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Hazard rates and causes of death in a captive group of crab-eating monkeys (Macaca fascicularis).

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American Journal of Primatology 30:13%147 (1993)
Hazard Rates and Causes of Death in a Captive Group
of Crab-Eating Monkeys (Macaca fascicufaris)
HANS U. LUDER
Department of Oral Structural Biology, Dental Institute, Uniuersity of Zurich,
Zurich, Switzerland
In an attempt to examine possible associations between stages of agespecific mortality and various causes of death, vital records of 159 male
and 192 female crab-eating monkeys (Mucaca fascicularis), housed as a
single group, were analyzed. Survival and hazard rates associated with
each of five distinct categories of causes of death were estimated for males
and females, using the nonparametric kernel method. The obtained overall survival and hazard functions were similar to those reported previously
for rhesus monkeys. Among two stages identified in age-specificmortality,
the first stage, characterized by rapidly decreasing hazard rates up to
about 1.5-2 years of age, was discriminated by the occurrence of deaths
due to unfitness for postnatal life. The second stage lasted up to the age of
10-15 years and was largely characterized by a high incidence of violent
deaths. The respective hazard rates in males and females attained peaks
during the early reproductive period of life and markedly decreased thereafter. This pattern was interpreted to indicate that second stage mortality
is unlikely related to senescence, but rather, seems to depend on extrinsic
environmental factors. Thus, when considering overall hazard rates in
Mucacu fusczculuris, the onset of senescence, as a result of the specific
aspects of simian reproduction, may be hidden from view, and mortality
due to aging may only be appreciable after 10 to 15 years of age.
0 1993 Wiley-Liss, Inc.
Key words: Macaca fascicularis, survival, hazard rate, causes of death,
type of mortality
INTRODUCTION
In search for an appropriate animal model for various aspects of human aging,
several studies of survival and mortality in nonhuman primates, mostly captive
rhesus monkeys, have been undertaken during the last decade [Smith, 1982; Rawlins et al., 1984; Dyke et al., 1986; Gage & Dyke, 1988; Tigges et al., 19881. In an
attempt to develop a mortality standard for larger Old World monkeys, Gage and
Dyke [1988] fitted the Siler model to data sets obtained from eight, mostly captive
populations of three monkey species. The Siler model is a three component com-
Received for publication February 13, 1991; revision accepted January 9, 1993.
Address reprint requests to Dr. H.U. Luder, Dental Institute University of Zurich, Department of Oral
Structural Biology, Plattenstrasse 11, CH-8028 Zurich, Switzerland.
0 1993 Wiley-Liss, Inc.
140 I Luder
peting hazard function allowing for a n immature and a senescent, in addition to a
residual, component of mortality. The latter component is assumed to be due to
“causes of death so severe that they kill regardless of age” and, therefore, to be
constant throughout life. Hence, residual mortality should be most evident during
a n age period when the immature and senescent components of mortality are low,
i.e., during adolescence and early adulthood. However, when applying the Siler
model, Gage and Dyke I19881 did not obtain significant values for the residual
component except in one animal group. This finding suggests that a residual hazard is essentially missing from populations of captive monkeys. Consequently, a n
early period characterized by deaths from causes associated with immaturity
would be continuous with a later period distinguished by causes of death due to
senescence.
It was the purpose of this study to test the above suggestion that simian
mortality lacks a distinct third component competing with the immature and senescent components. This was done by examining age-specific hazard rates and
causes of death in a group of captive monkeys.
METHODS
Vital records of 159 male and 192 female monkeys (Macuca fuscicularis) were
used for analysis. Animals were born between January 1,1961 and December 31,
1989 and belonged to a colony kept in the zoo of Base1 (Switzerland). Over the
entire observation period, a maximum of 80-90 animals lived together a t any one
time and were housed day and night as a single group. The animals did not receive
any special daily care except food and water. Disease prophyllaxis, such as vaccination against specific diseases, or routine veterinary care were not done. Medical
attention was confined to obvious illness and injuries. In such cases, animals were
isolated, usually for 1-2, a t most for 5 days, and then returned to the colony. With
few exceptions, these monkeys were reintegrated in the group and survived to
breed. Euthanasia was resorted to when a disease or injury proved resistant to
therapy or was considered by the veterinarian to be too severe to be cured. However, no animals, either newborn or very old, were killed so as to reduce the group
size. Population size was maintained by culling and removing animals to other
colonies.
Vital records included the exact dates of birth, of removal from the colony, and
of death, as well as of diseases and medical interventions. Euthanized animals
were classified as having died; stillbirths were excluded from the analysis.
Autopsy and microbiological tests were performed routinely on deceased animals except in a few cases where advanced autolysis or severe mutilation of the
cadavers prevented a postmortem examination. Based on the autopsy reports,
causes of death were assigned to the following categories:
(1) “Immaturity” was assumed, when animals apparently died, because they
were biologically unfit to cope with the demands of postnatal life. Thus, deaths
resulting, for instance, from severe birth defects a s well a s from maternal neglect
and subsequent starvation were summarized under this heading.
(2) “Violence” involved fights as well as accidents. In cases where the violent
event had not been observed directly, it was surmised based on the nature of the
injury evinced. Thus, bites were always assumed to have been incurred during
fights, while blunt trauma rather indicated a n accident. Clearly, these criteria did
not allow the determination whether a n accident had occurred in the course of a
fight.
Hazard Rates a n d Causes of Death I 141
(3) “Infections” were indicated by positive results of microbiological tests and
comprised infectious diseases as well as sepsis associated with severe injuries.
(4) “Other causes” included those which could not be assigned to one of the
above categories.
(5) An “unknown cause” was assumed when postmortem examination did not
allow a clear decision or when no autopsy could be performed.
In cases where two of the above possibilities could be considered, such as
combinations of severe injuries and infections, the cause of death was partitioned
equally to both categories.
Survival and mortality data of male and female animals were summarized in
separate life tables [Miller, 19811. From these life table values, smooth survival
and hazard functions were derived using the nonparametric kernel method and a
commercially available collection of FORTRAN subroutines (CURVDAT from
STATCOM, Neckargemund, Germany) running on a Micro PDP-11/73 (digital)
computer [Gasser & Muller, 1979; Miiller & Wang, 19901. While survival functions
were obtained directly from the life table data (i.e., as the zero derivative), hazard
rates were estimated as the first derivative of the cumulative hazard values. Kernels of order 2 (for zero derivatives) and 3 (for first derivatives) and fixed bandwidths were used for smoothing. The latter were selected so as to represent a
compromise between data-based optimal bandwidths for the curve segments with
the highest and lowest density of data points. By applying this procedure separately to the respective life table data, distinct curves of hazard rates against age
were obtained for each cause of death.
RESULTS
Most deaths of both male and female animals occurred within the first 3
months following birth (Tables I and 11). Thereafter, mortality rates dropped
sharply. Although one male and one female attained ages of 23 and 28 years,
respectively, the oldest deceased male was 12 and the oldest deceased female 26
years of age. Most animals removed from the colony and lost to follow-up ranged in
age from 1 to 10 years. As a result, the number of living males and females older
than about 15 and 20 years, respectively, was low.
Survival rates of male and female animals up to the age of about 7 years were
similar and characterized by a steep decline immediately after birth and a subsequent slow, though continuous, decrease (Fig. la ). Corresponding to a steep increase in hazard rate, the proportion of surviving males dropped markedly after
the age of about 7-8 years. By contrast, the hazard rate for female monkeys
remained low and started to increase only at the age of about 1 4 years.
Most deaths within the first 2 years of life in both genders were caused by
“immaturity,” “violence,” “infection,” and “unknown causes” (Fig. lb,c). Violent
deaths a t this early age usually resulted from deadly accidents, mostly falls, and
occurred somewhat more often in females than in males. Most of the infections
were related to diseases, e.g., pneumonia or gastrointestinal diseases, rather than
to severe injuries. During the period from about 2 to 12 years of age, “violence” in
both genders prevailed over the other causes of death. The respective hazard rates
attained a maximum around 8 years of age in females (Fig. lb) and two peaks
around 5 and 10 years of age in males (Fig. lc). After these peaks, the risk of dying
from violence dropped sharply. Violent events which occurred early in this age
period were partly accidents and partly fights, while violent deaths at higher ages
were related to injuries incurred during fights. In several instances, such injuries
were associated with sepsis. Thus, unlike infections occurring in the neonatal and
142 I Luder
TABLE I. Life Table for Male Animals
Number of animals
Alive a t
beginning
of
interval
Age
interval
(years)
0-0.25
0.25-0.5
0.5-0.75
0.75-1
1-2
2-3
3 -4
4-5
5-6
6-7
7-8
8 -9
9-10
10-11
11-12
12-13
13-14
14-15
15-16
16-17
17-18
18-19
19-20
20-21
21-22
22-23
23-24
24-25
~
159
139
137
136
131
118
99
78
68
54
48
31
24
17
13
8
7
7
7
6
3
2
2
1
1
1
1
0
Censored
within
interval
Exposed
to risk
of dying
Died
within
interval
0
1
0
3
9
18
18
10
11
6
16
6
6
3
4
0
0
0
1
3
1
0
1
0
0
0
1
159
138.9
137
134.7
126.2
109.1
91.5
72.3
62.6
51.5
40.1
28.1
21.2
14.4
10.9
8
7
7
6.7
5
2.7
2
1.6
1
1
1
0.3
20
1
1
2
4
1
3
0
3
0
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
Died
from
violence
2
0
0
0
1
1
0
0
2
0
0
0
0.5"
1
1
0
0
0
0
0
0
0
0
0
0
0
0
Died
from
infection
12
0
1
1
1
0
1
0
0
0
0
0
0.5"
0
0
0
0
0
0
0
0
0
0
0
0
0
0
~
"In these cases, no conclusive decision could be made as to one particular cause of death
infant period, infections recorded between 2 and 12 years of age in almost half of
the cases were related to severe injuries.
DISCUSSION
The present analysis was undertaken to determine whether particular causes
of death are associated with specific periods of the life cycle and could thus be used
to characterize the respective stage in age-specific mortality.
The chosen categories of causes of death compare to those based on the International Classification of Diseases, which were used for analyzing human mortality [Steffen et al., 19881. In agreement with this classification, fights as well as
accidents were considered violent events. Thus, the category ((violence"comprised
merely instantaneous deaths due to trauma, as against deaths resulting from
diseases or other natural causes. In addition to the classification used for causes of
death in humans, a category termed "immaturity" was introduced. This category
included deaths from such different causes as birth defects and starvation due to
maternal neglect. However, these deaths had in common that they resulted from
Hazard Rates and Causes of Death / 143
TABLE 11. Life Table for Female Animals
Number of animals
~
Age
interval
(years)
0-0.25
0.25-0.5
0.5-0.75
0.75-1
1-2
2-3
3-4
4-5
5-6
6-7
7-8
8-9
9-10
10-11
11-12
12-13
13-14
14-15
15-16
16-17
17-18
18-19
19-20
20-21
21-22
22-23
23-24
24-25
25-26
26-27
27-28
28-29
29-30
Alive at
beginning
of
interval
192
166
160
155
152
127
106
86
77
69
60
51
41
33
30
27
25
20
16
13
12
10
8
7
6
6
6
5
5
3
1
1
0
Censored
within
interval
Exposed
to risk
of dying
Died
within
interval
Died
from
violence
Died
from
infection
1
4
3
2
19
17
19
9
8
9
9
7
8
3
3
2
5
4
3
1
1
1
1
1
0
0
1
0
2
1
0
1
191.1
164.1
158.5
155
143.1
118
98.2
80.8
73.2
64.9
57.1
47.9
36.3
32
28.9
26.1
22.2
17.4
14.6
12.3
11.4
9.1
7.5
6.5
6
6
5.6
5
3.6
2.5
1
0.8
25
2
2
1
6
4
1
0
0
0
0
3
0
0
0
0
4.5"
2
1
0
4
1.5"
0
0
0
0
0
1.5"
0
0
0
0
8.5"
0
0
0
2
0.5"
1
0
0
0
0
0
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0.5"
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
"In these cases, no conclusive decision could be made as to one particular cause of death.
the animals' apparent biological unfitness for postnatal life and, therefore, were
summarized under the same heading. Further deviating from the classification of
Steffen et al. [19881, the category "infection" included all kinds of infectious diseases as well as sepsis associated with severe injuries.
For estimating survival functions and hazard rates, I have used the nonparametric kernel method. The most important feature of this method is that it does not
assume a specific functional model, i.e., a particular pattern of age-related survival
and mortality. This aspect seems to be essential when considering the large variability in survival characteristics of Old World monkeys [Gage & Dyke, 19881.
A major problem faced in this study was the large number of animals removed
from the group for the purpose of sale. Such a high degree of censoring seems
typical for active primate breeding colonies [Dyke et al., 19861 and apparently
144 I Luder
sunrival
Hazard Rate
- Female Survival
-- Male Survival
Female Hazard
....... Male Hazard
Hazard Rate
-All Causes
Immaturity
-v
i
Infection
-_
Other Causes
....... Unknown Cause
Hazard Rate
- All Causes
Immaturity
- VilenCe
Infection
--
Other Causes
....... Unknown Cause
Fig. 1. Age-specific survival and mortality. a represents overall survival and hazard rates for male and female
animals; b and c depict hazard rates related to the categories of causes of death “immaturity,” “violence,”
“infection,” as well as “other” and “unknown causes” for female (b) and male (c) animals.
affected most previous investigations of mortality in captive monkeys [Gage &
Dyke, 1988; Tigges et al., 19881.
As a result, the numbers of living animals and deaths recorded in the present
Hazard Rates a n d Causes of Death / 145
study at older ages were so low that hazard rates due to senescence could not be
estimated reliably. Furthermore, it cannot be quite ruled out that in a zoo, only
sickly and weak animals are culled for transfer. As a result, censoring could have
been related to health and vigor of the monkeys. Yet, no confirmation for this
hypothesis was obtained from the vital records, as they did not reveal antecedence
of particularly many fights or illnesses in censored animals. In fact, a majority of
culled monkeys were transferred for purposes of breeding, and observations in two
colonies which had obtained such animals indicated that they were healthy and
vigorous.
The obtained survival and hazard rates up to the age of about 10-15 years in
both male and female animals were in good agreement with those reported previously for rhesus monkeys, although housing conditions, management of the colonies, and standard animal care may have varied considerably [Rawlins et al., 1984;
Dyke et al., 1986;, Gage & Dyke, 1988; Tigges et al., 19881. When compared with
the standard survivorship developed by Gage and Dyke [1988], the survival functions of the animals analyzed in this study dropped more steeply after birth, but
subsequently exhibited flatter, almost linearly decreasing courses up to the ages of
about 8 years in males and 17 years in females. Corresponding with these survival
functions, hazard rates dropped markedly after birth. During adolescence and
early adulthood, they remained low and almost unchanged in females, whereas in
males, the curve exhibited a peak a t about 6 years. After the age of about 7 years
in males and 14 years in females, hazard rates increased steeply. Thus, on the basis
of age-specific mortality, two periods or stages can be identified.
During the first period after birth characterized by the rapid drop in overall
hazard rates, all categories of causes of death contributed similarly to overall
mortality. However, while “violence,” “infection,” as well as “other” and “unknown
causes” to some degree occurred throughout further life, deaths resulting from
“immaturity” were recorded only during the early period after birth. The association with deaths due to “immaturity,” therefore, seems to discriminate the first
stage of mortality and to justify the term “immature component” suggested by
Gage and Dyke 119881.
The second period of low overall mortality was determined largely by a high
incidence of violent deaths. In both genders, the respective hazard rates attained
peaks during the early reproductive period of life and thereafter decreased markedly. This pattern was particularly prominent in males, where a transient increase
in overall mortality around 6 years of age apparently was due to a high incidence
of violent deaths. It could be argued that the peaks in hazard rates resulted merely
from low numbers of deaths. However, the obtained rates for violent deaths probably are underestimates, as severe injuries often were associated with sepsis, and
consequently deaths were assigned equally to the categories “infection” and “violence,” although the violent event most likely was the primary cause of death.
Furthermore, a similar, uneven distribution of violent deaths among males and
females and among various age groups is also suggested by the recent results of
long-term demographic monitoring of free-ranging langurs [Rajpurohit & Sommer,
19911. In this population, (1)males faced a considerably higher risk to die from
violence than females; (2) deaths of infant animals were most frequently due to
intraspecific killing, which occurred only very rarely in the colony examined here;
(3) juvenile animals died particularly often from accidents; and (4) heavy wounding as a result of fights, in addition to accidents, appeared to be the most frequent
causes of death in subadult and adult animals. Conceivably, the high incidence of
violent deaths during adolescence and early adulthood might be linked to specific
aspects of simian reproduction, such as emigration of males from their natal
146 I Luder
groups and intermale competition for dominance in a group, in which females can
get involved as well. Thus, violent deaths could well account for a transient increase in overall mortality during the early reproductive period of life. In fact,
peaks in overall hazard rates around 8.5 and 6 years of age, respectively, can also
be demonstrated for the female and, most prominent, the male rhesus monkeys of
the Yerkes Regional Primate Research Center [Tigges et al., 19881.
Such a course is incompatible with current thinking of residual mortality, as
this component is assumed to be constant throughout life. In addition, such a
course is neither compatible with current concepts of senescence. As is clearly
indicated by the widely established use of the Gompertz and Weibull functions to
mathematically model the senescent component, this is commonly conceived as a
continuously increasing process which does not allow for peaks in hazard rate.
Thus, violent deaths and, hence, the major proportion of second stage mortality do
not seem to be related to senescence, but rather to extrinsic environmental factors.
This does not imply that biological aging processes could not be initiated already
during the second stage, as is suggested, for instance, by age-associated changes in
joint mobility of rhesus monkeys [DeRousseau et al., 19831. If so, however, the
expression of biological aging is not revealed by mortality, but rather masked by
the extrinsic factors prevailing during early adulthood. Therefore, when considering overall hazard rates in monkeys, senescence as the main cause of death should
be assumed only after the end of the second stage. Although the present data do not
allow me to estimate precisely the age of this end, they do suggest that in crabeating monkeys, it occurs between 10 and 15 years. This estimate is in good agreement with that suggested by the appearance of degenerative joint disease in rhesus
monkeys [DeRousseau, 19851. However, it assumes the onset of manifestations of
senescence clearly later than at puberty, as was done in a recent comparative
analysis [Finch et al., 19901.
CONCLUSIONS
These findings would allow me to hypothesize that: (1) in a population of
captive nonhuman primates, the period of mortality associated primarily with
senescence is preceded by two other distinct stages; (2) while the early period
following birth is characterized by deaths resulting from apparent unfitness for
postnatal life, the second stage seems to be related mainly to extrinsic environmental factors; and (3) when considering overall hazard rates, the onset of manifestations of senescence in Macaca fascicularis should be assumed between 10 and
15 years of age.
ACKNOWLEDGMENTS
I am indepted to Mr. F. Salz and Dr. E. Thommen, Zoo of Basel, Basel (Switzerland) for providing life history records of the monkeys. Heartfelt thanks are due
to Mrs. R. Kroni for preparing the manuscript. This study was supported by grants
of the Hartmann-Muller Foundation (298 and 3081, and the Foundation for Dental
Research of the Swiss Society of Dentists (144).
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