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Chagas Disease (American Trypanosomiasis)

Author: Louis V Kirchhoff, MD, MPH, Professor, Departments of Internal Medicine (Infectious Diseases) and Epidemiology, Carver College of Medicine and College of Public Health, University of Iowa; Staff Physician, Medical Service, Iowa City Veterans Affairs Medical Center
Contributor Information and Disclosures

Updated: Dec 17, 2009

Introduction

Background

Chagas disease, also known as American trypanosomiasis, is caused by infection with the protozoan parasite Trypanosoma cruzi. The organism T cruzi and infection in humans were first described in 1909 by the Brazilian physician Carlos R. J. Chagas.1 T cruzi is found mostly in blood‑sucking triatomine insects (kissing bugs) and small mammals in a sylvatic cycle that is enzootic from the southern and southwestern United States to central Argentina and Chile. T cruzi infection in humans occurs in a spotty distribution throughout the range of the sylvatic cycle.

New cases of vector-borne T cruzi infection usually occur in persons who live in primitive houses in an area where the sylvatic cycle is active. The living quarters are invaded by infected triatomines, which become domiciliary. Infected insects take blood meals from humans and their domestic animals and deposit parasite‑laden feces. The parasites are then transmitted via contact with breaks in the skin, mucosal surfaces, or the conjunctivas. Transmission can also occur congenitally or via blood transfusion or organ transplantation.

T cruzi infection is life-long. A minority of persons with long-standing T cruzi infection develop the serious cardiac and gastrointestinal problems that characterize chronic symptomatic Chagas disease.

The parasite

T cruzi is a member of the family Trypanosomatidae in the order Kinetoplastida and belongs to a special section called Stercoraria. The infective forms of T cruzi are contained in the feces of the insect vectors and gain entry into its mammalian hosts through contamination. This mechanism of transmission contrasts with that of the two subspecies of African trypanosomes that cause human disease, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, which are transmitted via the saliva of their vectors, and with the mechanism by which the nonpathogenic trypanosome found in the Americas, Trypanosoma rangeli, is transmitted to its mammalian hosts.

As with other parasites that infect both mammalian and insect hosts, the life cycle of T cruzi is complex. The T cruzi life cycle consists of 3 main developmental forms. Epimastigotes are an extracellular and noninfective form of the parasite found in the midgut of insect vectors, where they multiply by binary fission.

As epimastigotes (depicted in the first image below) move to the hindgut, they differentiate into metacyclic trypomastigotes (depicted in the second image below), which are nondividing forms resistant to mammalian complement that have the capacity to infect mammalian cells. They then enter local cells through breaks in the skin, mucous membranes, or the conjunctivas and transform into the third morphologic form, amastigotes. Amastigotes multiply intracellularly until the host cell is overwhelmed, at which point they transform into bloodstream trypomastigotes.

Chagas disease (American trypanosomiasis). The ep...

Chagas disease (American trypanosomiasis). The epimastigote form is the multiplying stage of the parasite in the insect vector and in the acellular culture medium. Image courtesy of Peter Darben, MD.

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Chagas disease (American trypanosomiasis). The ep...

Chagas disease (American trypanosomiasis). The epimastigote form is the multiplying stage of the parasite in the insect vector and in the acellular culture medium. Image courtesy of Peter Darben, MD.


Chagas disease (American trypanosomiasis). The tr...

Chagas disease (American trypanosomiasis). The trypomastigote is the infective flagellated form of the parasite found in the blood of the mammalian hosts (blood trypomastigote) and in the hindgut of vectors (metacyclic trypomastigote). Image courtesy of Peter Darben, MD.

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Chagas disease (American trypanosomiasis). The tr...

Chagas disease (American trypanosomiasis). The trypomastigote is the infective flagellated form of the parasite found in the blood of the mammalian hosts (blood trypomastigote) and in the hindgut of vectors (metacyclic trypomastigote). Image courtesy of Peter Darben, MD.


As the host cells rupture, the trypomastigotes are released into the lymphatics and bloodstream, through which they spread to distant sites and invade new host cells. This process continues asynchronously for the life of the host. Small numbers of trypomastigotes may be ingested in blood meals taken by uninfected triatomines. The trypomastigotes transform into epimastigotes in the midgut of these insects, thus completing the cycle.

T cruzi can also be transmitted when mammalian hosts ingest infected insects, and this mechanism of transmission may play a major role in maintaining the sylvatic cycle.

Numerous biological, biochemical, and molecular studies have shown that the population of T cruzi is heterogeneous.2,3,4 Although T cruzi is a diploid organism in which some genetic exchange may occur in insect vectors,5 its genetic and phenotypic diversity mainly results from the clonal multiplication of the epimastigote and amastigote forms. The current consensus is that T cruzi can be divided into two principal groups: T cruzi I and T cruzi II. The latter is more frequently involved in the domiciliary cycle, whereas T cruzi I is more often associated with the sylvatic cycle.6

Vectors of T cruzi

Triatomines, which transmit T cruzi, belong to the family Reduviidae in the order Hemiptera. Reduviidae has 22 subfamilies, including the Triatominae.7 ] Although the vectors of T cruzi are occasionally referred to as reduviids, this term is not appropriate since the vast majority of the species in the family Reduviidae are phytophagous or insectivorous and do not transmit the parasite.

All triatomine species are able to transmit T cruzi to humans, but only a handful become domiciliary to any great extent and are important as T cruzi vectors. Many more triatomine species are involved in the widespread sylvatic cycles. Triatomines have 5 nymphal stages (instars), all of which can harbor and transmit T cruzi.

The three vector species most important in the transmission of T cruzi to humans include Triatoma infestans, Rhodnius prolixus, and Triatoma dimidiata. Historically, T infestans has been by far the most important, as it has been the primary vector in the sub-Amazonian endemic regions. Since the early 1990s, many Chagas disease control programs have focused on eliminating domiciliary T infestans. These efforts have been successful in Uruguay, Chile, and, most recently, Brazil, all of which have been declared transmission‑free by the Pan American Health Organization.8

Major progress has also been made in Argentina and Bolivia. R prolixus is typically found in Central America and in the Andean nations. The range of T dimidiata is similar but also extends far into Mexico. Other domiciliary species occupy more restricted areas and play less-important roles in the transmission of T cruzi to humans. The sylvatic species can also colonize human dwellings and thus present a potential risk for transmission.

Mammalian hosts of T cruzi

T cruzi infection has been found in more than 100 mammalian species throughout the range mentioned above, which includes the southern and southwestern United States. Mammals typically involved in sylvatic cycles of transmission include opossums, armadillos, raccoons, monkeys, wood rats, and coyotes, among many others.

Pets such as dogs and cats can become infected in enzootic regions, likely as they eat parasitemic prey or ingest infected insects.9 It is of interest that Carlos Chagas observed T cruzi in the blood of wild marmosets and a domestic cat before he discovered the parasite in the blood of his first infected patient, Berenice.1 In some situations, dogs have been shown to be an important link in the maintenance of the domiciliary cycle and consequent transmission to humans.10

Livestock have occasionally been found to be infected with T cruzi, but the parasite is not known to affect the health of livestock. Birds, amphibians, and reptiles are naturally resistant to T cruzi infection; however, in some situations, birds may be important sources of blood meals for triatomines.

The modes of transmission of T cruzi to humans

Historically, most transmissions of T cruzi to humans have resulted from the contamination of vulnerable surfaces (eg, breaks in the skin, mucosae, and the conjunctivas) with the feces of infected vectors. However, as noted, vector‑borne transmission has been reduced markedly in many endemic countries.8,11,12 Transfusion-related transmission was a major public health problem in endemic countries for decades, but, as accurate serologic assays for T cruzi infection were developed, mandatory screening of donated blood became widespread.

Currently, transfusion-related transmission of T cruzi has been all but eliminated in most endemic countries and substantially reduced in a remaining few.13 Not surprisingly, T cruzi can also be transmitted via transplantation of organs obtained from persons with chronic infection, and occasional reports of this in Latin America14,15 and in the United States16,17 have appeared.

The rate of transplacental transmission from mothers with chronic T cruzi infection to their newborns is 2‑10%. To date, no measures have been defined to reduce or eliminate this form of transmission.18,19 In contrast to Toxoplasma gondii, vertical transmission of T cruzi is possible with successive pregnancies. Transmission of T cruzi via breast milk appears to be extremely rare.20 Several instances of transmission of T cruzi to groups of people via ingestion of food or drink presumably contaminated with the feces of infected vectors have been reported.21,22,23 Finally, the facility of producing infective forms of T cruzi in the laboratory has resulted in numerous accidental transmissions in this context.24

Pathophysiology

An inflammatory lesion caused by T cruzi that may appear at the site of entry in patients with acute Chagas disease is called a chagoma.25 Histologic changes may include interstitial edema, lymphocytic infiltration, and reactive hyperplasia of adjacent lymph nodes due to intracellular parasitism of muscle and other subcutaneous tissues. When parasitized host cells rupture, trypomastigotes are released and can often be detected by microscopic examination of anticoagulated blood. As the infection spreads systemically, muscles, including the myocardium, and various other tissues become parasitized.

Acute myocarditis, consisting of patchy areas of necrosis and infected cells, may develop.26,27 The pseudocysts occasionally seen in sections of infected tissues are intracellular aggregates of amastigotes. The patent parasitemias of the acute illness may be accompanied by lymphocytosis, and transaminase levels may be elevated. The cerebrospinal fluid may contain parasites.28

The heart is the most commonly affected organ in persons with chronic Chagas disease. Autopsy may reveal marked bilateral ventricular enlargement, often involving the right side more than the left, in the heart of patients who die of chagasic heart failure. The ventricular walls are often thin, and mural thrombi and apical aneurysms may be present. In addition, diffuse interstitial fibrosis, widespread lymphocytic infiltration, and atrophy of myocardial cells may all be present.

T cruzi parasites are rarely found during microscopic examination of stained sections of myocardial tissue; however, in numerous studies, T cruzi ‑specific polymerase chain reaction (PCR) assays have demonstrated parasites in areas of focal inflammation.29,30,31,32 Pathologic changes in the conduction systems of chronic chagasic hearts are also common and often correlate with dysrhythmias.33 Chronic inflammatory lesions and dense fibrosis frequently involve the right branch and the left anterior branch of the bundle of His, but lesions may also be found in other segments of the conduction system.

Salient features on gross examination of the colon or esophagus in patients with chronic chagasic gastrointestinal disease (megadisease) include dilatation and muscular hypertrophy of the affected organs.34,35 Focal inflammatory lesions with lymphocytic infiltration are visible on microscopy. The number of neurons in the myenteric plexus is often markedly reduced, and periganglion and intraganglion fibrosis with accompanying Schwann cell proliferation, along with lymphocytosis, are present. In most patients with megadisease, the functional effects of this parasympathetic denervation are limited to the esophagus or colon, but clinically manifest dysfunctions of the ureters, biliary tree, and other hollow viscera have been reported.

The pathogenesis of cardiac and gastrointestinal lesions of chronic Chagas disease has been a focus of debate for decades.36,37,38 In recent years, convincing evidence has shown that low levels of parasites in chronically affected tissue, detectable with molecular methods, provokes a chronic inflammatory response that eventually leads to the pathologic changes observed microscopically and organ dysfunction.31,39

Frequency

United States

Despite the presence of the sylvatic cycle of T cruzi transmission in the southern and southwestern United States, only 6 cases of autochthonous transmission of the parasite have been reported.26,40 Although many cases of T cruzi infection probably go unnoticed or unreported, autochthonous acute Chagas disease is rare in the United States. This concept is supported by the extreme rarity of T cruzi infection among US blood donors who were not born in or who have not traveled extensively in endemic countries (Susan Stramer, PhD, personal communication). The rarity of vector‑borne transmission of T cruzi to humans in the United States is likely due to the overall sparsity of vectors and the overall higher housing standards, which help prevent the vectors from becoming domiciliary.

In contrast, the epidemiology of chronic T cruzi infection in the United States has changed markedly in the last few decades owing to the large number of people from endemic countries who have moved to the United States. According to one recent estimate, 13 million persons from endemic countries now live in the United States, 80,000-120,000 of whom have chronic T cruzi infection.41 Approximately two thirds of immigrants from endemic countries are from Mexico, where the overall prevalence of T cruzi infection is 0.5-1%.

Five cases of transfusion-associated transmission of T cruzi have been reported in the United States, all in immunocompromised patients.42 Authorities believe that a substantially larger number of such cases have occurred but have not been recognized because the newly infected transfusion recipients were immunocompetent and presented with relatively few signs and symptoms. Five recipients of organ transplants from 3 donors with T cruzi infection developed acute Chagas disease in the United States, one of whom died of the illness.16,17

The number of blood donors with chronic T cruzi infection in the United States has been of great concern among US blood bank authorities since the first reported case of transfusion-related transmission in 1987. At a meeting of the Blood Products Advisory Committee of the Food and Drug Administration (FDA) in 2002, guidance was provided regarding the requirements for the development of tests for screening donated blood. In December 2006, the Ortho T cruzi ELISA Test System43,44,45 was approved by the FDA for blood screening, and, the following month, screening was implemented by the American Red Cross and Blood Systems, which together process about 70% of the blood donated in the United States.46 As of this writing, approximately 90% of units donated in the United States are screened for Chagas disease.

The radioimmune precipitation assay (RIPA) is performed by Quest Diagnostics for confirmatory testing of units that are found to be repeatedly reactive on Ortho assay.

The data accumulated so far indicate that about 1 in every 29,000 US blood donors is infected with T cruzi (ie, repeatedly reactive on the Ortho assay and positive on the RIPA), which is consistent with estimates by groups familiar with the epidemiology of T cruzi in the United States prior to the initiation of screening. However, this prevalence rate cannot be used to estimate the total number of persons infected with T cruzi in the United States because blood donors are not representative of the general population in a demographic sense. However, the screening data are shedding light on the frequency of autochthonous transmission. As noted above, RIPA positivity in persons who have no geographic risk for T cruzi infection is rare. In-depth perspectives on the frequency of autochthonous transmission of T cruzi in the United States will develop as millions of more donors are tested in the future.

International

T cruzi is found only in the Americas, except in isolated cases in which infected travelers have carried the parasites to other regions (eg, (the Far East, Australia, Europe).47,48,49,50,51 The Pan American Health Organization (PAHO) estimates that 7.7 million persons currently have T cruzi infection in the 21 endemic countries, which have a total population of 532 million.52 The PAHO also estimates that approximately 41,200 new vector‑borne cases of T cruzi infection arise per year and that 14,400 infants are born with congenital Chagas disease annually. According to PAHO estimates, the following are the countries most affected by Chagas disease: Bolivia (6.8% of reported cases); Argentina (4.1%); El Salvador (3.4%); Honduras (3.1%); Paraguay (2.5%); Guatemala (2%); Ecuador (1.7%); French Guyana, Guyana, and Surinam (1.2%); Venezuela (1.2%); Nicaragua (1.1%); Brazil (1%); and Mexico (1%).

In recent years, the epidemiology of T cruzi infection has improved markedly in many endemic countries, as blood bank and vector-control programs have been implemented. Because of the success of programs directed at domiciliary vector programs, prevalence rates in younger age groups have been decreasing in many areas.8,53,54,55 All endemic countries have statutory or regulatory mandates for screening donated blood for T cruzi, and, with a few notable exceptions, effective universal screening has been implemented.13

A major international vector-control program in the "Southern Cone" countries of South America (Bolivia, Argentina, Paraguay, Brazil, Chile, Uruguay), orchestrated by the World Health Organization (WHO) and PAHO, has provided the framework for much of this progress. As noted above, Uruguay and Chile were certified as free of T cruzi transmission in 1997 and 1999, respectively, and Brazil was certified in 2006. Argentina is approaching certification, and major progress toward this goal has also been made in both Paraguay and Bolivia. Importantly, similar control programs have been set up in the Andean nations and in Central America. In Mexico, legislation mandating nationwide screening is under consideration, and this reflects a growing awareness of T cruzi infection as a public health problem in that country.41,56 Currently, only about 13% of the blood donated in Mexico is screened for T cruzi.

In the author’s view, the enormous progress made in controlling Chagas disease in recent decades clearly indicates that the obstacles hindering the complete elimination of T cruzi transmission to humans are primarily economic and political. In this context, no additional major advances, such as a more detailed understanding of the pathogenesis of Chagas disease,57 further genetic analyses,58 new diagnostic techniques, or breakthroughs in vaccine development,59 are necessary for its completion. Other investigators take an opposing view regarding the application of high-technology approaches to the problem of Chagas disease.60

Mortality/Morbidity

Approximately 20,000 deaths attributable to Chagas disease occur annually, typically due to myocarditis26 or, much less frequently, meningoencephalitis.61 In persons with chronic T cruzi infection, mortality is primarily due to the rhythm disturbances and congestive heart failure that result from the chronic inflammatory cardiomyopathy due to the persistence presence of parasites in the heart tissue.62 Embolization of intraventricular clots to the cerebrum and lungs can also contribute to mortality. Patients with severe megaesophagus who do not receive medical attention can die of malnutrition and/or chronic aspiration pneumonitis. Megacolon (depicted in the image below) can also result in death, usually when volvulus develops and is not resolved surgically.

Chagas disease (American trypanosomiasis). Megaco...

Chagas disease (American trypanosomiasis). Megacolon.

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Chagas disease (American trypanosomiasis). Megaco...

Chagas disease (American trypanosomiasis). Megacolon.


Race

T cruzi infection does not have a racial predilection.

Sex

T cruzi infection does not have a sexual predilection.

Age

Morbidity during the acute phase of Chagas disease is more pronounced in children than in adults. The gastrointestinal and cardiac manifestations of chronic T cruzi infection become apparent many years or even decades after initial infection and thus occur almost exclusively in adults.

Clinical

History

  • Incubation period: The incubation period of vector-borne acute Chagas disease is thought to be 7-14 days, but definitive data are not available because persons who live in areas of active transmission are generally continually at risk for exposure to the vectors. Although newly infected persons may be aware that their living quarters are infested by triatomine vectors, most blood meals are taken while people are asleep, so they are unlikely to recall being bitten. The incubation period of acute T cruzi infection acquired through blood transfusion may be somewhat longer, but precise data are also lacking in this regard.
  • Acute phase
    • In most instances of acute T cruzi infection, a specific diagnosis is not made because of the nonspecific nature of the signs and symptoms and because most cases occur in poor people who have limited access to medical care.
    • Acute Chagas disease carries a mortality rate of less than 5%. However, this is likely a high estimate, since acute Chagas disease is rarely diagnosed specifically; thus, the denominator for the calculation of the fatality rate is not known. As noted above, death is typically caused by myocarditis63 and, less commonly, by meningoencephalitis.
    • In the vast majority of persons with acute Chagas disease, the manifestations resolve spontaneously within 3-8 weeks. This is followed by the chronic latent or indeterminate (asymptomatic) phase of the disease.
  • Indeterminate phase
    • By definition, the indeterminate phase of Chagas disease does not cause any symptoms.
    • Most adults with T cruzi infection are unaware of their parasitosis, and a history consistent with acute Chagas disease from years prior is rarely given.
    • Persons who are diagnosed with indeterminate Chagas disease are typically identified by chance through blood-donor screening or pre-employment serologic testing.
  • Chronic symptomatic Chagas disease
    • Ten to 30% of persons with chronic Chagas disease develop clinical manifestations of the disease. The most common and serious problems are cardiac, which are caused by an inflammatory cardiopathy that results from the persistence presence of the parasites in the heart.
      • A wide variety of atrial and ventricular rhythm disturbances, including right bundle branch block, left anterior hemiblock, and third-degree atrioventricular block can result in palpitations, dizziness, syncope, and even sudden death.
      • Cardiomyopathy and consequent congestive heart failure can result in shortness of breath, decreased exercise tolerance, easy fatigability, lower-extremity edema, and nocturia, as well as other signs and symptoms.
      • Thromboembolism can result in stroke, as well as pulmonary and arterial embolization.
    • The gastrointestinal symptoms associated with chronic T cruzi infection typically result from denervation of hollow viscera and consequent dysfunction.
      • Megaesophagus is the most common anatomic finding and typically results in symptoms similar to those of achalasia, such as dysphagia, odynophagia, substernal discomfort, and a sensation that ingested food and liquids do not move forward properly.
      • Megacolon usually results in constipation and pain, and some affected patients can go for long periods between bowel movements. In advanced cases, bowel obstruction and/or volvulus can occur, requiring surgical treatment.
      • Gastric dilatation in patients with Chagas disease has been described, as has megaureter, but these manifestations appear to be relatively rare.

Physical

  • Acute phase
    • Symptoms of acute Chagas disease may include malaise, anorexia, myalgia, and headache, but many recently infected persons are asymptomatic.
    • Intermittent fever occurs, but its frequency is unknown.
    • Some patients have lesions at the portal of entry of the parasites. Romaña sign (unilateral painless periorbital and palpebral edema) occurs when the parasites have contaminated the conjunctivae. Romaña sign is viewed as a classic sign of acute Chagas disease but develops in few newly infected persons. A chagoma, which is an indurated inflammatory skin lesion, may develop when parasites enter through a break in the skin. Romaña sign and chagomas may persist for several weeks. The lymph nodes that drain either of these lesions may be enlarged.
    • Hepatomegaly and splenomegaly may occur in children with acute Chagas disease, often accompanied by generalized lymphadenopathy.
    • Varying degrees of generalized edema may occur in acutely infected persons, particularly children.
    • Some patients with acute T cruzi infection develop a nonpruritic morbilliform rash called schizotrypanides.
    • Persistent tachycardia may be present.
    • Signs of acute myocarditis and resulting heart failure may develop in a small minority of patients with acute Chagas disease.26
    • Neurologic dysfunction may develop in acutely infected children with meningoencephalitis.64
    • Any of the physical findings of acute T cruzi infection can occur in chronically infected persons in whom the infection is reactivating due to natural (HIV infection) or iatrogenic immunosuppression.65
  • Chronic chagasic cardiomyopathy
    • Signs of congestion due to isolated left-sided heart failure may be present in the early stages of chronic chagasic cardiomyopathy. Biventricular failure with peripheral edema, hepatomegaly, ascites, and pulmonary congestion are more common in the later stages.
    • Signs of thromboembolism may appear, mostly with embolization to the brain, lungs, and extremities.
  • Chronic chagasic megaesophagus
    • Weight loss and cachexia (in severe cases)
    • Hypertrophy of the salivary glands
    • Pneumonitis related to regurgitation and aspiration of the stomach contents (particularly during sleep)
    • Erosive esophagitis, with increased risk for esophageal cancer
  • Chronic chagasic megacolon
    • Abdominal distention
    • Fecaloma
    • Signs of intestinal occlusion, sigmoid volvulus

Causes

It is not known which host factors or parasite characteristics cause some persons with chronic T cruzi infection to develop clinically apparent cardiac and gastrointestinal lesions, while others remain infected for life but develop no apparent symptoms. Parasite strain, host immunogenetics, nutrition, age at first infection, other medical conditions, and various other factors may play roles in the pathogenesis of chronic symptomatic Chagas disease. Currently, there is no way to predict if an infected person in the indeterminate phase of T cruzi infection is likely to develop symptomatic disease.

More on Chagas Disease (American Trypanosomiasis)

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Treatment & Medication: Chagas Disease (American Trypanosomiasis)
Follow-up: Chagas Disease (American Trypanosomiasis)
Multimedia: Chagas Disease (American Trypanosomiasis)
References
Further Reading
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References

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Keywords

Chagas disease, American trypanosomiasis, Trypanosoma cruzi, T cruzi, Trypanosoma infection , T cruzi infection , Chagas cardiomyopathy, parasitic protozoan, triatomine, kissing bugs, Trypanosomatidae, Stercoraria, trypanosome, trypomastigote, epimastigote, amastigote, Triatominae, Triatoma, triatomine, autochthonous acute Chagas disease, Triatoma infestans, T infestans, Rhodnius prolixus, R prolixus, Triatoma dimidiata, T dimidiata, acute Chagas disease, Romaña sign, congenital Chagas disease, chronic Chagas heart disease, chronic Chagas gastrointestinal disease

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Contributor Information and Disclosures

Author

Louis V Kirchhoff, MD, MPH, Professor, Departments of Internal Medicine (Infectious Diseases) and Epidemiology, Carver College of Medicine and College of Public Health, University of Iowa; Staff Physician, Medical Service, Iowa City Veterans Affairs Medical Center
Louis V Kirchhoff, MD, MPH is a member of the following medical societies: American Association of Blood Banks and American Society of Tropical Medicine and Hygiene
Disclosure: Abbott Laboratories, Inc. Consulting fee Consulting; Quest Diagnostics Inc. Consulting fee Consulting; Goldfinch Diagnostics Inc. Salary Equity owner; Quest Diagnostics Inc. Royalty Licensed technology

Medical Editor

Mary Nettleman, MD, MS, Chair, Department of Medicine, Michigan State University
Mary Nettleman, MD, MS is a member of the following medical societies: American College of Physicians, Association of Professors of Medicine, Central Society for Clinical Research, Infectious Diseases Society of America, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

John W King, MD, Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University Health Sciences Center; Consultant in Infectious Diseases, Overton Brooks Veterans Affairs Medical Center
John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association of Subspecialty Professors, Infectious Diseases Society of America, and Sigma Xi
Disclosure: emedicine $50.00 author of chapter

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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