Author
Lars Grimm, MD, MHS
House Staff
Department of Internal Medicine
Duke University Medical Center
Durham, North Carolina
Disclosure: Lars Grimm, MD, MHS, has disclosed no relevant financial relationships
Editor
Rick G. Kulkarni, MD
Vice President/Medical Director, WebMD; Editor-in-Chief, eMedicine;
New York, NY
Disclosure: Rick Kulkarni, MD, has disclosed that he is employed by WebMD. Dr. Kulkarni has also disclosed that he owns stock, stock options, or bonds in WebMD.
Reviewers
Richard S. Krause, MD
Senior Faculty
Department of Emergency Medicine
State University of New York at Buffalo School of Medicine
Buffalo, New York
Disclosure: Richard S. Krause, MD, has disclosed no relevant financial relationships.
Michael Stuart Bronze, MD
Professor; Stewart G Wolf Chair in Internal Medicine
Department of Medicine
University of Oklahoma Health Science Center
Oklahoma City, Oklahoma
Disclosure: Michael Stuart Bronze, MD, has disclosed no relevant financial relationships.
A 50-year-old man presents with a 5-day history of fever to 104°F, scleral icterus, abdominal pain, and malaise after returning from a trip to Equatorial Guinea, a country in mid-Africa. He has an enlarged liver and scattered petechiae. His indirect bilirubin is elevated at 3.7 mg/dL (63.27 µmol/L) as is his direct bilirubin at 4.5 mg/dL (76.95 µmol/L). Image courtesy of Wikimedia Commons.
The correct answer is: Malaria
Malaria, which predominantly occurs in tropical areas, is a potentially life-threatening infection caused by Plasmodium protozoa transmitted by an infective female Anopheles mosquito vector. Individuals with malaria may present with fever, but a wide range of symptoms such as headache, fatigue, nausea and vomiting, chills, splenomegaly, and rash may also be present. In this image malarial merozoites are present in the peripheral blood (arrows). Note that several of the merozoites have penetrated the erythrocyte membrane and entered the cells.
The Centers for Disease Control and Prevention (CDC) has stated that there were an estimated 190-311 million cases of malaria worldwide in 2008, and 708,000-1,003,000 people died. The 5 Plasmodium species known to cause malaria are P falciparum, P vivax, P ovale, P malariae, and P knowlesi. Symptoms typically present within a few weeks after exposure, but may be delayed up to 12 months for P vivax. The lifecycle of plasmodia is complex with mosquito, human liver, and human blood stages. In brief, infective mosquitoes transmit sporozoites, which infect human hepatocytes. These differentiate into merozoites, which are released into the blood stream and infect red blood cells where they multiply. Eventually the red cells rupture and the released merozoites can infect new red cells. The life cycle is completed when new mosquitoes are infected by taking a blood meal from an infected human. Image courtesy of the Centers for Disease Control and Prevention.
The rupture of red blood cells by Plasmodium merozoites induces a febrile reaction. The subsequent infection of additional red blood cells and rupture lead to the classic cyclic fever pattern. Tertian fever refers to a 48-hour cycle of fevers and is associated with P vivax, P ovale, and P falciparum. Quartan fever, or fever ever 72 hours, is associated with P malariae. These febrile patterns are most common in patients with long-standing infections as initially multiple broods emerge into the blood stream. The damage and rupture of red blood cells can lead to anemia, renal failure, metabolic acidosis, and coma. Image courtesy of Wikimedia Commons.
The patient is confirmed to be infected with P falciparum, most likely from the feeding of an Anopheles mosquito (shown). What is the first-line treatment of severe P falciparum malaria in the United States? Image courtesy of Wikimedia Commons.
• Chloroquine phosphate plus tetracycline
• Mefloquine plus azithromycin
• Quinidine gluconate plus doxycycline
• Atovaquone plus proguanil
Malaria treatment is not always straightforward. Consulting the CDC or an Infectious Disease specialist for the latest treatment guidelines and drug regimens should be considered. Speciating the parasite is critical as infection with P falciparum may be more severe and P falciparum is resistant to chloroquine treatment except strains from Haiti, the Dominican Republic, parts of Central America, and parts of the Middle East. In the United States, patients with P falciparum infection are often treated on an inpatient basis to observe for complications secondary to malaria or its treatment. Treatment regimens are dependent on the geographic origin of infection, the likely Plasmodium species, and the severity of disease presentation. Chloroquine phosphate remains the drug of choice if the patient is infected with a nonresistant strain of Plasmodium species. For chloroquine-resistant strains, a form of quinine is the drug next in line. Image courtesy of the Centers for Disease Control and Prevention.
In this case, the patient was quickly diagnosed on admission because of his travel history to an endemic area, clinical presentation consistent with severe malaria, and laboratory finding of intraerythrocytic trophozoites. Quinidine was not immediately available, so oral quinine and doxycycline were started after communication with the CDC. He did not require mechanical ventilation or hemodialysis. His parasitemia decreased to 3% after 3 days of oral antimalarial treatment, and his clinical condition gradually improved. Both his platelet count and renal function returned to normal. The patient had a complete recovery after 7 days of treatment with quinine and doxycycline. Image courtesy of Wikimedia Commons.
Another condition in the differential for malaria typically presents with abrupt onset of fever accompanied by frontal or retro-orbital headache both lasting 1-7 days and appearing in a biphasic pattern. A transient, generalized, macular, and blanching rash (shown) occurs in the first 1-2 days of fever. A second rash may occur within 1-2 days of defervescence, lasting 1-5 days. It is typically desquamating, morbilliform, and maculopapular with sparing of the palms and soles. Bone pain lasting several weeks is usually part of the presentation. Image courtesy of Wikimedia Commons.
What is the most likely diagnosis?
• Dengue fever
• Yellow fever
• Rocky Mountain spotted fever
• Leptospirosis
The correct answer is: Dengue fever
Dengue fever is the most common arboviral illness transmitted worldwide. It is caused by infection with 1 of the 4 serotypes of the dengue virus. Dengue is transmitted by mosquitoes of the genus Aedes, which are widely distributed in subtropical and tropical areas of the world and is in the differential for malaria. The worldwide distribution of the Aedes mosquito and dengue fever in 2005 is shown. Image courtesy of the Centers for Disease Control and Prevention.
Infection with dengue virus may produce 3 different disease patterns: classic dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Classic dengue fever presents with fevers and diffuse body pain, termed "breakbone," that typically persists for 1 week before resolving over the next week. It is usually self limited. Dengue hemorrhagic fever has a similar initial presentation but is followed by signs of plasma leakage. The minimum criteria for diagnosis include fever, hemorrhagic manifestations (eg, thrombocytopenia, hemoconcentration), circulatory failure, and hepatomegaly. This slide demonstrates delayed capillary refill in a child with dengue fever, which is one of the first signs of intravascular volume depletion.
If dengue hemorrhagic fever is untreated it may progress to dengue shock syndrome, which is characterized by abdominal pain, vomiting, restlessness, and severe circulatory failure. Patients may present severely hypotensive with disseminated intravascular coagulation (DIC), as shown. Crystalloid fluid resuscitation and standard DIC treatment, including blood product replacement, are critical to survival. No specific antiviral medication currently is available. Single-dose methylprednisolone showed no mortality benefit in a prospective, randomized, double-blind, placebo-controlled trial. Acetaminophen (paracetamol) is recommended for treatment of pain and fever. Aspirin, other salicylates, and nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided. Report known or suspected cases of dengue fever to public-health authorities.
The correct answer is: Babesiosis
In the United States, babesiosis is usually an asymptomatic infection in healthy individuals. It is caused by a protozoan of the genus Babesia. Babesia infection is transmitted by various tick vectors in Europe, Asia, and the northwestern and northeastern United States. Babesia microti is the main species that has been found to infect humans and other mammals in the United States. Transmission of the parasite is usually from the young nymph stage of the tick (shown). Image courtesy of the Centers for Disease Control and Prevention.
The life cycle of Babesia is complex and involves humans, ticks, and other host vectors (shown). The clinical signs and symptoms of babesiosis are related to the parasitism of red blood cells. Fever, hemolytic anemia, and hemoglobinuria may result from Babesia infection. As with malaria, red blood cell fragments may cause capillary blockage and/or microvascular stasis, explaining liver, splenic, renal, and central nervous system involvement. When severe enough to warrant therapy, babesiosis may be treated with atovaquone plus azithromycin or clindamycin plus quinine. Image courtesy of the Centers for Disease Control and Prevention.
This infectious process has a similar geographic distribution to malaria. Manifestations are protean but typically include significant gastrointestinal complications. There are no nonhuman vectors and a characteristic rash is shown. Image courtesy of Wikimedia Commons.
What is the diagnosis?
• Typhoid fever
• Brucellosis
• Leishmaniasis
• Tularemia
The correct answer is: Typhoid fever
Typhoid fever, or enteric fever, is a potentially fatal multisystem illness caused primarily by Salmonella typhi. It is most commonly found with poor sanitation and remains endemic in developing countries (shown in red for strongly endemic and orange for endemic). Transmission occurs via the oral-fecal route. Manifestations are protean, but classically involve stepwise worsening fevers, abdominal pain, constipation, dry cough, dull frontal headaches, delirium, stuporous malaise, truncal rose spots, and relative bradycardia. In the late stages, individuals may develop anorexia, green-yellow diarrhea, tachypnea, apathy, confusion, psychosis, myocarditis, and intestinal hemorrhage. Image courtesy of Wikimedia Commons.
Salmonella typhi has a preference for the gallbladder where it may colonize gallstones and cause a long-term carrier state. A gross pathology gallbladder specimen from typhoid fever cholecystitis shows both ulceration and perforation. The disease typically lasts for several weeks if untreated and can result in months of weight loss and debilitating weakness. Diagnosis is primarily clinical and antibiotic treatment should be initiated early, preferably fluoroquinolones or cephalosporins depending on local resistance patterns. Corticosteroids are controversial but may decrease the likelihood of mortality in severe cases complicated by neurologic changes. Mortality is 10%-20% for untreated cases and less than 1% for treated cases. Image courtesy of the Centers for Disease Control and Prevention.
Author
Lars Grimm, MD, MHS
House Staff
Department of Internal Medicine
Duke University Medical Center
Durham, North Carolina
Disclosure: Lars Grimm, MD, MHS, has disclosed no relevant financial relationships
Editor
Rick G. Kulkarni, MD
Vice President/Medical Director, WebMD; Editor-in-Chief, eMedicine;
New York, NY
Disclosure: Rick Kulkarni, MD, has disclosed that he is employed by WebMD. Dr. Kulkarni has also disclosed that he owns stock, stock options, or bonds in WebMD.
Reviewers
Richard S. Krause, MD
Senior Faculty
Department of Emergency Medicine
State University of New York at Buffalo School of Medicine
Buffalo, New York
Disclosure: Richard S. Krause, MD, has disclosed no relevant financial relationships.
Michael Stuart Bronze, MD
Professor; Stewart G Wolf Chair in Internal Medicine
Department of Medicine
University of Oklahoma Health Science Center
Oklahoma City, Oklahoma
Disclosure: Michael Stuart Bronze, MD, has disclosed no relevant financial relationships.
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