11
Babesiosis
Clinical Manifestations
Babesia infection is often asymptomatic or associated with mild, nonspecific symptoms.
The infection also can be severe and life threat- ening, particularly in people who are asplenic, immunocompromised, or elderly. Babesiosis, like malaria, is characterized by the presence of fever and hemolytic anemia; however, some infected people who are immunocompromised or at the extremes of age (eg, preterm new- borns) are afebrile. There can be a prodromal illness, with gradual onset of symptoms, such as malaise, anorexia, and fatigue, followed by development of fever and other influenzalike symptoms (eg, chills, sweats, myalgia, arthral- gia, headache, anorexia, nausea). Less common features include sore throat, nonproductive cough, abdominal pain, vomiting, weight loss, conjunctival injection, photophobia, emotional lability, and hyperesthesia. Congenital infec- tion with manifestation as severe sepsis syn- drome has been reported.
Clinical signs generally are minimal, often consisting only of fever and tachycardia, although hypotension, respiratory distress, mild hepatosplenomegaly, jaundice, and dark urine may be noted. Thrombocytopenia is common; disseminated intravascular coagula- tion can be a complication of severe babesiosis.
If untreated, illness can last for several weeks or months; even asymptomatic people can have persistent low-level parasitemia, sometimes for longer than 1 year.
Etiology
Babesia species are intraerythrocytic protozoa.
The etiologic agents of babesiosis in the United States include Babesia microti, which is the cause of most reported cases, and several other genetically and antigenically distinct organ- isms, such as Babesia duncani (formerly the WA1-type parasite).
Epidemiology
Babesiosis predominantly is a tick-borne zoonosis. Babesia parasites can also be trans- mitted by blood transfusion and through peri- natal routes. In the United States, the primary
reservoir host for B microti is the white-footed mouse (Peromyscus leucopus), and the primary vector is the tick Ixodes scapularis, which also can transmit Borrelia burgdorferi, the causative agent of Lyme disease, and Anaplasma phago
cytophilum, the causative agent of human granulocytic anaplasmosis. Humans become infected through tick bites, which typically are not noticed. The white-tailed deer (Odocoileus virginianus) is an important host for blood meals for the tick but is not a reservoir host of B microti. An increase in the deer population in some geographic areas, including some sub- urban areas, during the past few decades is thought to be a major factor in the spread of I scapularis and the increase in numbers of reported cases of babesiosis. The reported vector-borne cases of B microti infection have been acquired in the Northeast (particularly, but not exclusively, in Connecticut, Massachu- setts, New Jersey, New York, and Rhode Island) and in the upper Midwest (Wisconsin and Minnesota). Occasional human cases of babe- siosis caused by other species have been described in various regions of the United States; tick vectors and reservoir hosts for these agents typically have not yet been identified.
Whereas most US vector-borne cases of babe- siosis occur during late spring, summer, or autumn, transfusion-associated cases can occur year-round.
Incubation Period
1 to 5 weeks after a tick bite; 1 week after a con- taminated blood transfusion but occasionally is longer (eg, latent infection might become symptomatic after splenectomy).
Diagnostic Tests
Acute, symptomatic cases of babesiosis are typ- ically diagnosed by microscopic identification of the organism on Giemsa- or Wright-stained blood smears. If the diagnosis of babesiosis is being considered, manual (nonautomated) review of blood smears for parasites should be requested explicitly. If seen, the tetrad (Maltese cross) form is pathognomonic. B microti and other Babesia species can be difficult to distin- guish from Plasmodium falciparum; examina- tion of blood smears by a reference laboratory should be considered for confirmation of the diagnosis. Adjunctive molecular and serologic
46 BABESiOSiS
Image 11.1
infection with Babesia in a 6-year-old girl after a splenectomy performed because of hereditary spherocytosis (Giemsa-stained thin smears). A, The tetrad (left side of the image), a dividing form, is pathognomonic for Babesia. Note also the variation in size and shape of the ring stage parasites (compare A and B) and absence of pigment. Courtesy of Centers for Disease Control and Prevention.
testing is performed at the Centers for Disease Control and Prevention. If indicated, the possibility of concurrent B burgdorferi or Anaplasma infection should be considered.
Treatment
Clindamycin plus oral quinine for 7 to 10 days, or atovaquone plus azithromycin for 7 to 10 days, have comparable efficacy for mild to
moderate illness. Therapy with atovaquone plus azithromycin is associated with fewer adverse effects. However, clindamycin and quinine is preferred for severely ill patients.
Exchange blood transfusions should be con- sidered for patients who are critically ill (eg, hemodynamically unstable), especially, but not exclusively, for patients with parasit- emia levels of 10% or more.
Image 11.2
Babesia microti in a peripheral blood smear.
Note the typical intraerythrocytic location of the organisms. Babesiosis is often asymptomatic or associated with mild symptoms. The infection can be life-threatening in people who are asplenic or immunocompromised.
Image 11.3
A Giemsa stain of a blood film from an infected human used to identify the parasite Babesia microti. Babesiosis is caused by hemo-protozoan parasites of the genus Babesia. While more than 100 species have been reported, B microti and Babesia divergens have been identified in most human cases. Courtesy of Centers for Disease Control and Prevention/Dr George Healy.
BABESiOSiS 47
Image 11.4
The Babesia microti life cycle involves 2 hosts, which include a rodent, primarily the white-footed mouse (Peromyscus leucopus). During a blood meal, a Babesia-infected tick introduces sporozoites into the mouse host (1). Sporozoites enter erythrocytes and undergo asexual reproduction (budding) (2). in the blood, some parasites differentiate into male and female gametes, although these cannot be distinguished at the light microscope level (3). The definitive host is a tick, in this case the deer tick (Ixodes scapularis). Once ingested by an appropriate tick (4), gametes unite and undergo a sporogonic cycle, resulting in sporozoites (5). Transovarial transmission (also known as vertical, or hereditary, transmission) has been documented for “large” Babesia species but not for the “small” Babesia species, such as B microti (A). Humans enter the cycle when bitten by infected ticks. During a blood meal, a Babesia-infected tick introduces sporozoites into the human host (6). Sporozoites enter erythrocytes (B) and undergo asexual replication (budding) (7). multiplication of the blood stage parasites is responsible for clinical manifestations of the disease. Humans are, for all practical purposes, dead-end hosts, and there is probably little, if any, subsequent transmission that occurs from ticks feeding on infected persons. However, human-to-human transmission is well recognized to occur through blood transfusions (8). Note: Deer are the hosts on which the adult ticks feed and are indirectly part of the Babesia cycle, as they influence the tick population. When deer populations increase, tick population also increases, thus heightening the potential for transmission. Courtesy of Centers for Disease Control and Prevention.
48 BABESiOSiS
Image 11.5
Babesiosis is caused by parasites that infect red blood cells and are spread by certain ticks. in the united States, tick-borne transmission is most common in parts of the Northeast and upper midwest, and it usually peaks during the warm months. Although many people who are infected with Babesia do not have symptoms, effective treatment is available if symptoms develop.
Babesiosis is preventable if simple steps are taken to reduce exposure to ticks. Courtesy of Centers for Disease Control and Prevention.
Image 11.6
Number of reported cases, by county—united States, 2012. Courtesy of Morbidity and Mortality Weekly Report.
BACILLUS CEREUS iNFECTiONS 49
12
Bacillus cereus Infections
Clinical Manifestations
Bacillus cereus is primarily associated with 2 toxin-mediated foodborne illnesses, emetic and diarrheal, but it can also cause invasive extraintestinal infection. The emetic syndrome develops after a short incubation period, simi- lar to staphylococcal foodborne illness. It is characterized by nausea, vomiting, and abdominal cramps, and diarrhea can follow in 30% of patients. The diarrheal syndrome has a longer incubation period, is more severe, and resembles Clostridium perfringens food- borne illness. It is characterized by moderate to severe abdominal cramps and watery diarrhea, vomiting in approximately 25% of patients, and, occasionally, low-grade fever. Both ill- nesses are usually short-lived, but the emetic toxin has been associated with fulminant liver failure.
Invasive extraintestinal infection can be severe and can include a wide range of diseases, including wound and soft tissue infections;
bacteremia, including central line–associated bloodstream infection; endocarditis; osteo- myelitis; purulent meningitis and ventricular shunt infection; pneumonia; and ocular infec- tions. Along with staphylococci, B cereus is a significant cause of bacterial endophthalmitis.
Ocular involvement includes panophthalmitis, endophthalmitis, and keratitis.
Etiology
B cereus is an aerobic and facultatively anaero- bic, spore-forming, gram-positive bacillus.
Epidemiology
B cereus is ubiquitous in the environment and is commonly present in small numbers in raw, dried, and processed foods. The organism is a common cause of foodborne illness in the United States but may be under-recognized because physicians and clinical laboratories do not routinely test for B cereus.
Spores of B cereus are heat resistant and can survive pasteurization, brief cooking, or boil- ing. Vegetative forms can grow and produce
enterotoxins over a wide range of temperatures in foods and in the gastrointestinal tract; the latter results in diarrheal syndrome. The emetic syndrome occurs after eating contaminated food containing preformed emetic toxin. The best known association of the emetic syndrome is with ingestion of fried rice made from boiled rice stored at room temperature overnight, but illness has been associated with a wide variety of foods. Foodborne illness caused by B cereus is not transmissible from person to person Risk factors for invasive disease attributable to B cereus include history of injection drug use, presence of indwelling intravascular catheters or implanted devices, neutropenia or immuno- suppression, and preterm birth. B cereus endoph thalmitis has occurred after penetrat- ing ocular trauma and injection drug use.
Incubation Period
Emetic syndrome, 0.5 to 6 hours; diarrheal syndrome, 6 to 24 hours.
Diagnostic Tests
For foodborne outbreaks, isolation of B cereus from the stool or vomitus of 2 or more ill peo- ple and not from control patients, or isolation of 105 colony-forming units/g or greater from epidemiologically implicated food, suggests that B cereus is the cause of the outbreak.
Because the organism can be recovered from stool specimens from some well people, the presence of B cereus in feces or vomitus of ill people is not definitive evidence of infection.
Food samples must be tested for both entero- toxins because either alone can cause illness.
In patients with risk factors for invasive dis- ease, isolation of B cereus from wounds, blood, or other usually sterile body fluids is signifi- cant. The common perception of Bacillus spe- cies as “contaminants” may delay recognition and treatment of serious B cereus infections.
Treatment
B cereus foodborne illness usually requires only supportive treatment. Antimicrobial therapy is indicated for patients with invasive disease. Prompt removal of any potentially infected foreign bodies, such as central lines or implants, is essential. For intraocular
50 BACILLUS CEREUS iNFECTiONS
Image 12.1
Bacillus cereus subsp mycoides (Gram stain).
B cereus is a known cause of toxin-induced food poisoning. These organisms may appear gram-variable, as shown here. Courtesy of Centers for Disease Control and Prevention/
Dr William A. Clark.
Image 12.3
Blood agar and bicarbonate agar plate cultures of Bacillus cereus (negative encapsulation test).
rough colonies of B cereus on blood and bicar- bonate agars. Courtesy of Centers for Disease Control and Prevention/Dr James Feeley.
infections, an ophthalmologist should be con- sulted about use of intravitreal vancomycin therapy in addition to systemic therapy.
B cereus usually is resistant to β-lactam anti- biotics and clindamycin but is susceptible to vancomycin, which is the drug of choice.
Image 12.2
Leifson flagella stain. Bacillus cereus food poisoning is often associated with contaminated rice containing heat-resistant B cereus spores.
Courtesy of Centers for Disease Control and Prevention/Dr William A. Clark.
Image 12.4
Bacillus cereus on sheep blood agar. Large, circular, β-hemolytic colonies are noted. The greenish color and ground-glass appearance are typical characteristics of this organism on culture media. Courtesy of Julia rosebush, DO;
robert Jerris, PhD; and Theresa Stanley, m(ASCP).