Influenza

Background
Influenza virus infection, one of the most common infectious diseases, is a highly contagious airborne disease that causes an acute febrile illness and results in variable degrees of systemic symptoms, ranging from mild fatigue to respiratory failure and death. These symptoms contribute to significant loss of workdays, human suffering, mortality, and significant morbidity. The 1918-1919 H1N1 type influenza pandemic killed an estimated 20-50 million persons, with 549,000 deaths in the United States alone.

Accurately diagnosing influenza A or B infection based solely on clinical criteria is difficult because of the overlapping symptoms caused by the various viruses associated with upper respiratory tract infection (URTI). In addition, several serious viruses, including adenoviruses, enteroviruses, and paramyxoviruses, may initially cause influenzalike symptoms. The early presentation of mild or moderate cases of flavivirus infections (eg, dengue) may initially mimic influenza. For example, some cases of West Nile fever acquired in New York in 1999 were clinically misdiagnosed as influenza.

Patients with influenza frequently present with various symptoms shared by many other viral infections. In the northern and southern hemispheres, these symptoms are more common in the winter months. As a result, during the winter, clinics and emergency department waiting rooms fill with patients who have influenza or other URTIs.
Pathophysiology
Influenza results from infection with 1 of 3 basic types of influenza virus—A, B, or C—which are classified within the family Orthomyxoviridae. These single-stranded RNA viruses are structurally and biologically similar but vary antigenically.

The RNA core consists of 8 gene segments surrounded by a coat of 10 (influenza A) or 11 (influenza B) proteins. Immunologically, the most significant surface proteins include hemagglutinin and neuraminidase. The viruses are typed based on these proteins. For example, influenza A subtype H3N2 expresses hemagglutinin 3 and neuraminidase 2.

The most common prevailing influenza A subtypes that infect humans are H1N1 and H3N2. Each year, the trivalent vaccine used worldwide contains A strains from H1N1 and H3N2, along with an influenza B strain.

Influenza virus infection occurs after transfer of respiratory secretions from an infected individual to a person who is immunologically susceptible. If not neutralized by secretory antibodies, the virus invades airway and respiratory tract cells. Once within host cells, cellular dysfunction and degeneration occur, along with viral replication and release of viral progeny. Systemic symptoms result from inflammatory mediators, similar to other viruses. The incubation period of influenza ranges from 18-72 hours.

Influenza A is generally more pathogenic than influenza B. Influenza A is a zoonotic infection, and more than 100 types of influenza A infect most species of birds, pigs, horses, dogs and seals. Indeed, the 1918 pandemic that resulted in millions of human deaths worldwide is believed to have originated from a virulent strain of H1N1 from pigs or birds. Recently, scientists obtained and sequenced the 1918 H1N1 strain from a frozen corpse found in Alaska. The virus was reconstructed at the Centers for Disease Control and Prevention (CDC) laboratory in Atlanta and was found to be highly lethal when tested in mice; the virus was also found to be lethal to chicken embryos. This unique N1 neuraminidase is being studied in order to provide better insight into the N1 found in H5N1, the type responsible for avian influenza (also known as bird flu). Read more »

Brain Abscess

Background

Intracranial abscesses are uncommon, serious, life-threatening infections. They include brain abscess and subdural or extradural empyema and are classified according to the anatomical location or the etiologic agent. The term brain abscess is used in this article to represent all types of intracranial abscesses.

Intracranial abscesses can originate from infection of contiguous structures (eg, otitis media, dental infection, mastoiditis, sinusitis) secondary to hematogenous spread from a remote site (especially in patients with cyanotic congenital heart disease), after skull trauma or surgery, and, rarely, following meningitis. In at least 15% of cases, no source can be identified.

In recent years, the complex array of etiologic agents that cause brain abscess has become better understood.

Pathophysiology

Brain abscess is caused by intracranial inflammation with subsequent abscess formation. In at least 15% of cases, the source of the infection is unknown (cryptogenic). Infection may enter the intracranial compartment directly or indirectly via 3 routes.

Contiguous suppurative focus (45-50% of cases)

Direct extension may occur through necrotic areas of osteomyelitis in the posterior wall of the frontal sinus, as well as through the sphenoid and ethmoid sinuses.This direct route of intracranial extension is more commonly associated with chronic otitic infection and mastoiditis than with sinusitis. Odontogenic infections can spread to the intracranial space via direct extension or a hematogenous route. Contiguous spread could extend to various sites in the central nervous system, causing cavernous sinus thrombosis; retrograde meningitis; and epidural, subdural, and brain abscess. Read more »

Rheumatic Fever

Background

Acute rheumatic fever (ARF) is an autoimmune inflammatory process that develops as a sequela of streptococcal infection. ARF has extremely variable manifestations and remains a clinical syndrome for which no specific diagnostic test exists. Persons who have experienced an episode of ARF are predisposed to recurrence following subsequent (rheumatogenic) group A streptococcal infections. The most significant complication of ARF is rheumatic heart disease, which usually occurs after repeated bouts of acute illness.

Pathophysiology

ARF is characterized by nonsuppurative inflammatory lesions of the joints, heart, subcutaneous tissue, and central nervous system. An extensive literature search has shown that, at least in developed countries, rheumatic fever follows pharyngeal infection with rheumatogenic group A streptococci. The risk of developing rheumatic fever after an episode of streptococcal pharyngitis has been estimated at 0.3-3%. More recent investigations of rheumatic fever occurring in the aboriginal populations of Australia suggest that streptococcal skin infections might also be associated with the development of rheumatic fever. In Oceania and Hawaii, streptococcal strains that are not typically associated with rheumatic fever have been found to cause the disease.

Molecular mimicry accounts for the tissue injury that occurs in rheumatic fever. Both the humoral and cellular host defenses of a genetically vulnerable host are involved. In this process, the patient’s immune responses (both B- and T-cell mediated) are unable to distinguish between the invading microbe and certain host tissues.The resultant inflammation may persist well beyond the acute infection and produces the protean manifestations of rheumatic fever.

Frequency

United States

The incidence of ARF has declined markedly in the past 50 years in both the United States and Western Europe. Most Western physicians see only the late sequelae of rheumatic heart disease; the diagnosis of an acute case is usually reason enough for a ground rounds presentation. This remarkable decline of rheumatic fever likely reflects improved socioeconomic conditions, as well the decline in prevalence of the classically described rheumatogenic strains of group A streptococci.

Following two decades of almost total absence, a resurgence of ARF occurred in the 1980s among middle-class white children in Salt Lake City, Utah. Clusters were also reported in US Army and Navy training camps during the same period. These limited outbreaks were associated with mucoid rheumatogenic strains that were rarely seen in the preceding 20 years. Today, ARF remains a rarity in most of the United States, although Hawaii and American Samoa continue to see a significant number of cases, many of which are caused by streptococcal strains not usually associated with rheumatic fever in persons of Polynesian descent. Read more »

Typhus

Background

Typhus refers to a group of infectious diseases that are caused by rickettsial organisms and that result in an acute febrile illness. Arthropod vectors transmit the etiologic agents to humans. The principle diseases of this group are epidemic or louse-borne typhus and its recrudescent form known as Brill-Zinsser disease, murine typhus, and scrub typhus. (For more information on pediatric scrub typhus, see the eMedicine article Scrub Typhus in the Pediatric: General Medicine volume.)

Pathophysiology

Epidemic typhus is the prototypical infection of the typhus group of diseases, and the pathophysiology of this illness is representative of the entire category. The arthropod vector of epidemic typhus is the body louse (Pediculus corporis). This is the only vector of the typhus group in which humans are the usual host. Rickettsia prowazekii, which is the etiologic agent of typhus, lives in the alimentary tract of the louse. A Rickettsia- harboring louse bites a human to engage in a blood meal and causes a pruritic reaction on the host’s skin. The louse defecates as it eats; when the host scratches the site, the lice are crushed, and the Rickettsia- laden excrement is inoculated into the bite wound. The Rickettsia travel to the bloodstream and rickettsemia develops.

Rickettsia parasitize the endothelial cells of the small venous, arterial, and capillary vessels. The organisms proliferate and cause endothelial cellular enlargement with resultant multiorgan vasculitis. This process may cause thrombosis, and the deposition of leukocytes, macrophages, and platelets may result in small nodules. Thrombosis of supplying blood vessels may cause gangrene of the distal portions of the extremities, nose, ear lobes, and genitalia. This vasculitic process may also result in loss of intravascular colloid with subsequent hypovolemia and decreased tissue perfusion and, possibly, organ failure. Loss of electrolytes is common.

Some people with a history of typhus may develop a recrudescent type of typhus known as Brill-Zinsser disease. After a patient with typhus is treated with antibiotics and the disease appears to be cured, Rickettsia may linger in the body tissues. Months, years, or even decades after treatment, organisms may reemerge and cause a recurrence of typhus. How the Rickettsia organisms linger silently in a person and by what mechanism recrudescence is mediated are unknown. The presentation of Brill-Zinsser disease is less severe than epidemic typhus, and the associated mortality rate is much lower. Risk factors that may predispose to recrudescent typhus include improper or incomplete antibiotic therapy and malnutrition.

Murine typhus and scrub typhus share the same pathophysiology as epidemic typhus, although they are somewhat milder. The incubation period is approximately 12 days for the typhus group. Prior infection with Rickettsia typhi provides subsequent and long-lasting immunity to reinfection. Read more »