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lab animal
11/10

primates
david martin, VMD

slide: this is 
a monkey in ironwork, from the Philadelphia Zoo. what species is this? it 
has long arms so probably brachiates - moves through foliage rather than 
over ground. but tail isn't truly long enough to be prehensile. is 
probably not a real species. just art.

slide: etching of some sort of 
macaque - the genus macaca is southeast asian. but no idea what spp. 


here's what you need to know - a wide view of the order of primates. also 
some information that may save your life - some zoonotic dzs carried by 
primates are fatal to man but not to monkeys. also these monkeys are very 
very strong. a small 15 kg baboon can crush an apple into applesauce with 
one hand. 

one of the best statements he's heard - a friend of his 
defined rhesus monkey as an evil spirit covered with feces. ok, that may 
not be true, but these animals can be dangerous and carry disease. of 
course, they are also cute :)

slide: some cynomologus monkeys with eyes 
blacked out (censored)
slide: drawing of longnosed monkey
slide: photo of 
longnosed monkey - nasalis longatus from borneo, the proboscis monkey


red something from upper amazon basin. these slides should be 
demonstrating to you that this monkey's nostrils open to the side - New 
World monkey. Old World ones have nostrils opening downward. 


characteristics of the order of primates (in handout) - no one feature is 
shared by all primates, no one primate has all the features. there are 
about 190 primate spp.
opposable digits - thumb and big toe
flat nails 
instead of sharp claws
2 pectoral mammae
clavicle present
there is a lot 
more.

like guinea pig and man, there is a dietary vitamin C requirement. 
even with modern diets, there are reported cases of scurvy. some primate 
center was feeding animals soaked biscuits - but the vitamin C was 
sprayed onto the biscuits and soaking them washed it off. 

slide: 
primates are divided into prosimians, tarsiers, and anthropoids (which 
include man). the anthropoidea include the platyrrhini (new world) and 
catarrhini (old world) including lesser apes, great apes, and man.

in 
general, as you move from left to right on our chart here, you find small 
animals and then larger animals. left side - more colorful; right side - 
usually plain brown.

sexuality of animals in terms of anatomy and 
physiology gets more complex toward the right. animals toward the left 
tend to have twinning, which is more uncommon in higher animals. in man, 
1 in 5, in rhesus, 1: 1000 (what??)
also time til weaning increases as 
you move to the right. prosimians, months. simians, about a year; great 
apes, about 10 years, and man - well, 35 years. :)

living nonhuman 
primate families overlaid over a map of the world. 
the family cebidae, 
callitrichidae are in central and south america - New World monkeys. all 
others are old world monkeys. the NW monkeys pose little risk to humans 
with normal immune systems. three islands on chart - St Kitts, Barbados - 
both of these have indigenous population of African Green Monkeys 
imported 300 yrs ago by sailors. these are now agricultural pests, and 
St. Kitts actually harvests and exports them. Madagascar is an 
interesting island off the coast of Africa - the only place where Lemurs 
are found - highly endangered species. finally off the east coast of 
madagascar is Mauritius, where cynomologus monkeys live. most cynos live 
in southeast asia, but a group of them was imported to Mauritius, and the 
Mauritian cynos do NOT carry Herpesvirus Simiae (Herpes B) for some 
reason, so that's good. 

Old World vs New World characteristics:
NW: no 
cheek pouches, no ischial pads, nostrils to the side, often prehensile 
tails, need D3 in diet
OW: have cheek pouches, ischial pads, nostrils 
open downward, no prehensile tails, need D2 or D3 in diet

slide: various 
fingers of primates - different types of nails. most are like man, a 
couple are more similar to claws. 
slide: uteri - bicornate uterus is 
present in say the tree shrew; unicornuate uterus of anthropoids is seen 
in man, great apes, some old world simians.

galago: this mother has 
twins, that's normal. the claw on 2nd toe of the foot of these prosimians 
is specialized grooming claw! other toes have nails like ours. on female 
- her vulva is closed during nonbreeding season. when in breeding season, 
vulva opens. 

ringtailed lemur from madagascar: note black streak inside 
the wrist, and posture with tail being held up in the air. 
these animals 
commonly sit on their butt, open armed, facing the sun to gain heat. 
these black things on the forearms are antebrachial glands - more 
prominent in males. the male will run his tail along the glands, to pick 
up scent, then waft his tail back and forth over his back to attract 
females.

slide: from South Carolina primate facility - variety of lemurs 
- ring tailed, brown, and ruffed. there are about 30 spp of lemur. 


Tarsier: the one little group that doesn't fit. teeth are primitive. very 
big ears, used for hunting. eyes are a giveaway to the nocturnal habits. 
eyes are huge. 

NW animals: 
cebidae (look like monkeys)
Callitrichidae 
(marmosets, tamarins)

common marmoset: used in research. twinning is 
very common - most common. they do a lot of scent marking. if you keep 
them caged, and provide nest box, we've found over the years it is not 
good to take cage and nest box to washer at same time. leave one or the 
other - alternate them - otherwise it takes him a few hours to scent mark 
everything when it gets back.

cotton topped marmoset: twins again, 
except when young are not nursing the dad carries them around

golden 
lion tamarin from brazil - these are hopefully coming back from near 
extinction.

Cebus monkey - NW monkey with side facing nostrils. he has 
an autoimmune dz. 

Owl monkey - another nocturnal spp - Aotus 
triburgatus (or something liek that). used in malaria research. different 
subspp have different # of chromosomes, so you have to consider this in 
breeding programs. 

squirrel monkey: tough little bugger  weighs 
700-1100 grams. various facial markings vary with site of origin of 
monkey. most common health problem in these is impacted tooth - roots of 
upper teeth are only mm from the skin so may see red swelling below the 
eye which will burst. 

spider monkey - a true prehensile tail is present 
- these tails have prints like fingerprint/palmprint. a truly amazing 
appendage. they can use these tails, move them around without looking at 
them - one monkey used to keep all four feet attached to cage bars and 
then probe into your pockets with the tail. this spp has female clitoris 
longer than male penis!

Old World spp:

Cercopithecoidea: most often 
used in biomedical research
the main one is Rhesus monkey -found all over 
SE asia. the main NHP for research until India found that USA was lying 
about use of them in nuclear research and cut off supply. other countries 
exported them a bit, then we started using cynomologus monkeys more. 
there are 16 macaque spp. there are Japanese Snow Monkeys that spend 
their time in the hotsprings - those are macaques.

closeup of rhesus 
monkey: this one has a suntan - wow. he lives on an island. generally, 
tattoos are the way we ID NHPs in the lab - we tattoo the lower chest or 
upper abdomen so we can see it; here this animal is tattooed on inner 
thigh and on the face. this means if he's out free ranging, people can 
see the tattoo more easily - although people who know the animals 
probably know them by their appearance.

slide: people tattooing monkey - 
wearing gloves but no mask or eye protection. not cool. if you find 
yourself in a lab and are asked to tattoo them, it's better to do it 
yourrself, not take it to a tattoo shop :)

female rhesus - large 
swelling on forehead - "sex skin" - edematous skin found on face and in 
some animals around perineum, rises and falls with sexual cycle. other 
spp have even more pronounced sex skin; that can be used in predicting 
ovulation. 

original rhesus family group - unmasked, this time - this is 
a good picture. they are grooming - well, female is grooming the male. 
this is a social behavior. it's very important. less dominant animal 
always grooms more dominant animal. 

slide: another group of rhesus 
monkeys - subrace called golden rhesus. they're pretty! these are in the 
Frankfurt zoo. in the wild, maybe 1:2000 of them are this color.

in the 
wild - there is a troop of monkeys consisting of a few adult males (maybe 
three), many adult females, and the 1-2 year old offspring. it's a 
matriarchal society. status of young depends on status of mom. young 
males are driven off at sexual maturity and become "migrant males." if 
they are lucky, they go to another colony and set up residence but to do 
that, they have to kick out existing males. so often these males just 
die. this is a great way to avoid inbreeding, though.

slide: mom and 
baby - rhesus and cynos have single births, one per year, usually at 
night. offspring carried for a year. gestation about 5 mos. 

slide: 
menstrual card - you can train these animals to present perineum for 
swabbing. you determine cycle and then find day 12 which is good breeding 
day.

slide: artificial insemination - note ischial pads/callosities 
present here. upon ejaculation, the semen of the male coagulates - so 
that keeps it in the female. sometimes you find plugs in male macaque 
cages, b/c they masturbate. sometimes it looks like a cast of the urethra 
- called a "sperm worm". that's normal. 

another normal rhesus monkey 
eating an apple - note the "swelling" in the area of the cheek pouches - 
he's filling them with apple.

slide: teeth and cheeck pouch opening - 
lateral to lower dental arcade is opening to the pouch.

cynomologus - 
macacus fascicularis, aka longtail or crabeating macaque. these are found 
throughout SE asia, popular research animal. this one has measles. high 
morbidity and low mortality with this disease. should vaccinate them 
while in quarantine to avoid this. use human vaccine.

slide: TB testing 
of macaque. TB is more acute in these monkeys. test - inject 1/10 cc 
mammalian tuberculin (Not PPD) into eyelid. read 3 times 24, 48, 72 hrs.

if positive, euthanize, usually. don't confuse bruising with positive TB 
test. 
more problematic - slight erythematous swelling of eyelid in this 
one - could quarantine and retest in other eye in two weeks, or just 
euth.

gibbon - false positive TB test b/c this reaction occurred within 
2 hrs and was gone in 4 hrs. has to do with prior injection of freund's 
adjuvant.

blood collection from femoral vein (femoral triangle)
slide: 
saphenous vein running down back of leg - common site for IV injection.


marbury macaque - of N Africa, gibraltar. huge canine teeth. this guy is 
opening the monkey's mouth with no gloves on. holding this animal 
barehanded while smoking a cigarette is a bad idea. 

pigtailed macaque 
not commonly used in research - note curly little tail and much more 
consistent sex skin response than the other monks.

stump tailed macaque 
- babies are born light, change to dark color at about 7 or 8 mos. this 
is normal. 


lion tailed macaque - endangered, not  used in reserach


african green monkey with albino baby - rare

military monkey - has 
mustache :)
hold monkeys with both of their arms behind their backs. 
the 
females exhibit color changes of the nose with pregnancy - usually brown, 
turns white. males also have huge canine teeth

to catch animals - double 
glove of cowhide and elkhide (toughest leather) - still can get bitten 
through it.

Baboons - various spp of them - in egypt, sacred baboon - 
these females show huge sex skin responses. the one on the right is 
"blooming" - this goes away the day after she ovulates. chimps do this 
too.

mandrill - not used in research

review of animals most used in 
research is in handout. 

Gibbon - brachiating animal - arms very long. 
5-6 kg animals 
hand of baboon, btw, looks like ours!
hand of gibbon is 
long and slender - four long fingers, almost vestigial thumb.

chimpanzee 
- this is an adult at about 40 kg
yet another chimp spp - the one with 
highly reviewed sex life - 
both spp take 8-10 years  to wean, females 
weigh about 30 kg

orang-utan - this one is in a sycamore tree at the 
zoo. 

learn the names of macaca mulatta (rhesus) and macaca fasicularis 
(cyno); remember all macaques can carry herpes B which is fatal to man. 


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dave johnson

Primate diseases:

many diseases are applicable 
to humans or medical research in some way.

Macaca mulatta - rhesus 
monkey (short tail)
Macaca fasciculata - cynomologus monkey (long tail)


there are still a lot of pet primates out there. it is illegal to import 
monkeys for pets, but if they are already here, they can't do anything 
about that, and someone has to take care of them so now you are going to 
learn how. or something.

there are zoonotic diseases - about 70% of 
natural diseases of NHPs are transmissible to humans. human diseases also 
transmissible to NHPs. 
femoral bleeding site, saphenous IV route 
important.
sex skin being shown again - don't panic, it's not a problem.  
it's a normal physiological response and affects perineum, forehead, and 
legs of some animals. 

the buccal cheek pouch can become impacted or 
abscessed. 

Enteric infections - these are common and important. they 
can get all the ones we can get and they go back and forth.
shigellosis 
causes profound bloody dysentery
shigella is the most common etiology, 
causes hemorrhagic colitis and enterotoxin. nonclinical shedders can 
exist; high morbidity and mortality occurs.
NHPs do not show a lot of 
clinical signs - they are fairly stoic. so, it takes an aggressive 
therapy b/c by the time you see it it is severe.

salmonellosis - 

campylobacter jejuni - small and large intestine, may lead to abortion


enteric parasites:
entamoeba histolytica - four nuclei - pathogenic form

strongyloides sp - parthenogenesis occurs
oesophagostomum sp - 
helminthomas in humans

TB - important disease. 
etiology: M.TB, M.bovis, 
M.avium; atypical mycobacterium: M. intracellulare, M. kanasii.

in our 
lives, TB is low incidence disease *unless* we interact with people who 
carry it and unless we get stuck with one of those resistant organisms. 
NHPs are susceptible to a number of mycobacteria. we use mammalian 
tuberculin to TB test NHP - not human or bovine type, b/c it will not 
elicit the right response. 

it does go into lungs in these guys - the 
LNs will swell up, get large granulomatous lesions - in primates, mimics 
human juvenile form - rapid, fulminating, miliary without calcification 
so it won't show up as coalescing mineralized areas on rads.
can affect 
liver - we see little white granulomas all over it.
it can occur in 
fingers and look like trauma. 
sometimes stuff shows up on rads, but more 
often looks more like a pneumonia. 

TB test is intradermal, just like 
you do in other animals or people. why do we put it in eyelid? so we can 
see it. observe at 24, 48, 72 hrs. in cattle, you do it under the tail. 
that's b/c you examine dairy cows at the back end more often. 

it's 
critical to give this ID not SQ - SQ doesn't provide adequate exposure. 
you can miss the DTH reaction that way. if you need to retest b/c you are 
not sure, you can do it in the abdomen - this positive animal has two 
testing sites - PPD and mammalian TB - the response to PPD is minimal 
compared to the other one which is why we use mammalian type.  this 
disease spread so rapidly that tx is very difficult and unless animal is 
very valuable we do not treat. you can use the same regimes as used in 
humans - we do this for great apes. can't cure it but can stop it from 
spreading, keep animal from shedding.

clinical signs of TB in primates:


debilitation, lack of wt gain or simply loss of weight, dyspnea, 
coughing, nasal d/c, lymphadenopathy, nonhealing wounds, chronic 
diarrhea.

some animals with fulminant TB become anergic to tuberculin 
and do not show a positive reaction. those are tough cases. these animals 
shed a lot of organisms and are very dangerous wrt zoonotic potential. 


enlarged LNs - hilar, mesenteric, peripheral
granulomatous necrosis: 
lung, spleen, liver, etc.

dx: positive skin test with compatible lesion, 
positive skin test with acid fast organisms, neg skin test with 
compatible lesions, neg skin test with acid fast organisms, neg skin test 
with isolation of mycobacterium.

transmission: aerosol, ingestion, 
direct contact, etc.

prevention: routine testing, health monitoring, 
routine necropsy of all dead animals, quarantine program, vaccination 
does NOT work (BCG), occupational health program (TB test personnel 
routinely, use protective equipment)

false negative tests: poor 
technique, anergic, early case, weak tuberculin, concurrent 
immunosuppressive dz or tx: measles, SAIDS, cyclosporin A.

False 
positive TB tests: poor technique, freund's adjuvant or BCG, local 
sensitivity, lookalike dzs.

managing false positives: special tattoos, 
retest to verify, review medical records (BCG, freunds), radiograph, 
other.

pulmonary diseases to consider: measles, klebsiella pneumonia, 
rubeola, strep pneumoniae, bordetella bronchiseptica, pasteurella 
multocida, pneumonyssus simicola (lung mites). realize humans give 
diseases to monkeys as much as they give diseases to us. 

pneumonyssus 
isn't zoonotic - causes granulomatous lesions, with mites in them.
tends 
to be self limiting - not sure why, really. that's interesting, though.


melanomas in the sinclair farm miniature swine - if you breed two 
melanoma parents, half the piglets will have melanomas. tumors will grow, 
metastasize to regional LNs, but after about a year, disease will fade 
away and pigs will not die from it. why??? obviously something weird is 
happening in these pigs.

Herpes viruses: probably 60% or more of the 
people in the class of 2000 have had cold sores, or some experience with 
them. herpesvirus hominis aka herpes simplex is widespread in humans and 
people who have it get recurrent small ulcers on lips, eyes, or genitals. 
you don't die of it though. but if you give this virus to rabbit, 
marmoset, or owl monkey, you cause acute encephalitis and death.


Herpesvirus simiae - herpes B - reservoir is macaque - in humans causes 
peracute to acute hemorrhagic encephalitis and death within 30 days. 
doesn't bother macaque much. 

herpes T affects squirrel monkey - can 
kill owl monkey or marmoset.

slide: cold sore on lip of rhesus monkey.


virus lives in ganglia, remember, and travels to surface now and then.

the other similar dz is varicella which causes chicken pox. shingles in 
older people. 

10 yrs ago an article was published - "rare virus takes 
life of lab man." this was about herpes B, which really isn't a "rare 
virus" but is rare in man. 

patient 1: primate handler - known bites

patient 2: research tech - probable bite/scratch
patient 3: no exposure 
known - recovered on acyclovir
patient 4: wife of patient 2 who treated 
husband: day 30: seropositive, acyclovir given, recovered.

fewer than 50 
cases of documented death from herpes B in humans. but if you do get 
herpes B you will probably die. IV acyclovir started early can work. you 
have to stay on acyclovir.

if bitten - scrub 15 minutes with 
antimicrobial soap. use 1:20 dilution  (12.5 cc bleach in 250 mL sterile 
water) of bleach and soak 5 min, then scrub again for 15 min. 

Pox 
virus: monkey pox, Yaba, BEMP:

monkeypox is a typical pox disease, very 
pruritic so monks will scratch a lot and make it look worse.
BEMP: benign 
epidermal monkey pox - makes multiple raised oncologic lesions that do 
resolve over time. 
YABA: first reported in Yaba, Niger - histiocytomas 
caused by direct contact and fomites
Yaba and BEMP are zoonotic but not 
fatal to humans. 

Melioidosis: pseudomonas pseudomallei: endemic in SE 
Asia. dx in humans, macaques, orangutans, and chimps. long incubation 
period, slow, nonhealing abscesses form - osteomyelitis, septicemia - 
high mortality in humans. 

fibrous osteomalacia - simian bone disease - 
secondary hyperparathyroidism. Ca++/PO4 imbalance - vitamin D2 in NW 
monkeys isn't good enough! they need D3. D3 now used in all commercial 
primate feeds.

Scurvy - vit C deficiency - seen in NHP and G.pigs. also 
some exotics like Indian Fruit Bats or whatever but basically just 
monkeys and guinea pigs. we see it when there isn't enough C in the diet, 
or diet expires, or whatever. bleeding of gums, swelling of knees. 

if 
you see a lot of weird animals in your practice, contact Purina. they 
make special diets for all these animals :) many people want to put their 
exotic pets on home made diets but there are usually commercial diets 
available that are much better. 

The Hot Zone: 
Filovirus family - 
ebola, marburg, ebola zaire
we still do not know the reservoir - probably 
some animal it is nonfatal for, maybe a rodent or something, not sure. 

imported cynomolgus monkeys - numerous cases of death in quarantine 
attributed to filoviruses.

cynos, rhesus, and african greens have all 
tested positive. the only ones that didn't have any positives were from 
Mauritius.
simian hemorrhagic fever isn't a filovirus but causes similar 
signs in primates. 

it turned out for the problem of ebola virus that an 
NHP-ebola was affecting those primates, it didn't affect people. 

so, 
for NHPs - there's a baboon center in TX which has been maintained for 
30-40 yrs, baboons have a big caged area where they live in groups.  huge 
outdoor area. from a strict medical view, we're now exposing more 
opportunities for disease transmission by keeping them in groups, but 
they are happier in groups, so there you go. 

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