Andrew Spielman

Atovaquone and azithromycin for the treatment of babesiosis

BACKGROUND Babesiosis is a tick-borne, malaria-like illness known to be enzootic in southern New England. A course of clindamycin and quinine is the standard treatment, but this regimen frequently causes adverse reactions and occasionally fails. A promising alternative treatment is atovaquone plus azithromycin. METHODS We conducted a prospective, nonblinded, randomized trial of the two regimens in 58 subjects with non-life-threatening babesiosis on Nantucket, on Block Island, and in southern Connecticut. The subjects were assigned to receive either atovaquone (750 mg every 12 hours) and azithromycin (500 mg on day 1 and 250 mg per day thereafter) for seven days (40 subjects) or clindamycin (600 mg every 8 hours) and quinine (650 mg every 8 hours) for seven days (18 subjects). RESULTS Adverse effects were reported by 15 percent of the subjects who received atovaquone and azithromycin, as compared with 72 percent of those who received clindamycin and quinine (P<0.001). The most common adverse effects with atovaquone and azithromycin were diarrhea and rash (each in 8 percent of the subjects); with clindamycin and quinine the most common adverse effects were tinnitus (39 percent), diarrhea (33 percent), and decreased hearing (28 percent). Symptoms had resolved three months after the start of therapy in 65 percent of those who received atovaquone and azithromycin and 73 percent of those who received clindamycin and quinine (P=0.66), and after six months no patient in either group had symptoms. Three months after the completion of the assigned regimen, no parasites could be seen on microscopy, and no Babesia microti DNA was detected in the blood of any subject. CONCLUSIONS For the treatment of babesiosis, a regimen of atovaquone and azithromycin is as effective as a regimen of clindamycin and quinine and is associated with fewer adverse reactions.

Persistent Parasitemia after Acute Babesiosis

BACKGROUND Babesiosis, a zoonosis caused by the protozoan Babesia microti, is usually not treated when the symptoms are mild, because the parasitemia appears to be transient. However, the microscopical methods used to diagnose this infection are insensitive, and few infected people have been followed longitudinally. We compared the duration of parasitemia in people who had received specific antibabesial therapy with that in silently infected people who had not been treated. METHODS Forty-six babesia-infected subjects were identified from 1991 through 1996 in a prospective, community-based study designed to detect episodes of illness and of seroconversion among the residents of southeastern Connecticut and Block Island, Rhode Island. Subjects with acute babesial illness were monitored every 3 months for up to 27 months by means of thin blood smears, Bab. microti polymerase-chain-reaction assays, serologic tests, and questionnaires. RESULTS Babesial DNA persisted in the blood for a mean of 82 days in 24 infected subjects without specific symptoms who received no specific therapy. Babesial DNA persisted for 16 days in 22 acutely ill subjects who received clindamycin and quinine therapy (P=0.03), of whom 9 had side effects from the treatment. Among the subjects who did not receive specific therapy, symptoms of babesiosis persisted for a mean of 114 days in five subjects with babesial DNA present for 3 or more months and for only 15 days in seven others in whom the DNA was detectable for less than 3 months (P<0.05); one subject had recrudescent disease after two years. CONCLUSIONS When left untreated, silent babesial infection may persist for months or even years. Although treatment with clindamycin and quinine reduces the duration of parasitemia, infection may still persist and recrudesce and side effects are common. Improved treatments are needed.

Disease-Specific Diagnosis of Coinfecting Tickborne Zoonoses: Babesiosis, Human Granulocytic Ehrlichiosis, and Lyme Disease

To determine whether a unique group of clinical and laboratory manifestations characterize certain major deer tick-transmitted human pathogens in North America, we compared the symptoms, short-term complications, and laboratory test results of New England residents who became ill due to > or =1 of these pathogens. Patients completed a uniformly structured questionnaire and submitted blood samples for serologic and polymerase chain reaction (PCR) testing after developing symptoms of Lyme disease, human babesiosis, or human granulocytic ehrlichiosis (HGE). Complete blood count with thin blood smear, PCR, and immunoglobulin M antibody tests helped differentiate the acute manifestations of these diseases. Physicians should consider use of tests designed to diagnose babesiosis and HGE in patients with Lyme disease who experience a prolonged flulike illness that fails to respond to appropriate antiborrelial therapy.

Persistent and Relapsing Babesiosis in Immunocompromised Patients

BACKGROUND Human babesiosis is a tickborne malaria-like illness that generally resolves without complication after administration of atovaquone and azithromycin or clindamycin and quinine. Although patients experiencing babesiosis that is unresponsive to standard antimicrobial therapy have been described, the pathogenesis, clinical course, and optimal treatment regimen of such cases remain uncertain. METHODS We compared the immunologic status, clinical course, and treatment of 14 case patients who experienced morbidity or death after persistence of Babesia microti infection, despite repeated courses of antibabesial treatment, with those of 46 control subjects whose infection resolved after a single course of standard therapy. This retrospective case-control study was performed in southern New England, New York, and Wisconsin. RESULTS All case patients were immunosuppressed at the time of acute babesiosis, compared with <10% of the control subjects. Most case patients experienced B cell lymphoma and were asplenic or had received rituximab before babesial illness. The case patients were more likely than control subjects to experience complications, and 3 died. Resolution of persistent infection occurred in 11 patients after 2-10 courses of therapy, including administration of a final antimicrobial regimen for at least 2 weeks after babesia were no longer seen on blood smear. CONCLUSIONS Immunocompromised people who are infected by B. microti are at risk of persistent relapsing illness. Such patients generally require antibabesial treatment for >or=6 weeks to achieve cure, including 2 weeks after parasites are no longer detected on blood smear.

Corpus allatum control of ovarian development in Aedes aegypti.

Ovarian follicles of Aedes aegypti normally pass through a potential stage of arrest 1 day after adult ecdysis and after blood feeding. Removal of the corpora allata or decapitation within an hour of these events interrupts normal development, and development is restored by reimplantation of active allata or by administration of synthetic analogues of juvenile hormone. Only follicles in the normal stage of arrest deposit yolk when stimulated by exogenous ecdysone or after the female takes a meal of blood. Follicles that ceased development as a result of allatectomy or decapitation respond to these oogenic stimuli, but degenerate without depositing yolk.

Salivary apyrase of Aedes Aegypti: Characterization and secretory fate

Salivary gland homogenates of female adult Aedes aegypti hydrolyzed ATP and ADP thereby defining an apyrase activity. Activity is divalent cation dependent with an optimum pH of 9.0. ATPase and ADPase activities could not be dissociated thus suggesting the presence of a true apyrase enzyme. Apyrase activity is low on the day of emergence but increases to 160 mU per pair of glands on the second day. The site at which mosquitoes probed into warm polyacrylamide gels retains apyrase activity, confirming the secretory fate of this activity.

Coinfecting Deer-Associated Zoonoses: Lyme Disease, Babesiosis, and Ehrlichiosis

The heightened worldwide recognition of the health burden of tickborne infection derives largely from the increasing incidence of Lyme disease, human babesiosis, and human granulocytic ehrlichiosis, both individually and in concert. Because these infections share the same rodent reservoir and tick vector hosts, they can be cotransmitted to human hosts. Indeed, human coinfections involving various combinations of these pathogens are common, and some tend to be particularly severe. Diagnostic procedures and clinical management of the resulting disease syndrome is rendered complex by the diversity of pathogens involved and by the unusual diversity and duration of symptoms.

Rapid emergence of a focal epidemic of Lyme disease in coastal Massachusetts

We describe a focal epidemic of Lyme disease, which spread from a nature preserve and affected an adjacent community of permanent residents in coastal Massachusetts. The attack rate from 1980 through 1987 was 35 percent among 190 residents living within 5 km of the nature preserve and was greatest (66 percent) among those living closest to the preserve. The risk of infection bore little relation to sex or age. Late Lyme disease, which clustered near the preserve, occurred mainly in residents infected early in the epidemic who did not have a history of erythema migrans and did not receive antibiotic therapy. All the residents with serologic evidence of infection had early or late clinical manifestations of Lyme disease, or both, during the period of study. The seasonal risk of infection was bimodal--greatest in June, with a secondary peak in October--and corresponded to periods of increased transmission. In the nature preserve, the density of the vector tick, Ixodes dammini, exceeded that in other New England sites. The zoonosis rapidly became endemic, and the severity of its impact correlated with the abundance of deer. This epidemic of Lyme disease demonstrated that outbreaks can be focal and can spread rapidly within a community of permanent residents.

Structure and seasonality of nearctic Culex pipiens populations.

Abstract: The abundance and structure of urban autogenous and anautogenous populations of Culex pipiens mosquitoes were documented systematically in Boston, MA, during three successive years. Autogenous larvae become abundant mainly in enclosed sites and anautogenous larvae in sites that provide free access and egress. Both populations begin to proliferate when the water temperature exceeds 15°C during June. Larval anautogenous mosquitoes increase in abundance 10‐fold in two weeks and autogenous in three weeks. Although anautogenous larvae rapidly disappear after mid‐August when winter diapause commences, the abundance of autogenous larvae continues to increase until mid‐October. The forms generally are reproductively isolated in nature but occasionally hybridize during August and thereafter. Anautogenous females feed mainly on birds; autogenous females generally never feed on blood; and hybrid females appear to feed indiscriminately on avian or mammalian hosts. Such northern C. p. pipiens mosquitoes range as far south as 33°N. Taken together, these observations suggest that C. p. pipiens‐borne pathogens may proliferate in the northern United States until mid‐August and affect human hosts thereafter. Intensity of transmission decreases toward the south.

Ixodes dammini: Salivary anaphylatoxin inactivating activity

Saliva of the tick, Ixodes dammini, antagonizes anaphylatoxin, abolishing both the effects of anaphylatoxin on guinea pig ileum preparations regularly stimulated with histamine and the local edema caused by intradermal injection of anaphylatoxin into guinea pigs. Saliva of these ticks, however, did not modify polymorphonuclear leukocyte aggregation induced by anaphylatoxin. Bradykinin and lysil-bradykinin were inactivated, but angiotensin I, angiotensin II, and substance P were not affected. Amino acids were released rapidly following incubation of saliva with bradykinin, but slowly from des-arg-9-bradykinin. These results suggest the presence of a salivary carboxypeptidase with specificity for terminal basic amino acids. Such activity may inactivate anaphylatoxin and bradykinin at the site of tick attachment.