Epidemiology of Human Babesiosis
Human babesiosis, a malaria-like infection that is sometimes fatal, was first convincingly diagnosed in the United States on Nantucket Island, Massachusetts in 1970s. In the Northeast, the blacklegged deer tick (Ixodes scapularis) is the principal vector transmitting the etiologic agent, Babesia microti. This tick is also the primary vector of Lyme disease spirochete, Borrelia bugdorferi. Natural maintenance of both infections in the Northeast appears to mainly involve interactions between Peromyscus leucopus and the blacklegged tick. In areas where these diseases are endemic, concurrent infections by both pathogens in P. leucopus and in I. scapularis are common. It has been experimentally demonstrated that a single tick bite can transmit either one of the pathogens alone or both together during a blood meal. Therefore, the potential for simultaneous acquisition of two infections through the bite of an infective tick seems similar. Currently, Lyme disease is the most frequently reported arthropod-borne disease in the United States, however, far fewer cases of human babesiosis have been reported than those of Lyme disease. According to the Centers for Disease Control and Prevention (CDC), USA, more than 13,000 cases of Lyme disease were reported in 1994 from 43 states, nearly a sixty percent increase over the number reported in 1993 and approximately a 26-fold increase from the 491 cases reported from 11 states in 1982. Contrarily, only a few hundred cases of human babesiosis have been reported nation wide in the last two decades.
Human babesiosis remained unknown in the United States until 1966 when one case was diagnosed in California. To date, approximately three hundred human cases have been documented nation wide. Most cases appear to involve residents on coastal islands in the Northeast including Nantucket Island, Martha's Vineyard and various sites on Cape Cod in Massachusetts, Block Island in Rhode Island, and Long Island and Shelter Island in New York. Human babesiosis was also diagnosed in inland areas in southern Connecticut and in Wisconsin. Thus, this zoonosis is not limited to the northeastern United States.
There appears to be two distinct epidemiological patterns of babesiosis in human populations in the U. S. The first pattern typically involves spleen-intact human cases who were frequently subclinical and reported mainly from coastal islands in the Northeast. The main etiologic agent was proven to be Babesia microti, transmitted by the blacklegged ticks. The second pattern included those cases reported from California, Georgia, and Washington. The etiologic agents involved have not be morphologically identified. Improved serodiagnostic and molecular techniques are needed for characterizing Babesia species and elucidating the epidemiology of babesiosis in these areas.
Clinical presentations of human Babesia microti infection appear to vary among patients. The severity of the disease can be affected by several risk-increasing factors. Splenectomy appears to correlate with life-threatening and fatal cases. Simultaneous occurrence of Lyme disease and babesiosis in humans has been commonly observed in areas endemic for both infections. In addition, patients with HIV infection and AIDS have presented severe manifestations of babesiosis. Age appears to be another important risk factor. The intensity of clinical babesiosis caused by Babesia microti has been greater in adults over 40 years of age than in younger adults or children, although debilitating illness appears to occur among all age groups.
Sufficient transmission of Babesia microti through the bite of an infective tick requires approximately 36-48 hours of attachment. Both the nymphal and adult stages of Ixodes scapularis are proven competent vectors of the infection, however, the role of adults in transmission of the infection to humans appears to be limited. On one hand, it is easier for people to notice the attachment of an adult tick, thus the tick is more likely removed before transmission occurs. On the other hand, people tend to have less outdoor activities during the cold months in early spring and late fall when adult ticks are more active. The risk of acquiring Babesia microti infection is greatest during June and July when the nymphal stage of Ixodes scapularis is most abundant. Transfusion of platelets, liquid red blood cells, and frozen-thawed red blood cells from asymptomatic donors may result in human babesiosis. However, such a risk is minimal.
Babesia microti infection in humans frequently remains asymptomatic. Severe and fatal cases of human babesiosis usually diagnosed in patients possessed a weakened immune system, especially those without an intact spleen. Clinical signs of the disease vary from one individual to another and symptoms are typically present within 1 to 4 weeks following a tick bite. A gradual onset of malaise, anorexia, and fatigue are commonly observed in the early stages of the disease and within a week or so, fever, drenching sweats, and myalgia can develop. A skin rash (erythema migrans), the telltale sign of Lyme disease, is not associated with human babesiosis. Patients typically have fever that range from 37.8 to 40.3 C and commonly show signs of nausea, vomiting, headache, shaking chills, hemoglobinuria, hyperresthesia, and emotional lability and depression. Pulmonary edema is occasionally presented by the patients. In addition, splenomegaly may occur, but it is rather atypical. Parasitemias which develop are usually at low levels. In spleen-intact patients, parasitemias may range from 1 to 20%, however, a parasitemic level of 85% in severe human babesiosis has been reported. Hemolytic anemia and thrombocytopenia have been frequently found, and dark urine also may be observed. Patient leukocyte counts are typically in the low to normal ranges. In some patients, elevated levels of dehydrogenase, bilirubin, and transaminase may be encountered.
Babesia microti is an intracellular parasite within the erythrocytes, therefore, diagnosis of human babesiosis has relied heavily upon the determination of the presence of the erythrocytic stage of the organism. Examination of Giemsa-stained thin blood smears is considered the most useful diagnostic procedure. The tetrad forms (Maltese-cross) of the parasite are believed to be the primary diagnostic character for the disease. However, the predominant forms in most of the blood smears closely resemble rings of Plasmodium spp., with small to large cytoplasmic vacuoles. Therefore, it is difficult to differentiate Babesia microti from Plasmodium spp., especially Plasmodium falciparum. It is recommended that diagnosis of clinical case of human babesiosis be made by a combination of criteria including the presence of intense parasitemias (1-50%), erythrocytes infected by multiple basket-shaped parasites, and the presence of extracellular merozoites. In addition, Babesia microti infection in humans appears to trigger humoral immune responses. An indirect immunofluorescent antibody assay (IFA) procedure has been widely used in the diagnosis of clinical cases and in prevalence determination of the infection in human populations. Although high titers (even at 1:4096) have been detected in patients during the acute phase, a cut-off point of 1:64 is generally accepted as diagnostic in IFA testing Cross-reaction does occur in anti-sera to Babesia microti with other Babesia species including Babesia argentina, Babesia bigemina, and Babesia caballi, particularly at lower dilutions and during the acute phase of the disease. However, it does not cross react with other arthropod-borne pathogens such as those causing malaria and Colorado tick fever. Subinoculation of blood samples from patients into hamsters may provide assistance in diagnosis by amplifying the parasitemia. In addition, use of Polymerase Chain Reaction (PCR )has proven to facilitate the diagnosis of zoonotic babesial infections. By using genus- and species-specific primers, a definitive diagnosis can be made within a day and may further improve the sensitivity of the hamster inoculation method.
Most patients infected with Babesia microti appear to experience only mild clincal manifestations; therefore, they normally require no specific treatment. For those who do need treatment, the drugs administered have not been reliable but in some instances toxicity of the therapeutic procedures seems to be problematic. Chloroquine was first recommended and used as the chemotherapeutic choice for the treatment. Although, the therapy improves symptoms of some patients with Babesia microti infection, the parasitemias appear to be maintained. Similar studies in hamsters also revealed that treatments with chloroquine, metronidazole, primaquine, and sulfadiazine in combination with pyrimethamine have no effects on the elimination of the parasitemia. In addition, the effectiveness of quinine and pyrimethamine in babesiosis treatment has been inconclusive. The use of cotrimoxazole is generally an ineffective treatment method for human babesiosis. Both pentamidine and berenil therapies can effectively control the parasitemia, but fail to eliminate the parasites completely. Furthermore, administrating 50 mg/kg of pentamidine resulted in 100% mortality in animals. Currently, administration of quinine combined with clindamycin is the treatment of choice for human babesiosis. The parasitemia is consistently eradicated after the administration of the drugs and that there is no recurrance of the babesial infection after the discontinuation of the treatment.
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