Table Of ContentAmebiasis:
Infection and Disease
by
Entamoeba histolytica
Editor
Roberto R. Kretschmer
Head, Division of Immunology
Unidad de Investigacion Biomedica
Instituto Mexicano del Seguro Social and Subdivision de Medicina Experimental
Facultad de Medicina
Universidad Nacional Autonoma de Mexico
Mexico, D. F.
CRC Press
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To
Liliana, Verónica, and Kilian
PREFACE
There were mixed feelings when the invitation to write a book on amebiasis reached
me in 1985. First, several excellent reviews, both in specialized journals and in books, had
appeared recently or were in press.13 A. Martínez-Palomo, a leader in the field of amebiasis,
had just contributed to re-establish the scientific relevance of this parasite — recently de-
serving only chapter treatment in the Anglo-Saxon literature — by publishing a book totally
devoted to the subject.4 He subsequently edited another book on amebiasis, where several
authors rendered their ''state-of-the-art" account of a field that had witnessed a remarkable
progress in the last two decades.5 Furthermore, there lurked in the background the imminent
appearance of J. I. Ravdin's extensive text with 50 chapters covering virtually every aspect
of this remarkable parasite.6 To make matters worse for me, most of the collaborators I
could think of for such a new book on amebiasis had, not unexpectedly, contributed to one
or the other of the aforementioned texts.
After some internal and external deliberation, however, I decided to accept the challenge
of presenting yet another medium-size book on amebiasis, provided two conditions could
be met. In the first place, the enterprise would have be be postponed for at least 2 years in
order to allow enough new information to accumulate. I thought this not to be an unreasonable
proposition in a field of such remarkable vitality. Second — and foremost — the authors
should be allowed, alas invited, not to shun controversy, and in fact engage in reasonable,
constructive speculation, a salutary exercise in a field where so much and sometimes so
conflicting information is at hand. Such an effort could help pave the way for future de-
velopment by perhaps suggesting pathways for research.
Having agreed upon these two premises, the chosen collaborators — all experts in their
own field with immediate experience with amebas and their victims — responded positively
to the invitation, and the signal to start was given in the summer of 1987.
Most recent texts on amebiasis stress the importance of this disease as a worldwide
health problem that has been surprisingly and systematically neglected by the international
health agencies.7 Ranking diseases by importance can be a treacherous and thankless task.8
Still, is is obvious that amebiasis has not received its due priority i f one considers its
prevalence (500,000,00 0 infection s pe r annum), its morbidity (50,000,00 0 diseases per
annum ranging from trivial to life-threatening) an d its mortality (50,000 to 100,000 per
annum).9 Thus, amebiasis still kills annually more people than AIDS has killed in the decade
since its recognition (an estimated 75,000), yet receives only a very small fraction (ca. 10~3)
of the financial suppor t deservedly allotte d to HIV research.10 Granted, amebiasi s is in
principle a reasonably preventable and curable disease that has apparently reached a certain
epidemiological stability affecting mostly underdeveloped countries. AIDS in contrast, though
theoretically perhaps as preventable as amebiasis, is still an incurable disease that is undergo-
ing an explosive epidemiological expansion, most alarmingly in rich, industrialized countries.
Curiously, both diseases are converging in some individuals at risk with striking but as yet
unpredictable long-term consequences.11 For physicians in developed countries, amebiasis
may soon cease to be a forgotten problem affecting forgotten people.12 Moreover, AIDS is
revealing the fallacy of strictly nationally oriented disease-control strategies. Or confront,
if you wish, amebiasis with other leading parasitic diseases of mankind: malaria,8 with a
very well-known mode of transmission (and thus potentially effective control) produces far
more recurring illness and death than amebiasis, killing alone in Africa yearly ten times
more people (mostly children) than amebiasis worldwide.13 Yet, among protozoarian diseases
the death toll of amebiasis is only second to that of malaria.9 South American trypanosomiasis
is way down in prevalence (12,000,000 infections per annum), but morbidity and mortality
(60,000 deaths per annum) are only slightly below those of amebiasis. Giardiasis is perhaps
as prevalent as amebiasis, but its morbidity — occasionally in epidemic bursts — is lower,
and its mortality practically nil. As far as transmission is concerned, both diseases have
much in common (fecalism), an d are therefore equally difficult t o control in daily life.
Among the larger parasites (helminths), schistosomiasis is about half as prevalent and morbid
(ca. 200,000,000 and 20,000,000 cases per annum respectively) as amebiasis but its mortality
(1,000,000 deaths per annum) is much higher. Finally, ascaris, the giant intestinal round-
worm, is the most prevalent infection of man (ca. 1,000,000,000 cases per annum) but has
a relatively insignificant morbidity and only rarely causes death. As in the case of amebiasis,
its control is difficult a s it would ultimately require massive, long-term improvements in
sanitary and agricultural practices. Clearly, the priorities for disease control advocated by
the international health agencies take into consideration not only prevalence, the age group
mostly affected, morbidity, and mortality but, quite importantly, the feasibility of adequate
and effective control as well.7 That explains, on the one hand, the high priority bestowed
on malaria and the upgrading of schistosomiasis, and on the other hand the low priority
assigned to ascariasis, giardiasis, and amebiasis, notwithstanding their high prevalences,
and in the case of amebiasis also its relatively high mortality. In spite of its relatively high
morbidity and mortality (only slightly lower than amebiasis), South American trypanosom-
iasis (Chagas' disease) is also ranked low because of its difficult control.
All this provides insight into the complex if not bizarre sociological interactions of
ranking, promoting, lobbying, and funding that a given disease experiences on its way to
public recognition. Through the efforts of the Rockefeller Institute, amebiasis has at least
been identified as a pristine example in their Great Neglected Diseases Program.7 This timely
strategic decision led to a multicentric renaissance in amebic research, reaping a generous
harvest of challenging new knowledge. The late Bernardo Sepulveda was the undisputed
pioneer of this awakening in Mexico, a country where E. histolytica is particularly at home.
It is in his spirit that we embarked in this enterprise.14
The text is organized in 11 chapters. It follows the traditional distribution of first basic
and then clinical material, preceded by a chapter on the history of amebiasis that adds some
fascinating material on the Mexican contribution in this field of human knowledge. The
chapter on Immunology wa s split into four subchapter s (antigens , humoral immune re-
sponses, cellular immune responses, and effector events). Likewise, the chapter devoted to
the clinical aspects of amebiasis was divided into two parts: one covering adults, the other
children.
To all collaborators I wish to express my gratitude for their enthusiastic response. Special
thanks should go to our colleagues in Israel and in the U.S., as they had to suffer th e
additional burden of slow communication with the editor, in a world where only bad news
appears to travel fast and cheap. The encouragement and seasoned advice received from Dr.
Ruy Pérez-Tamayo and Dr. Adolfo Martínez-Palomo is greatly appreciated. We all benefited
from the translating and editorial skills of our Editorial Secretary, Ms. Isabel Pérez-Montfort,
to whom our gratitude is hereby expressed.
Finally, the writing of this book was supported by a generous grant (PCSACNA-451740-
A) from the Mexican Council for Science and Technology (CONACYT). In doing so it
recognized both the paramount importance of this disease on a national scale and the con-
tributions made by Mexican scientist s to the understanding o f this cosmopolitan healt h
problem.
Roberto R. Kretschmer
Ciudad Universitaria
México, D.F.
1989
CONTRIBUTORS
Ingeborg Becker Armando Isibasi
Subdivisión de Medicina Experimental Head, Division of Immunochemistry
Facultad de Medicina Unidad de Investigación Biomédica
UNAM Instituto Mexicano del Seguro Social
México, D.F., México México, D.F., México
Bibiana Chavez
Roberto R. Kretschmer
Department of Experimental Pathology
Head, Division of Immunology
Centro de Investigación y Estudios
Unidad de Investigación Biomédica
Avanzados del IPN
Instituto Mexicano del Seguro Social
México, D.F., México
and Subdivisión de Medicina
Experimental
Ann Chayen
Facultad de Medicina
Department of Biophysics
UNAM
Weizmann Institute
México, D.F., México
Rehovot, Israel
Jesus Kumate
Louis S. Diamond
Secretary of Health
Head, Section of Parasite Growth &
Secretaría de Salud
Differentiation
México, D.F., México
Laboratory of Parasitic Diseases
NIAID
National Institutes of Health Martha López-Osuna
Bethesda, Maryland Division of Immunology
Unidad de Investigación Biomédica
Araceli Gonzalez Instituto Mexicano del Seguro Social
Departamento de Inmunología México, D.F., México
Instituto de Investigaciones Biomédicas
UNAM
México, D.F., México Adolfo Martinez-Palomo
Head, Department of Experimental
Arturo González-Robles Pathology
Department of Experimental Pathology Centro de Investigación y Estudios
Centro de Investigación y Estudios Avanzados del IPN
Avanzados del IPN México, D.F., México
México, D.F., México
Marco Antonio Meraz
Vicente Guarner
Department of Cellular Biology
Professor
Centro de Investigación y Estudios
Universidad Lasalle
Avanzados del IPN
Hospital Angeles del Pedregal
México, D.F., México
México, D.F., México
Gonzalo Gutierrez Isaura Meza
Director de Planeación, Head, Department of Cellular Biology
Información y Evaluación Centro de Investigación y Estudios
Secretaría de Salud Avanzados del IPN
México, D.F., México México, D.F., México
David Mirelman Ruy Pérez-Tamayo
Professor Head, Subdivisión de Medicina
Department of Biophysics Experimental
Weizmann Institute Facultad de Medicina
Rehovot, Israel UNAM
México, D.F., México
Irmgard Montfort
Blanca Ruiz
Subdivisión de Medicina Experimental
Research Associate
Facultad de Medicina
Departamento de Biologia Molecular
UNAM
Instituto de Investigaciones Biomédicas
México, D.F., México
Facultad d e Medicina
UNAM
Onofre Muñoz
México, D.F., México
Director
Hospital de Pediatría del Centro Médico
Norberto Treviño García-Manzo
Nacional, Instituto Mexicano dei
Director General de los Servicios
Seguro Social
Médicos del Departamento del Distrito
México, D.F., México
Federal, México
México, D.F., México
Ruy Pérez-Montfort
Senior Researcher Haydee K. Torres-Guerrero
Departamento de Microbiología Department of Cellular Biology
Instituto de Fisiología Celular Centro de Investigación y Estudios
UNAM Avanzados del IPN
México, D.F., México México, D.F., México
Librado Ortiz-Ortiz Kenneth S. Warren
Director, Instituto de Investigaciones Professor
Biomédicas Department of Medicine
Instituto de Investigaciones Biomédicas New York University School of
UNAM Medicine
México, D.F., México New York, New York
THE EDITOR
Roberto R. Kretschmer, M.D., is Professor of Immunology at the Faculty of Medicine,
Universidad Nacional Autónoma de México (UNAM), and head of the Division of Immu-
nology, Unidad de Investigación Biomédica, Instituto Mexicano del Seguro Social, Mexico
City/Division of Experimental Medicine, Faculty of Medicine (UNAM).
Dr. Kretschmer received his M.D. from the Faculty of Medicine, UNAM in 1963. He
pursued his training in Pediatrics and Immunology at the University of Tubingen, West
Germany and at Children's Hospital Medical Center, Harvard Medical School, Boston ,
Massachusetts (1963—1968). He became an Assistant Professor of Pediatrics at the Pritzker
School of Medicine, University of Chicago, and Director of Pediatric Immunology at Michael
Reese Hospital Medical Center, Chicago, IL (1974—1978), before returning to Mexico to
his present position. Dr. Kretschmer is a member of the American Association of Immu-
nologists, Infectious Diseases Society of America, Clinical Immunology Society, American
Academy of Pediatrics and American Academy of Allergy and Clinical Immunology, Society
of Pediatric Research, New York Academy cff Sciences, Sociedad Mexicana de Inmunología
(past president), Academia Nacional de Medicina (México) and Academia Nacional de la
Investigación Científica (México) among others.
He has received the "Gabino Barreda" award for distinguished studies (UNAM) (1963)
and the "Eduardo Liceaga" award for research (Academia Nacional de Medicina, México)
(1986).
Dr. Kretschmer has been the recipient of fellowships from the Mexican and West German
governments and from the Panamerican Organization of States, as well as research grants
from the National Council of Science and Technology (CONACYT, México). He has pub-
lished over 90 specialized papers and contributed to 18 books. His current research interests
are in immunology of amebiasis, chemotaxis, and the immunoinflammatory capacitie s of
the newborn.
REFERENCES
1. Brandt, H. and Pérez-Tamayo, R., Amibiasis, La Prensa Médica Mexicana, México, D.F., 1970.
2. Ravdin, J. I. and Guerrant, R. L., A review of the parasite cellular mechanisms involved in the path-
ogenesis of amebiasis, Rev. Infect. Dis., 4, 1185, 1982.
3. Gitler, C. and Mirelman, D., Factors contributing to the pathogenesis behaviour of Entamoeba histolytica,
Annu. Rev. Microbiol., 40, 237, 1986.
4. Martínez-Palomo, A., The Biology of Entamoeba histolytica, Research Studies Press, John Wiley & Sons,
Chichester, 1982.
5. Martínez-Palomo, A., Amebiasis. Human Parasitic Diseases Series, Vol. 2, Ruitenberg, F. J. and Maclnnis,
A. J., Eds., Elsevier, Amsterdam, 1986.
6. Ravdin, J. L, Amebiasis. Human Infection by Entamoeba histolytica, John Wiley & Sons, New York,
1988.
7. Warren, K. W., Foreword, in Amebiasis. Human Infection by Entamoeba histolytica, John Wiley & Sons,
New York, 1988.
8. Walsh, J. A. and Warren, K. W., Selective primary care. An interim strategy for disease control in
developing countries, N. Engl. J. Med., 301, 967, 1979.
9. Guerrant, R. L., The global problem of amebiasis: current status, research needs, and opportunities for
progress. Introduction, current status and research questions, Rev. Infect. Dis., 8, 218, 1986.
10. Gallo, R. C. and Montaigner, L., The AIDS epidemic, in The Science of Aids, Piel, J., Ed., W. H.
Freeman, New York, 1989, 1.
11. Petri, W. and Ravdin, J. I., Entamoeba histolytica, in Parasitic Infections in the Compromised Host,
Walzer, P. D. and Genta, R. M., Eds., Marcel Dekker, New York, 1989, 385.
12. Schultz, M. G., Current concepts in parasitology, N. Engl. J. Med., 297, 1259, 1977.
13. W.H.O. Expert Committee on Malaria: sixteenth report, W.H.O. Tech. Rep. Ser., 549, 1, 1974.
14. Carpizo, J., Del Médico. Homenaje a Bernardo Sepúlveda, Universidad Nacional Autónoma de México,
México, D.F., 1987.
