Anemia

Background
Anemia, like a fever, is a symptom of disease that requires investigation to determine the underlying etiology. Often, practicing physicians overlook mild anemia. This is similar to failing to seek the etiology of a fever. The purpose of this article is to provide a method of determining the etiology of an anemia.

Anemia is strictly defined as a decrease in red blood cell (RBC) mass. Methods for measuring RBC mass are time consuming, are expensive, and usually require transfusion of radiolabeled erythrocytes. Thus, in practice, anemia is usually discovered and quantified by measurement of the RBC count, hemoglobin (Hb) concentration, and hematocrit (Hct). These values should be interpreted cautiously because they are concentrations affected by changes in plasma volume. For example, dehydration elevates these values, and increased plasma volume in pregnancy can diminish them without affecting the RBC mass.
Pathophysiology
Erythroid precursors develop in bone marrow at rates usually determined by the requirement for sufficient circulating Hb to oxygenate tissues adequately. Erythroid precursors differentiate sequentially from stem cells to progenitor cells to erythroblasts to normoblasts in a process requiring growth factors and cytokines. This process of differentiation requires several days. Normally, erythroid precursors are released into circulation as reticulocytes.

Reticulocytes remain in the circulation for approximately 1 day before reticulin is excised by reticuloendothelial cells with the delivery of the mature erythrocyte into circulation. The mature erythrocyte remains in circulation for about 120 days before being engulfed and destroyed by phagocytic cells of the reticuloendothelial system. Read more »

Malaria

Background
Malaria, which predominantly occurs in tropical areas, is a potentially life-threatening disease caused by infection with Plasmodium protozoa transmitted by an infective female Anopheles mosquito vector. Individuals with malaria may present with fever and a wide range of symptoms.

The 4 Plasmodium species known to cause malaria include Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae. A fifth species, Plasmodium knowlesi, has recently been identified as a clinically significant pathogen in humans. Timely identification of the infecting species is extremely important, as P falciparum infection can be fatal and is often resistant to standard chloroquine treatment. In some cases, individuals with malaria are infected with multiple Plasmodium species. P falciparum and P vivax are responsible for most new infections. Each Plasmodium species has a defined area of endemicity, although geographic overlap is common. Species can usually be distinguished by morphology on a blood smear. P falciparum is distinguished from the rest of plasmodia by its high level of parasitemia and the banana shape of its gametocytes.

Malaria in travelers typically manifests weeks after the individual leaves the endemic area. Presentation more than 4 weeks after returning from the endemic area is unusual. In some individuals, disease manifests months or years later, usually due to the presence of P vivax or P ovale hypnozoites, which can remain dormant in the liver and reactivate years after infection. Relapse with P vivax or P ovale infection is rare more than 5 years after initial infection. Because symptomatic delay is common, history of even a remote exposure to an endemic area should be elicited. Symptoms of malaria are nonspecific, and, because timely diagnosis and treatment are necessary, malaria should be considered in all patients from tropical areas who present with fever. 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 »