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Diseases and pathology of chimpanzees at the southwest foundation for biomedical research.

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American Journal of Primatology 24:273-282 (1991)
Diseases and Pathology of Chimpanzees at the
Southwest Foundation for Biomedical Research
'Department of Laboratory Animal Medicine and 'Department of Virology and Immunology,
Southwest Foundatzon for Biomedical Research, Sun Antonio, Texas
The Southwest Foundation for Biomedical Research (SFBR) chimpanzee
colony is a conventionally housed production and research population. The
present population is 203 chimpanzees, consisting of 87 males and 116
females. Fifty-four apes were born between 1985 and 1989, 56 from 1980
to 1985,49 from 1975 to 1980,24 from 1965 to 1975, and 20 from 1954 to
1965. Twenty-five apes were added t o the colony from outside sources over
the last 10 years. The average yearly mortality for the past 8 years was
2.4%. The primary causes of death since 1982 were heart disease (6),
trauma (5), and respiratory disease (4). The heart lesions included myocarditis, necrosis, fibrosis, and mineralization. The respiratory disease
deaths were due to Streptococcus pneumoniae and Klebsiella pneumoniae.
The traumatic deaths were primarily in young chimpanzees and were
caused by adults. Since 1976,20 stillbirths occurred and were not included
in the total deaths. There were two cases of placenta previa and one of
abruptio placentae. Clinical conditions not leading to death included respiratory disease, parasitism, alopecia, diarrhea, maternal rejection, and
trauma. The most significant commonly isolated bacteria were Staphylococcus, Streptococcus, Haemophilus, Klebsiella, Citrobacter, and Campylobacter. The most common intestinal parasites were Balantidium, Entamoeba, Chilomastix, Iodamoeba, Giardia, Trichuris, Enterobius, and
Strongyloides. The colony pathology is sketchy from 1967 to 1981, but the
main causes of death during this period were probably pneumonia and
intestinal disease.
Key words: Pan troglodytes, pneumonia, leprosy
The disease problems in the Southwest Foundation for Biomedical Research
(SFBR) chimpanzee colony since its establishment in 1967 have been reviewed and
compared with those reported in other facilities [Bourne & Sandler, 1973; McClure
& Guilloud, 1971; Schmidt, 19781. The information concerning disease in chimpanzees in these references is very similar to the disease experience in the SFBR
Received for publication August 7, 1989; revision accepted September 26, 1990.
Address reprint requests to Gene B. Hubbard, Department of Laboratory Animal Medicine, P.O. Box
28147, Southwest Foundation for Biomedical Research, San Antonio, Texas 78228-0147.
0 1991 Wiley-Liss, Inc.
274 I Hubbard et al.
TABLE I. Chimpanzee Mortality-SFBR
8 year average
a t 6 months
colony and indicates there has been little change in chimpanzee disease in the past
20 years. This paper summarizes the most significant disease entities, pathology,
and clinical experience at the SFBR since 1967 so that those reading the paper can
use the information to better recognize, compare, and manage disease in chimpanzees.
A total of 181 retired chimpanzee records were evaluated for this paper. The
records document all chimpanzee deaths from the establishment of the colony in
1967 through 1989. Prior to 1982 the records were often incomplete or sketchy and
were not easily evaluated other than for major disease diagnoses and possibly
cause of death. Computer records were not maintained until 1979 and computer
pathology files were not established until 1987. Therefore the information presented here is a n overview of what appear to be the most important disease problems based on available information rather than a detailed evaluation of the total
disease occurrence in the colony. In 1970 a viral isolation survey was done in the
colony and no additional surveys have been done. Since 1982, clinical pathology,
microbacteriology, and parasitology examinations have been routinely performed
annually or more frequently on all colony chimpanzees. Complete necropsies were
done on all chimpanzees that died, the tissues preserved in 10% neutral buffered
formalin, embedded in paraffin, cut a t 5 p.m, and stained with hematoxylin and
eosin. Special stains and electron microscopy were done as needed.
Table I illustrates the chimpanzee inventory and percent mortality since 1981.
The main categories of causes of death in order of importance at the SFBR from
1967 to 1979 were respiratory, gastrointestinal, cardiovascular, central nervous
system, trauma, and reproductive. The main categories of causes of death in order
of importance from 1982 to 1989 were cardiovascular, trauma, respiratory, and
Twenty documented stillbirths have occurred since 1979. The primary criteria
to diagnose a stillbirth were failure of the lungs to float in formalin and a fetus
that was 7 months of age or older. There were 126 livebirths during this period.
Premature births were the most common occurrence, with 1 deformed fetus and 4
first pregnancy stillbirths. One set of twins were stillbirths. There were 2 cases of
placenta previa and 1 of abruptio placentae.
Diseases and Pathology of Chimpanzees 1 275
Six colony chimpanzees that died because of myocardial disease had similar
histologic lesions, including lymphocytic myocarditis, myocardial fibrosis, mineralization, and necrosis (Figs. 1, 2, 3). No etiologic agent was isolated from
any of the chimpanzees. Arteriosclerosis was not a prominent lesion in these
Respiratory disease was the third most important cause of death after cardiovascular and chimpanzee-induced trauma. Streptococcus pneumoniae and Klebsiella pneumoniae infections caused both morbidity and mortality in the colony.
Streptococcal disease occurred most frequently in chimpanzees less than 5 years of
age, but did occur in adults. Clinical signs included coughing, clear nasal discharge
that became purulent in 24-48 hours, and central nervous system signs. Pathology
included bronchopneumonia, pleuritis, lymphadenitis, tonsillitis, and splenitis
(Figs. 4, 5). Klebsiella pneumonia infection was similar to streptococcal pneumonia, with infection of the young, and primarily elicited respiratory symptoms and
lesions [Eichberg, 19851.
The significant microorganisms routinely identified from colony chimpanzees
included Campylobacter fetus, Streptococcus species, Klebsiella pneumoniae, Hemophilus parainfluenzae, Staphylococcus species, Citrobacter freundii, Candida
albicans, Acinetobacter species, Enterobacter species, and, recently, Mycobacterium
leprae .
The case of leprosy occurred in a 28-year-old male. The ape had multiple red,
typically nodular, often eroded, skin lesions (Fig. 6). Histopathology of skin biopsies showed epidermal thinning and subepidermal clear-zones (Fig. 7). Dermal
inflammatory cells consisted of macrophages, lymphocytes, plasma cells, and occasional neutrophils. The inflammatory cells localized around neurovascular bundles in the deep dermis with perineural thickening and nerve hypercellularity
(Fig. 8). Acid fast stains of skin and liver biopsies showed intracellular bacilli in
histiocytes, nerves, walls of blood vessels, and hepatic cells. The Ridley-Jopling
classification was subpolar to borderline-lepromatous (LL,-BL) diseases [Ridley &
Jopling, 19661. Other confirmatory tests included negative cultures for acid fast
bacilli, negative old tuberculin skin test, negative chest radiographs, positive antibody titers for IgG and IgM anti-LAM a common mycobacterial antigen, and IgG
and IgM anti-PGL-I which is specific for M. Zeprae [Gormus et al., 1988; Leininger
et al., 19781.
Baseline virology indicates that the enteroviruses are the most prevalent followed by adenoviruses and unclassified viruses.
Intestinal protozoa routinely identified in fecal exams included: Balantidium
coli, Entamoeba histolytica, Trichornonas species, Giardia species, Entamoeba
polecki, Entarnoeba coli, Chilornastix species, and Iodamoeba butschlii.
Intestinal nematodes identified included Enterobius uermicularis, Trichuris
species, and Strongyloides species. These have not caused significant clinical
problems, although a jejunal Enterobius vermicularis induced granuloma was
surgically removed from a n ape because of nonspecific enteric problems (Figs.
9, 10).
Alopecia totalis was reported in a female chipanzee. The chimpanzee lost all
body hair, and histology revealed a basketweave stratum corneum, reduced granular cell layer, and minimal epidermal acanthosis.
A 15-year-old female chimpanzee developed nasal polyposis when she was 10
years old. The polyps severely compromised respiration.
Miscellaneous significant pathologic lesions encountered in the colony included meningitis, encephalitis, choroiditis, nephrosis, glomerulonephritis, splenitis, tonsillitis, and vasculitis.
276 I Hubbard et al.
Fig. 1. Photograph illustrating the irregular pitted myocardial surface associated with heart disease in a
Fig. 2. Photograph of chimpanzee myocardium illustrating the myodegeneration, fibrosis (F), mineralization
(arrows), and inflammatory (I) response causing the gross changes seen in Figure 1. H&E ~ 2 0 0 .
Fig. 3. Photograph illustrating the perivascular lymphocytic myocarditis (L) typical of heart disease in the
chimpanzee hearts. H&E x 200.
Diseases a n d Pathology of Chimpanzees / 277
Fig. 4. Photograph illustrating typical Streptococcus pneumoniae induced pneumonia with congestion (C) and
suppuration (arrows).
Fig. 5. Photograph illustrating the severe necrosis, suppurative inflammatory (I)response, and obstruction of
major and minor airways (A) in a lung infected by Streptococcus pneumoniae. H&E x 200.
The colony chimpanzee mortality has stabilized to approximately 2%, which
seems satisfactory for a production research colony. The low mortality probably
reflects the fact that the colony is well managed. The diseases and pathology
278 I Hubbard et al.
Fig. 6 . Photograph illustrating leprosy in a chimpanzee with variably sized cutaneous nodules of the face and
ears (arrows).
documented for the colony are not significantly different from the experience of
other properly managed chimpanzee colonies. Prior to 1982, the individual records
were inadequate and not all apes were necropsied. However, these data reflect the
period during which the colony was founded, when the population was young and
constantly changing. From 1982 to the present, all chimpanzees that died were
necropsied and clinical records maintained. The primary cause of death was cardiovascular disease, which has been reported by others [Schmidt, 19781. The cause
of the cardiovascular disease has not been determined, but diet, environmental
stress, high blood pressure [Eichberg & Shade, 19871, and microbial agents must
all be considered a s etiologic factors. Vegetarian and low sodium diet trials are
currently underway to study the effects of these dietary alterations on cardiovascular disease.
Only 4 of the stillbirths were associated with first pregnancies. This was contrary to common opinion that more stillbirths occur in primiparous females.
Respiratory disease probably represents the greatest threat to any chimpanzee
colony [Schmidt, 1978; Schmidt & Butler, 1971; Solleveld et al., 19841. Upper
respiratory disease of viral etiology probably predisposes chimpanzees to bacterial
Diseases and Pathology of Chimpanzees / 279
Fig. 7. Photograph illustrating the histology of a cutaneous nodule from the chin of the chimpanzee in Figure
6 . The significant histologic changes are thinning of the epithelium (arrows), reduction of rete ridges, and
replacement of the dermis by inflammatory cells. H&E x 60.
Fig. 8. Photograph illustrating a cutaneous (N) nerve with perineuronal and intraneural inflammatory cell
infiltration (I). Note the thickened perineurium (arrow). H&E x 200.
infection [Butler, 1973; Jones et al., 19841. The central nervous system pathology
documented in the SFBR colony and other colonies is probably generally caused by
systemic illness originating from bacterial respiratory disease [Eichberg, 1985;
280 I Hubbard et al.
Fig. 9. Photograph illustrating a parasitic granuloma (GI in the wall of the jejunum of a chimpanzee.
Fig. 10. Photograph illustrating a cross section of a parasite morphologically consistent with Enterobius uerrniculuris in the wall of the jejunal granuloma in Figure 9. Note the lateral alae (arrow). H&E x 200.
Schmidt, 1978; Schmidt & Butler, 1971; Solleveld et al., 19841. This again emphasizes the importance of early detection and therapy of respiratory disease.
The source of leprosy infection has not been determined yet, but probably
occurred 8 years prior to diagnosis by indirect contact with a n asymptomatic ex-
Diseases and Pathology of Chimpanzees / 281
perimentally infected ape. The clinical signs, pathology, and classification were
consistent with documented leprosy in apes [Gormus et al., 1988; Leininger et al.,
19781. Antibiotic therapy has proven to be effective.
None of the protozoa appear to have been pathogenic t o the chimpanzees and
this is the majority experience in other colonies [Butler, 1973; McClure, 1971;
Schmidt, 19781, there is evidence that Balantidium coli and Entamoeba histolytica
are enteric pathogens [Schmidt, 19781. Intestinal granulomas caused by Enterobius vermicularis have been reported [Schmidt, 19781.
Virus isolates from 5 chimpanzee colonies indicate essentially the same baseline viral information, with the enteroviruses the most prevalent group [Kalter &
Guilloud, 19701.
The alopecia totalis was considered to be an anutoimmune phenomenon, as
therapy with immunosuppressive drugs resulted in hair regrowth. After therapy
was discontinued, the hair was again totally lost [Eichberg & De Villez, 19841.
The nasal polyposis was the only condition that approached neoplasia in the
chimpanzee colony. The gross and histologic examination confirmed the polyps
were indistinguishable morphologically from human polyps [Jacobs et al., 19841.
1. Cardiovascular, respiratory, and gastrointestinal disease and chimpanzeeinduced trauma remain the main causes of morbidity and mortality in the chimpanzee.
2. The definition and solution of cardiovascular disease should be a high priority for chimpanzee care personnel.
3. Constant vigilance and immediate care are necessary to prevent morbidity
and mortality by respiratory diseases.
4. Mycobacterium leprae infection may occur in the chimpanzee and colony
managers should be alert for the disease.
We wish to thank Dr. Chester Gleiser, Marie Silva, Sherrian McAnn, Jo
Fletcher, and Dennis Have1 for making this paper possible. This work was supported in part by contract N01-HB-7-7029 from the National Heart, Lung, and
Blood Institute.
Bourne, G.N.; Sandler, M. Atherosclerosis in
chimpanzees. Pp. 248-264 in THE CHIMPANZEE, Vol. 6, ANATOMY AND PATHOLOGY. Baltimore, University Park
Press, 1973.
THE CHIMPANZEE. (Aeromedical Review, Rev. 1-73). Brooks Air Force Base,
Texas, Aerospace
Medical Division
(AFSC), USAF School of Aerospace Medicine, 1973, 81 pp.
Eichberg, J.W. Changes in infant husbandry
in respone to a Klebsiella pneumoniae outbreak. MONOGRAPHS IN PRIMATOLOGY 5:43-45, 1985.
Eichberg, J.W.; De Villez, R.L. Alopecia totalis in a chimpanzee. JOURNAL OF
Eichberg, J.W.; Shade, R.E. “Normal” blood
pressure in chimpanzees. JOURNAL OF
Gormus, B.J.; Ohashi, D.K.; Ohkawa, S.;
Walsh, G.P.; Meyers, W.M.; Brennan, P.J.;
Trygg, C. Serologic responses to Mycobacterium leprae-specific phenolic glycolipid-1
antigen in sooty mangabey monkeys with
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Leininger, J.R.; Donham, K.J.; Rubino, M.J.
Leprosy in a chimpanzee. Morphology of
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McClure, H.M.; Guilloud, N.B. Comparative
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havior, Growth, and Pathology of Chimpanzees. Pp. 104-244 in THE CHIMPANZEE. G.H. Bourne ed. Baltimore,
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Ridley, D.S.; Jopling, W.H. Classification of
leprosy according to immunity: A fivegroup-system. INTERNATIONAL JOURNAL OF LEPROSY AND OTHER MYCOBACTERIAL DISEASES 34:255-273,
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