Virus

A virus is a single- or double-stranded DNA or RNA molecule enclosed within a protein coat. Some may also have a lipoprotein envelope. They may contain proteins that cause antigenic reactions or enzymes that initiate viral replication. The virus lacks metabolic functions and must rely on the host cell for the metabolism or synthesis of chemicals. According to the definition of life, viruses are not alive. They do not eat or produce waste. They do not reproduce independently.

DNA viruses include herpesviruses (e.g., chickenpox, shingles, herpes), adenoviruses (e.g., conjunctivitis, pharyngitis), hepadna viruses (e.g., hepatitis B), and papillomaviruses (e.g., warts). RNA viruses include rubella (e.g., German measles), rhabdoviruses (e.g., rabies), picornaviruses (e.g., poliomyelitis, meningitis, colds), arboviruses (e.g., yellow fever), orthomyxoviruses (e.g., influenza), and paramyxoviruses (e.g., measles and mumps). The retroviruses are a subgroup of RNA viruses that are discussed in the chapter on antiretroviral medications (see Chapter 68). Several other viruses are discussed in the chapter on immunization and immunity (see Chapter 70). Some of the less common viruses are not described in this text.

Protozoa

The word parasite is used to refer to protozoa, helminths, and arthropods. Parasites are metabolically dependent on a host. This chapter discusses only a few of the many protozoa that are most commonly seen in the United States. Malaria is included in this discussion because it is such an important disease worldwide.

Protozoa, which are small and unicellular, are the simplest organisms in the animal kingdom. They are divided into categories based on their type of locomotion. Important protozoal diseases include amebiasis, caused by Entamoeba histolytica; giardiasis, caused by Giardia lamblia; and trichomoniasis, caused by Trichomonas vaginalis.

Protozoa also cause malaria. These organisms include Plasmodium falciparum, P. vivax, P. malariae, and P. ovale.

Herpes Simplex

Herpes simplex virus type 1 (HSV-1) causes infections of the mouth and face (herpes labialis), and of the skin, esophagus, and brain. Vesicles form moist ulcers after several days and epithelialize over 2 to 3 weeks. In some geographic locations, HSV-1 infection is a common cause of first episodes of genital herpes. These may occur in stable, monogamous relationships and are less likely to recur than genital infections caused by HSV-2.

HSV-2 causes infection of the genitals, rectum, skin, hands, and meninges. Asymptomatic shedding of the virus is commonly the mechanism of transmission. Thus, the disease can be transmitted sexually. Recent serologic surveys, which employ type-specific antibody assays, show a rising prevalence of previous HSV-2 infection in postadolescent populations in developed countries; many of these infections were asymptomatic.

Herpes simplex can be a primary infection (which can be asymptomatic) or can result from activation of a latent infection. It is unknown what triggers activation. Type 2 is latent in the presacral ganglia. Both type 1 and type 2 can cause keratitis, encephalitis, recurrent meningitis, disseminated infection, and Bell’s palsy.

The varicella-zoster virus (VZV) is the human herpesvirus 3. This virus causes chickenpox in children, which is highly contagious and is spread by inhalation of infective droplets or contact with lesions. In older adults or immunocompromised patients, the virus can cause shingles. Shingles is caused by reactivation of the virus that is latent in the nerve ganglion. It causes a vesicular rash that appears on an erythematous base in a dermatome pattern, accompanied by pain and systemic symptoms.

Influenza

Influenzavirus causes epidemics of acute illness that is transmitted by the respiratory route. Influenza is diagnosed by association with an epidemic that is confirmed by viral cultures. The standard trivalent influenzavirus vaccine provides partial immunity to certain strains of influenza A and B that vary from year to year.

Giardiasis (Giardia)

This is the most common cause of waterborne diarrheal disease in the United States. It is transmitted by fecal-oral spread of cysts via contaminated food or water. It is resistant to chlorination levels found in water supplies and can survive freezing for several days. Symptoms include diarrhea, fatigue, malaise, abdominal cramps, and weight loss. A diagnostic test is available to detect antigens in the stool.

Malaria

Malaria is the most significant protozoal disease in the world, causing 1.5 to 2.7 million deaths annually. Symptoms of malaria include periodic attacks of chills, fever and sweating, headache, myalgia, splenomegaly, anemia, and leukopenia. Increasing drug resistance has caused treatment of malaria to be problematic. An additional complication is the fact that plasmodia go through distinct stages that affect their susceptibility to different agents. For example, chloroquine is active against asexual blood stages but not against sexual blood stages or asexual liver stages. Prophylaxis of malaria in travelers depends on risk factors, including the area to be visited and the type of malaria that is active in that area. Chloroquine and primaquine are used in non–chloroquine-resistant areas.

Metronidazole

Metronidazole is considered a cytotoxic agent, but its exact mechanism of action is not well understood. Metronidazole damages DNA synthesis, resulting in cell death. Most probably, metronidazole initially enters cells by passive diffusion and then is activated by an enzymatic system that is present only in certain cells, such as anaerobic cells and protozoa. A reaction occurs, and a nitrogen group is reduced. The metabolites are toxic substances that bind to DNA and RNA and interrupt synthesis.

Chloroquine

The exact mechanism of action is unknown. Chloroquine raises the internal pH of parasites. It also may influence hemoglobin digestion or interfere with parasite/nucleoprotein synthesis.

Herpes Simplex Treatment

Acyclovir, famciclovir, and valacyclovir all are useful in the treatment of herpesviruses. They are used as treatment for acute infection and for chronic suppression and recurrences. Systemic therapy for initial episodes does not prevent the establishment of latency or the development of future recurrences, even when given in high or prolonged dosage. Oral acyclovir is the most useful and effective form of the drug for the treatment of herpes simplex virus and varicella infection. In patients with frequent recurrences, oral acyclovir has prevented or reduced the frequency or severity of recurrences in more than 95% of patients. Topical acyclovir is significantly less effective but will shorten healing time and the duration of viral shedding and pain in patients with an initial outbreak of herpes. No clinical benefit was found when the topical form was given in recurrent episodes of genital herpes. Topical acyclovir is effective against herpes labialis; it reduces the duration of the condition by about half a day.

When prescribing these drugs, the practitioner should understand two important principles. First, the peak of viral activity and reproduction occurs prior to the appearance of any symptoms. Therefore, therapy is prescribed late in the disease process. Second, viral agents work by inhibiting reproduction without eradicating latent viruses. Elimination of the virus is not complete, but these agents can assist in reducing and suppressing symptoms. The effectiveness of the drug depends on how early treatment is initiated.

Almost all persons with initially symptomatic HSV-2 infection have symptomatic recurrences. More than 35% of such patients have frequent recurrences. Recurrence rates are especially high in persons with an extended first episode of infection, regardless of whether or not they receive antiviral chemotherapy with acyclovir. Men with genital HSV-2 infection have about 20% more recurrences than do women—a factor that may contribute to the higher rate of HSV-2 transmission from men to women than from women to men and to the continuing epidemic of genital herpes in the United States.

These antiviral drugs are indicated for the treatment of genital herpes in the following circumstances: initial episode of genital herpes, frequently recurring episodes (more than six per year), immunocompromised patients (treatment or long-term suppression), and severe genital herpes. Antivirals should not be used in mildly affected patients because resistance to the medication can occur. Although resistance is rare, it is more likely to occur with prolonged or repeated therapy in severely immunocompromised patients. Use of acyclovir, valacyclovir, and famciclovir in the nonpregnant and the pregnant woman can significantly alter the disease and influence transmission rates, along with decreasing morbidity and mortality associated with HSV infection. The three oral antiherpes medications are equally effective; acyclovir is less expensive than the others.