TB infection in the nonhuman primate biomedical model: tip of the iceberg?

Biomedical research in the 21st century increasingly relies on pathogen-free nonhuman primates (NHPs) to model human pathophysiology. Despite adherence to protocols designed to maintain pathogen-free colonies, reports of tuberculosis regularly appear. We hypothesize that, undetected by standard screening protocols, mycobacteria of the Mycobacterium tuberculosis complex (MTBC) continue to circulate in established NHP colonies and may, in addition, be periodically reintroduced with newly imported animals. The tuberculin skin test (TST), the accepted standard screening test for tuberculosis, relies on the host's immune response to detect infection, but empirical data suggest that TST lacks both specificity and, particularly in certain NHP species and in immune compromised animals, sensitivity. In order to improve the detection of MTBC infection in NHP colonies we propose new screening protocols that incorporate molecular methods to detect mycobacteria. These new tests do not rely on the host's immune response and may allow for strain typing of the pathogens - enhancing our ability to elucidate patterns of disease transmission. Moreover, the ability to rapidly and noninvasively collect specimens could lead to an improved appreciation of the burden of MTBC circulating in populations of NHPs and humans, including drug-resistant strains, data that are invaluable to public health efforts.

Primates and primatologists: social contexts for interspecies pathogen transmission.

Humans and nonhuman primates (NHP) interact in a variety of contexts. The frequency, duration, and intensity of interspecies interaction influence the likelihood that contact results in cross-species transmission of infectious agents. In this study, we present results of a cross-sectional survey of attendees at a national conference of primatologists, characterizing their occupational exposures to NHP. Of 116 individuals who participated in the study, 68.1% reported having worked with NHP in a field setting, 68.1% in a laboratory setting, and 24.1% at a zoo or animal sanctuary. Most subjects (N=98, 84.5%) reported having worked with multiple NHP taxa, including 46 (39.7%) who had worked with more than five distinct taxa. Sixty-nine subjects (59.5%) recalled having been scratched by a NHP and 48 (41.1%) had been bitten; 32 subjects reporting being bitten more than once. Eleven subjects (9.5%) reported having been injured by a needle containing NHP tissue or body fluids. We conclude that primatologists are at high risk for exposure to NHP-borne infectious agents. Furthermore, primatologists' varied occupational activities often bring them into contact with multiple NHP species in diverse contexts and geographic areas, over extended periods of time, making them a unique population with respect to zoonotic and anthropozoonotic disease risk.

Disease risk analysis: a tool for primate conservation planning and decision making.

Concern about emerging and re-emerging diseases plays an increasing role in conservation and management of both captive and free-ranging nonhuman primates (NHPs). Managers and policy makers must formulate conservation plans in an arena plagued by uncertainty, complexity, emotion, and politics. The risk analysis paradigm provides a framework that brings together scientists and policy experts to make better decisions for both people and animals. Risk analysis is a multidisciplinary, science-based process that provides an organized and logical approach for incorporating scientific information into policy development in the real world. By blending four specific goal-oriented stages-hazard identification, risk assessment, risk management, and risk communication-one can logically assess the probability that an adverse event, such as the introduction of an emerging disease into a naïve population, will occur. The following is a review of this process as it pertains to NHP conservation and risks associated with infectious diseases.

Detection of antibodies to selected human pathogens among wild and pet macaques (Macaca tonkeana) in Sulawesi, Indonesia.

Human-to-primate disease transmission can potentially cause significant morbidity and mortality among wild primate populations and thus constitutes an important conservation issue. Our cross-sectional study examines serological evidence of exposure to human pathogens among wild and pet macaques in Sulawesi. Serum samples taken from 11 pet and 15 wild macaques (Macaca tonkeana) were analyzed for antibodies to a panel of viruses commonly encountered in human populations. Antibodies to measles, influenza A, and parainfluenza 1 were detected in sera of both pet and wild macaques. Antibodies to parainfluenza 2 and 3 were found in the sera of wild macaques only. Possible routes of exposure, as well as implications for conservation are discussed.

The effects of maxillary quad-helix appliance expansion on cephalometric measurements in growing orthodontic patients.

This study was conducted to examine the effects of maxillary quad-helix expansion on frontal and lateral cephalometric measurements in growing orthodontic patients. Twenty subjects, nine girls and eleven boys (x age = 10 years 3 months), each exhibiting at least a unilateral posterior lingual cross-bite that had been treated with a maxillary quad-helix appliance, were selected for this study. Posteroanterior and lateral cephalometric radiographs were taken at the beginning of treatment (T1), when the appliance was removed (Tprog, x time = 9 months), and at retention (T2) and subsequently traced. The T1 and T2 dental casts were also measured as supplements to the cephalometric measurements. Significant orthodontic changes, as seen on the frontal radiographs from T1 to Tprog, included a mean increase in maxillary intermolar width of 5.88 mm, a mean increase in average frontal molar relation of 2.95 mm., and a mean increase in maxillary intercanine width of 2.74 mm. The orthopedic changes, as evidenced radiographically, included a mean increase in maxillary width of 0.92 mm. and an increase in average maxillomandibular width of 0.89 mm. From the above data, a 6:1 ratio of orthodontic movement to orthopedic movement was determined. No significant change in mandibular intermolar width was observed from the cephalometric data or from the cast measurements. The most stable cases after expansion had normal nasal widths and narrow maxillary widths. No correlation was shown between the age of the patients and the orthopedic expansion recorded or between the amount of orthodontic/orthopedic expansion and facial type. It was concluded that all expansion changes showed little relapse from Tprog to T2 and that moderate orthopedic expansion is possible with the quad-helix, but only slight orthopedic expansion was consistently demonstrated.

A comparative analysis of intrusion of incisor teeth achieved in adults and children according to facial type.

A comparison was made of incisor intrusion achieved in adults and children with deep bite. Facial type was also examined for effect upon intrusion achieved. Fifty-five cases treated with bioprogressive mechanics were studied cephalometrically; subjects included twenty-four adults and thirty-one children. Neither age nor facial type was found to be statistically related to the amount of incisor intrusion achieved in this sample. A method of measuring intrusion at the root apices was devised and was thought to give a more accurate indication of actual bodily intrusion. More external root changes during treatment were observed for adults than for growing children. There was a wide latitude in the amount of intrusion observed in both groups and in all three facial types. Considerable overbite reduction was noted for the sample, and intrusion was found to be but one factor in this.

Nasopharyngeal cephalometrics.

A sample of 104 patients, males and females between the ages of 6 and 16 years, was studied. The sample included patients with clinically diagnosed nasopharyngeal obstruction, patients with no obstruction, and random sample of patients for whom the presence or absence of obstruction was not known. More than 200 cephalometric measurements were used in an attempt to identify differences between the first two groups. Statistical t tests revealed four variables, all primarily related to adenoid size and nasopharyngeal dimensions, for which the mean values of the two groups were significantly different. Cephalometric norms for these four measurements were established, using the random sample patients, and these norms were calculated for various ages and both sexes. A method of identifying the degree of obstruction was then formulated on the basis of the four significant measurements. Preliminary results indicate that this method is highly correlated with observed clinical results.

Preformed arch wires: reliability of fit.

The preformed arch wires currently available are unsuitable for many orthodontic cases, since these arch wires do not take into account all the variations in the size and dimensions of the human arch. In this study, nine theoretical arch wires are derived, based upon two-parameter curves. Tests were conducted which demonstrated that arch wires performed to these nine sets of dimensions would correspond with a reasonable degree of accuracy to a large section of the orthodontic population.

Soft-tissue change as a result of maxillary surgery. A preliminary study.

A retrospective investigation of soft-tissue changes following two types of maxillary surgical procedure (anterior alveolar segmental, LeForte I) in nineteen adult patients was undertaken. Several hard-tissue coordinates were correlated to each coordinate of eleven soft-tissue points by multivariate regression analysis. This new method was compared to a previously derived nonsurgical prediction method (Ricketts). The following results were observed: 1. For eight horizontal and vertical coordinates (Glh, Glv, Nah, Av, Nch, Ncv, Pnh, and Pnv), neither method was accurate. 2. For ten horizontal and vertical coordinates (Snh, Snv, Ah, Av, ULh, ULv, Stv, LLh, Bv, and Pogv), the mean prediction residuals for the multivariate method were significantly smaller than those for the modified nonsurgical method. 3. For three horizontal and vertical coordinates (LLv, Bh, and Pogh), there were no significant differences between the mean prediction residuals of both methods. Two additional cases were used to test the new method for general applicability. Visual examination reveals that the predictions for these cases are clinicallly acceptable. Only further testing can establish the true validity of the new method.