Over the last year many articles have mentioned the measurement of IgG as a method of evaluating the future health of a newborn llama. More farms are beginning to utilize this technique and veterinarians look at the level of this protein in older animals with signs of sickness finding indications that IgG may be useful in determining treatments. Insurance companies are beginning to require IgG levels on animals to be insured as a method of indicating an animals susceptibility to infection. To make matters more confusing for the beginning breeder we are starting to see articles on "organic" llama raising indicating that breeders have raised animals for years without these tests, why start using them now? References are made to the raising of alpacas and llamas in South America and how these animals are raised without special care. What is not mentioned many times is a 7 year study in Peru showing a mortality in alpaca crias ranging from 9 to 57% with a large percentage of mortality in the first four weeks as a result of gastrointestinal and pulmonary infections. In newborn calves, lambs, foals and alpacas Travis McGuire of Washington State University has documented these infections as a result of the failure of passive transfer (FPT).
The intent of this article is to bring the reader or his veterinarian up to date on what researchers have been seeing with Camelid IgG levels, what they might mean as indicated from studies with foals and other species and then decide for themselves what all the commotion is about.
Triple J Farms is associated with Kent Laboratories, which has been manufacturing human diagnostics reagents including radial immunodiffusion plates since 1974. For the past twelve years Triple J has been raising llamas. Over four hundred babies have been born and raised on the farm and various types of research, such as progesterone studies with Utah State University and immunoglobulin studies utilizing our own tests have been done. Information has been exchanged between our farm, various universities and large breeders giving direction to what kinds of information we should be accumulating. The following information is what our farm has found and what we think to date.
Immunoglobulin G or IgG is a protein found in adults in normal concentrations ranging from 900 mg/dl to 2400 mg/dl. This is approximately 20% of the total protein found in serum or plasma. IgG has a half life of 23 days. It contributes immunity to bacteria, viruses, parasites, some fungi and provides antibody activity in tissue. IgG is able to activate complement which triggers the inflammatory response and is a subject unto itself. IgG provides protection to various viruses and such for the animal through inoculations or natural barnyard exposure. Once exposure occurs a memory is developed which allows they body to rapidly manufacture needed antibodies to fight specific infections. In man IgG is transferred to the baby through the placenta. In horse, cow, sheep or camelids IgG cannot pass through the multiple placental membranes and is therefore only available to the baby by colostral intake. This is why IgG titers in the 24 hour cria is so important. If IgG is present the animal has immunity allowing it time to start manufacturing it's own IgG. If IgG is not present or in low levels, animals have poor defenses against any infectious agent to which it might be exposed.
Studies on foals have shown that FPT occurs in 2.5 to 17% of newborns. Reasons range from an animal not nursing in the first 16 hours to mothers not having adequate levels of colostrum to give a foal good protection. In 1988 a survey was done by the International Society of Veterinary Perinatology on 287 foals seven days of age or younger admitted to intensive care services. Of these foals 21% had generalized infections, 17% had localized infections and 33% had gastrointestinal diseases, such as diarrhea, sepsis or E. Coli infection. The overall data suggested that adequate passive transfer is associated with lack of infectious disease and survival. Dr. Tim Cudd did another body of work showing infection rates of 6% in foals with IgG less than 800 mg/dl and 3% in foals greater than 800 mg/dl. A study by Dr. Baldwin collected data from 132 foals suggesting that the level of IgG was not related to the occurrence or severity of illness in foals. Some speculation has been made that these studies were made on well managed horse farms with close to hospital sanitation controls for newborn foals keeping the exposure of the foals to possible infections at a minimum. In a separate study Dr. Stoneham discovered that by changing management practices alone the incidence of failure of passive transfer could be reduced from 19% to 11% two years later. Out of all these studies we can come up with two ideas. #1 - The amount of IgG needed to be present in a newborn to protect the animal from infection depends on the infectious agents present in the birthing area and #2 - the ingestion of the colostrum is dependent upon management of the newborn ensuring colostral intake.
From a three year study on colostrum levels of llamas measured before the baby can nurse we have averaged 15,958 mg/dl of IgG on 210 samples. We have found the viscosity or thickness to be directly related to the titer. If a sample sloshes like 2% milk the titer will probably be 3000 to 5000 mg/dl. If the sample has the consistency of Elmers Glue we're talking 15,000 to 20,000 mg/dl. Mothers seem to have approximately the same titer from year to year plus or minus 2000 mg/dl. Some females always stay around 18,000 to 20,000 mg/dl. Others are down around 6,000 to 8,000 mg/dl. We don't believe titers of 8,000 to 10,000 mg/dl always mean low passive transfer. It seems that these mothers have more colostrum available and we see passive transfer titers of 1500 mg/dl to 2500 mg/dl.
In horses a study by Dr. Lablanc found colostral IgG titer varies with the breed. 25 Arabians averaged 6100 mg/dl while 65 standard breeds averaged 4000 mg/dl. Maybe we'll be seeing the same thing in llama types.
Colostrom's importance is not limited to only the transfer of IgG. Other benefits are high levels of solids, minerals, proteins, vitamins and energy giving carbohydrates supplied in a concentrated form easily absorbed by the newborn. Lactoferrin is supplied which binds iron removing it's use from damaging micro-organisms which require iron to grow and thrive. Also present are beneficial microflora which inoculate the gut out competing and creating a disadvantageous environment for pathogenic bacteria. In studying the absorption of cow colostrum in baby llamas we have found absorption rates ranging from 2 to 26% of the total cow IgG supplied in 30 animals. Premature babies had the lowest absorptions. We also found similar absorption rates in 10 baby llamas supplemented with llama colostrum. As time got longer the % proteins absorbed decreased giving us the impression that llamas like other animals have 16 to 18 hours to absorb colostral antibodies before loosing the ability to transfer antibodies directly from the gut to the lymph system to the blood.
One of the advantages of measuring IgG in a 24 hour cria is that it's presence documents the babies absorption of colostrum. It indicates that the baby has nursed even if no one was present to witness the actual nursing. It also signifies whether or not the baby will or will not be susceptible to future problems. Along with this pattern of thinking would be to evaluate whether or not the baby is a high risk cria. Dr. Frank Garry and Dr. Regan Adams of Colorado State University have come up with a list modified from what hospitals use for humans and Dr. Ann Koterba used in foals as a sepsis scoring system. High risk crias can be considered under the following conditions such as born premature, dam had a vaginal discharge or previous infection, C-section delivery, difficult birth, born with poor sucking reflex and finally born small and or weak. Dr. Adams notes the earliest signs of a septic horse foals are subtle and include slight lethargy, weakening suckle reflex, diminishing appetite, and excessive time spent sleeping. Indications have been that by the time clinical signs become apparent the disease process is well advanced. In our experience with llamas crias we have observed these same descriptions in crias with FPT. Management is important because these animals are 48 hours from being dead by the time the obvious signs are seen, such as diarrhea and respiratory problems.
We've established that IgG measurement in crias might not be such a bad idea especially if we have a high risk crias. What test do we use to measure the IgG and how does it compare to other tests? In many cases it gets down to individual preferences. There are several types of tests available many offering a yes or no answer, others are very specific. A zinc sulfate test is one of the basic tests measuring all the immunoglobulins. This test is based on the fact that immunoglobulins precipitate out at a certain concentration of salt. By comparing precipitates the crias versus a known concentration you can get an idea if passive transfer has occurred. Latex tests are based on the agglutination of latex particles when exposed to llama serum. The amount of IgG present is relevant to the concentration, however you must be sure of using a test specific for camelid IgG and not horse or cow. Some people have tried to use enzyme tests specific for horse IgG and get variable results. Depending on cross reactions between animal IgG's is not reliable and will vary from batch to batch. Our test is based on the principle of Radial Immunodiffusion (RID) and is specific for camelid IgG (Alpaca, Guanaco, Llama). The principle is simple anti camelid IgG is produced in goat, processed and immobilized in agarose. The sample of llama blood is placed in a well in the agarose and a precipitate forms in a circle growing in proportion to it's concentration stopping when it reaches equilibrium. This ring can be measured and given an exact concentration enabling one to monitor changes in IgG levels, a handy tool to have during long term treatments. Currently six veterinary colleges and roughly 50 veterinarians across the country are using our RID test. All numbers mentioned in this article will be from our RID test. M and M Labs of Michigan uses RID in a panel with total protein and albumin. They have found that the three tests compliment one another for spotting problem animals. Other veterinarians have a problem spotting low IgG titers with total protein alone.
One of the problems in the foals and what we're now seeing in the crias is how to define the failure of passive transfer. One hundred and thirty tests run on crias born on this farm and other surrounding farms have ranged in titer from less than 100 mg/dl to 4000 mg/dl. The average number is currently 1426 mg/dl. Our thinking is that if we can achieve half of normal between 700 and 800 mg/dl we feel our newborns will stay healthy. Further justifying this number has been the observation of healthy crias with bleeds every 3 days for the first month. One cria's IgG started at 823 mg/dl and 27 days later had dropped to 188 mg/dl. Three days later the IgG went to 306 mg/dl and continued climbing. A cria born the same day started out a 3100 mg/dl and dropped to 614 mg/dl on day 27 before climbing upwards. Neither animal exhibited unusual behavior or illness. This observation which needs to be confirmed on more animals would indicate that IgG levels have to be high enough to prevent infections and be consumed for roughly the first 27 days of life. Personal observations of others have seen a healthier, faster growing baby at levels above 800 mg/dl but at this time we have no hard data to prove it. IgG titers on weanlings between 4 and 6 months of age have ranged from 450 to 1560 mg/dl the average being 746 mg/dl on 33 weanlings tested. We are currently measuring IgG levels at weaning to try and determine what effects, if any, weaning and in our case lead training can have on the immune system through stress. Adult levels of IgG on 38 samples ranged from 798 to 2520 mg/dl with the average being 1574 mg/dl. These averages on newborn, weanlings and adults help us to spot possible problems in animals that seem off. Reports from around the country are indicating that a weak immune system represented by lower IgG makes animals susceptible to parasites like giardia and EPE. Some animals have encountered chronic respiratory problems while others exhibit lethargy, loss of weight and sometimes diarrhea. Invariably most of the animals have lower IgG. The question many researchers are trying to answer is does the sickness lower the IgG or was the illness opportunistic and invaded for some reason while the animal's IgG was temporarily lowered?
At this time no one knows if the animals are picking up some sort of infection that incubates for a period and emerges at a stressful time or if the animals immune system just fails to recognize some sort of localized bug. What is becoming more and more apparent is that whatever is causing the problem it can be attacked with extensive transfusions allowing the animal time to manufacture it's own IgG. This is not true in all cases but in the farms we have worked with in this state eight of ten cases started manufacturing their own IgG after transfusions. Dr. Norm Evans in Kentucky has seen eight of nine cases start manufacturing average levels of IgG again after falling to a low of 200 mg/dl. After nine months they remain normal. Many of these animals have exhibited low weight gains, lethargy, poor skin tone, diarrhea and poor appetites. IgG's were below 300 mg/dl. Transfusions of liter quantities seemed to raise the IgG titer and allow the immune system a temporary respite giving it time to return to normal levels in about 30 days. After 30 days all signs of illness were gone and weight gains returned to normal. The animals on which this did not work were in a severely weakened state and could not be saved. Dr. Adams and Dr. Garry have both noted a massive consumption of IgG in sick crias brought into intensive care at Colorado State. Normal transfusions of plasma are quickly consumed sometime necessitating more transfusions to bring a sick cria out of critical care. On the subject of transfusions we have to look at research done on foals and humans and the little documented research on llamas.
Research on transfusions in humans concentrating particularly on isolated IgG was initiated more than 30 years ago. Studies have shown therapeutic success with chronic inflammatory disorders and autoimmune diseases. Some studies have shown that septic shock due to infection by gram negative bacteria causes endotoxemia which may be the result of an ineffective immune response. Glinz and co-workers in Zurich showed that the use of IgG in patients lowered the incidence of pneumonia by one-third and reduced the need for antibiotics significantly. Some possible causes of failure of immunity to viral infection are immunological tolerance, weak immunogenicity of the virus, infection of cells involved in antigen recognition, immunosuppression and just an ineffective immune response in an otherwise healthy individual. Dr. Morrell and Dr. Nydegger have speculated that in humans transfusions of IgG may shift the balance between the infectious agent causing the suppression of the host allowing the host to overcome the problem and return to normal. More studies need to be done. An interesting note on the use of hyperimmune sera in humans was it's widespread use to treat life threatening bacterial diseases. This use disappeared with the introduction of antibiotics. Now the thinking is that there are limitations to the use of antibiotics and therapies are going back to the use of antibiotics or IgG specific for gram negative infections. Dr. Sharon Spiers has investigated the use of horse plasma hyperimmunized with antibodies to endotoxins (J5). In the study 32 horses with acute stages of disease such as severe diarrhea, intestinal inflammation and a high suspicion of gram negative septicemia were given either J5 hyperimmune plasma or plasma not immunized with J5. The people giving the plasma were not aware of which type they were giving. In the results it was found plasma containing antibodies to J5 improved the survival and clinical appearance of horses with evidence of endotoxemia. Similar studies have occurred n humans. The complicating factor in the final analysis of whether or not anti J5 antibodies help is that cross reactivities between antibodies and proteins make it almost impossible for researchers to define what is occurring. We are currently investigating antibodies developed to J5 in llamas with Dr. Spiers documenting it's presence and how long it lasts in a transfused animal. Also under investigation is the transfer of J5 antibodies in colostrum to the cria and how long it lasts.
Not investigated but should be mentioned is that there are many other beneficial enzymes, proteins, electrolytes and hormones present in normal plasma. All of which benefit a sick animal.
We've discussed IgG, what it means, what we see in normal animals, what good it does when transfused and speculations about what the mechanism might be for helping sick animals. What is not addressed is the attitude some people are beginning to express. The comment has been heard that if the animal is sick and doesn't respond to antibiotics it should be allowed to die. No extraordinary procedures should be made to save the animal because you are weakening the gene pool. What they don't address is how you determine if the problem or sickness you're dealing with is genetic or just bad luck? Babies can have poor passive transfer because they got stuck in the birth canal and weakened before finally coming out. Maybe they are a bit dazed and dumb and don't really start to nurse for 2 to 3 days. Weanlings can encounter stress coupled with exposure to some sort of bug and become sick with a low IgG. Llama breeders who work 9 to 5pm jobs can't always be on the farm during the day and need a management tool which helps give an early evaluation of a possible problem. I think transfusions and the measurement of IgG are just another tool of the trade that veterinarians should start to evaluate. Decisions about whether transfusions are good or bad should be put off until more data is accumulated.
