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The rising incidence of clinical Babesia microti infection
HUMAN
PATHOLOGY--VOLUME
12, N U M B E R
5
May 1981
2. Yu, C., T'ung, C., tluang, H., Tfao, T., Kn, tt., Yu, C., and Liu, C.: Histiocytic medullary reticulosis. Chinese Med. J., 80:466, 1960. 3. Natelsou, E. A., Lynch, E. C., Hettig, R. A., and Alfrey, C. D.: Histiocytic medullary rcticulosis: the role of phagocytosis in pancytopenia. Arch. Intern. Med., 122:223, 1968. 4. Farqubar, J. w., and Claireaux, A. E.: Familial haemophagocytic reticulosis. Arch. Dis. Clfild., 27:519, 1952. 5. MacMahon, It. E., Bedizel, M., and Ellis, C. A.: Familial erythropbagocytic lympholfistiocytosis. Pediatrics, 32:868, 1963. 6. Byrne, G. E., and Rappaport, H.: Malignant histiocytosis. Gann Mono. Cancer Res., 15:145, 1973. 7. Warnke, R. A., Kim, H., and Dorfman, R. F.: Malignant histioeytosis (histiocytic medullary reticulosis). 1. Clinicopathologic study of 29 cases. Cancer, 35:215, 1975. 8. Lampert, I. A., Catovsky, D., and Bergier, N.: Malignant lfistiocytosls: a clinico-patbological study of 12 cases. Br. J. Haematol., 40:65, 1978. 9. Chandra, P., Chaudhery, S. A., Rosner, F., and Kagen, M.: Transient histiocytosis with striking pbagocytosis of platelets, leukocytes, and erythrocytes. Arch. Intern. Med., 135:989, 1975. 10. Risdall, R.J., McKenna, R. W., Nesbit, M. E., Kri~t, W., Balfour, H. H., Simmol'lS, R. 1.., and Brmnfing, R. D.: Virns associated hemophagocytic syndrome: a benign histiocytic proliferation distinct from malignant histiocytosis. Cancer, 44:993, 1979. 11. Zinkham, W. tt., Medearis, D. N., and Osborn, J. E.: Blood and bone marrow findings in congenital rubella. J. Pediatrics, 71:512, 1967. 12. Weller, T. H.: The cytomegalovirus: ubiquitous agents with protean clinical manifestations. N. Engl. J. Med., 285:203,267, 1971. 13. Purtilo, D. T., DcFIorio, D., Hutt, L. M., Bhawan,J., Yang,J. P. s., Otto, R., and Edwards, W.: Variable phenotypic expression of an X-linked recessive lymphoproliferative syndrome. N. Engl. J. Med., 297:1077, 1977. 14. Ladish, S., Itoliman, B., Poplack, D. G., and Blaese, R. M.: hnmunodcficieney in familial erythroplmgocytic lymplmhistiocytosis. Lancet, 1:581, 1978. 15. Fullerton, P.; Ekert, H., Hosking, C., and Tauro, G. P.: Hempbagocytic reticulosis: a case report with investigations of inmmne and white cell function. Cancer, 36:441, 1975. 16. Scott, H., Moynahan, E.J., Risdon, R. A., Harvey, B. A. M., and Soodfill, J. F.: Fanfilial opsonization defect associated with fatal infantile dernmtitis, infections, and Ifistiocytosis. Arch. Dis. Child., 50:311, 1975. 17. Gehrz, R. C., Knorr, S. O., Marker, S. C., Kalis, J. M., anti Balfour, tl. H.: Specific cell-mediated immune defect in active cytomegalovirus infection of young chiIdren and their mothers. Lancet, 2:844, 1977. 18. Fernandes-Costa, F., and Eintracht~ I.: [tistiocytic medullary reticulosls. Lancet, 2:20t, 1979. ' 19. Zuazu, J. P., Duran, J. W., and Julia, A. F.: I-/emophagocytosis in acute brucellosis. N. Engl. J. Med., 301:1185, 1979. 20. Broeckaert-Van Orshoven, A., Michielsen, P., and Vandeplue, J.: Fatal leisbmaniasis in renal-transplant patient. Lancet, 2:740, 1979. Department of Laboratory Medicine and PathologT University of Minnesota Medical School Box 198, Mayo Memorial Building 420 Delaware Street, S. E. Minneapolis, Mimlesota 55455 (Dr. McKenua)
T h e incidence o f h u m a n babesial infection has accelerated in recent )'ears as a result o f an increase in infections caused by Babesia microti. Since the first human B. microti infection occurred on Nantucket in 1969, 98 additional infections have bcen recognized. O f titese, 57 were clinical infections, with 15 recorded in 1980, the largest number per )'ear recorded to date (Table 1). All the tick transmitted B. microti infections were contracted on the offshore islands o f the northeastern United States and on Cape Cod (Table 2). T h e 57 clinical infections included three transfusion transmitted infections, two of wlfich occurred in splenectomized patients. T h e infections ranged widely in severity, but only one patient died. T h e fatality involved an elderly, spleen intact patient who developed a transftlsion transmitted infection. T h e rodent Babesia is enzootic in white footed mice (l'eromyscus leucopus) in t h e e n d e n f i c r e g i o n s listed in T a b l e 2. T i r e i n f e c t i o n is m a i n t a i n e d in t h e r o d e n t p o p u l a t i o n s by t h e n o r t l t e r n d e e r tick, a r e c e n t l y c h a r a c t e r i z e d n e w lxodes s p e c i e s ? D e e r a r e tire princil)al hosts f o r t h e a d u l t tick, b u t larvae and nymt)hs are abnndant on both mice and deer. Human infection resuhs when the nymplL while feeding, i n o c u l a t e s Babesia i n t o man. B. microti is t r a n s m i t t e d t r a n s stadially, f r o m l a r v a to n y m p h ; tltere is n o e v i d e n c e f o r t r a n s o v a r i a l t r a n s n t i s s i o n . T i r e larva a c q u i r e s B. microti wltile f e e d i n g o n a n i n f e c t e d wltite f o o t e d m o u s e , t h e r e b y initiating the sequence of parasite transmission just mentioued. P o t e n t i a l l y i n f e c t i o u s n y m p h s f e e d m a i n l y f r o m May t h r o u g h S e p t e m b e r , a t t d h u m a n i n f e c t i o u g e n e r a l l y o c c u r s o n e to t h r e e weeks later. A l t h o u g h clinical B. microti i n f e c t i o n o f t e n m i m i c s m a l a r i a , it is g e n e r a l l y m i l d e r . S e v e r e illness h a s o c c u r r e d in b o t h s p l e e n i n t a c t a n d p r i o r s p l e n e c t o m i z e d p a t i e n t s b u t is m o r e f r e q u e n t in t h e latter. T h e r e a r e n o c h a r a c t e r i s t i c skin lesions s u c h as t h o s e t h a t o f t e n h e r a l d t h e clinical p h a s e o f c e r t a i n o t h e r tick t r a n s m i t t e d diseases o c c u r r i n g in t h e n o r t h e a s t e r n U n i t e d States, e.g., L y m e disease, Rock), Mountain spotted fever, and tularemia. A history of recent r e s i d e n c e in a k n o w n e n d e m i c r e g i o n assists in t h e d i f f e r e n tial d i a g n o s i s o f s u m m e r f e b r i l e illnesses. M i c r o s c o p i c diagnosis c a n b e p r o m p t a n d d i r e c t i f t h e c h a r a c t e r i s t i c t e t r a d stage o f B . microti is f o u n d in p e r ! p h e r a l b l o o d e r y t h r o c y t e s T A B L E 1. T E M P O R A L D I S T R I B U T I O N BABESIA MICROTI I N F E C T I O N S
THE RISING INCIDENCE OF CLINICAL BABESIA MICROTI INFECTION GUSTAVE J . DA.Xl.XlIN, M.D.,* ANDREW SPIEL.MAN, Sc.D.,I" JORGE L. BENACH, PmD.,:~ AND JOSEPtt PIES.XtA,~, D.Sc.w Accepted tbr publication July 31, 1980. Stud)' supported in part by research grant 1746 from the.~ew York State Health Research Council and research grant AI-15886 from the United States Public H e a h h Serice *Professor of Pathology, Emeritns, Harvard Medical School. Constfltant in Pathology, Brigham-Wonaen's Hospital, Boston, Massachttsetts. ?Professor, Departntent of Tropical Public l lealth, Harvard School of Public i-tealth, Boston, Massadmsetts. +Assistant Professor, Department of Pathology, School of ,Medicine, State Uifiversity of New York at Stony Brook. Research Scientist, Bureau of Disease Control, New York State Departlnent of Health, Stony Brook, New York. w Associate, Departutent of Tropical Public Heahh, Harvard School of Public Health, Boston, Massachusetts.
398
Year
Massachusetts SubClinical clinical
1969 1973 1974 1975 1976 1977 1978 1979 198{)
1 1 0 I1 6 1 1 6~ 8~w
0 0 0 0 3 15" 0 1 1
Total
35
20 u 0
Splenectomy 3
OF
Rhode Island Subclinical
Total
0 0 0 0 0 1 10 9 1
0 0 0 0 0 0 0 1 0
1 I I 12 11 19 13 24 17
22
2!
1
99
7
0
0
10
N e w York SubClinical clinical 0 0 l l 2 2 2 7t 7~
*Front the report of Rtiebush et al. Oil a 1975-1976 survey; see reference 2. t T h r e e cases occurred before 1979 but were serologically proven that )ear. ~:Includes one transfnsion transmitted infection. w transmitted infection fatal.
CURRENT TOPICS T A B L E 2. G E O G R A P H I C D I S T R I B U T I O N OF BABESIA MICROTI I N F E C T I O N S State
Massachusetts
New York
Rhode Island
Clinical Subclinical
Community
Nantucket Martha's Vineyard Cape Cod Naushon Island Boston l'ittsfield
27 5 I 0 I* l*t
16 0 ! 3 0 0
Total
35
20
Shelter Island Other areas of l.ong Islaqd New York City
8 13 !*
16 5 0
Total
'2'2
21
Block Island
Total
0
1
57
42
*Transfllsion transmitted. t'Fatal infection. and if extracelhdar forms are present. In addition, B. microti can be distinguished from Plasmodium falciparum by the central pallor occasionally found in large trophozoites o f intraerythrocytic B. microti. 8 T h e absence o f hemazoin in the B. microti infected erythrocyte may help to distinguish it from the plasmodia,- but in its early d e v e l o p m e n t P. falciparum seldom produces this brownish pigment. Because microscopic distinction between these protozoa has been difficult, many B. microti infections have been diagnosed initially as malaria and so treated. Serologic diagnosis o f clinical B. microti infection is possible at its onset, and the p..arasite can be isolated a n d identified by h a m s t e r inoculation. Mild B. microti infections have r e s p o n d e d to symptomatic treatment with analgesics and antipyretics. Moderately severe infections with falling hematocrit values d u e to hemolysis have required transfusions. Specific d r u g treatment is n e e d e d in such cases, and quinine and pyrimethamine seem to have been effective in two trials. Pentamidine has p r o d u c e d symptomatic relief and has r e d u c e d the parasitemia, which, however, may persist at low levels. In fitlminating infections with high fever and parasitemia, exchange transfilsions have resulted in m a r k e d symptomatic i m p r o v e m e n t and reduction in parasitemia. Such infecT A B L E 3.
tions have been tnore frequent ill previously splenectomized patients than in spleen intact patients. Prevention consists largely o f avoiding contact with the nymphal stage o f the vector tick, Ixodes dammini. W h e n entering terrain inhabited by mice and d e e r in B. micmti enzootic regions d u r i n g May t h r o u g h September, one is at risk for Lyme disease as well as babesiosis. I f such terrain must be freqnented, nse o f a repellant containing diethyl toluamide is advised. U p o n leaving the location, one should be e x a m i n e d t h o r o u g h l y for nymphal lxodes, which measure only 2 to 3 mm. in length in the unfed state. W h e n found to be attached, ticks should be r e m o v e d p r o m p t l y using fine forceps placed close to the point o f attachment. T h e risk o f acquiring babesial infection increases with the duration o f the feeding period. Attempts to control the mammals involved in zoonotic m u r i n e babesiosis would e n c o u n t e r many obstacles, and thus far no such efforts have been undertaken. A pilot tick control project is now u n d e r w a y in one o f the endemic areas. T h e first h u m a n babesial infection was caused by a bovine Babesia sp., occurring in Yugoslavia in 1956. T h e patient was a y o u n g man who had been splenectomized in 1945. His infection was fuhninant, terminating fatally within two weeks after onset. Six subsequent cases were recognized in Europe, all caused by bovine Babesia spp. (mainly B. divergens), and all occurred in splenectomized individuals (Table 3). All patients were seriously ill and four died. T h e tick vector o f bovine Babesia spp. in E u r o p e is Ixodes ricinus. T h e rising t r e n d o f case incidence encountered in the northeastern United States has no parallel in Europe. H u m a n B. microti infection is difficult to control, and procedures must be d e v e l o p e d if the c u r r e n t trend o f increasing morbidity is to be reversed. Public heahh attention should be directed toward transfusion transmission as well as tick transmission o f the parasite. Most o f the cases listed in the tables occurred before 1978 and are described in articles listed in the bibliography o f reference 2. Reports o f o t h e r cases are listed in the references for this article, a n d the r e m a i n d e r have been r e p o r t e d to us by the physicians whose generous assistance is recognized u n d e r Acknowledgments. Acknowledgments
We are deeply grateful for the help e x t e n d e d to us by the physicians whose names are listed below. T h e i r help
B A B E S I A L I N F E C T I O N S C A U S E D BY BABESIA O T H E R T H A N B. MICROTI
France
Clinical Russia Ireland
Scotland
California
Subclinical Mexico Georgia
Year
Yugoslavia
1956 1967 1969 1975 1976 1977 1978 1979
1 Bb
Total
2
2
1
1
!
2
Splenectomy
2
2
1
1
i
2
9
Fatal cases
2
0
1
1
1
0
5
1 Bd 1 Bd
1 Bsp 2 Bd
3 Bsp 1 Bsp 1 Bd 1 Bd 1 Bsp 3
1
Total
1 1 2 5 1 I 1 1 13
Bb, Babesia boris. Bd, Babesia dive~gens. Bsp, Babesia sp. (not classified).
399
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m a d e it possible f o r us to anal)'ze t h e essdntial clinical, l a b o r a t o r y , a n d e p i d e m i o l o g i c d a t a r e l a t i n g to babesial i n f e c t i o u s t h e y h a d t r e a t e d d u r i n g t h e p e r i o d 1976 to 1980. M a n y r e p o r t s s u b m i t t e d to us c o n c e r n e d i n d i v i d u a l o r Small g r o u p s o f cases, m o s t o f w h i c h w e r e n o t b e i n g p r e p a r e d f o r p u b l i c a t i o n . T h e s e r e p o r t s a n d t h o s e c o n t a i n e d in the r e f e r e n c e s c o n s t i t u t e a c o m p r e h e n s i v e analysis o f t h e curr e n t status o f h u m a n babesiosis: W e e x t e n d ore- t h a n k s to D o c t o r s S t a n l e y A m e l k i n , Michael S. A s c h e r , A l l e n B. B r e d t , E. L a n g d o n Burwell, K e v i n M. Cahill, Patricia G i a r d i n a , B e n j a m i n Glick, Ellie G o l d s t e i n , E d g a r G r u n w a l d t , T h o m a s J . J o s e p h , T h o m a s C. J o n e s , M a r k H. K a p l a n , Earle B. M a h o n e y , H a r o l d C. N e u , David R a p p a p o r t , S t a n l e y R e e d , J a n t e s L. A. R o t h , Gabriel Spergel, a n d Marvin T e n e n b a u m .
3. Rabinovich,S. A., Voronina, L. K., Stepanova, N. I., Marvashvily,G. M., Bakradze, T. L., Odisharla, M. S., and Gvasalia, N. J.: The first case of human babesiosis detected in the U.S.S.R. Med. Parasltol., 3;97, 1978. 4. Entrican, J. tL, Williams, H., Cook, I. A., Lancaster, W. M., Clark,J. C., Joyner, L. P., and Lewis, D.: Babesiosisin man: a report of a case from Scotland with observations on the infecting strain. J. Inf. Dis., 1:227, 1979. 5. Filstein, M. R., Benach,J. L, White, D.J., Brody, B. A., Goldman, W. D., Bakal, C. W., and Schwartz, R. S.: Serosurvey for human babesiosisin New York.J. Inf. Dis., 141:518, 1980: 6. Ruebnsh, T. K., II: 11mnan lmbesiosls in North America. Trans. Roy. Soc. Trop. Med. Hyg., 74:149, 1980. 7. Teutsch, S. M., Etkind, P., Burwell, E. L., Sato, .K., Dana, M. M., Fleishmml, P. R., and Jaranek, 1). I).: Babesiosis in posl-.,~plenectomy hosts. Am. J. Trop. Med. ttyg.,29:738, 1980. 8. Garnham, 1'. C. C.: tltnnan babesiosis: European aspects. Trans. Roy. Soc_Trop. Med. ltyg., 74:153, 1980. 9. Jact)by, G. A., et al.: Treatment of transfusion-transmitted babesiosis by exchange transfilslon. New F.ng.J. Med., 303:1098.1980.
References 1. Spiehnan, A., Clifford, C. M., Picsman,J., and Corwin, M. D.: Human babesiosison Nantucket Island, U.S.A.: description of the vector, lxodes (lxodes) damrMni, n.sp. (Acarina: Ixodidae). J. Med. Ent., 15:918, 1979. 2. l)ammin, G.J.: Babexiosis.In Weinstein, L., and Fields, B. N. (Editors): Seminars in hffectious Disease. New York, Stratton Intercontinental Book Ca~., 1978, pp. 169-199.
400
Department rffTropical Public ttealth ltarvard School of PaNic ttealth 665 Huntington Avenue Boston, Massachuselts0211:5 (Dr. Dammiu)
PATHOLOGY--VOLUME
12, N U M B E R
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May 1981
2. Yu, C., T'ung, C., tluang, H., Tfao, T., Kn, tt., Yu, C., and Liu, C.: Histiocytic medullary reticulosis. Chinese Med. J., 80:466, 1960. 3. Natelsou, E. A., Lynch, E. C., Hettig, R. A., and Alfrey, C. D.: Histiocytic medullary rcticulosis: the role of phagocytosis in pancytopenia. Arch. Intern. Med., 122:223, 1968. 4. Farqubar, J. w., and Claireaux, A. E.: Familial haemophagocytic reticulosis. Arch. Dis. Clfild., 27:519, 1952. 5. MacMahon, It. E., Bedizel, M., and Ellis, C. A.: Familial erythropbagocytic lympholfistiocytosis. Pediatrics, 32:868, 1963. 6. Byrne, G. E., and Rappaport, H.: Malignant histiocytosis. Gann Mono. Cancer Res., 15:145, 1973. 7. Warnke, R. A., Kim, H., and Dorfman, R. F.: Malignant histioeytosis (histiocytic medullary reticulosis). 1. Clinicopathologic study of 29 cases. Cancer, 35:215, 1975. 8. Lampert, I. A., Catovsky, D., and Bergier, N.: Malignant lfistiocytosls: a clinico-patbological study of 12 cases. Br. J. Haematol., 40:65, 1978. 9. Chandra, P., Chaudhery, S. A., Rosner, F., and Kagen, M.: Transient histiocytosis with striking pbagocytosis of platelets, leukocytes, and erythrocytes. Arch. Intern. Med., 135:989, 1975. 10. Risdall, R.J., McKenna, R. W., Nesbit, M. E., Kri~t, W., Balfour, H. H., Simmol'lS, R. 1.., and Brmnfing, R. D.: Virns associated hemophagocytic syndrome: a benign histiocytic proliferation distinct from malignant histiocytosis. Cancer, 44:993, 1979. 11. Zinkham, W. tt., Medearis, D. N., and Osborn, J. E.: Blood and bone marrow findings in congenital rubella. J. Pediatrics, 71:512, 1967. 12. Weller, T. H.: The cytomegalovirus: ubiquitous agents with protean clinical manifestations. N. Engl. J. Med., 285:203,267, 1971. 13. Purtilo, D. T., DcFIorio, D., Hutt, L. M., Bhawan,J., Yang,J. P. s., Otto, R., and Edwards, W.: Variable phenotypic expression of an X-linked recessive lymphoproliferative syndrome. N. Engl. J. Med., 297:1077, 1977. 14. Ladish, S., Itoliman, B., Poplack, D. G., and Blaese, R. M.: hnmunodcficieney in familial erythroplmgocytic lymplmhistiocytosis. Lancet, 1:581, 1978. 15. Fullerton, P.; Ekert, H., Hosking, C., and Tauro, G. P.: Hempbagocytic reticulosis: a case report with investigations of inmmne and white cell function. Cancer, 36:441, 1975. 16. Scott, H., Moynahan, E.J., Risdon, R. A., Harvey, B. A. M., and Soodfill, J. F.: Fanfilial opsonization defect associated with fatal infantile dernmtitis, infections, and Ifistiocytosis. Arch. Dis. Child., 50:311, 1975. 17. Gehrz, R. C., Knorr, S. O., Marker, S. C., Kalis, J. M., anti Balfour, tl. H.: Specific cell-mediated immune defect in active cytomegalovirus infection of young chiIdren and their mothers. Lancet, 2:844, 1977. 18. Fernandes-Costa, F., and Eintracht~ I.: [tistiocytic medullary reticulosls. Lancet, 2:20t, 1979. ' 19. Zuazu, J. P., Duran, J. W., and Julia, A. F.: I-/emophagocytosis in acute brucellosis. N. Engl. J. Med., 301:1185, 1979. 20. Broeckaert-Van Orshoven, A., Michielsen, P., and Vandeplue, J.: Fatal leisbmaniasis in renal-transplant patient. Lancet, 2:740, 1979. Department of Laboratory Medicine and PathologT University of Minnesota Medical School Box 198, Mayo Memorial Building 420 Delaware Street, S. E. Minneapolis, Mimlesota 55455 (Dr. McKenua)
T h e incidence o f h u m a n babesial infection has accelerated in recent )'ears as a result o f an increase in infections caused by Babesia microti. Since the first human B. microti infection occurred on Nantucket in 1969, 98 additional infections have bcen recognized. O f titese, 57 were clinical infections, with 15 recorded in 1980, the largest number per )'ear recorded to date (Table 1). All the tick transmitted B. microti infections were contracted on the offshore islands o f the northeastern United States and on Cape Cod (Table 2). T h e 57 clinical infections included three transfusion transmitted infections, two of wlfich occurred in splenectomized patients. T h e infections ranged widely in severity, but only one patient died. T h e fatality involved an elderly, spleen intact patient who developed a transftlsion transmitted infection. T h e rodent Babesia is enzootic in white footed mice (l'eromyscus leucopus) in t h e e n d e n f i c r e g i o n s listed in T a b l e 2. T i r e i n f e c t i o n is m a i n t a i n e d in t h e r o d e n t p o p u l a t i o n s by t h e n o r t l t e r n d e e r tick, a r e c e n t l y c h a r a c t e r i z e d n e w lxodes s p e c i e s ? D e e r a r e tire princil)al hosts f o r t h e a d u l t tick, b u t larvae and nymt)hs are abnndant on both mice and deer. Human infection resuhs when the nymplL while feeding, i n o c u l a t e s Babesia i n t o man. B. microti is t r a n s m i t t e d t r a n s stadially, f r o m l a r v a to n y m p h ; tltere is n o e v i d e n c e f o r t r a n s o v a r i a l t r a n s n t i s s i o n . T i r e larva a c q u i r e s B. microti wltile f e e d i n g o n a n i n f e c t e d wltite f o o t e d m o u s e , t h e r e b y initiating the sequence of parasite transmission just mentioued. P o t e n t i a l l y i n f e c t i o u s n y m p h s f e e d m a i n l y f r o m May t h r o u g h S e p t e m b e r , a t t d h u m a n i n f e c t i o u g e n e r a l l y o c c u r s o n e to t h r e e weeks later. A l t h o u g h clinical B. microti i n f e c t i o n o f t e n m i m i c s m a l a r i a , it is g e n e r a l l y m i l d e r . S e v e r e illness h a s o c c u r r e d in b o t h s p l e e n i n t a c t a n d p r i o r s p l e n e c t o m i z e d p a t i e n t s b u t is m o r e f r e q u e n t in t h e latter. T h e r e a r e n o c h a r a c t e r i s t i c skin lesions s u c h as t h o s e t h a t o f t e n h e r a l d t h e clinical p h a s e o f c e r t a i n o t h e r tick t r a n s m i t t e d diseases o c c u r r i n g in t h e n o r t h e a s t e r n U n i t e d States, e.g., L y m e disease, Rock), Mountain spotted fever, and tularemia. A history of recent r e s i d e n c e in a k n o w n e n d e m i c r e g i o n assists in t h e d i f f e r e n tial d i a g n o s i s o f s u m m e r f e b r i l e illnesses. M i c r o s c o p i c diagnosis c a n b e p r o m p t a n d d i r e c t i f t h e c h a r a c t e r i s t i c t e t r a d stage o f B . microti is f o u n d in p e r ! p h e r a l b l o o d e r y t h r o c y t e s T A B L E 1. T E M P O R A L D I S T R I B U T I O N BABESIA MICROTI I N F E C T I O N S
THE RISING INCIDENCE OF CLINICAL BABESIA MICROTI INFECTION GUSTAVE J . DA.Xl.XlIN, M.D.,* ANDREW SPIEL.MAN, Sc.D.,I" JORGE L. BENACH, PmD.,:~ AND JOSEPtt PIES.XtA,~, D.Sc.w Accepted tbr publication July 31, 1980. Stud)' supported in part by research grant 1746 from the.~ew York State Health Research Council and research grant AI-15886 from the United States Public H e a h h Serice *Professor of Pathology, Emeritns, Harvard Medical School. Constfltant in Pathology, Brigham-Wonaen's Hospital, Boston, Massachttsetts. ?Professor, Departntent of Tropical Public l lealth, Harvard School of Public i-tealth, Boston, Massadmsetts. +Assistant Professor, Department of Pathology, School of ,Medicine, State Uifiversity of New York at Stony Brook. Research Scientist, Bureau of Disease Control, New York State Departlnent of Health, Stony Brook, New York. w Associate, Departutent of Tropical Public Heahh, Harvard School of Public Health, Boston, Massachusetts.
398
Year
Massachusetts SubClinical clinical
1969 1973 1974 1975 1976 1977 1978 1979 198{)
1 1 0 I1 6 1 1 6~ 8~w
0 0 0 0 3 15" 0 1 1
Total
35
20 u 0
Splenectomy 3
OF
Rhode Island Subclinical
Total
0 0 0 0 0 1 10 9 1
0 0 0 0 0 0 0 1 0
1 I I 12 11 19 13 24 17
22
2!
1
99
7
0
0
10
N e w York SubClinical clinical 0 0 l l 2 2 2 7t 7~
*Front the report of Rtiebush et al. Oil a 1975-1976 survey; see reference 2. t T h r e e cases occurred before 1979 but were serologically proven that )ear. ~:Includes one transfnsion transmitted infection. w transmitted infection fatal.
CURRENT TOPICS T A B L E 2. G E O G R A P H I C D I S T R I B U T I O N OF BABESIA MICROTI I N F E C T I O N S State
Massachusetts
New York
Rhode Island
Clinical Subclinical
Community
Nantucket Martha's Vineyard Cape Cod Naushon Island Boston l'ittsfield
27 5 I 0 I* l*t
16 0 ! 3 0 0
Total
35
20
Shelter Island Other areas of l.ong Islaqd New York City
8 13 !*
16 5 0
Total
'2'2
21
Block Island
Total
0
1
57
42
*Transfllsion transmitted. t'Fatal infection. and if extracelhdar forms are present. In addition, B. microti can be distinguished from Plasmodium falciparum by the central pallor occasionally found in large trophozoites o f intraerythrocytic B. microti. 8 T h e absence o f hemazoin in the B. microti infected erythrocyte may help to distinguish it from the plasmodia,- but in its early d e v e l o p m e n t P. falciparum seldom produces this brownish pigment. Because microscopic distinction between these protozoa has been difficult, many B. microti infections have been diagnosed initially as malaria and so treated. Serologic diagnosis o f clinical B. microti infection is possible at its onset, and the p..arasite can be isolated a n d identified by h a m s t e r inoculation. Mild B. microti infections have r e s p o n d e d to symptomatic treatment with analgesics and antipyretics. Moderately severe infections with falling hematocrit values d u e to hemolysis have required transfusions. Specific d r u g treatment is n e e d e d in such cases, and quinine and pyrimethamine seem to have been effective in two trials. Pentamidine has p r o d u c e d symptomatic relief and has r e d u c e d the parasitemia, which, however, may persist at low levels. In fitlminating infections with high fever and parasitemia, exchange transfilsions have resulted in m a r k e d symptomatic i m p r o v e m e n t and reduction in parasitemia. Such infecT A B L E 3.
tions have been tnore frequent ill previously splenectomized patients than in spleen intact patients. Prevention consists largely o f avoiding contact with the nymphal stage o f the vector tick, Ixodes dammini. W h e n entering terrain inhabited by mice and d e e r in B. micmti enzootic regions d u r i n g May t h r o u g h September, one is at risk for Lyme disease as well as babesiosis. I f such terrain must be freqnented, nse o f a repellant containing diethyl toluamide is advised. U p o n leaving the location, one should be e x a m i n e d t h o r o u g h l y for nymphal lxodes, which measure only 2 to 3 mm. in length in the unfed state. W h e n found to be attached, ticks should be r e m o v e d p r o m p t l y using fine forceps placed close to the point o f attachment. T h e risk o f acquiring babesial infection increases with the duration o f the feeding period. Attempts to control the mammals involved in zoonotic m u r i n e babesiosis would e n c o u n t e r many obstacles, and thus far no such efforts have been undertaken. A pilot tick control project is now u n d e r w a y in one o f the endemic areas. T h e first h u m a n babesial infection was caused by a bovine Babesia sp., occurring in Yugoslavia in 1956. T h e patient was a y o u n g man who had been splenectomized in 1945. His infection was fuhninant, terminating fatally within two weeks after onset. Six subsequent cases were recognized in Europe, all caused by bovine Babesia spp. (mainly B. divergens), and all occurred in splenectomized individuals (Table 3). All patients were seriously ill and four died. T h e tick vector o f bovine Babesia spp. in E u r o p e is Ixodes ricinus. T h e rising t r e n d o f case incidence encountered in the northeastern United States has no parallel in Europe. H u m a n B. microti infection is difficult to control, and procedures must be d e v e l o p e d if the c u r r e n t trend o f increasing morbidity is to be reversed. Public heahh attention should be directed toward transfusion transmission as well as tick transmission o f the parasite. Most o f the cases listed in the tables occurred before 1978 and are described in articles listed in the bibliography o f reference 2. Reports o f o t h e r cases are listed in the references for this article, a n d the r e m a i n d e r have been r e p o r t e d to us by the physicians whose generous assistance is recognized u n d e r Acknowledgments. Acknowledgments
We are deeply grateful for the help e x t e n d e d to us by the physicians whose names are listed below. T h e i r help
B A B E S I A L I N F E C T I O N S C A U S E D BY BABESIA O T H E R T H A N B. MICROTI
France
Clinical Russia Ireland
Scotland
California
Subclinical Mexico Georgia
Year
Yugoslavia
1956 1967 1969 1975 1976 1977 1978 1979
1 Bb
Total
2
2
1
1
!
2
Splenectomy
2
2
1
1
i
2
9
Fatal cases
2
0
1
1
1
0
5
1 Bd 1 Bd
1 Bsp 2 Bd
3 Bsp 1 Bsp 1 Bd 1 Bd 1 Bsp 3
1
Total
1 1 2 5 1 I 1 1 13
Bb, Babesia boris. Bd, Babesia dive~gens. Bsp, Babesia sp. (not classified).
399
HUMAN
PATHOLOGY--VOLUME
12, N U M B E R
5
Ma)' 1981
m a d e it possible f o r us to anal)'ze t h e essdntial clinical, l a b o r a t o r y , a n d e p i d e m i o l o g i c d a t a r e l a t i n g to babesial i n f e c t i o u s t h e y h a d t r e a t e d d u r i n g t h e p e r i o d 1976 to 1980. M a n y r e p o r t s s u b m i t t e d to us c o n c e r n e d i n d i v i d u a l o r Small g r o u p s o f cases, m o s t o f w h i c h w e r e n o t b e i n g p r e p a r e d f o r p u b l i c a t i o n . T h e s e r e p o r t s a n d t h o s e c o n t a i n e d in the r e f e r e n c e s c o n s t i t u t e a c o m p r e h e n s i v e analysis o f t h e curr e n t status o f h u m a n babesiosis: W e e x t e n d ore- t h a n k s to D o c t o r s S t a n l e y A m e l k i n , Michael S. A s c h e r , A l l e n B. B r e d t , E. L a n g d o n Burwell, K e v i n M. Cahill, Patricia G i a r d i n a , B e n j a m i n Glick, Ellie G o l d s t e i n , E d g a r G r u n w a l d t , T h o m a s J . J o s e p h , T h o m a s C. J o n e s , M a r k H. K a p l a n , Earle B. M a h o n e y , H a r o l d C. N e u , David R a p p a p o r t , S t a n l e y R e e d , J a n t e s L. A. R o t h , Gabriel Spergel, a n d Marvin T e n e n b a u m .
3. Rabinovich,S. A., Voronina, L. K., Stepanova, N. I., Marvashvily,G. M., Bakradze, T. L., Odisharla, M. S., and Gvasalia, N. J.: The first case of human babesiosis detected in the U.S.S.R. Med. Parasltol., 3;97, 1978. 4. Entrican, J. tL, Williams, H., Cook, I. A., Lancaster, W. M., Clark,J. C., Joyner, L. P., and Lewis, D.: Babesiosisin man: a report of a case from Scotland with observations on the infecting strain. J. Inf. Dis., 1:227, 1979. 5. Filstein, M. R., Benach,J. L, White, D.J., Brody, B. A., Goldman, W. D., Bakal, C. W., and Schwartz, R. S.: Serosurvey for human babesiosisin New York.J. Inf. Dis., 141:518, 1980: 6. Ruebnsh, T. K., II: 11mnan lmbesiosls in North America. Trans. Roy. Soc. Trop. Med. Hyg., 74:149, 1980. 7. Teutsch, S. M., Etkind, P., Burwell, E. L., Sato, .K., Dana, M. M., Fleishmml, P. R., and Jaranek, 1). I).: Babesiosis in posl-.,~plenectomy hosts. Am. J. Trop. Med. ttyg.,29:738, 1980. 8. Garnham, 1'. C. C.: tltnnan babesiosis: European aspects. Trans. Roy. Soc_Trop. Med. ltyg., 74:153, 1980. 9. Jact)by, G. A., et al.: Treatment of transfusion-transmitted babesiosis by exchange transfilslon. New F.ng.J. Med., 303:1098.1980.
References 1. Spiehnan, A., Clifford, C. M., Picsman,J., and Corwin, M. D.: Human babesiosison Nantucket Island, U.S.A.: description of the vector, lxodes (lxodes) damrMni, n.sp. (Acarina: Ixodidae). J. Med. Ent., 15:918, 1979. 2. l)ammin, G.J.: Babexiosis.In Weinstein, L., and Fields, B. N. (Editors): Seminars in hffectious Disease. New York, Stratton Intercontinental Book Ca~., 1978, pp. 169-199.
400
Department rffTropical Public ttealth ltarvard School of PaNic ttealth 665 Huntington Avenue Boston, Massachuselts0211:5 (Dr. Dammiu)