False-positive Monospot Tests
in Malaria
R O B E R T E. R E E D ,
M.D.
Department of Internal Medicine, Ann Arbor Veterans Administration
Hospital, and University of Michigan Medical School (Simpson
Memorial Institute), Ann Arbor, Michigan
ABSTRACT
Reed, Robert E.: False-positive monospot tests in malaria. Am. J. Clin. Pathol.
61: 173-175, 1974. Two of fourteen consecutive patients with malaria had
positive Monospot tests. Neither had a history of other recent febrile illness,
and tests for heterophil and Epstein-Barr virus antibodies were negative.
Another instance of a positive Monospot test in a patient with malaria in which
the positive Monospot test contributed to a delay in the diagnosis of malaria has
been reported. Because infectious mononucleosis and malaria can initially
cause similar signs and symptoms, physicians should be aware of this possibility
to avoid such delays in diagnosis and institution of proper treatment. (Key
words: Monospot test; Malaria; Infectious mononucleosis.)
WHILE MALARIA and infectious mononucleosis can both manifest as febrile illnesses
with splenomegaly, there are sufficient distinguishing characteristics so that usually
the differential diagnosis between the two
should not be difficult. Pharyngitis,
a d e n o p a t h y , m o r e than 20% atypical
lymphocytes in the blood, and a positive
serologic test for heterophil antibodies are
all hallmarks of infectious mononucleosis,
while the identification of Plasmodium organisms in the blood smear confirms the
diagnosis of malaria. However, recent experience indicates that these conditions
may be confused during the first few days
of illness. Many patients with infectious
mononucleosis do not have pharyngitis,
and the adenopathy and increase in atypical
Received April 9, 1973; received revised manuscript
August 8, 1973; accepted for publication August 24,
1973.
Address reprint requests to: Dr. Robert E. Reed,
Ann Arbor Veterans Administration Hospital, 2215
Fuller Road, Ann Arbor, Michigan 48105.
173
lymphocytes in the blood may not appear
for several days to a week after the onset of
symptoms. Likewise, the level of parasitemia can be low in early cases of malaria,
and organisms may not be found unless
suspicion is high and thick blood films
are carefully examined. I, and others, 3
have found atypical lymphocytes in the
blood films of patients with malaria and,
while in my cases they have amounted to
less than 10% of total leukocytes, a laboratory report indicating some atypical lymphocytes may be confusing.
Because the presenting picture of infectious mononucleosis can be so nonspecific,
clinicians have used, and in many cases
over-relied on, serologic tests to confirm the
diagnosis. Recently, the Monospot test 1,5,9
has replaced the Paul-Bunnell test as a
more efficient and equally sensitive
serologic test for infectious mononucleosis.
The presence of false-positive Monospot
tests in cases of malaria, therefore, could
cause diagnostic confusion.
174
REED
AJ.C.P.—Vol.
61
Report of Cases
Comment
A 21-year-old Caucasian man, recently
returned from service in South Viet Nam,
was seen because of fever, chills, and
malaise. There was no past history of infectious mononucleosis or other significant illness, but he did admit that he had not taken
the recommended course of weekly chloroquine and primaquine after returning to
the United States. Physical examination
showed no pharyngitis or adenopathy. The
spleen tip was palpable with deep inspiration. A Monospot test was ordered as part
of the evaluation of a young adult with a
febrile illness; however, blood smears were
also obtained a n d Plasmodium
vivax
organisms were seen. The patient's condition responded promptly to chloroquine
and primaquine. The laboratory reported a
positive M o n o s p o t test, which was
confirmed on repeat testing. The patient
was asymptomatic when seen two months
later, and blood smear, Monospot test, and
Epstein-Barr virus titer were negative.
After this experience, a Monospot test was
performed in every case of malaria, and
one positive test was found in the next 13
cases. This patient also had Plasmodium
vivax malaria, denied previous infectious
mononucleosis, and had no evidence of
adenopathy, pharyngitis, or splenomegaly.
He responded promptly to treatment but
did not return for a scheduled follow-up
visit.
While the "false-positive" Monospot tests
of these patients did not cause diagnostic
confusion, a case where this did occur has
recently been reported. 6 A 13-year-old boy
was d i a g n o s e d as having infectious
mononucleosis on the basis of the clinical
picture and a positive Monospot test. A few
days later his mother was found to have
malaria and, on re-evaluation, the boy's
blood smear also showed P. falciparum
organisms. Both patients responded to appropriate therapy. Epstein-Barr virus titers
were not mentioned in this report.
T h e Monospot test appears to be a very
sensitive test for the antibody typically present in cases of infectious mononucleosis;
however, several instances of false-positive
reactions have been reported. 7 - 1 0 Some of
these patients had low Epstein-Barr virus
antibody titers, and the Monospot test
therefore could have been an indication of
recent or concurrent infectious mononucleosis. In most of these reports, EpsteinBarr virus titers were not determined. In
the cases reported here, the negative histories, the absence of physical or blood
findings of infectious mononucleosis, and
the negative Epstein-Barr virus antibody
titers rule out, as nearly as possible, previous unrecognized or c o n c u r r e n t infectious mononucleosis as the cause of
these positive tests.
Finch has stated regarding infectious
Both patients had normal leukocyte
mononucleosis:
"The diagnosis is often
counts a n d differentials, but reactive
made
on
clinical
grounds
alone, sometimes
lymphocytes were noted by technicians
solely
on
the
basis
of
a
few
atypical lymphodoing the differentials. Some of these cells
cytes
and
sometimes
on
the
basis of only a
were plasmacytoid, while others were
moderately
elevated,
and
unabsorbed,
titer
"virocyte" in type with abundant clear cyto2
of
heterophil
agglutinins."
He
was
referplasm, immature nuclei, and easily indented margins. All 14 patients had nega- ring to the diagnosis of mononucleosis in
tive heterophil agglutination studies 11 and publications on that disease, and the criteria
in day-to-day practice are frequently no
Epstein-Barr virus titers. 4 *
more stringent.
* T h e heterophil and Epstein-Barr virus antibody
studies were performed in the laboratory of Lybucia
Dabich, M.D., Simpson Memorial Institute, University
of Michigan Medical Center.
Unless the possibility of malaria is
realized and organisms searched for diligently, a nonspecific clinical picture, a few
February 1974
FALSE-POSITIVE MONOSPOT TEST
atypical lymphocytes, a n d a positive
Monospot test can lead to a misdiagnosis of
infectious mononucleosis and potentially
dangerous delays in treatment of Plasmodium infections.
References
5.
6.
7.
8.
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Oxford and Edinburgh, Blackwell Scientific
Publications, 1969, pp 19-46
3. Hoaglund RJ: Infectious Mononucleosis. New
York, Grune and Stratton, 1967, p 113
4. Henle G, Henle W: Immunofluorescence in cells
9.
10.
11.
175
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