Amyloidosis in pigtailed macaques (Macaca nemestrina): epidemiologic aspects

A retrospective study of amyloidosis in pigtailed macaques (Macaca nemestrina) at the Washington Regional Primate Research Center (WRPRC) was conducted. Between 1971 and 1985, 248 of 1,952 (13%) necropsies revealed amyloidosis in pigtailed macaques. The influence of demographic factors, diseases and experimental interventions on amyloidosis was examined. Univariate analyses, using two controls for each case, indicated that age, sex, birthplace and residence were related to amyloidosis. After adjusting for age, females were not at greater risk. However, monkeys born at the WRPRC were at greater risk and monkeys 0 to 5 years old residing at the breeding colony were at greater risk than monkeys at the research center. After adjustment for age, monkeys were at greater risk of developing amyloidosis if they had a history of episodes of diarrhea, respiratory disease or trauma. As the number of episodes increased, the risk increased. Monkeys with retroperitoneal fibromatosis, a manifestation of simian D retrovirus infection, were also at greater risk. Using logistic regression and controlling for age, sex, birthplace and residence, monkeys with diarrhea remained at an elevated risk for amyloidosis. Compared with a model combining diarrhea, respiratory disease, septicemia, surgery, trauma and retroperitoneal fibromatosis, a model with diarrhea alone accounted for most of the increased risk.     

Amyloidosis in pigtailed macaques (Macaca nemestrina): pathologic aspects

The pathologic aspects of 248 cases of amyloidosis in pigtailed macaques (Macaca nemestrina) at the Washington Regional Primate Research Center from 1971 through 1985 were studied. Amyloid was present in the spleen, liver and gastrointestinal (GI) tract, either alone or in combination, in nearly 75% of the monkeys. Its occurrence declined with age in the spleen and the GI tract, but increased with age in the liver. Both intestinal inflammation and retroperitoneal fibromatosis were strongly associated with amyloid deposition in the GI tract. Monkeys with histopathologic findings of enteritis or enterocolitis and glomerulonephritis were at increased risk of developing amyloidosis. Forty cases of amyloidosis with a history of chronic diarrhea had type AA amyloid by histochemical tests.     

Effect of weaning time and associated management practices on postweaning chronic diarrhea in captive rhesus monkeys (Macaca mulatta)

OBJECTIVE: Our purpose was to assess the extent to which early weaning and other weaning-management factors affect development of postweaning chronic diarrhea in captive rhesus monkeys at the California Regional Primate Research Center between 1992 and 1995. METHODS: Data for weaning, management, and onset of diarrhea were obtained from daily records. The Cox proportional hazard model was used to assess whether the risk of chronic diarrhea was related to early weaning. RESULTS: Monkeys that were lighter at weaning had a threefold increase in risk of postweaning chronic diarrhea (P = 0.07), compared with that in heavier monkeys. An episode of preweaning diarrhea increased the risk of postweaning chronic diarrhea twofold (P = 0.08). Relocation of monkeys to outdoor facilities in the fall was associated with a fivefold decrease in risk (P < 0.001), compared with that of other seasons, and weaning in 1993 was associated with a twofold decrease in risk, compared with that of other years (P = 0.04). CONCLUSIONS: Multiple factors need to be considered for prevention of postweaning chronic diarrhea, including weaning weight, preweaning diarrhea, season weaned, and weaning conditions that change from year to year.     

婴幼儿腹泻患者肠道菌群分布特点研究

目的研究不同年龄段腹泻患儿肠道菌群分布特点,探讨不同年龄腹泻患儿肠道菌群与疾病的关联。方法选取9例符合临床诊断标准的0~1岁婴儿腹泻患者和8例符合临床诊断标准的1~3岁幼儿腹泻患者的粪便样本,同时于健康儿童中随机选取6例粪便样本作为对照,提取各组对象粪便总DNA,采用PCR-DGGE进行菌群多样性与差异性分析。结果 0~1岁腹泻患儿肠道菌群与健康对照组相比,肠道菌群构成差异显著,条件致病菌巴黎链球菌数量显著增加。1~3岁腹泻患儿肠道菌群与健康对照组相比,条件致病菌解没食子酸链球菌、屎肠球菌数量显著增加,长双歧杆菌数量下降。结论婴幼儿腹泻患者肠道菌群的构成与健康对照组相比差异显著,该特点可作为婴幼儿腹泻早期诊断的实验依据。     

人工饲养条件下死亡实验恒河猴肠道病理改变特点分析

目的观察人工饲养条件下实验恒河猴肠道病理改变,探讨实验猴肠道疾病分布规律和病理改变特点,丰富实验猴自发病变基本研究资料。方法对1998-2008年云南地区饲养的自然死亡的155只恒河猴（年龄2-20岁）的肠道进行病理检查,按年龄分为幼年组、成年组、老年组,并对观察结果进行统计学分析。结果155例恒河猴中58例检出肠道病变,有慢性肠炎、急性肠炎、黏膜充血水肿、出血、糜烂、溃疡、穿孔、寄生虫共8种主要病变,出现率最高的为急性肠炎（20．00％）。实验猴不同年龄组肠道病变类型分布基本相同,肠道病变率随年龄增长而增高,不同年龄组间统计学分析差异无显著性。结论人工饲养条件下死亡实验猴肠道病变检出率较高,急性肠炎是实验猴的主要致死原因之一,实验猴肠道病理改变随年龄增长而病变加重。对实验猴饲养和研究时,应重视肠道病变因素,尤其是急性肠炎。死亡实验猴肠道病变研究对实验猴的质量控制和相关动物实验有重要指导价值。     

Epidemiology and etiology of diarrhea in colony-born Macaca nemestrina

The epidemiology of diarrhea in colony-born M. nemestrina was studied in 205 neonates and infants in an Infant Primate Research Laboratory (IPRL), and in 248 neonates, juveniles and adolescents up to 4 years of age at a separate breeding and holding facility (Primate Field Station, PFS). Computerized medical records of individual animals over a 5-year period were analyzed to determine the incidence of diarrhea; age, duration and number of episodes; mortality and etiology. The incidence of diarrhea at the IPRL was highest in infants at less than 1 month of age (18.6 cases per 1000 animal days) and at 1-6 months olds (2.0 cases per 1000 animals days). Many infants had multiple episodes. All episodes were less than 10 days in duration. Mortality was low. At the PFS, the highest incidence occurred in infants at 6-12 months of age (1.36 cases per 1000 animal days). Multiple episodes were less common. Duration was variable. The infectious agents diagnosed at both facilities were Shigella, Campylobacter and Cryptosporidium. No pathogens were identified in many episodes. Shigella was more common at PFS than at the IPRL. Chronic diarrhea occurred in approximately 10% of animals at PFS. Intestinal amyloidosis and retroperitoneal fibromatosis were found in 13 animals with chronic diarrhea. Further studies are needed to determine the pathogenesis of chronic diarrhea, the etiologic significance of Campylobacter, and the causes of diarrhea when no pathogens are isolated.     

Evaluation on monkeys of reactogenicity and effectiveness of the complex immunoglobulin preparation formulation

Experiments on 75 monkeys, 20--healthy and 75--with diarrhea, showed that ready medicinal forms of the complex immunoglobulin preparation in tablets, capsules or in a dried form (vials) were safe, well tolerated, clinically and bacteriologically effective. When used simultaneously with antiparasitic treatment, this preparation, irrespective of the kind of its ready medicinal form, showed high curative effect (80-90%). The diarrhea ceasing was accompanied by the gradual normalization of intestinal microbiocenosis (an increased concentrations of Escherichia coli and Bifidobacterium, a decreased amount of opportunistic bacteria). The complex method of the treatment of diarrhea in monkeys (antibiotics, trichopol, phage and probiotics) made it possible to achieve curative effect only in 60% of cases, which required the additional course of treatment, namely the use of rehydration therapy.     

Relationship of mitogen reactivity to type D retrovirus infection in Celebes black macaques (Macaca nigra)

The Celebes black macaque (Macaca nigra) colony at the Oregon Regional Primate Research Center has a high incidence of an immunodeficiency syndrome characterized by recurrent diarrhea and the development of retroperitoneal fibromatosis (RF). We have examined the relationship of type D viral infection to the immunodeficiency syndrome by surveying the colony for viral infection and for mitogen reactivity. Type D virus-positive monkeys (28% of the colony) have a higher prevalence of diarrhea, splenomegaly, lymphadenopathy and weight loss than do virus-negative monkeys, and RF has been found to occur only in virus-positive animals. Comparison of the concanavalin A (con-A) and phytohemagglutinin reactivities of the virus-positive and -negative populations has revealed no significant difference. However, within the virus-positive population, those with RF have reduced con-A reactivity and there are both high and low mitogen responders in the groups lacking RF. Thirty-two percent of the virus-positive monkeys are free of clinical symptoms, 40% have clinical symptoms but no RF, and 27% have clinical symptoms and RF. Five of the six monkeys with RF are older than the RF-free monkeys but monkeys are susceptible to type D retrovirus infection regardless of age or sex. The progressive nature of this immunodeficiency syndrome, its broad age range, and the probability that the etiological agent is also a type D retrovirus and the similarity of RF to Kaposi's sarcoma make this a potentially useful model for human AIDS.     

Campylobacter jejuni isolated from patas monkeys with diarrhea

Campylobacter jejuni was isolated from 11 (46%) of 24 patas monkeys with chronic diarrhea. Eight of these 11 (73%) monkey were characterized clinically by mucohemorrhagic diarrhea for periods up to a month followed by loose, semi-formed feces for a 12-month period. Half of the monkeys were treated with erythromycin for 10 days and the other half with tetracycline for 10 days, with all responding to treatment. Despite treatment, all monkeys again had an outbreak of mucohemorrhagic diarrhea. Biopsy specimens were taken from all eight monkeys over a period of 3 months. The clinical signs, treatment, and the gross and microscopic lesions seen in these monkeys were similar to those reported in humans and animals infected with Campylobacter jejuni.     

Serologic prevalence of antibodies to Helicobacter pylori in internationally adopted children

Background. Helicobacter pylori (H. pylori) infection has been linked to gastritis, diarrhea, peptic ulcers, failure‐to‐thrive, anemia, as well as predisposition to gastric malignancies. Because many internationally adopted children have diarrhea, failure‐to‐thrive, and anemia on arrival to the US, we determined the prevalence of HP antibodies among these children. Methods. Serum samples from 226 unselected children from 18 countries who were evaluated in the International Adoption Clinic at New England Medical Center were tested for antibodies to H. pylori. The results of serologic screening were analyzed in relation to age at adoption, site of residence prior to adoption, weight and height, and the presence or absence of anemia, diarrhea, or intestinal parasites. Results. 31% of internationally adopted children had antibodies to H. pylori. The presence of H. pylori‐antibodies was associated with residence in an orphanage (vs. foster care) prior to adoption, older age at adoption, and coinfection with intestinal parasites. No direct effects on height or weight were identified; no associations with diarrhea or anemia were found. Conclusions. Internationally adopted children have a high incidence of exposure to H. pylori, as diagnosed serologically. Residence in an orphanage (compared with foster care), older age at adoption, and coinfection with intestinal parasites were more common among children seropositive for anti‐H. pylori antibodies.     

Virus detection in monkeys with diarrhea: the association of adenoviruses with diarrhea and the possible role of rotaviruses.

To explore the role of viruses in the etiology of diarrhea in colony-reared monkeys, direct electron microscopy, the fluorescent virus precipitin test and cell culture inoculation were used to examine the stools of monkeys with and without diarrhea. The animals were predominantly rhesus with a few macaques of other species, and included infants, juveniles and adults. Adenoviruses were isolated from a higher proportion of specimens from rhesus monkeys with diarrhea (73% of specimens from infants and 78% of specimens from juveniles and adults) than from control monkeys without diarrhea (22% of specimens from infants and 26% of specimens from juveniles and adults). SV 20 was the most frequently isolated simian adenovirus type; SV 17 and SV 32 also were recovered. Noncultivable adenoviruses detectable only by electron microscopy were not seen. Although adenovirus excretion was associated with diarrhea, the causal role of adenoviruses was difficult to assess. When serial specimens from animals with chronic or intermittent episodes of diarrhea were examined, sequential infections with different viruses were found to be common. Rotaviruses were detected by electron microscopy and isolated in cell cultures from two infant rhesus monkeys with diarrhea. However, the low detection rate, together with negative serologic data on 40% of infant monkeys with diarrhea, suggested that rotaviruses were not the major cause of gastroenteritis in the monkeys under study.     

Geophagy as a therapeutic mediator of endoparasitism in a free-ranging group of rhesus macaques (Macaca mulatta)

Parasite levels were determined for 141 members of a naturally formed social group of rhesus macaques living under free-ranging conditions. Results indicate that group members harbor Trichuris trichiura, Balantidium coli, and large numbers of Strongyloides fuelleborni. Parasite counts decrease significantly with age in this population. Females have significantly fewer parasites than males and a significantly lower prevalence of multiple infections. There were no rank effects regarding parasitosis. While 89% of the animals examined are infected with one or more species of enteric parasite, the prevalence of diarrhea is negligible (2%). The low prevalence of diarrhea in the presence of high parasite loads may be due to the practice of geophagy, which is engaged in by 76% of group members. Soil eaten by these monkeys contains large amounts of kaolinitic clays. Kaolin-based pharmaceuticals (i.e. Kaopectate^®) are commonly used in human populations to treat diarrhea and intestinal upsets. The mechanical and pharmaceutical properties of the natural kaolinite-based clays may counteract the effects of parasitosis in this free-ranging population. Am. J. Primatol. 44:71-82, 1998. © 1998 Wiley-Liss, Inc.     

Diarrhea rates and risk factors for developing chronic diarrhea in infant and juvenile rhesus monkeys.

Ten independent risk factors were evaluated in an effort to identify predictors of problem diarrhea at weaning and chronic diarrhea in infant and juvenile rhesus monkeys (Macaca mulatta) at the California Primate Research Center. None of the variables proved to be a significant predictor of problem diarrhea at weaning; however, two of the variables were significant predictors for developing chronic diarrhea. Odds ratios, adjusted for other variables in the logistic regression model, showed that compared with females, males were nearly three times more likely to develop chronic diarrhea, and nursery-reared animals were 7.5 times more likely to develop chronic diarrhea than were breast-fed animals. The annual incidence rates for problem diarrhea at weaning for 1978, 1979, and 1980 were 49%, 37%, and 41%, respectively. A weighted average annual incidence rate for problem diarrhea at weaning for the 3-year period was 39%. The incidence rate for chronic diarrhea for the 3-year period was 49%.     

Experimental group A rotaviral infection in cynomolgus monkeys raised on formula diet

Rotaviral infections in cynomolgus monkeys (Macaca fasicularis) were studied to ascertain its suitability as a model of infection and diarrhea caused by group A human rotaviruses. Formula-fed monkeys were used as they could be observed closely. Experimental rotaviral infection of cynomolgus monkeys was age-dependent; only young monkeys were readily infected. Formula-fed newborns were readily infected with cell-culture-adapted human (WA) and simian (SA11) viruses and with a rotavirus from a human fecal specimen. However, diarrhea was detected only in very young animals. A number of rotaviral shedding patterns as a function of time were observed. Although there was no typical viral shedding pattern which represented exclusive association of viral infection with diarrhea, the initial level of viral excretion and the maximum level of viral shedding attained were much higher in animals with diarrhea. Seroconversion occurred in less than half of the inoculated animals. The presence of maternal rotaviral antibodies did not prevent infection or diarrhea.     

Bone Marrow Depletion as a Coincidental Finding to Hypothermia in Macaca mulatta

Three of 16 juvenile rhesus monkeys (Macaca mulatta) and 1 rhesus of 79 adult rhesus and cynomolgus monkeys (Macaca fascicularis) were found comatose in a state of profound hypothermia after a heating failure occurred in the room in which they were housed. One juvenile monkey died shortly thereafter. The three other monkeys were revived with gradual warming and supportive therapy but later experienced separate acute clinical crises manifesting shock and died at 19, 31, and 51 days after the initial episode. Histopathologic findings of severe bone marrow depletion were observed in each of the three monkeys that died after the initial episode.     

Synthesis and release of steroids in intestines from cynomolgus monkeys (Macaca fascicularis)

To examine the synthesis and release of steroids in intestinal tissues from cynomolgus monkeys (Macaca fascicularis), we performed the following experiments: 1) incubated prepared intestinal tissues with [(3)H]testosterone to study the conversion to other steroids; 2) used a radioimmunoassay to determine steroid levels in six segments of intestinal tissues and contents (duodenum, jejunum, ileum, cecum, colon, and rectum); 3) localized testosterone in the six intestinal segments by immunofluorescence histochemistry; and 4) determined steroid levels in feces from males and females of various ages by radioimmunoassay to examine a correlation between steroid levels and age or sex. In prepared intestinal tissues, testosterone was converted into androstenedione, 5 alpha-dihydrotestosterone, and an unidentified substance; all of these steroids were detected in all segments of the intestinal tissues and contents by radioimmunoassay. Immunofluorescence showed that testosterone was located in all segments of intestinal epithelia. Androstenedione, testosterone, 5 alpha-dihydrotestosterone, and the unidentified substance were also detected in feces, and their levels were not affected by the age or sex of the animal. The present findings in cynomolgus monkeys led us to conclude that 1) steroids were synthesized in the intestines; 2) intestinal steroids were released from the six intestinal tissues to the intestinal cavities and excreted outside the body with feces; and 3) intestinal steroids were released irrespective of age or sex of the animal. Intestinal steroids seem to be paracrine or exocrine agents and to have different characteristics from classical serum steroids.     

Secondary amyloidosis in rhesus monkeys with chronic indwelling venous catheters

Secondary amyloidosis was diagnosed in five Rhesus monkeys with chronic indwelling venous catheters. Diagnostic enzymology demonstrated normal serum alanine aminotransferase concentration and consistently elevated serum alkaline phosphatase. Serum protein electrophoresis on all five animals showed a typical pattern of decreased albumin and increased gamma globulin. Necropsy or biopsy specimens verified the presence of amyloid deposits in all animals. The diagnostic usefulness of clinical enzymology, serum protein electrophoresis and liver biopsy were demonstrated and the importance of considering amyloidosis as a differential diagnosis in monkeys with indwelling vascular catheters is emphasized.     

Prevalence of Intestinal Protozoans among Schoolchildren in Suburban Areas near Yangon,Myanmar

Although intestinal protozoans are common etiologies of diarrhea, few studies have been conducted in Myanmar. This study planned to investigate the prevalence of Giardia lamblia, Entamoeba coli, Entamoeba histolytica, and Endolimax nana among schoolchildren and their guardians in suburban areas near Yangon, Myanmar. We performed a cross-sectional survey among schoolchildren and their guardians from 7 primary schools in South Dagon and Hlaing Thar Yar districts, Yangon, Myanmar. Stool samples were observed with a microscope after concentration technique and iodine staining. Total 821 stool samples, including 556 from schoolchildren and 265 from guardians, were examined. The median age was 6 years old for schoolchildren and 36 years old for guardians. A 53.1% of the school children and 14.6 % of the guardians were males. The overall prevalence of each intestinal protozoan species was as follows: 3.4% (28/821) for G. lamblia; 3.5% (29/821) for E. coli; 1.2% (10/821) for E. histoytica, and 3.0% for E. nana. This study showed that intestinal protozoans are common in primary schoolchildren and their guardians in suburban areas near Yangon, Myanmar. Health interventions, such as hand washing education, improvement of sanitation, and establishment of water purification systems are urgently needed in this area.     

2009~2012年黑龙江省细菌性腹泻症候群病原菌检测结果分析

为了解黑龙江省细菌性腹泻病原谱构成,探讨主要病原体的变异和流行变迁规律,提高监测实验室腹泻病原实验室诊断、监测预警、突发细菌性腹泻疫情的处置能力,并为进一步防治工作提供科学依据。收集哨点医院肠道门诊的细菌感染性腹泻患者粪便,采用分离培养、生化鉴定和血清分型的方法,检测沙门氏菌、志贺氏菌、致泻大肠杆菌等肠道致病菌。检测细菌性腹泻症候群患者标本537份,检出率为36.69%,其中,主要致病菌为致泻性大肠杆菌、志贺氏菌、副溶血弧菌、沙门氏菌、类志贺邻单胞菌、嗜水气单胞菌、小肠结肠炎耶尔森菌、霍乱弧菌、空肠弯曲菌、大肠埃希氏菌、检出率分别为9.31%、6.89%、1.30%、3.35%、0.56%、0.19%、0.37%、0.74%、5.40%、16.95%;性别差异不显著,各年龄组病原菌检出率和各月病原菌检出率差异显著,病原菌检出率存在季节性差异,其中6、7、8、9月份病原菌检出率高,检出率之和占总检出率的93.40%,0～10岁年龄组患病人数和检出率均高于其他年龄组。 分析发现:黑龙江省夏秋两季是细菌感染性腹泻高发季节,主要致病菌为大肠杆菌埃希氏菌、志贺氏菌、沙门氏菌、空肠弯曲菌。     

Failure to induce tumors in the large intestine of Capuchin mokeys (Cebus apella) by using 1,2-dimethylhydrazine

The purpose of this study was to produce tumors in the large intestine of Capuchin Monkeys (Cebus apella) by the administration of the colonotropic carcinogen 1,2-dimethylhydrazine (DMH). The subjects were 12 monkeys, all males, age 30 months, with a mean weight of 2.858 kg. The DMH was administered subcutaneously to six of the monkeys at a dosage of 25 mg/kg of body weight once a week for 16 weeks; control monkeys received an equivalent volume of the stock solution without DMH. Twenty months after administration of the first dose, the animals were sacrificed. None of the monkeys showed intestinal tumors. Samples of the gastrointestinal tract were removed, fixed, and stained according to standard histological techniques. Histological changes were seen in all of the DMH-treated animals; these consisted of glandular hyperplasia and hyperplasia of the epithelium overlying the lymphoid nodules. In addition, foci of dysplasia were found in three of the animals. Our results suggest that the DMH induced pre-neoplastic changes, characterized by hyperplasia and dysplasia, in the mucosa of the large intestine.