BOX B-1
Influenza

Infectious Agent: Orthomyxoviruses, RNA viruses that infect birds and mammals. Three genera cause influenza: Influenza A, which is the most common cause of disease and has varying serotypes; Influenza B, which has only one serotype; and Influenza C, the least common.

Routes of Transmission: Airborne aerosols and direct contact with secretions or contaminated surfaces.

Health Effects: Influenza illness typically begins with chills or fever. The illness often involves cough, sore throat, nasal congestion, muscle aches, headache, and fatigue. It typically lasts for several days. In contrast with common colds, influenza usually has high fever with sudden onset and extreme fatigue. Influenza can also cause pneumonia either directly or through secondary bacterial infection.

Incidence, Prevalence, and Mortality: Influenza causes annual seasonal epidemics throughout the world as well as periodic pandemics. In the United States influenza has been estimated to cause an average of approximately 36,000 annual deaths during 1990–1999 and 226,000 annual hospitalizations during 1979–2001.

The incidence (or attack rate) varies from year to year and is highest in children aged 0 to 4 years old and in the elderly aged 65 years and older. One paper from the Centers for Disease Control and Prevention estimated seasonal influenza attack rates in the United States ranging from 6.6 percent in healthy young adults to 20 percent in the youngest children.

The 2009 pandemic influenza virus A (H1N1) infected an estimated 11 to 21 percent of the populations where the incidence could be studied. The highest incidence (34–43 percent) occurred in school-aged children. The severity of the disease, in terms of hospitalizations and pneumonia, was similar to that of recent seasonal influenza strains.

Prevention and Treatment: Annual influenza vaccination is the primary tool for prevention. The vaccine is reformulated each year to prevent the strains of the virus that the World Health Organization predicts will be most prevalent during the coming year. In addition, antiviral treatment is most effective when initiated within 48 hours of symptom onset and has typically been directed to persons at high risk of complications due to influenza.

Vaccine: In the United States, vaccination has been recommended for all persons 6 months and older since 2006. Two types of vaccines are produced: inactivated (for intramuscular administration) and live attenuated (for intranasal administration).

BOX B-2
Tuberculosis

Infectious Agent: Mycobacteria in the M. tuberculosis complex, primarily M. tuberculosis, M. bovis, and M. africanum.

Routes of Transmission: Inhaling droplet nuclei in airborne aerosols generated by coughing or sneezing by individuals with pulmonary tuberculosis and consuming contaminated, unpasteurized cow’s milk.

Health Effects: In a small proportion of newly infected individuals, especially infants, initial infection progresses rapidly—in weeks to months—to primary tuberculosis, which often disseminates to blood, bone, and other distant sites. Pulmonary tuberculosis produces cough, fever, night sweats, fatigue, and weight loss; it often goes undiagnosed for a number of months, during which time infection is transmitted to others, especially to close contacts, such as household members. However, infection in the lung can be contained by the immune system and remains latent; fewer than 10 percent of latently infected individuals subsequently develop reactivation pulmonary tuberculosis, generally when age, malnutrition, HIV infection, or other conditions suppress the immune system and thereby allow latent infection to reactivate.

Incidence, Prevalence, and Mortality: Approximately one-third of the world’s population is estimated to be latently infected with M. tuberculosis, but only a small proportion of these individuals will develop tuberculosis. WHO estimated that in 2010, 8.8 million people developed tuberculosis worldwide, yielding an incidence of 128 cases per 100,000 people. About 650,000 cases were caused by multi-drug-resistant strains of M. tuberculosis, and 1.4 million with tuberculosis died of the

disease. The incidence rate, number of cases, and deaths from tuberculosis has been declining in recent years, mainly due to increased attention and resources devoted to diagnosing cases and assuring that patients receive and complete the lengthy treatment regimen.

Prevention: In most wealthy countries with low incidence rates, prevention of tuberculosis primarily rests on prompt diagnosis, correct multi-drug treatment, and ensuring completion of treatment among those with pulmonary tuberculosis. Latent infected individuals are also treated with drugs, especially those at high risk of reactivation tuberculosis, such as HIV-infected individuals. In poor countries with high incidence rates of tuberculosis, prevention of tuberculosis, while also dependent on prompt diagnosis, correct treatment, and ensuring completion of treatment, primarily rests on targeting all infants with a single dose of the vaccine, given shortly after birth.

Treatment: Successful treatment of tuberculosis requires multiple drugs (at least three) given for a lengthy time period (9 to 12 months), even though the patient is usually asymptomatic (and non-infectious) after a few weeks of treatment. Treatment of latently infected individuals to prevent reactivation tuberculosis is generally accomplished with a single drug (example, isoniazid), also given for an extended period of time (6 to 12 months).

Vaccine: Bacille Calmette-Guerin (BCG) vaccine is widely used at birth throughout South Africa, where there is a high burden of pediatric HIV infection. BCG is given to all newborns as soon as possible after birth to protect infants infected with tuberculosis from progressing to the more dangerous forms of meningeal and miliary tuberculosis.

BOX B-3
Group B Streptococcus

Infectious Agent: Group B Streptococcus (Streptococcus agalactiae) is a gram-positive organism found as a normal inhabitant of the gastrointestinal and genital tract of humans. The majority of the disease is caused by five serotypes.

Routes of Transmission: Transmission from mother to infant occurs in utero or at the time of delivery. Exposure to GBS in the hospital, at home, or in the community may result in late-onset disease.

Health Effects: Group B Streptococcus (Streptococcus agalactiae) is a leading cause of disease in young children. There are two distinct presentations: Early-onset disease (days of life 0–6) is the result of vertical transmission from a colonized mother, and late-onset disease (days of life 7–89) is acquired from either the mother or environmental sources. Early-onset disease is characterized by sepsis or meningitis with a high mortality rate. Late-onset disease often presents as meningitis with a somewhat lower mortality rate but with prominent sequelae.

Incidence, Prevalence, and Mortality: Group B Streptococcus is the most common cause of sepsis and meningitis in infants from developed countries and one of the most common causes in infants globally. The mean invasive GBS disease incidence is 0.53 per 1,000 live births. The mean incidence of early-onset disease is 0.43 per 1,000 live births, with

the highest incidence reported from Africa: 0.53 per 1,000 live births. The mean incidence of late-onset disease (7–89 days) is 0.24 per 1,000 live births. Incidence is again highest in Africa, at 0.7 per 1,000 live births. Typically, early-onset disease is more likely to cause mortality (case fatality rate of 12.1 percent) than the late-onset disease (case fatality rate of 6.8 percent).

Prevention: Currently, to control group B streptococcus intrapartum antibitotics are administered to pregnant women with either known risk factors for group B streptococcos or documented carriage of the bacteria. This approach was widely adopted in the United States and many developed countries and resulted in substantial declines in disease in infants younger than 7 days. In the United States, culture-based screening is used to identify candidates for chemoprophylaxis, but implementing this strategy has been a difficult in low- and middle-income countries.

Treatment: Supportive care and antibiotics are needed for the successful treatment of GBS in infants. Benzylpenicillin or amoxicillin combined with aminoglycosides is the mainstay of therapy at the onset when GBS is suspected. When GBS is confirmed, benzylpenicillin or amoxicillin can be used as a single agent. Treatment duration for sepsis is generally 10 days, but meningitis is treated for a minimum of 14 days, with more prolonged therapy in complicated cases.

Vaccine: A vaccine is not currently available for group B streptococcal infection.