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The disease is easily spread by airborne microdroplets. Geography and a history

of recent travel to affected areas are believed to be important to an individual’s

likelihood of contracting the disease. In a sample of 100 suspected patients in the

United States, 94% traveled within the 10 days before illness onset to an area listed

in SARS case definitions.

162 SARS is believed to be transmitted mostly by close

contact with an infected person (e.g., sharing eating utensils, <3-foot conversations).

A novel coronavirus, SARS coronavirus (SARS-CoV), was isolated from patients

and identified as the causative agent of SARS. Inoculations of a Vero E6 cell line

with throat swab specimens from patients with the diagnosis of SARS showed

cytopathologic features.

163 Although the natural reservoir of SARS-CoV has not been

identified, the virus has been detected in the Himalayan masked palm civet, the

Chinese ferret badger, and the raccoon dog.

Clinical Presentation

The case definition of SARS established by the CDC includes clinical,

epidemiologic, laboratory, and exclusion criteria.

164 Symptoms of early disease

include fever, chills, rigor, myalgia, headache, diarrhea, sore throat, or rhinorrhea.

Mild-to-moderate illness includes temperature higher than 100.4°F and clinical

findings of lower respiratory illness such as cough or shortness of breath. Severe

illness is characterized by the previous criteria plus radiographic evidence of

pneumonia or acute respiratory distress syndrome.

Probable or likely exposure to SARS-CoV is a critical component of the SARS

case definition. Travel to a location with documented or suspected recent

transmission of SARS-CoV and close contact with a person with mild-to-moderate

or severe respiratory illness in the 10 days before the onset of symptoms are defined

as possible exposures to SARS-CoV. Likely exposure is defined as close contact

with a person with confirmed disease or symptoms of disease.

165

For patients suspected of having SARS in the United States, laboratory diagnosis

can be confirmed by an enzyme immunoassay detecting serum antibody to SARSCoV, isolation of SARS-CoV from a clinical specimen, or detection of SARS-CoV

RNA by a reverse transcriptase PCR. Both the enzyme immunoassay and the PCR are

validated by the CDC.

163

Information regarding the most recent criteria for laboratory

diagnosis can be found at the CDC website.

Although the majority of cases of infection are self-limited, initial symptoms may

be followed by hypoxemia, which may progress to the need for intubation and

mechanical ventilation. Typically, patients do not manifest neurologic or GI

symptoms.

Treatment

Treatment for SARS during the 2002 through 2003 outbreak included broad-spectrum

antibiotics, ribavirin, lopinavir/ritonavir, corticosteroids, interferon, and

immunoglobulin.

165 Broad-spectrum antibiotics are recommended to cover other

potential pathogens until infection attributable to SARS-CoV is confirmed. Ribavirin

has been used in doses ranging from 400 mg IV every day to 2 g IV followed by 1 g

IV every 6 hours with a duration of 4 to 14 days.

166

Interestingly, ribavirin does not

inhibit SARS-CoV in vitro, and viral loads remained elevated after death despite

therapy with ribavirin.

167,168 Furthermore, adverse drug reactions, including hemolytic

anemia (61%), hypocalcemia (58%), and hypomagnesemia (46%), were common.

Two of three in vitro studies of lopinavir and ritonavir showed activity against

SARS-CoV. Lopinavir 400 mg PO BID with ritonavir 100 mg BID may be useful in

the treatment of SARS, but data are limited.

165 Treatments with various

corticosteroids, interferon, and immunoglobulin remain controversial. No treatment

guidelines are available owing to the lack of prospective randomized controlled

trials.

MIDDLE EAST RESPIRATORY SYNDROME

Middle East Respiratory Syndrome (MERS) was first reported in 2012 in Saudi

Arabia. As of June 2015, a total of 1,130 cases have been reported, primarily in the

Arabian Peninsula and most recently in the Republic of Korea.

169,170 To date, only

two cases have been reported in the United States, both in health care workers who

lived in Saudi Arabia and traveled to the United States. Both received supportive

care at a hospital and were discharged.

171

The causative organism of MERS is the Middle Eastern Respiratory Syndrome

coronavirus (MERS-CoV). Symptoms of MERS include fever, cough, and shortness

of breath. In some patients, gastrointestinal symptoms such as nausea, diarrhea, and

vomiting have been reported. The infection progresses to complications including

pneumonia and renal failure. Those at greatest risk for death have comorbid

conditions, such as diabetes, cancer, heart disease, lung disease, or chronic kidney

disease. Individuals with an underlying immunodeficiency may be at the greatest risk

of death.

169

MERS-CoV appears to be transmitted through close contact with an infected

individual, likely through respiratory droplets. Most infections reported have

occurred in hospitals or in individuals caring for or living with an infected

individual.

169 Treatment of MERS is directed as supportive care for symptoms and

complications.

ZIKA VIRUS

The Zika virus was first reported in 2007 in the Pacific Islands, with other rare

outbreaks in Africa and Southeast Asia. In 2015, it was detected in Brazil and as of

May 2016 reported areas of transmission include the Pacific Islands, the Caribbean,

and South and Central America. Also as of May 2016, 503 cases related to travel

have been reported in the United States.

172

Zika is an RNA virus belonging to the Flaviviridae family. The most common

symptoms of infection include fever, maculopapular rash, arthralgia, and

conjunctivitis.

173 The infection is mild and self-limiting and generally resolves in 1

week. In some individuals,

p. 1660

p. 1661

neurologic and autoimmune complications, such as Guillain–Barré syndrome, have

been reported. Neonatal transmission in pregnant women infected with Zika virus has

occurred resulting in microcephaly in the infant and loss of fetus in some instances.

173

Diagnosis is confirmed with RT-PCR, immunoglobulin M, and neutralizing antibody

testing.

Zika is transmitted via a mosquito vector and can be transmitted sexually.

174

Women, particularly pregnant women, should use latex condoms or abstain from

sexual activity with men who have traveled to an area with active Zika. The virus has

been detected in the semen for up to 60 days after exposure.

175 Transmission from the

female to the male has not been documented.

174 There is currently no vaccine or

medication to prevent Zika virus infection. All travelers to or residents of areas with

ongoing Zika virus transmission should follow steps to avoid mosquito bites because

of the potential for exposure to Zika. Protective measures for prevention of infection

with Zika include wearing long sleeve shirts and pants, remaining in air-conditioned

areas with screens on windows, using insect repellent containing N,N-Diethyl-metatoluamide (DEET), and sleeping in a mosquito net if traveling to an area with

reported Zika.

176 Treatment of Zika virus is supportive.

177 Development of a vaccine

against Zika virus is ongoing.

THE COMMON COLD

The most prevalent viral infection is the common cold. In the United States,

approximately 62 million cases of the common cold occur annually.

178 An estimated

20 million and 22 million days of absence from work and school, respectively,

occur. The frequency of the occurrence of a cold is greater in younger children and

decreases with increasing age. Although the common cold is self-limiting, otitis

media occurs in approximately 20% of children after infection.

179

Many viruses have been isolated from patients with respiratory infections, but

rhinovirus is the most common viral pathogen.

180 Rhinovirus accounts for

approximately 34% of all respiratory illnesses. More than 100 different serotypes of

rhinovirus exist, and the prevalence of each varies with time and geography. Other

pathogens include coronavirus, parainfluenza, RSV, adenovirus, and enterovirus.

Because of the number of pathogens known to cause the common cold, development

of an effective vaccine remains difficult.

Treatment for the common cold is directed at pharmacologic treatment of

symptoms. Nonsteroidal anti-inflammatory drugs, oral or intranasal decongestants,

antihistamines, and antitussives may be used. However, these products provide

minimal relief of symptoms and do not shorten the natural course of infection.

181–183

In

pediatric patients younger than 4 years, the use of cough and cold medications is not

recommended by the FDA because of the deaths associated with their use.

184–186

Currently, there are no specific antiviral treatments for the common cold.

Prevention

CASE 79-15

QUESTION 1: J.C. comes into the pharmacy asking for an herbal product that will help him prevent colds this

upcoming cold season. He states that last year he had three colds and his neighbor had none. His neighbor had

mentioned an herbal product he had been taking. J.C. cannot remember the name of the product but wonders

whether there are any products that may be helpful.

ZINC

Zinc, a dietary supplement, has been studied in both the prevention and treatment of

the common cold. The proposed mechanism of action is that the rhinovirus 3C

protease is inhibited by zinc, and the inhibition of this enzyme prevents viral

replication. In vitro, zinc has been shown to have antiviral activity. Several trials

conducted in the past several decades have produced conflicting results on the

benefits of zinc in decreasing symptom severity or duration. If started within 24 hours

of symptom onset, zinc may shorten symptoms but not severity of the cold. Zinc

lozenges, dosed at a minimum of 75 mg per day for the duration of cold symptoms, is

recommended.

187 Patients who took zinc lozenges for the common cold complained of

mouth irritation, unpleasant taste, feeling sick, and diarrhea. Daily administration of

zinc is not currently recommended for prophylaxis of the common cold.

ECHINACEA

Echinacea is an herbal product extracted from the Echinacea plant, which belongs to

the Compositae family. Echinacea is believed to stimulate the immune system,

specifically phagocytosis. Some clinical trials using echinacea have shown positive

results in decreasing the incidence of infection when compared with placebo, but the

results remain inconclusive.

188 One study showed no benefit of echinacea versus

placebo but did show an increased incidence of rash in the treatment group.

189

Because the current data are inconclusive and owing to the variability of echinacea

concentrations in the available products, use of echinacea in the prevention and

treatment of the common cold is not recommended.

190

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and websites for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

Key References

Chen N et al. Corticosteroids for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2010;

(12):CD005582. (95)

Grohskopf LA et al. Prevention and control of influenza with vaccines: recommendations of the advisory

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Rep. 2015;64:818. (107)

Harpaz R et al. Prevention of herpes zoster. Recommendations of the Advisory Committee on Immunization

Practices (ACIP). MMWR Recomm Rep. 2008;57(RR-5):1. (94)

James SH et al. Antiviral therapy for herpesvirus central nervous system infections: neonatal herpes simplex virus

infection, herpes simplex encephalitis, and congenital cytomegalovirus infection. Antiviral Res. 2009;83:207. (10)

[No authors listed]. American Academy of Pediatrics Committee on Infectious Diseases: the use of acyclovir in

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Ralston SL et al. Clinical Practice Guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics.

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Vassilev ZP et al. Safety and efficacy of over-the-counter cough and cold medicines for use in children. Expert

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Key Websites

Centers for Disease Control and Prevention. All About Hantaviruses. Hantavirus Pulmonary Syndrome (HPS).

http://www.cdc.gov/hantavirus/. Accessed August 9, 2015.

Centers for Disease Control and Prevention. Severe Acute Respiratory Syndrome.

http://www.cdc.gov/sars/index.html. Accessed August 9, 2015.

Centers for Disease Control and Prevention. West Nile Virus. http://www.cdc.gov/westnile/index.html.

Accessed August 9, 2015.

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