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Emerging Infectious Diseases
Volume 2, Number 2, April-June 1996
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Letters
Transfusion-Associated Malaria
To the Editor: A recent article by Zucker (1) described two cases of
malaria that were probably transfusion associated. A case of
transfusion-associated malaria in which the source was identified was
reported in San Francisco in 1991. The case was in an elderly man in whom
malaria infection developed after coronary bypass surgery.
The patient was born in China and immigrated to the United States in 1940.
His only travel outside the United States was a trip to Hong Kong in 1951
for 6 months. The patient’s wife was born in China and had malaria in 1941
during World War II. She received no treatment at that time or at any other
time. She came to the United States in 1960 and has not left the country
since.
The patient had six donors, five of whom had no history of malaria, and had
negative serologic test results for all four malaria species. Both the
patient and his wife had blood smears positive for P. malariae. The
patient’s wife had positive serologic test results for P. vivax and P.
ovale (1:64), for P. falciparum (1:258), and for P. malariae (1:1024).
Frances Taylor, M.D., M.P.H.
Director of Communicable Disease Control
City and County of San Francisco
Department of Public Health
Bureau of Epidemiology
Disease Control, and AIDS
San Francisco, California, USA
Reference
1. Zucker J. Changing patterns of autochthonous malaria transmission in the
United States: A review of current outbreaks. Emerging Infectious Diseases
1996: 2:37-43.
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Letters
Reply to F. Taylor:
Dr. Taylor’s letter calls attention to the small but important number of
induced malaria cases that occur in the United States. From 1957 to 1994,
101 such cases were reported to the Centers for Disease Control and
Prevention (CDC); these (including the 1990 case described by Dr. Taylor
[1]) are reviewed annually and reported by CDC (2). The occasional
occurrence of induced malaria further emphasizes the importance of
including malaria in the differential diagnosis of fevers of unknown
origin, even in patients who have not traveled to countries where malaria
is endemic. Preventing induced malaria requires screening potential blood,
tissue, and organ donors and deferring those with a history of malaria or
travel to malarious areas. Furthermore, timely surveillance must be
maintained to detect induced cases promptly, identify infected blood
donors, and prevent additional cases.
The case described by Dr. Taylor was not included in “Changing patterns of
autochthonous malaria transmission in the United States: a review of recent
outbreaks” (3) because it was a case of induced rather than autochthonous
malaria. Each reported malaria case is classified according to standardized
terminology (4). Imported malaria (which accounts for most cases in this
country) is acquired outside the United States and its territories. Malaria
acquired within the United States is rare and occurs by one of three
mechanisms: Autochthonous malaria is acquired through the bite of an
infective mosquito. Congenital malaria is acquired when a child is infected
in utero. Induced malaria is transmitted by mechanical means such as
transfusion of blood or blood products, organ transplant, deliberate
infection for malariotherapy, or contaminated needles or injection
equipment. Congenital and induced cases were not included in this review.
When an investigation fails to identify the source of transmission and a
case cannot be epidemiologically linked to another case of malaria, the
case is classified as cryptic. Most cryptic cases are believed to be
autochthonous, and there is often evidence to suggest mosquito-borne
transmission, even when the source of infection remains unidentified. For
this reason, most cryptic cases were included in this review of
autochthonous malaria. The two exceptions noted in the article were
excluded because both patients had recent histories of blood transfusion,
suggesting that their infections were induced.
Jane R. Zucker, M.D., M.Sc., and S. Patrick Kachur, M.D., M.P.H.
Centers for Disease Control and Prevention, Atlanta, Georgia, USA
References
1. Zucker JR, Barber AM, Paxton LA, Schultz LJ, Lobel HO, Roberts JM, et
al. Malaria Surveillance—United States, 1992. In: CDC Surveillance
Summaries, October 20, 1995. MMWR 1995:44(SS-5):1-17.
2. Centers for Disease Control. Malaria Surveillance Annual Summary, 1990.
Atlanta: Centers for Disease Control, 1991.
3. Zucker JR. Changing patterns of autochthonous malaria transmission in
the United States: a review of recent outbreaks. Emerging Infectious
Diseases 1996;2:37-43.
4. World Health Organization. Terminology of malaria and malaria
eradication. Geneva: World Health Organization, 1963:32.
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Letters
An Outbreak of Hemolytic Uremic Syndrome due to Escherichia coli O157:H-:
Or Was It?
To the Editor: Since the first reported outbreaks of hemolytic uremic
syndrome (HUS) and related conditions more than 10 years ago (1), outbreaks
of HUS due to Escherichia coli O157 have been reported from many parts of
the world, particularly North America and Europe. While most of these
reports have incriminated the motile strains of serotype O157:H7, nonmotile
serotypes (e.g., O157:H-) have also been associated with HUS; these two
serotypes are most commonly associated with both outbreaks and sporadic
cases of HUS and related conditions. Over the last decade, a number of
techniques for the rapid identification of these organisms have been
developed. Of these, the use of sorbitol-MacConkey agar (2) has perhaps
been the most valuable. This technique is based on the fact that these
organisms rarely ferment sorbitol on primary isolation, while most other E.
coli usually ferment this substrate. We believe that outbreaks due to other
enterohemorrhagic E. coli may have been attributed to serogroup O157
because of the limited technology used in investigating these outbreaks.
No outbreaks of HUS due to serogroup O157 have occurred in Australia
despite sporadic cases of HUS caused by such strains. Other serogroups
(particularly serotype O111:H-) have been associated with most cases of HUS
and related conditions in Australia (3). No outbreak of HUS had been
reported in Australia until January 1995, when an outbreak associated with
the consumption of contaminated mettwurst (fermented sausage) was reported
from South Australia (4). Twenty-three children with HUS were hospitalized.
Most required hemodialysis; one died. Verocytotoxigenic strains of E. coli
O111 producing Shiga-like toxin (SLT) I and II were isolated from 19
patients and from samples of mettwurst. In addition, strains of E. coli
O157:H- that produced SLT-I and SLT-II were isolated from three of the
patients and the mettwurst. These strains did not ferment sorbitol on the
sorbitol-MacConkey agar, which facilitated their isolation. The predominant
O111 strains were sorbitol-positive, unlike the O111 strains, recently
described as being sorbitol-negative (5). Symptoms of the patients from
whom theO157:H- strains were isolated, in addition to E. coli O111:H-, were
not significantly different from those of the patients whose specimens
yielded only E. coli O111:H-. In addition to O111 (and O157), other
serotypes of enterohemorrhagic E. coli, including strains of serogroup O23,
O26, and O91, were isolated from the patients. However, antibodies to O111
were detected in nearly all patients, which indicates the serogroup’s
leading role in the outbreak. The isolation of serogroup O157 is
comparatively easy; therefore, it is less likely that these strains would
have been missed, than it is that O111 and other serotypes would have been.
Even though a negative finding can never be considered conclusive, we
consider the inability to isolate serogroup O157 more conclusive than the
same result for other serotypes. It has frequently been suggested that the
O157 serogroup is cleared from the patient relatively rapidly, which makes
its isolation difficult or impossible. We found a similar situation with
other enterohemorrhagic E. coli serotypes. The fact that most patients
elicited an O111 antibody response (and no anti-O157) almost certainly
proves this serotype’s causal role in this outbreak.
The laboratory in South Australia was particularly well disposed to deal
with such an outbreak because some of its ongoing research programs
included studies on aspects of enterohemorrhagic E. coli and related
organisms. The most sophisticated molecular biologic techniques were
immediately available to investigate the outbreak accurately and confirm
epidemiologic leads regarding a common source. Polymerase chain reaction
(PCR) played a major role not only in identifying SLT-I, SLT-II, and SLT-I
and SLT-II producing bacteria in the stool of patients, but also in
identifying the suspected source (mettwurst). In addition, PCR, utilizing
sequences specific for the O111 serogroup, enabled this serogroup to be
rapidly identified in patients’ feces samples and suspected source
material. Without this technology, the outbreak would not have been
contained so rapidly. On the other hand, if the laboratory had to rely on
conventional microbiologic culture procedures, including sorbitol-MacConkey
agar, strains of serogroup O157 would have been identified from three
patients, as well as from the epidemiologically incriminated mettwurst. The
laboratory would not have found the O111 strains because they all fermented
sorbitol readily and would have been discarded as normal flora as would the
other enterohemorrhagic E. coli serotypes. The outbreak would have been
reported as another O157 outbreak, from which only about 15% of the
patients yielded the incriminating strains. This outbreak could be
recognized as one caused by a number of different enterohemorrhagic E. coli
serotypes, of which serotypes O111:H- and O157:H- were the most prominent.
Other serotypes, however, such as O23, O26, and O91, were also present.
With the widespread nature of verocytotoxigenic strain of different
serotypes as has been reported from many environmental studies, it is not
surprising that a product, such as mettwurst, which is made from meats from
various sources, would contain a number of these potential pathogens.
A large number of E. coli serotypes can be verocytotoxigenic and, in a few
cases, outbreaks due to such strains have been reported. Most notable have
been reports from Italy of outbreaks due to enterohemorrhagic E. coli O111
(6); however, the impression is that these are the exception and that the
most prominent serotype is O157:H7. Some of the reported outbreaks due to
O157 strains may in fact have been due to other serotypes and the O157
strains were only present in comparatively small numbers; however, because
of the ease with which these strains can be identified using
sorbitol-MacConkey agar, they were believed responsible for the outbreaks.
For example, in Argentina, E. coli O157:H7 was found in only one (2%) of 51
children with HUS (7) and in the Netherlands, only 5 (19%) of 26 HUS
patients yielded E. coli O157:H7 (8). In a 10-year, retrospective,
population-based study of HUS, this serotype was isolated in 13 (46%) of 28
patients (9), and in their review, Su and Brandt (10) put an overall figure
of 46% to58% as the incidence range of E. coli O157:H7 infection in cases
of HUS. Finding SLT sequences in a fecal specimen by PCR, or free fecal
toxins in many patients of an outbreak while isolating strains of O157 from
only a few, does not exclude the presence of other serotypes, but culture
methods now available would rarely pick these up. Thus there is ample room
to speculate that approximately half the cases of HUS may be caused by
serogroups other than O157 and, by inference, at least half the outbreaks
may be wrongly attributed to this serogroup. We recognize that
enterohemorrhagic E. coli O157 have become extraordinarily widespread
throughout the world since their first description (1); this does not mean
that other serotypes are not also causing infections, either alone, in
conjunction with O157, or even with other known or unknown enteric
infections. It is important to be aware of the existence of these other
serotypes and be vigilant for them. The isolation and characterization of
strains of serogroup O157 from patients with HUS is certainly noteworthy,
but so is the finding of O111 or any other serogroup. Serogroup O111 has
amply demonstrated the ability to cause extensive outbreaks (6). Even
though many laboratories are becoming aware of the importance of testing
for serogroup O157:H7, we think that testing for this serotype only is a
disservice; simple culture techniques can identify this serogroup, but
always at the risk of missing other serogroups. The development of simple
methods to detect all enterohemorrhagic E. coli is now required.
P.N. Goldwater, F.R.A.C.P., F.R.C.P.A.,* and K.A. Bettelheim, Ph.D.†
*Women’s and Children’s Hospital, Adelaide, South Australia; †Biomedical
Reference Laboratory, Victorian Infectious Diseases Reference Laboratory,
Fairfield Hospital, Victoria, Australia
References
1. Riley LW, Remis RS, Helgerson SD, McGee HB, et al. Hemorrhagic colitis
associated with a rare Escherichia coli serotype. N Engl J Med
1983;308:681-5.
2. March SB, Ratnam S. Sorbitol-MacConkey medium for detection of
Escherichia coli O157.H7 associated with hemorrhagic colitis. J Clin
Microbiol 1986;23:869-72.
3. Goldwater PN, Bettelheim KA. The role of enterohemorrhagic Escherichia
coli serotypes other than O157:H7 as causes of disease. Communicable
Disease Intelligence 1995;19:2-4.
4. Cameron S, Walker C, Beers M, Rose N, and Anear E, et al.
Enterohemorrhagic Escherichia coli outbreak in South Australia
associated with consumption of mettwurst. Communicable Disease
Intelligence 1995;19:70-1.
5. Ojeda A, Prado, V, Martinez, J, et al. Sorbitol-negative phenotype
among enterohemorrhagic Escherichia coli strains of different
serotypes and from different sources. J Clin Microbiol
1995;33:2199-201.
6. Caprioli A, Luzzi I, Rosmini F, Resti C, et al. Communitywide outbreak
of hemolytic-uremic syndrome associated with non-O157
verocytotoxin-producing Escherichia coli. J Infect Dis
1994;169:208-11.
7. Lopez EL, Diaz M, Grinstein S, Devoto S, et al. Hemolytic uremic
syndrome and diarrhea in Argentine children: the role of Shiga-like
toxins. J Infect Dis 1989;160:469-75.
8. van der Kar NCAJ, Roelofs HGR, Muytjens HL, et al.
Verocytotoxin-producing Escherichia coli infection in patients with
hemolytic uremic syndrome and their family members in the Netherlands.
In: Kaarmali MA, Goglio AG, editors. Recent advances in
verocytotoxinproducing Escherichia coli infections. Amsterdam:
Elsevier, 1994.
9. Martin DL, MacDonald KL, White KE, Soler JT, Osterholm MT. The
epidemiology and clinical aspects of the hemolytic uremic syndrome in
Minnesota. N Engl J Med 1990;323:1161-7.
10. 10. Su C, Brandt LJ. Escherichia coli O157:H7 infections in humans.
Ann Intern Med 1995;123:698-714.
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Letters
The Dilemma of Xenotransplantation
To the Editor:
I read with considerable interest Robert E. Michler’s commentary on
xenotransplantation (1).
From my point of view, that of a basic virologist, the dilemma is not to
know in what “foreseeable future, clinical xenotransplantation may achieve
its targeted goal of extended graft survival, but what deadly emerging
infectious disease, most probably viral in nature, would arise in a
recipient of a baboon or chimpanzee heart. While we face the terrific
threat of AIDS, which clearly emerged from Africa and non-human primates 40
to 50 years ago, we are preparing a new infectious Chernobyl.
Monkeys and apes harbor approximately 50 simian viruses; some of them pose
a serious threat to humans, especially the heavily immunosuppressed.
Recently, an outbreak of encephalitis related to a new type of reovirus (2)
occurred among baboons from a colony used in human organ transplants.
Moreover, once unknown or unrecognized simian viruses, like HIV, may be
efficient invaders of the entire earth’s population.
Xenotransplantation does not simply pose an ethical problem; it concerns
the survival of the human species, an endangered species if transplant
practitioners continue their course. Ronald Montalero, a virologist, was
right when he said “unknown viruses were always a major concern in
xenotransplants (2). A moratorium on these procedures seems the best
solution until all simian pathogens are identified and the risks they pose
to humans are clearly established.
Claude E. Chastel
Virus Laboratory, Faculty of Medicine
29285 Brest Cedex, France
References
1. Michler RE. Xenotransplantation: risks, clinical potential, and future
prospects. Emerging Infectious Diseases 1996; 2; 64-70.
2. Mystery virus fells donor baboons. Science 1994; 264; 1523.
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Letters
The Thucydides Syndrome: Ebola Déjà Vu? (or Ebola Reemergent?)
To the Editor:
The plague of Athens (430-427/425 B.C.) persists as one of the great
medical mysteries of antiquity (1-5). Sometimes termed “the Thucydides
syndrome” for the evocative narrative provided by that contemporary
observer (6, 7), the plague of Athens has been the subject of conjecture
for centuries. In an unprecedented, devastating 3-year appearance, the
disease marked the end of the Age of Pericles in Athens and, as much as the
war with Sparta, it may have hastened the end of the Golden Age of Greece
(3). Understood by Thucydides to have its origin “in Ethiopia beyond Egypt,
it next descended into Egypt and Libya” and then “suddenly fell upon”
Athens’ walled port Piraeus and then the city itself; there it ravaged the
densely packed wartime populace of citizens, allies, and refugees.
Thucydides, himself a surviving victim, notes that the year had been
“especially free of disease” and describes the following major findings:
After its “abrupt onset, persons in good health were seized first with
strong fevers, redness and burning of the eyes, and the inside of the
mouth, both the throat and tongue, immediatelywas bloody-looking and
expelled an unusually foul breath. Following these came sneezing,
hoarseness . . . a powerful cough . . . and every kind of bilious vomiting
. . . and in most cases an empty heaving ensued that produced a strong
spasm that ended quickly or lasted quite a while.” The flesh, although
neither especially hot nor pale, was “reddish, livid, and budding out in
small blisters and ulcers.” Subject to unquenchable thirst, victims
suffered such high temperatures as to reject even the lightest coverings.
Most perished “on the ninth or seventh day . . . with some strength still
left or many later died of weakness once the sickness passed down into the
bowels, where the ulceration became violent and extreme diarrhea
simultaneously laid hold (2.49).” Those who survived became immune, but
those who vainly attended or even visited the sick fell victim (2.51).
By comparison, a modern case definition of Ebola virus infection notes
sudden onset, fever, headache, and pharyngitis, followed by cough,
vomiting, diarrhea, maculopapular rash, and hemorrhagic diathesis, with a
case-fatality rate of 50% to 90%, death typically occurring in the second
week of the disease. Disease among health-care providers and care givers
has been a prominent feature (8, 9). In a review of the 1995 Ebola outbreak
in Zaire, the Centers for Disease Control and Prevention reports that the
most frequent initial symptoms were fever (94%), diarrhea (80%), and severe
weakness (74%), with dysphagia and clinical signs of bleeding also
frequently present. Symptomatic hiccups was also reported in 15% of
patients (10).
During the plague of Athens, Thucydides may have made the same unusual
clinical observation. The phrase lugx kene, which we have translated as
“empty heaving,” lacks an exact parallel in the ancient Greek corpus (5).
Alone, lugx, means either “hiccups” or “retching” and is infrequently used,
even by the medical writers. Although contexts usually dictate “retching,”
we note unambiguous “hiccups” in Plato’s Symposium (185C). In his thorough
commentary on the Thucydides passage, the classicist D. L. Page remarks:
“Hiccoughs is misleading, unless it is enlarged to include retching.”
Regarding “empty, unproductive retching [he] has noted no exact parallel
. . . in the [writings of the] doctors, but . . . tenesmus comes very close
to it” (5). A CD-ROM search of Mandell, Bennett, and Dolin discloses no
reference to either “hiccups” or “singultus” in the description of any
disease entity (6).
The profile of the ancient disease is remarkably similar to that of the
recent outbreaks in Sudan and Zaire and offers another solution to
Thucydides’ ancient puzzle. A Nilotic source for a pathogen in the Piraeus,
the busy maritime hub of the Delian League (Athens’ de facto Aegean
empire), is clearly plausible. PCR examination of contemporaneous skeletal
and archaeozoological remains might test this hypothesis against the 29 or
more prior theories.
*P. E. Olson, M.D., *C. S. Hames, M.D., †A. S. Benenson, M.D., and †E. N.
Genovese, Ph.D.
U. S. Navy Balboa Hospital, San Diego, California, USA; †San Diego State
University, San Diego, California, USA
References
1. Langmuir AD, Worthen TD, Solomon J, Ray CG, Petersen E. The Thucydides
syndrome: a new hypothesis for the cause of the plague of Athens. N
Engl J Med 1985;313:1027-30.
2. Morens DM, Littman RJ. Epidemiology of the plague of Athens. Trans Am
Philological Assn 1972;122:271-304.
3. Morens DM, Littman RJ. The Thucydides syndrome reconsidered: new
thoughts on the plague of Athens. Am J Epidemiol 1994;140:621-7.
4. Grmek MD. History of AIDS: emergence and origin of a modern
pandemic.Princeton, NJ: Princeton University Press, 1990.
5. Page DL. Thucydides’ description of the great plague. Classical Quart
1953;47 n.s. 3:97-119.
6. Thucydides. Peloponnesian War. Bk. 2, chs. 47-52.
7. Major RH. Classical descriptions of disease. 3rd ed. Springfield, IL:
Charles C Thomas, 1945.
8. Benenson AS, editor. Control of communicable diseases manual. 16th ed.
Washington, DC: American Public Health Association, 1995.
9. Mandell GL, Bennett JE, Dolin R. Mandell, Douglas and Bennett’s
principles and practice of infectious diseases. 4th ed. New York:
Churchill Livingston, 1995.
10. Centers for Disease Control and Prevention. MMWR 1995;44:25:468-75.