productive lytic infection by mitogenic stimulation.

Cytomegalovirus

CMV is ubiquitous, and in developed countries ~50% of adults have developed antibody (Box 7). Age-specific prevalence rates show that ~ 10-15% of children are infected by CMV during the first 5 years of life, after which the rate of new infections levels off. The rate subsequently increases during young adulthood, probably through close personal contact or sexual transmission of the virus.

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Neurotoxicity secondary to aciclovir is rare and is associated with high plasma concentrations, such as result from impaired renal function. Although the risk is greatest with intravenous administration, neurotoxicity has previously been noted with oral use. Symptoms of neurotoxicity, which usually appear within the first 24-72 hours of administration, include tremor, myoclonus, confusion, lethargy, agitation, hallucinations, dysarthria, asterixis, ataxia, hemiparesthesia, and seizures.

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Torsade de pointes and cardiorespiratory arrest have been reported in a patient with congenital long QT syndrome who took azithromycin. In a prospective study of 47 previously healthy people, there was a modest statistically insignificant prolongation of the QTC interval without clinical consequences after the end of a course of azithromycin 3 g/day for 5 days. Azithromycin can cause ototoxicity. In one study, 8 (17%) of 46 HIV-positive patients had probable (n = 6) or possible (n = 2) ototoxicity with azithromycin.

Intestinal Helminths

Infections are often asymptomatic. In the immuno-compromised host, Strongyloides can progress to a fatal hyperinfection syndrome. Helminths include the roundworms (nematodes), flukes (trematodes), and tapeworms (cestodes). These parasites are large, ranging in size from 1 cm to 10 m, and they often live in the human gastrointestinal tract without causing symptoms.

Anti-Infective Therapy

Despite dire warnings that we are approaching the end of the antibiotic era, the incidence of antibiotic-resistant bacteria continues to rise. The proportions of penicillin-resistant Streptococcus pneumoniae, hospital-acquired methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus strains continue to increase. Community-acquired methicillin-resistant Staphylococcus aureus is now common throughout the world.

HIV / AIDS

P. carinii pneumonia is the most common life-threatening opportunistic infection in patients with AIDS. The taxonomy of the organism is unclear, having been classified as both protozoan and fungal.

Central Nervous System Infections

Central nervous system infections include a wide variety of clinical conditions and etiologies: meningitis, meningoencephalitis, encephalitis, brain and meningeal abscesses, and shunt infections. The focus of this chapter is meningitis. N. meningitidis meningitis is the leading cuase of bacterial meningitis in children and young adults in the United States.

Infectious disorders

Infectious diseases comprise those illnesses that are caused by microorganisms or their products. Clinical manifestations of infection occur only when sufficient tissue injury has been inflicted directly by microbial products (e.g., endotoxins and exotoxins), or indirectly by host responses (e.g., cytokines and hydrolytic enzymes released by polymorphonuclear leukocytes). Despite the extraordinary recent advances that have occurred in therapeutics for infectious diseases, a number of basic principles should be followed to prescribe antimicrobials and vaccines is an optimal manner.

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