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The data show the rate of viral conversion for septic patients whose blood or plasma initially tested negative for virus and who subsequently became positive during the course of their sepsis. A provocative study links prolonged episodes of sepsisa€”a life-threatening infection and leading cause of death in hospitalsa€”to the reactivation of otherwise dormant viruses in the body.
The research, published June 11 in PLOS One, suggests that drugs that "rev up" the immune system could be incorporated into the treatment of prolonged sepsis.
Surprisingly, the researchers detected levels of viruses in sepsis patients that were on par with those seen in patients who have had organ transplants and are taking immune-suppression drugs to prevent rejection. Earlier research at Washington University and other institutions has hinted that lingering sepsis may be linked to immune suppression. For the current study, first authors Andrew Walton and Jared Muenzer, MD, used polymerase chain reaction (PCR) testing to detect a range of viruses in blood and urine samples from 560 critically ill patients with sepsis, who were treated in the surgical and medical intensive care units at Barnes-Jewish Hospital. Patients with lingering sepsis had markedly higher levels of viruses detectable in the blood, compared with the healthy controls and critically ill patients without sepsis. These viruses generally don't lead to significant illness in people who are healthy but can cause problems in patients who are immune-suppressed.
The researchers noted that 43 percent of patients with sepsis had two or more viruses detected in their blood or urine during their hospital stays. Additionally, the researchers found that septic patients with higher levels of viruses detected in their blood were more likely than critically ill patients without sepsis to have more severe illnesses, secondary fungal and bacterial infections, and longer stays in the intensive care unit. Also, septic patients with evidence of cytomegalovirus in plasma, a component of blood, had significantly higher 90-day death rates than septic patients who tested negative for the virus, although it is not clear whether the cytomegalovirus contributed to the additional deaths. A further direction for researchers is to determine whether PCR testing for a panel of latent viruses could be used as a readout of the state of a person's immunity. A recent study led by Boston University School of Medicine (BUSM) shows that "practice may make perfect" when it comes to caring for patients with severe sepsis.
An analysis that included approximately 7 million hospitalizations finds that sepsis contributed to 1 in every 2 to 3 deaths, and most of these patients had sepsis at admission, according to a study published by JAMA. Scientists at the University of Bristol have identified the trigger for immune cells' inflammatory response a€“ a discovery that may pave the way for new treatments for many human diseases.
Yale scientists have solved a puzzle of the immune systema€”how antibodies enter the nervous system to control viral infections. University of Adelaide researchers have developed a new theory for the causes of dementia and other neurodegenerative diseases, involving an out-of-control immune system.
This section on Primate Medicine will give you a good review of the major husbandry challenges, diseases, and clinical approaches to primate health issues. Gain an appreciation for the significant zoonotic diseases, especially viral diseases such as Herpes B and bacterial diseases such as tuberculosis.
Be familiar with the preventative health measures recommended for non-human primates in a variety of settings. Primates are a diverse group of mammals representing over 600 distinct species and subspecies with worldwide distribution.
Understanding primate taxonomic categories also helps in determining specific husbandry needs and disease susceptibilities. In general, the order primates share many behavioral and anatomical features that make them somewhat unique in the animal kingdom. All of these physical and mental adaptations make the husbandry of non-human primates complex and demanding.
Since October 10, 1975, US Public Health regulation 42 CFR 71.53 has prohibited the importation of nonhuman primates (NHP) into the United States as pets, and neither nonhuman primates imported since that date nor their offspring may be legally bred or distributed for any uses other than bona fide science, university level education programs, or full time zoological exhibition.
Despite all of the federal regulations and state regulations, there are still plenty of NHP in the pet sector. Is there a veterinarian in your area willing to care for the monkey and who has enough experience to provide quality care?
Nutritional deficiencies, usually because of owner ignorance, are common problems in pet monkeys.
Commercially available dietary products for both New World and Old World primates offer the most balanced nutrition.
Hepatic iron storage disease has been reported in lemurs and marmosets and may impact other neotropical primates. Because of the evolutionary closeness between non-human primates and human primates, they share a lot of the same disease concerns. This viral family is one of the more common groups of viruses found in NHPs, as well as one of the best publicized. Probably the most famous of the herpes viruses is Herpes B (Macacine herpesvirus 1 or herpesvirus simiae), which is a disease of all macaque species, including rhesus, cynomolgus, bonnet, Japanese, Taiwan, stump tail, and pigtail macaques. Only a small percentage of infected macaques will present with clinical signs of ulcers and white plagues on lips, nares, tongue, genitalia, and palate and they may have conjunctivitis. Although symptomatic human infections from exposure to herpes B virus are rare, when symptomatic infection does occur, the infection is severe and often fatal (79%).
Diagnostic testing for the detection of Herpes B can be done by serology to detect antibodies. It is safest to assume that all macaques are carrying and capable of transmitting Herpes B infection. Immediately scrub the wound with running water and detergent for 15 minutes; or flush mucous membrane for 15 minutes with running water or saline. Human herpesvirus 1 (Herpesvirus simplex): Both HSV1 and HSV2 have been known to be transmissible from man to monkeys (experimentally). Herpesvirus tamarinus: viral herpes in tamarins and marmosets that may cause severe clinical disease, including hepatitis, in those species.
Simian Varicella viruses (SVV): This is a group of seven simian herpesviruses that closely resemble varicella-zoster in man. Simian Cytomegaloviruses (CMV): Cytomegaloviruses are relatively host specific and in its natural hosts tend to cause latent infections with relatively no clinical signs. Due to the risk of cross species transmission NEVER mix primate species in the same exhibit! There are three genera of poxviruses that infect NHP: orthopoxviruses, yatapoxviruses and molluscipoxviruses.
Two orthopoxviruses (monkeypox and cowpox) can cause infection of NHPs resulting in typical cutaneous lesions and occasionally disseminated disease with death.
Molluscum contagiosum is a benign epidermal proliferative disorder that has been described in human, horses and chimpanzees. The viral infectious hepatitis virus (Hepatitis A) has been identified in chimpanzees, patas, wooley monkey, gorilla, cebus, aotus, macaques and some tamarins. Hepatitis C has been reported in chimpanzees and produces a chronic active hepatitis, cirrhosis and hepatocellular carcinoma. Filoviruses belong to the family Filoviridae, one of several groups of viruses that can cause hemorrhagic fever in animals and humans. SIVs are lentiviruses, morphologically similar and biologically related to HIV-1 and HIV-2. These viruses cause widespread infection of many African species of NHP but not Asian species or new world primates.
Evidence of SIV infection has been reported for over 30 different species of African nonhuman primates (see table 3). SFVs are common in captive NHPs; greater than 95% of captive macaques over 3 years of age are seropositive. Spumaviruses differ from other retroviruses in several respects including the viral polymerase gene is expressed from a spliced sub-genomic RNA and the extracellular particle contains large amounts of reverse-transcribed DNA.
SFV can be readily isolated from infected animals saliva or from peripheral blood lymphocytes and it has been isolated in approximately 3% of tested laboratory and zoo workers with NHP exposure. To date, there have been no ill effects to health in either the humans that are positive for SFV or the positive NHP.
Type D retroviruses have been documented to cause a form of chronic immunodeficiency disease in several macaque species, including the natural hosts. The virus has wide tropism for epithelial cells, macrophages, B cells and T cells causing a pancytopenia in peripheral blood.
Infection has also beendescribed in Hanuman langurs (Semnopithecus entellus) and baboons (Papio cynocephalus) but not associated with clinical disease.Simian retrovirus is a serious health threat to captive bred populations of macaques and potential confounder of experimental work. STLV1 and STLV2 share an extensive genomic sequence with human T-lymphotropic virus type 1 and 2 (HTLV1, 2) and are associated with T-cell lymphomas in non-human primates.
Cross species transmission has resulted in epizootics of malignant lymphoma in captive colonies of baboons.
Mycobacteria are responsible for tuberculosis, an increasingly rare disease in captive primates. Yersinia pseudotuberculosis is a zoonotic, infectious bacterial agent that has a worldwide distribution and is endemic in European countries.
This syndrome seen in great apes has many etiologic agents and may be zoonotic depending on the agent involved. Giardia lamblia, Cryptosporidium, Enterocytozoon bieneusi, Balantidium coli, and Entamoeba histolytica are all intestinal protozoa that can infect monkeys and humans.
Toxoplasmosis gondii can be potentially devastating with high mortality and permanent neurological problems in surviving animals in naïve populations of Prosimians and NWPs. Blood borne parasites are rare in captively bred monkeys but may be seen in wild caught monkeys.

Trypanosoma cruzi has been isolated from recently imported and domestic squirrel monkeys, tamarins, marmosets and macaques and causes Chagas' disease. Elimination of infectious diseases from NHP colonies has proven difficult for many reasons and infectious diseases continue to seriously impact wild populations. Our research program addresses pathogenic and therapeutic questions of some the most devastating viral and neuroimmune disorders facing the global community including molecular, epidemiological, and biochemical approaches to address fundamental questions concerning viral replication, latency, assembly and pathogenesis. Evaluating different immunization strategies using adjuvants and antibody immunotherapies to enhance protective immune responses induced by HIV vaccine candidates. It involves the SENSORY ganglia and their areas of innervation and is characterized by severe neuralgic pain along the distribution of the affected nerve and crops of clustered vesicles over the area. The condition develops when the body mounts a massive immune response to infection, triggering excessive inflammation that can lead quickly to organ failure.
As a comparison, they performed the same test on 161 critically ill patients in the hospital who did not have sepsis and 164 healthy patients who were having outpatient surgery.
Among the sepsis patients, for example, the researchers found that 53 percent had Epstein-Barr virus, 24 percent had cytomegalovirus, 14 percent had herpes-simplex virus, and 10 percent had human herpes simplex virus-7.
However, this finding may underestimate the frequency of viral infections because some of these patients were not tested for all viruses. If this is the case, doctors could perform PCR testing in patients with cancer, autoimmune diseases and infections and use results to guide treatments.
Over the years, a number of treatments have been evaluated to treat sepsis, but none has worked well. The blood infection, most commonly caused by bacteria, can lead to septic shock, organ failure, loss of limbs, and even death. Color coded topics indicate learning objectives that the student should become familiar with. It is also important to understand these categories when discussing zoonotic disease risks. Among these features are their well-developed manual dexterity, their well-developed sense of sight and good hand-eye coordination.
The regulation also states that the maintenance of nonhuman primates as pets, hobby, or an avocation with occasional display to others is not a permissible use.
Unfortunately, many of these regulations do not extend to privately owned non-human primates. The nutritional requirements of non-human primates are quite complex and vary greatly between the different species. Although most commercial feeds have adequate levels of vitamin C at the time of packaging, after 90 days of storage, these levels decrease dramatically.
This is likely due to increased availability of dietary iron and the lack of tannins in the diet which are found in their natural environment (similar to the etiology suspected for toucans). Zoonotic risks are higher to humans when dealing with non-human primates, and diseases that are transferred from natural host reservoirs to non-natural hosts can often become devastating clinical syndromes. They can be both diagnostically challenging, as well as devastating, when passed from the NHP to humans. Herpes infections are responsible for a wide range of symptoms ranging from inapparent infections to fatal disease.
Between 1933 and 1994, fewer than 40 cases of herpes B in humans had been documented by the CDC and of the 24 known symptomatic cases reviewed by 1992, 79% were fatal. All facilities that house animal potentially infected with B virus should have a comprehensive B virus prevention and control program in place. In owl monkeys, tree shrews, gibbons, marmosets and cebus monkeys, HSV1 causes high morbidity and mortality following transmission from human handlers.
They include Liverpool vervet monkey virus, Patas monkey herpesvirus, Delta herpesvirus, Medical Lake macaque virus, Herpesvirus cyclopis, Chimpanzee herpesvirus, and Gorilla herpesvirus.
Nearly all NHPs are infected with species specific lymphocrytpoviruses related to human EBV. Although measles is not considered a naturally occurring disease in NHPs, it is one of the most frequently reported viral diseases.
Benign epidermal Monkeypox (BEMP) is a nonfebrile disease seen in macaques and is serologically related to the Yaba pox and Yaba-like pox viruses. In areas where polio vaccination of humans is routine, this usually does not present a problem to these animals due to the lack of disease in the human population.
Marburg virus was the first filovirus to be discovered in 1967 in a shipment of African green monkeys imported into Marburg, Germany. Non-human primates are the natural hosts for a variety of retroviruses including viruses in the betaretrovirus, gammaretrovirus, deltavirus, lentivrus and spumavirus genera. In 1993, the CDC and the National Institutes of Health implemented a voluntary testing and counseling surveillance program for SIV following detection of SIV in a worker at a primate facility.
SIV can cause acquired immunodeficiency syndrome (AIDS) - like illnesses in susceptible macaque monkeys and when it crosses from host-specific species natural host to non-natural host species.
SIV is genetically and antigenically related to HIV-2, resulting in substantial serological cross-reactivity. Two of these viruses, SIVcpz from chimpanzees and SIVsm from sooty mangabeys, have been shown to be the source of HIV1 and HIV2 and acquired immunodeficiency syndrome (AIDS) in humans. Blood donation and organ donation research is also concerned with possible transmission of these viruses. This virus has been referred to as the virus in search of a disease, because it does have the capacity to incorporate itself into DNA and is routinely transmitted between NHP without signs of disease. Clinical tuberculosis causes severe weight loss, lethargy, and coughing and is almost always fatal in NHP. The infection can affect a wide range of host species but in particular has caused numerous deaths in tamarins, marmosets and Goeldi's monkeys in captivity. The syndrome can present as either acute or chronic meningitis and prompt, effective diagnosis and treatment is required to avoid fatalities or chronic, persistent clinical impairments. The most common species cultured in old world monkeys is Shigella flexneri, while the most common isolate from humans is S. Some of the most frequently seen are Oesophagostomum, Strongyloides, and Dipetalonema species. These infections are usually asymptomatic in the natural host but may cause disease when animals are stressed or treated with immune modulatory drugs.
Of the septic patients, overall 24 percent were positive for CMV, 53 percent for EBV, 14 percent for HSV, 10 percent for HHV-6 and 78 percent for TTV. Louis provides strong evidence that when sepsis lingers for more than a few days, which is common, viruses re-emerge and enter the bloodstream, signaling that the immune system has become suppressed.
While some patients die soon after the condition develops, most sepsis deaths occur four or more days after onset. In a subgroup of 209 sepsis patients tested for all viruses, 54 percent were positive for two or more. The new research indicates that, in addition to using powerful antibiotics to fight off infections in patients with sepsis, immunotherapy drugs that boost the immune system may be an effective therapy. While all non-human primates carry zoonotic diseases, the phylogenetic closeness of the Old World primates makes their zoonoses of particular concern.
They have highly developed cerebral cortices, long infant dependency periods and tend to have very complex social organizations. All states require that citizens comply with applicable federal regulations but many state officials may be unaware of regulatory restrictions and may be confused by the distinctions among federal agencies regarding restrictions on captively bred animals. Most owners lack the knowledge, devotion, and constant vigilance needed to properly maintain a non-human primate. They do serve as excellent standards for minimum quality of care for commercial and research organizations and should be followed by private owners as well. Diets are complex and consist of fruits, vegetables, commercially available monkey chow, and food enrichment items.
This is critical for New World Primates who rely heavily on exogenous sources of vitamins C and D3. Vitamin C deficiency typically presents as scurvy, with clinical signs including swelling of the epiphyses of long bones, hemorrhaging of the gums and periosteum and cephalohematoma. It is beyond the scope of this report to cover, in depth, all of the zoonotic diseases transmissible from nonhuman primate (NHP) to humans. B-virus may be fatal in several non-macaque species of monkeys including patas, black and white colobus, capuchin, Debrazza monkeys and common marmosets. Like herpes simplex virus infections in humans, B-virus infections in monkeys can be characterized by life long infections with periodic activation and viral shedding in saliva and genital secretions. The incubation period in man is anywhere from 2 weeks to 6 months and clinical signs starting out as pain, numbness, vesicles, and neuresthesia or paresthesia at site of exposure. If B-virus is cultured from any of these sites, that is confirmation that an animal is actively shedding virus. Infection results in a disseminated disease causing encephalitis, stomatitis and severe hepatitis. Infection with any of the seven viruses, in general, causes high morbidity and mortality and varies greatly depending on the virus and species involved. Herpes virus saimiri is found in nearly all squirrel monkeys that is carried asymptomatically and without clinical effect. Infection in NHPs occurs as a result of human contact, and then the infected primate can shed the virus, and re-infect man.
It produces a typical proliferative epithelial lesion on the skin surface of the face and extremities.

Because of their heightened sensitivity to polio, all monkeys, especially the great apes, should be vaccinated for the disease as juveniles.
This study was later expanded to include voluntary testing and counseling for exposures to SFV, STLV, and simian type D retroviruses. All of the simian immunodeficiency viral isolates have characteristics in common with HIV, including genomic organization and some serological cross reactivity Immunodeficiency results from progressive loss of CD4 T cells and results in reactivation of latent infections or acquisition of environmental and other opportunistic pathogens. Historically, the three major species of Mycobacteria - avium, bovis, and tuberculosis, have been incriminated as causing disease in NHPs.
In both humans and NHPs the skin test detects only mycobacterial infection, not active disease. Clinical signs of infection can range from asymptomatic animals that shed the bacteria, to nonspecific signs of systemic or enteric diseases or sudden death that may be difficult to diagnose. The most prevalent pathogens implicated are Streptococcus pneumoniae, Neisseria meningitides, and Hemophilus influenza type B.The N. Some monkeys may exhibit mild to severe diarrhea accompanied by weight loss, dehydration and bloody feces. These organisms may or may not be associated with clinical disease in NHPs and one negative culture does not indicate a disease free animal. There have been a few documented cases of fatalities in neonatal and juvenile monkeys due to these protozoa.
Cockraoches may serve as mechanical vectors and NHPs may be infected through ingestion of tissue cysts in rodent vectors. Other GI parasites sometimes seen are Hymenolepis nana, Echinococcus granulosus and Prosthenorchus elegans.
The most important point in any discussion of NHP zoonotic disease is the idea of disease prevention.
Other projects involve chronic and latent infections caused by viruses such as herpes simplex, Epstein-Barr and Kaposi's Sarcoma associated herpesvirus. This state of immune suppression may leave patients unable to fight off secondary infections, such as pneumonia associated with being on a ventilator. The Washington University team is planning several clinical trials of such drugs in sepsis patients in the near future. Physically they are set apart by their prehensile, opposable thumbs, tactile pads and nails on fingers and toes, a precise grip and extremely mobile, strong arms. Captive bred offspring of animals purported to have been imported before October 10, 1975, are frequently offered for sale.
Major concerns include specialized nutritional requirements, behavioral changes through puberty, proper sanitation and zoonotic disease control. Primates may be primarily omnivorous, frugivorous, vegetarian, and foragers and their social standing may affect how much and what they eat.
It would be negligent not to state that the keeping of NHP as pets should be strongly discouraged, both from an animal health and welfare point of view, as well as a human health concern. The primary mode of transmission between monkeys is by sexual activity and bites, while transmission to humans may be through bites, scratches, or contact with infected blood or urinary secretions to mucus membranes. In the exposed extremity there may be a regional lymphadenopathy, fever, muscle weakness or paralysis and conjunctivitis, often accompanied by generalized malaise and flu-like symptoms. A negative antibody test or viral culture result, however, does not exclude the possibility of B-virus infection or viral shedding.
Rarely infection may be associated with malignant lymphoma or lymphoproliferative disorders.
Clinical signs in NHP can range from fever, conjunctivitis, coryza, bronchitis and Koplik spots on oral mucosa. Monkeys are thought to get this infection from mice in the exhibit, or from being fed pinkie mice as treats in their diet. There are significant implications for laboratory workers and zoo personnel that work with NHPs.
Common AIDS defining clinical diseases include wasting, CMV, LCV lymphoma, Pneumocystis pneumonia, Cryptosporidia and Mycobacterium avium and closely paraellel the spectrum of diseases observed in human patients.
Active disease is diagnosed either by recovery of the organisms in culture or by thoracic radiographic lesions consistent with active TB. The disease in humans may cause debilitating diarrhea and people may also shed the bacteria asymptomatically.
Many plasmodium species that naturally infect NHPs have been proven to infect humans as well. This is the key to maintaining both healthy NHPs and minimizing the risk to pet owners and veterinary staff.
Monkeys deficient in vitamin D3 develop soft bones (metabolic bone disease), long bone deformities, multiple fractures, and increased levels of serum alkaline phosphatase. It should also be pointed out that seeing NHPs in a private veterinary clinical setting should be approached with caution. The disease then may progress to cause persistent hiccups, sinusitis, neck stiffness, headache, flu-like symptoms, nausea, vomiting, confusion, brain stem damage and fatal meningoencephalitis in humans. Clinical signs can range from severe dermatitis to a severe, life threatening and often-fatal exanthematous disease. It appears as large subcutaneous, tumor like lesions that may undergo spontaneous regression. Ebola virus has now been subtyped into these four distinct viral groups: Zaire, Sudan, Ivory Coast, and Ebola-Ralston. PCR and other amplification tests can also detect organisms but the sensitivity of PCR for the detection of latent infection is not well established. The organism can live in the soil for long periods of time and asymptomatic animals, combined with the difficulties in culturing the organism from rectal or fecal swabs, can all lead to difficulties in controlling the organism. The American Veterinary Medical Association also has a policy opposing the keeping of wild animals as pets and advising veterinarians to exert their influence to discourage this practice.
Only a well-equipped practice, with staff that have been properly trained in primate handling and have been informed about and screened for zoonotic disease, should take on this challenge. The virus may induce sever immunosuppression that can lead to the acquisition of opportunistic infections. Other potential sources include exposure to infected feral rodents in a naturalistic setting. These relatively newly recognized strains of filoviruses have been given special attention due to a viral outbreak in a Virginia quarantine facility in recently imported cynomolgus monkeys (Ebola-Reston).
Preventative measures such as quarantine, good sanitation, good hygiene, especially in food preparation, and pest control, together with a vaccination program in endemic areas, are all recommended in preventing infection, although vaccination is not 100% effective. Protection from blood-borne pathogens, respiratory pathogens, gastrointestinal, and cutaneous diseases must be instituted.
This treatment halts the progression of the process but the major bone deformities are irreversible. Even then, the occupational health and safety hazards, ethical and legal ramifications can be enormous. Antiviral treatments given early in the course of the disease may prevent progression of the disease and has proven to be life saving in some patients. No filovirus-related illness was observed in any humans who had been in contact with these infected monkeys, but antibody titers were detected, indicating transmission did occur.
All staff handling both the animal and its biological products must be well educated in the risks they are taking and in the ways of disease prevention. UVB or natural sunlight may be helpful in treatment and should be considered for prevention of the problem. These antiviral medications must be taken continuously throughout life to prevent recrudescence of disease. Because Monkeypox is serologically related to smallpox, it has the potential to be devastating in unvaccinated human populations.
The three subtypes that are known to cause disease in humans are Ebola-Zaire, Ebola-Sudan and Ebola-Ivory Coast. The NHP owner must also be aware of the risks to both humans who have contact with the animal and also the risks to the animal from the contacted humans.
Rapid diagnosis and treatment is essential in preventing permanent disability and death in patients that are symptomatic. The disease is called Ebola Virus Hemorrhagic Fever and clinical signs in both humans and NHP are: fever, chills, headaches, muscle aches, and anorexia. Eggs are passed in the feces and the ex vivo development leads to the maturation of an infective cystacanth.
As the disease progresses, vomiting, diarrhea, abdominal pain, sore throat, and chest pain may develop. A coagulopathy then develops and bleeding may occur from injection sites as well as into the gastrointestinal tract, skin, and internal organs.
Because of the high mortality rate from human filovirus infections (Ebola, Marburg-Europoe, Sudan and Zaire strains), the CDC has updated regulations and inspections of imported primates.
Recent evidence has shown that wild primates, especially the great apes, may be susceptible to naturally occurring Ebola outbreaks in Africa.

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