Etiology of reactive arthritis in Pan paniscus P. troglodytes troglodytes and Pкод для вставкиСкачать
American Journal of Primatology 66:219–231 (2005) RESEARCH ARTICLE Etiology of Reactive Arthritis in Pan paniscus, P. troglodytes troglodytes, and P. troglodytes schweinfurthii BRUCE M. ROTHSCHILD1–5n and FRANK J. RÜHLI6,7 1 Arthritis Center of Northeast Ohio, Youngstown, Ohio 2 Department of Medicine, Northeast Ohio Universities College of Medicine, Rootstown, Ohio 3 Department of Biomedical Engineering, University of Akron, Akron, Ohio 4 Division of Earth Sciences, Carnegie Institute, Pittsburgh, Pennsylvania 5 Kansas University Museum of Natural History, Lawrence, Kansas 6 Clinical Paleopathology Team, Orthopaedic University Clinic Balgrist and Institute for the History of Medicine, University of Zurich, Zurich, Switzerland 7 Institute of Anatomy, University of Zurich, Zurich, Switzerland The character of arthritis has not received the same attention in Pan paniscus as it has in P. troglodytes. Reactive arthritis (a form of spondyloarthropathy) in the latter has been considered to be either a sexually transmitted or an infectious-agent diarrhea-related disorder. The unique sexual promiscuity of P. paniscus enables us to distinguish between those hypotheses. The macerated skeletons of 139 adult P. paniscus, P. troglodytes troglodytes, and P. troglodytes schweinfurthii were macroscopically analyzed for osseous and articular pathologies. The sex of the animal was recorded at the time of acquisition. Twenty-one percent of the P. paniscus, 28% of the P. t. troglodytes, and 27% of the P. t. schweinfurthii specimens had peripheral and central joint erosive disease characteristic of spondyloarthropathy. Subchondral pauciarticular distribution and reactive new bone clearly distinguish this disease from rheumatoid arthritis, osteoarthritis, and direct bone/joint infection. The fact that P. paniscus and P. t. troglodytes were similar in terms of disease frequency makes the notion of sexual transmission unlikely. While the frequencies of spondyloarthropathy were indistinguishable among all species/subspecies studied, the patterns of joint involvement were disparate. The Pan paniscus and P. t. troglodytes home ranges are geographically separate. We assessed possible habitat factors (e.g., exposure to specific infectious agents of diarrhea) by comparing P. paniscus and P. t. troglodytes with P. t. schweinfurthii. The latter shared similar patterns and habitats (separated by the Congo River) with P. paniscus. The explanation offered for habitat-specific patterns is differential bacterial exposure–most likely Shigella or Yersinia in P. n Correspondence to: Bruce M. Rothschild, M.D., Arthritis Center of Northeast Ohio, 5500 Market, Youngstown, OH 44512. E-mail: firstname.lastname@example.org Received 29 June 2004; revised 23 October 2004; revision accepted 26 November 2004 DOI 10.1002/ajp.20140 Published online in Wiley InterScience (www.interscience.wiley.com). r 2005 Wiley-Liss, Inc. 220 / Rothschild and Rühli paniscus and P. t. schweinfurthii. Am. J. Primatol. 66:219–231, 2005. r 2005 Wiley-Liss, Inc. Key words: arthritis; spondyloarthropathy; chimpanzee; primate infectious-agent diarrhea; Shigella INTRODUCTION The study of articular and osseous disease in the chimpanzee Pan paniscus (bonobo, also referred to as the pygmy chimp because it shares a habitat with pygmies) has been limited to traumatic, congenital abnormalities; direct, suppurative infections; and ‘‘degenerative articular disease’’ [Jurmain, 1977, 2000; Kano, 1984; Zihlman, 1987], in contrast to Pan troglodytes [Jurmain, 1989; Lovell, 1991; Rothschild & Woods, 1991a]. Occasional notations of osteoarthritis and hypertrophic osteoarthropathy in wild-caught P. troglodytes [Marzke & Merbs, 1984] contrast with the 28% frequency of a form of reactive erosive arthritis in that species [Rothschild & Woods, 1991a]. In humans, reactive arthritis, or Reiter’s syndrome, is a predominantly pauciarticular disorder that predominantly affects the extremities, spine, and sacroiliac joints [Arnett, 1987; Resnick, 2002; Rothschild, 1982; Rothschild & Martin, 1993]. The terms ‘‘pauciarticular’’ and ‘‘oligoarticular’’ both describe arthritis that occurs in less than five peripheral joints. In genetically-predisposed individuals, this phenomenon, which is a subclass of spondyloarthropathy, frequently complicates genital infections and infectious-agent diarrhea. Chlamydia and perhaps Mycoplasma have been implicated for the former, while Shigella, Salmonella, Yersinia, Campylobacter, and enteropathic Escherichia coli have been implicated for the latter in humans and other primates [Ahvonen et al., 1969; Bardin & Lathrop, 1992; Bengtsson et al., 1983; Borg et al., 1992; Buxton et al., 2002; Calin & Fries, 1976; Cheevers and McGuire, 1988; Cohen et al., 1987; Cole et al., 1970; Deighton, 1993; Dworkin et al., 2001; Graham, 1919; Granfors et al., 1988; Hannu & Leirisalo-Repo, 1988; Hannu et al., 2002; Held & Whitney, 1978; Herrlinger & Asmussen, 1992; Hughes et al., 1991; Kanakoudi-Tsakalidous et al., 1998; Katz, 1989; Kvien et al., 1994; Laasila & Leirisalo-Repo, 1999; Leino et al., 1980; Leirisalo-Repo et al., 1997; Locht & Krogfelt, 2002; Locht et al., 1993, 2002; Maki-Ikola & Granfors, 1992; Maximov et al., 1992; Merilahti-Palo et al., 1991; Putterman & Rubinow, 1993; Rothschild & Woods, 1993; Rudwaleit et al., 2001; Simon et al., 1981; Snoy et al., 1985; Solitar et al., 1998; Stein et al., 1980; Taccetti et al., 1994; Thompson-Handler et al., 1984; Thomson et al., 1994, 1995; Tupchong et al., 1999; Yli-Kerttula et al., 1995; Zeidler et al., 2004]. Shigellarelated disease has also been documented in nonhuman primates [Brancker, 1985; Chapman & Crowell, 1977; Good et al., 1969; Griner, 1980; Klumpp et al., 1986; Kourany & Porter, 1969; McClure, 1980; Neiffer et al., 2000; Urvater et al., 2000]. Disorders in apes that must be distinguished from spondyloarthropathy include osteoarthritis and infectious arthritis. The primary osseous changes that occur with osteoarthritis are remodeling with spur or osteophyte formation, an increase in the density of the subchondral plate, and formation of distal metaphyseal interosseous cysts [Jaffe, 1972; Moskowitz et al., 1984]. The first is recognized grossly. Subchondral plate changes and cysts must be identified by x-rays or cross-sections. Occasionally, with very severe osteoarthritis the articular surfaces may even become grooved and eburnated. Osteoarthritis is basically a Bonobo/Chimpanzee Arthritis / 221 noninflammatory type of arthritis. Erosions or holes may disrupt the joint surface cartilage, but actual erosion of subchondral bone is not found. In osteoarthritis, overgrowth of bone occurs, but there is no bone resorption. The area between the cartilage-covered bone and the site of insertion of the synovial membrane into the bare or marginal area of bone is unaffected in osteoarthritis. It retains its normal smooth, uninterrupted appearance. Infectious arthritis is characterized by reactive bone formation with gross distortion of the joint surface and underlying bone [Resnick, 2002; Rothschild & Martin, 1993]. While not all infectious arthritis is associated with a filigree type of bone reaction, such a reaction is essentially pathognomonic for infectious arthritis. Occasionally, infectious arthritis may so distort the bony architecture so as to cause actual fusion (bony ankylosis) of the joint. The gross distortion of bony architecture, as recognized on x-ray, makes the diagnosis obvious. Both osteoarthritis and infectious arthritis are clearly distinguishable from spondyloarthropathy, which is the subject of this report. Given the dichotomy of sexual behavior between P. paniscus and P. troglodytes [Boesch et al., 2002; de Waal, 1995; Dixson, 1998; Kano, 1980], it is of interest to ascertain differential susceptibility and distribution of arthritis among the species and subspecies. The especially promiscuous, frequent, and variable sexual activities of P. paniscus [de Waal, 1995; Kano, 1990] include female–female genito–genito rubbing, male–male mounting and rump contact, and juvenile and adolescent copulation without intromission [Badrian & Badrian, 1984; Furuichi, 1987, 1989; Ihobe, 1992; Kano, 1980, 1992, 1996; SavageRumbaugh & Wilkerson, 1978]. The disparate sexual behaviors between these two species enable investigators to assess the role of sexually-transmitted diseases (e.g., Chlamydia) [Nunn et al., 2000; Thrall et al., 1997] or AIDS (immunodeficiency virus-related disease) in the development of primate arthritis. Sexual transmission is considered because in humans, reactive arthritis is 100–200 times more common in those affected by AIDS [Tehranzadeh et al., 2004], which suggests a relationship with sexual behavior or the virus itself. MATERIALS AND METHODS The articular surfaces of 34 P. paniscus, 79 P. t. troglodytes, and 26 P. t. schweinfurthii skeletons were examined by both authors, with concurrence on the findings. Seventy-five percent of the P. paniscus, 30% of the P. t. troglodytes, and 55% of the P. t. schweinfurthii specimens were male. We analyzed the articular manifestations in seven P. paniscus, 22 P. t. troglodytes, and seven P. t. schweinfurthii specimens with sacroiliac or erosive disease. The P. t. troglodytes specimens were examined by B.M.R., with concurrence by Robert Woods [see Rothschild & Woods, 1991a]. The study was limited to primates with M3 eruption. The P. paniscus and P. t. schweinfurthii skeletons (from the Musée Royal de l’Afrique Centrale, Tervuren, Belgium) were compared with P. t. troglodytes skeletons. All of the specimens were collected in the 1920s and 1930s from free-ranging animals shot in the wild. The P. t. troglodytes specimens were taken from the French Cameroons in coastal West Africa, Congo, Gabon, and Nigeria; and P. t. schweinfurthii and P. paniscus were taken from the Democratic Republic of Congo between 1935 and 1959. The habitat of P. t. troglodytes ranges from the mouth of the Congo River into Cameroon. That of P. Paniscus extends south of the Congo River into Congo and Zaire, while P. t. schweinfurthii ranges north of the Congo River [Groves, 2001]. The sex of the specimens was determined on the basis of data recorded at the time of acquisition. 222 / Rothschild and Rühli The macerated skeletons were treated when they were acquired to remove the soft tissues, and surveyed for visible evidence of articular and periarticular joint pathology. Each skeletal element of the sampled individuals was carefully observed independently by both authors, with concurrence as to whether the observation represented an erosion, and to rule out artifacts such as postmortem trauma (e.g., drawer damage). For the purposes of this study, articular surfaces were considered missing if artifactual damage precluded the demonstration of joint disease. RESULTS Moderate to severe osteoarthritis was present in six P. t. troglodytes, one P. t. schweinfurthii, and one P. paniscus (Fisher’s exact test, P = 0.0266; Table I). Infections in a proximal interphalangeal joint and an ischial tuberosity were noted in two P. t. troglodytes. No osteoarthritis was noted in P. t. schweinfurthii, and one instance of osteoarthritis (affecting the tibial component of one knee) was noted in P. paniscus. We analyzed the articular manifestations in the seven P. paniscus, 22 P. t. troglodytes, and seven P. t. schweinfurthii individuals with sacroiliac or erosive disease (Table I). This represents 21% of the P. paniscus, 28% of the P. t. troglodytes, and 28% of the P. t. schweinfurthii specimens, which are statistically indistinguishable frequencies (w2=0.6567). In the specimens whose sex was recorded at the time of acquisition, this form of arthritis was five times more common in female P. paniscus, compared to a 1:1.5 male predominance in P. t. troglodytes. The difference was not statistically significant (Fisher’s exact test, P = 0.3292), but the Beta error associated with such small numbers precludes a confident exclusion of difference. We were unable to determine the sex ratio in afflicted P. t. schweinfurthii individuals, because the sex of the affected animals of that subspecies was not recorded at the time of acquisition. The erosions (Figs. 1 and 2) were subchondral in distribution. The term ‘‘marginal,’’ as used herein, denotes the zone of metaphyseal bone that is within the synovial membrane but is extrinsic to the cartilage-lined bone [Martel et al., 1965; Resnick, 2002; Rothschild & Martin, 1993]. ‘‘Subchondral’’ refers to the portion of the articular surface that was originally covered by cartilage. All erosions were associated with the formation of new bone in a peri-erosional pattern (Fig. 3). The new or reactive bone, bordering the rim of the erosion, was TABLE I. Patterns of Arthritis in Pan Species Character Osteoarthritis Infectious arthritis Spondyloarthropathy Pauciarticulara Polyarticulara Sacroiliac involvementa Pan paniscus (34) Pan t. troglodytes (79) Pan t. schweinfurthii (26) 3 3 21 67 14 100 8 3 28 23 77 18 4 0 27 67 14 71 n Numbers in parentheses are the number examined. Values represent the % frequency for each of the characters examined. a Of specific Pan species members with spondyloarthropathy. Bonobo/Chimpanzee Arthritis / 223 Fig. 1. Inferior oblique view of a distal tibia in Pan schweinfurthii. Large marginal erosions disrupt the articular surface in their subchondral extension. Fig. 2. Superior oblique view of the distal clavicles in Pan paniscus. Subchondral erosions can be seen. distinct from the metaphyseal bone surrounding it. Reactive bone was recognizable as a smooth, billowy, sclerotic growth at the periphery of the resorbed lesion. Reactive bone was easily distinguished from the cracked and ragged edges that are typically observed on the border of pseudo-erosions associated with artifact. A lytic lesion, from which bone tissue has been removed by osteoclasts, 224 / Rothschild and Rühli Fig. 3. Anterior-oblique view of proximal humeri in Pan paniscus. Marginal erosions with reactive new bone formation can be seen. presents smooth, rounded edges of any surfaces within and at the boundaries of the lesion in dry bone [Leisen, 1987; Rothschild et al., 1988; Rothschild & Woods, 1991b]. Transitions from one plane of bone tissue to another are smoothed. The edges of all exposed trabeculae, as in metaphyses of dense cortical bone, meet with a rounded edge. Although inflammation lesions may activate osteoclastic resorption of perilesional trabeculae, they subsequently activate osteoblastic deposition in the same region [Leisen, 1987]. Thus, any trabecular edges that are initially exposed at the lesion boundary by osteolysis subsequently appear thicker than trabecular edges revealed by postmortem processes in the same region. The two groups with erosive disease exhibited different patterns of arthritis: the erosions in all of the affected P. paniscus, P. t. troglodytes, and P. t. schweinfurthii individuals were associated with reactive new bone formation (Figs. 2 and 3; Table I). Peripheral joint erosive disease was predominantly pauciarticular and symmetrical in two of three P. paniscus (67%) and two of three P. t. schweinfurthii (67%), but only six of 22 P. t. troglodytes (27%) with peripheral joint damage. A polyarticular pattern was found in one (14%) afflicted P. paniscus and one (14%) P. t. schweinfurthii, compared to 17 (77%) P. t. troglodytes (w2 = 13.6192, Po0.0001). Five joints were affected in each of the P. paniscus and P. t. schweinfurthii specimens with polyarticular disease. Five to 14 affected joints were found in P. t. troglodytes with polyarticular disease, for an average of nine affected joints. The same joints were predominantly affected in both P. paniscus and P. troglodytes. Metacarpal phalangeal and metatarsal phalangeal joints were more commonly affected in P. t. troglodytes,(w2 = 8.1119, Po0.005). Peripheral joint fusion of an ankle was present in one P. t. schweinfurthii. Bonobo/Chimpanzee Arthritis / 225 Fig. 4. En face view of the auricular area of the iliac portion of the sacroiliac joint in Pan troglodytes schweinfurthii. Erosions with reactive new bone formation are evident. Four (18%) of the afflicted P. t. troglodytes had sacroiliac erosions (Fig. 4) or fusion, as did five of seven (71%) of P. t. schweinfurthii (Fisher’s exact test, P = 0.0170) and all seven P. paniscus (w2 = 15.099, Po0.0001). The erosions appeared as multiple small crater-shaped holes with smooth, rounded edges. Syndesmophytes, presenting as calcification in the anulus fibrosus, and costovertebral joint fusion were present in a single P. paniscus specimen. DISCUSSION Osteoarthritis The occurrence of osteoarthritis in Pan was documented in previous studies [Goodall, 1986; Rothschild & Woods, 1991a; Woods, 1986]. Osteoarthritis is pathologically quite distinct from the erosive disease described in the current study. Infectious Arthritis Infectious arthritis was actually quite rare in all of the Pan specimens studied. Another variety of joint disease is erosive arthritis. This type of arthritis leads to disruption of bone in either the marginal area or the subchondral bone, resulting in grooves or holes (Figs. 1–4). Spondyloarthropathy In humans, spondyloarthropathy is generally associated with spinal involvement, similar to that noted in chimpanzees. Appendicular reactive erosive disease in chimpanzees displays characteristics and distribution patterns similar to those of spondyloarthropathy in humans [Rothschild & Woods, 1991a,b]. Given the 226 / Rothschild and Rühli pattern of involvement, and the nature of the lesions, erosive disease in Pan appears to be attributable to a specific clinical diagnosis: spondyloarthropathy [Rothschild et al., 1988; Woods & Rothschild, 1988; Rothschild & Woods, 1991b]. Reactive arthritis is the most likely variety. The remodeling that occurred around erosions (Figs. 2–4) was more exuberant than that seen in human rheumatoid arthritis [Rothschild et al., 1988; Woods & Rothschild, 1988], but was quite similar to that noted in human spondyloarthropathy [Rothschild & Woods, 1991b]. In contrast to the minimal or absent peri-erosional bone reaction noted in human rheumatoid arthritis [Rothschild et al., 1988; Woods & Rothschild, 1988], the bone alterations in all species of chimpanzees corresponded more to the reactive bone seen in human spondyloarthropathy [Rothschild & Woods, 1991b]. Reactive Arthritis: Phylogenetic, Behavioral, or Environmental Derivation The original purpose of this study was to compare the frequency and character of spondyloarthropathy (reactive arthritis) in P. paniscus and P. troglodytes (specifically P. t. troglodytes). While the frequencies and characteristics of disease were identical in the two groups (w2=0.6567), skeletal distribution (w2 = 8.1119, Po0.005), extent of peripheral erosive disease (w2 = 13.6192, Po0.0001), extent of sacroiliac joint disease (w2=15.099, Po0.0001), and perhaps sex ratios (Fisher’s exact test, P = 0.3292, large Beta error) varied. The identical frequency of reactive arthritis in hypersexed bonobos and in chimpanzees with more conventional sexual activity is strong evidence against the sexual-transmission hypothesis, and therefore of a role for Chlamydia, Mycoplasma, or AIDS in its dénouement. This supports the notion of an infectious-agent diarrhea etiology, but raises an interesting question: Is the difference in patterns related to habitat? Another potential contribution by behavior was knuckle walking, attributed to P. paniscus [Boesch et al., 2002]. However, knuckle involvement is characteristically noted in P. t. troglodytes, not P. paniscus. This and observations in mountain Gorilla beringei and lowland G. gorilla (Rothschild and Ruhli, 2005, this issue) do not support that possibility. To address the question about habitat, we examined a second subspecies of chimpanzee: P. t. schweinfurthii. This subspecies exhibits different sexual habits, but shares habitats (separated only by the Congo River) with P. paniscus. Agents of infectious diarrhea may be differentially represented in lowland animals (i.e., P. t. troglodytes) and those who live in more mountainous terrain (i.e., P. paniscus and P. t. schweinfurthii). We analyzed arthritis in the P. t. troglodytes, P. paniscus, and P. t. schweinfurthii specimens to determine whether the difference in skeletal distribution correlated with species or habitat. Infections were rare and occurred at indistinguishable frequencies among all three. However, osteoarthritis was more common in P. t. troglodytes than in either P. t. schweinfurthii or P. paniscus (Fisher’s exact test, P = 0.0266), confirming this was not determined by species, but was rather a subspecies phenomenon. The frequencies of osteoarthritis, however, were indistinguishable between P. t. schweinfurthii and P. paniscus (Fisher’s exact test, P = 0.4994), suggesting that a habitat-dependent factor might be more important. While their habitats are separated by a river (the Congo River) [Groves, 2001], we hypothesize that conditions may have been sufficiently similar on both sides of the river to ‘‘cultivate’’ similar bacterial flora. Bonobo/Chimpanzee Arthritis / 227 Osteoarthritis was more common in the lowland animals than in those that lived in a mountainous terrain. It is difficult to compare our results with those reported by Jurmain , because of the sample sizes and the different diagnostic criteria used in the previous study, which may not have distinguished between osteoarthritis and reactive arthritis. Reactive arthritis in P. paniscus and P. t. schweinfurthii was indistinguishable in frequency, skeletal distribution, and extent of erosive peripheral joint and sacroiliac joint disease. The indistinguishable character and statistics across (rather than within) species lines further suggest that the character of reactive arthritis is determined by a habitat-related factor. Habitat and Microorganisms In humans, the causative organisms Escherichia coli, Salmonella, Campylobacter, Streptococcus pyogenes, Clostridium difficile, and Giardia lambdia are predominantly associated with polyarticular disease, while Yersinia, Shigella, and Chlamydia are associated with a pauciarticular pattern of arthritis (Table II). We propose that this suggests identical susceptibility, but different ‘‘precipitating’’ organisms in P. paniscus and P. troglodytes (Escherichi coli, Salmonella, or Camplyobacter for the former, and Shigella or Yersinia for the latter). The patterns of disease in P. t. schweinfurthii and P. paniscus were indistinguishable. Therefore, sexually transmitted/derived spondyloarthropathy is less likely. That leaves the possibility that P. paniscus and P. t. schweinfurthii were both exposed to the same organism–most likely Yersinia or Shigella. We believe the different patterns of disease are not related to the primate species or subspecies, but rather to the infecting organism. Similar patterns of disease have been demonstrated in humans (Table II) [Ahvonen et al., 1969; Bardin & Lathrop, 1992; Bengtsson et al., 1983; Borg et al., 1992; Buxton et al., 2002; Calin & Fries, 1976; Cheevers and McGuire, 1988; Cohen et al., 1987; Cole et al., 1970; Deighton, 1993; TABLE II. Frequency and Character of Reactive Arthritis Complicating Infectious Agent Diarrhean Organism Frequency (%) Oliogoarticular (%) Polyarticular (%) Mean number of affected joints Streptococcus pyogenes Escherichia coli Salmonella typhimuriu Salmonella enteritidis Giardia lambdia Clostridium difficile Camplobacter jejuni Chlamydia Yersinia enterocolitica Shigella flexneii n.a. 6 2–15 14–33 n.a. n.a. 1–24 n.a. 11–33 14–24 20 20 20 24 25 42 50 67 64–84 80–100 80 80 80 76 75 58 50 33 8–36 0–20 5+ 5+ 10 4.7–8.0 6 4+ 5+ 3 3.3–3.8 2.3–2.8 n Derived from Ahvonen et al. ; Bardin and Lathrop ; Borg et al. ; Buxton et al. ; Calin and Fries ; Cohen et al. ; Deighton ; Dworkin et al. ; Graham ; Hannu and Leirisalo-Repo ; Hannu et al. ; Herrlinger and Asmussen ; Hughes et al. ; KanakoudiTsakalidous et al. ; Kvien et al. ; Laasila and Leirisalo-Repo ; Leino et al. ; Leirisalo-Repo et al. ; Locht and Krogfelt ; Locht et al. [1993, 2002]; Maki-Ikola and Granfors ; Maximov et al. ; Merilahti-Palo et al. ; Putterman and Rubinow ; Rudwaleit et al. ; Simon et al. ; Solitar et al. ; Stein et al. ; Taccetti et al. ; Thompson et al. [1994, 1995]; Tupchong et al. ; Yli-Kerttula et al. . 228 / Rothschild and Rühli Dworkin et al., 2001; Graham, 1919; Hannu & Leirisalo-Repo, 1988; Hannu et al., 2002; Herrlinger & Asmussen, 1992; Hughes et al., 1991; Kanakoudi-Tsakalidous et al., 1998; Kvien et al., 1994; Laasila & Leirisalo-Repo, 1999; Leino et al., 1980; Leirisalo-Repo et al., 1997; Locht & Krogfelt, 2002; Locht et al., 1993, 2002; MakiIkola & Granfors, 1992; Maximov et al., 1992; Merilahti-Palo et al., 1991; Putterman & Rubinow, 1993; Rudwaleit et al., 2001; Simon et al., 1981; Solitar et al., 1998; Stein et al., 1980; Taccetti et al., 1994; Thomson et al., 1994, 1995; Tupchong et al., 1999; Yli-Kerttula et al., 1995]. The indistinguishable population penetrance in all three chimpanzee species/ subspecies (28% for P. t. troglodytes, 27% for P. t. schweinfurthii, and 21% for P. paniscus) suggest that this is not the pertinent issue. This pattern is similar to that observed in lowland gorillas (G. g. gorilla), 20% of which are afflicted [Rothschild & Woods, 1991a], and with whom eastern chimpanzees share similar habitat and extent and severity of disease, all much greater than the disease in the mountain gorilla G. beringei habitat shared by P. t. troglodytes and P. paniscus. Different habitat-related enteropathic infections are suspected. Shigella-associated spondyloarthropathy presents as pauciarticular disease in zoo colonies of lowland apes. In the wild, lowland apes exhibit spondyloarthropathy with the same frequency, but with a polyarticular pattern [Rothschild & Woods, 1989]. This supports the notion that the occurrence of this disease is influenced more by habitat (and probably organism) than by species or subspecies. CONCLUSIONS The characteristics of spondyloarthropathy in Pan enable us to distinguish between sexual transmission and infectious-agent diarrhea transmission as disease vectors, and to identify the latter as the predominant cause of this disease in nonhuman primates. Chimpanzees and humans share a heritage and susceptibility to infectious-agent diarrhea-related pathologies. Further genetic and habitat analyses may help identify new approaches for preventing this common scourge. ACKNOWLEDGMENTS We thank Drs. Wim van Neer and Wim Wendelen (Musée Royal de l’Afrique Centrale), Bruce Lattimer and Lyman Jellema (Cleveland Museum of Natural History), and Linda Gorden (National Museum of Natural History) for their logistical and technical support in examining the collection. REFERENCES Ahvonen P, Sievers K, Aho K. 1969. 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