Search

Measles virus causes a highly infectious disease in NHP. Clinical signs range from asymptomatic to fatal, although measles virus is most well-known for its characteristic generalized maculopapular rash. Along with appropriate quarantine practices, restricted human access, and appropriate personal protective equipment, vaccines are used to combat the risk of infection. The canine distemper-measles vaccine (CDMV), administered at the manufacturer's standard dose (1.0 mL IM), has been shown to be effective against clinical measles disease in rhesus macaques ( Macaca mulatta ). The goal of the current study was to test whether doses smaller than the manufacturer's recommended dose stimulated adequate antibody production to protect against infection. We hypothesized that either 0.25 or 0.5 mL IM of CDMV would stimulate antibody production comparable to the manufacturer's recommended dose. We found that the 0.25-mL dose was less effective at inducing antibodies than either the standard (1.0 mL) or 0.5-mL dose, which both yielded similar titers. The primary implication of this study informs balancing resource allocation and providing efficacious immunity. By using half the manufacturer-recommended dose, the 50% cost reduction may provide sufficient monetary incentive to implement, maintain, or modify measles vaccination programs at NHP facilities.

Predicting susceptibility of various species to a virus assists assessment of risk of interspecies transmission. Evaluation of receptor functionality may be useful in screening for susceptibility. In this study, docking simulation was conducted for measles virus hemagglutinin (MV-H) and immunoglobulin-like variable domain of signaling lymphocyte activation molecule (SLAM-V). It was observed that the docking scores for MV-H and SLAM-V correlated with the activity of SLAM as an MV receptor. These results suggest that the receptor functionality may be predicted from the docking scores of virion surface proteins and cellular receptor molecules., (© 2017 The Societies and John Wiley & Sons Australia, Ltd.)

Measles is a highly contagious viral disease in NHP. The infection can range from asymptomatic to rapidly fatal, resulting in significant morbidity and mortality in captive populations. In addition to appropriate quarantine practices, restricted access, the immunization of all personnel in contact with NHP, and the wearing of protective clothing including face masks, measles immunization further reduces the infection risk. Commercially available measles vaccines are effective for use in NHP, but interruptions in their availability have prevented the implementation of ongoing, consistent vaccination programs. This need for a readily available vaccine led us to perform a broad, multicenter safety and immunogenicity study of another candidate vaccine, MVac (Serum Institute of India), a monovalent measles vaccine derived from live Edmonston-Zagreb strain virus that had been attenuated after 22 passages on human diploid cells.

Measles virus (MV), an enveloped negative-strand RNA virus, remains a major cause of morbidity and mortality in developing countries. MV predominantly infects immune cells by using signaling lymphocyte activation molecule (SLAM; also called CD150) as a receptor, but it also infects polarized epithelial cells, forming tight junctions in a SLAM-independent manner. Although the ability of MV to infect polarized epithelial cells is thought to be important for its transmission, the epithelial cell receptor for MV has not been identified. A transcriptional repressor, Snail, induces epithelial-mesenchymal transition (EMT), in which epithelial cells lose epithelial cell phenotypes, such as adherens and tight junctions. In this study, EMT was induced by expressing Snail in a lung adenocarcinoma cell line, II-18, which is highly susceptible to wild-type MV. Snail-expressing II-18 cells lost adherens and tight junctions. Microarray analysis confirmed the induction of EMT in II-18 cells and suggested a novel function of Snail in protein degradation and distribution. Importantly, wild-type MV no longer entered EMT-induced II-18 cells, suggesting that the epithelial cell receptor is down-regulated by the induction of EMT. Other polarized cell lines, NCI-H358 and HT-29, also lost susceptibility to wild-type MV when EMT was induced. However, the complete formation of tight junctions rather reduced MV entry into HT-29 cells. Taken together, these data suggest that the unidentified epithelial cell receptor for MV is involved in the formation of epithelial intercellular junctions.

Despite numerous advances in the diagnosis and control of infectious diseases of nonhuman primates in the laboratory setting, a number of infectious agents continue to plague colonies. Some, such as measles virus and Mycobacterium tuberculosis, cause sporadic outbreaks despite well-established biosecurity protocols, whereas others, such as retroperitoneal fibromatosis-associated herpesvirus, have only recently been discovered, often as a result of immunosuppressive experimental manipulation. Owing to the unique social housing requirements of nonhuman primates, importation of foreign-bred animals, and lack of antemortem diagnostic assays for many new diseases, elimination of these agents is often difficult or impractical. Recognition of these diseases is therefore essential because of their confounding effects on experimental data, impact on colony health, and potential for zoonotic transmission. This review summarizes the relevant pathology and pathogenesis of emerging and reemerging infectious diseases of laboratory nonhuman primates.

Measles is a respiratory virus that is endemic to humans. Human-nonhuman primate (NHP) transmission of the measles virus has been shown to cause significant morbidity and mortality in NHP populations. We investigated serological evidence of exposure to measles virus in two free-ranging populations of macaques at the Bukit Timah (BTNR) and Central Catchment Nature (CCNR) reserves in Singapore and the Swoyambhu Temple in Katmandu, Nepal. At BTNR/CCNR none of the 38 macaques (Macaca fascicularis) sampled were seropositive for antibodies to measles virus. In contrast, at Swoyambhu 100% (n = 39) of the macaques (M. mulatta) sampled were seropositive for antibodies to the measles virus. Here the contrasting seroprevalences of the two sites are analyzed using risk analysis. These case studies show how risk analysis can be used to approach the phenomenon of cross-species pathogen transmission., (Copyright 2006 Wiley-Liss, Inc.)

Retrospective analyses of banked serum samples and medical records from captive western lowland gorillas (Gorilla gorilla gorilla) at Lincoln Park Zoo showed that vaccination of gorillas with a human vaccine induced antibody production. No significant relationship was found between the groups that received one, two, or three vaccinations and the probability of seroconversion. These data also suggested that antibodies in western lowland gorillas persist for at least 11 yr. This information is useful in the assessment of vaccination protocols for captive gorillas and in the implementation of preventive care in wild gorilla populations.

To eradicate measles in developing nations a vaccine capable of being administered at birth may be necessary. We immunized newborn rhesus macaques with naked DNA encoding the measles virus hemagglutinin, fusion and nucleoprotein genes. Prior to vaccination we passively transferred measles immunoglobulin to mimic maternal antibody. In the presence or absence of measles immunoglobulin, 23 of 25 infant macaques had detectable cell mediated immunity and 16 had protective levels of neutralizing antibody. The co-administration of an IL-2/IgG plasmid augmented the vaccine, increasing cell mediated immunity in all infants and increasing the antibody response in infants vaccinated without immunoglobulin. We show for the first time that DNA vaccination can protect a newborn primate from the high-level viremia that correlates with severe measles, even in the presence of maternal antibody. Further, the addition of a molecular IL-2 adjuvant augments this DNA vaccine.

Measles virus (MV), a highly infective paramyxovirus, has caused sporadic epizootics characterized by high morbidity and increased mortality in nonhuman primates. Measles vaccines for human use, although effective, are cost prohibitive for use in primate colonies. We compared the efficacy of one or two doses of Vanguard D-M, a canine distemper-measles (CD-M) vaccine, with a single dose of Attenuvax, a human measles vaccine. Compared with 81% of animals inoculated with Attenuvax, all animals inoculated with one or two doses of Vanguard developed detectable MV antibodies. One year after immunization, six juveniles from each vaccine group, along with three unvaccinated controls, were challenged with pathogenic MV and were monitored for clinical signs of disease, viremia, viral shedding, and immune response. All uninoculated controls developed clinical disease and viremia, and shed virus in nasopharangeal secretions. Subclinical viremia without viral shedding was identified in two Attenuvax- and two single-dose Vanguard-inoculated animals. Viremia was not detected in any two-dose Vanguard-inoculated animals. Significantly higher neutralization antibody titers were observed in animals receiving Vanguard. Results of this study indicate that Vanguard is at least as efficacious as Attenuvax for protection of rhesus macaques. The considerably lower cost of Vanguard makes vaccination against measles in large breeding colonies economically feasible.

There is a very close contact among humans, cattle, dogs and monkeys in developing countries. That could lead to genetic alteration in morbillivirus isolates of measles, rinderpest, canine distemper. Emergence of novel morbillivirus strains and failures of prophylactic viral vaccines should be monitored by characterisation of genetic profiles of isolates in different species. Incorporation of additional epitopes in existing prophylactic vaccines should minimise vaccine failures attributable to such novel strains.

An adult wild-caught female tamarin (Saguinus mystax) housed in a biomedical research facility was found moribund and extremely dehydrated, with severe diarrhea. She initially responded to supportive therapy but died 3 days later. Necropsy findings included hyperemia of the colonic mucosa, mesenteric lymphadenopathy, acanthocephalid parasites (Prosthenorchis elegans) embedded in the mucosa of the terminal ileum and cecum, and free filarid nematodes (Dipetalonema sp.) in the abdominal cavity. Campylobacter sp. was recovered from the colon. With the exception of changes associated with the parasites, significant histologic changes were limited to the colon. Changes consistent with acute enteric viral infection were found against a background of chronic inflammation. Enterocytes were variably hypertrophied, degenerate, and attenuated. Numerous epithelial syncytial cells were present, and some affected cells (uni- as well as multinucleated) contained intranuclear inclusions. Lymphoid follicles were mildly depleted and contained rare syncytia. Measles (Morbillivirus) infection was confirmed by using immunohistochemistry, reverse transcriptase polymerase chain reaction, and Southern blot analysis. In contrast to the cutaneous rash, respiratory involvement, and low mortality characteristic of Old World monkeys with measles, severe diarrhea with high mortality occurs in New World monkeys with this disease. In addition, our case differs from previous reports of measles in New World monkeys in that syncytial cell formation apparently was limited to the colon of our animal.

An outbreak of natural measles virus infection occurred in a group of Japanese macaques (Macaca fuscata). Over a period of 4 months, 12 of 53 Japanese macaques died following a 2-23-day history of anorexia, diarrhea, and dermatitis. The monkeys were kept in outdoor exhibits but had been moved temporarily into indoor caging and then transferred to new outdoor exhibits. Ten monkeys died while they were in temporary caging, and two monkeys died after they were moved to new outdoor exhibits. The diagnoses were made based on the results of histopathology, immunohistochemistry (IHC), in situ hybridization (ISH), and electron microscopy. Measles virus antigens were detected in the lung, stomach, skin, salivary gland, spleen, and lymph nodes. Tangled, tubular nucleocapsids compatible with paramyxovirus were noted in the lung tissue. As a result of immunosuppression following measles virus infection, various secondary infections including disseminated cytomegalovirus infection, adenoviral and bacterial pneumonia, and Candida albicans-associated gingivitis and esophagitis were noted. The primary infective source or the mode of infection could not be determined in this outbreak, but measles virus may have been transmitted to the monkeys from human visitors while the monkeys were on exhibit.

Background and Purpose: A measles outbreak in a facility housing Old World nonhuman primates developed over a 2-month period in 1996, providing an opportunity to study the epidemiology of this highly infectious disease in an animal-handling setting., Methods: Serum and urine specimens were collected from monkeys housed in the room where the initial measles cases were identified, other monkeys with suspicious measles-like signs, and employees working in the affected areas. Serum specimens were tested for measles virus-specific IgG and IgM antibodies, and urine specimens were tested for measles virus by virus isolation or reverse transcriptase-polymerase chain reaction (RT-PCR)., Results: A total of 94 monkeys in two separate facilities had evidence of an acute measles infection. The outbreak was caused by a wild-type virus that had been associated with recent human cases of acute measles in the United States; however, an investigation was unable to identify the original source of the outbreak. Quarantine and massive vaccination helped to control further spread of infection., Conclusions: Results emphasize the value of having a measles control plan in place that includes a preventive measles vaccination program involving human and nonhuman primates to decrease the likelihood of a facility outbreak.

Wild measles virus isolated in a marmoset lymphoblastoid B95a cell line induced rashes and Koplik's spots when inoculated parenterally in cynomolgus and squirrel monkeys. Marked leukopenia. associated with transient decrease in the CD4(+)-to-CD8+ T-cell ratio also was induced. Virus growth, as well as histologic lesions of necrosis and giant cell formation, was observed in the lymphoid tissues. Thus clinical signs of acute measles were successfully induced in monkeys by inoculation with cell-culture-grown measles virus. These nonhuman primate models of measles will be useful for study of the pathogenesis of acute measles virus infection in terms of generalized clinical signs of disease, leukopenia, and changes in the lymphocyte subsets.

Isomer-specific concentrations of polychlorinated biphenyls (PCBs) including planar, mono- and di-ortho congeners and concentrations of DDT were determined in striped dolphins affected by a morbillivirus epizootic in the western Mediterranean in 1990. Extremely high concentrations of PCBs ranging from 94 to 670 micrograms/g (wet wt) were detected in the blubber. Similarly, DDT concentrations were high, between 22 and 230 micrograms/g (wet wt). The concentrations of three non-ortho coplanar PCBs were 43 (3,3',4,4'-T4CB), 6.8 (3,3',4,4',5-P5CB), and 7.8 (3,3',4,4',5,5'-H6CB) ng/g (wet wt), respectively, the highest residue levels reported to date. The estimated 2,3,7,8-TCDD toxic equivalents of non-, mono- and di-ortho PCB congeners in striped dolphins were several times higher than those observed for other marine mammals and humans. Mono-ortho congeners contributed greater 2,3,7,8-TCDD toxic equivalents than non-ortho members. The higher ratio of 3,3',4,4',5,5'-H6CB/3,3',4,4',5-P5CB (IUPAC 169/126) suggested a strong induction of mixed function oxidase enzymes and highlighted the possibility of using this ratio as an index for risk assessment of PCB contamination in marine mammals. Elevated concentrations of PCBs may have played a role in the immune depression in striped dolphins, ultimately leading to the development of morbillivirus disease.

Macaque monkeys are susceptible to measles infection which triggers temporary immuno-depression similar to the well known phenomenon in humans. It is known that feral monkeys become infected with measles virus when they are exposed to humans. Since Macaca mulatta and M. fascicularis are species used to assay the neurovirulence of oral poliovirus vaccine, the immunodepression caused by measles infection of the test monkeys could significantly alter the results of the neurovirulence test. The serum titers of measles-neutralizing antibodies were studied in over 1500 monkeys used for neurovirulence tests. A high proportion of the feral monkeys had measles antibodies (51-100%); in contrast, none of 493 M. fascicularis monkeys which had been bred in a primate colony under strict isolation measures was found positive for measles antibodies. An increase in the prevalence of measles in the population of Ontario and Quebec provinces was accompanied with an increase in the proportion of measles-positive monkey and their serum antibody titers were found higher. It was observed that monkeys used in tests that had been performed during high measles prevalence presented with a poliomyelitis of more pronounced severity clinically and histologically. The analysis of 29 tests conducted on type 1 vaccines over several years showed a positive correlation (correlation coefficient = 0.5141, P less than 0.0022) between severity of poliomyelitis and the presence of measles serum antibodies in test monkeys (some animals seroconverted during the test). A similar observation, when type 3 Sabin vaccines were tested in M. fascicularis, was recently reported from another laboratory in Ontario.

A morbillivirus was isolated from the organs of a seal (Phoca sibirica) which had died during 1987-1988 epizootic in Baikal. This Baikal seal morbillivirus (BSM) was adapted to Vero cell cultures in which it induced a cytopathic effect developing to complete destruction of the monolayer. Typing of BSM was done by indirect immunofluorescence test and enzyme immunoassay using antibodies to distemper and measles viruses. A method for virus concentration and purification was developed. According to electron microscopic examinations, the virus virions were spherical particles of heterogeneous sizes over 100 nm in diameter. The clinical picture of seal infection, pathological anatomy and histopathology are described. A possible role of BSM in the epizootics of Baikal seals is discussed.

The recent occurrence of fatal Herpesvirus simiae (B virus) infection in human subjects has again focused the attention of primatologists on this virus. B virus, however, is only one of a number of viral diseases that plays a role in primate colony management. This report is to emphasize to the primatologist a number of viruses other than H. simiae, with high morbidity and mortality rates, of importance for health management of nonhuman primate animal colonies. This concept is supported by the recent occurrence in colonies of nonhuman primates of simian hemorrhagic fever virus, SA8, herpesvirus, respiratory syncytial virus, encephalomyocarditis virus, Ebola virus, and simian immunodeficiency viruses.

This study describes aspects of measles in non-human primates. Monkeys infected before importation are shown to produce non-immune offspring in captivity in England. The high antibody titres found in most recently imported monkeys decline slowly during captivity in England. While measles is often fatal to monkeys, we have described an outbreak in which a number of symptomless infections occurred. Histological examination of fatal cases produced evidence of infection in the wall of the urinary bladder in one monkey. The close similarity between measles in humans and monkeys has been confirmed. It is considered that the study of infection among the latter may have significance for the former.

One hundred and eighty-one cynomolgus monkeys born and raised at Tsukuba Primate Center for Medical Science (TPC) were serologically examined for the presence of antibodies against simian virus 5, measles virus and herpes simplex virus. All of them were virtually free from infections with these viruses, whereas wild-originated breeders kept at TPC were highly positive for these antibodies. These results can be regarded as demonstrating that an indoor breeding system such as TPC's is useful and valuable for producing nonhuman primates of good quality being completely free from those viral infections.

On 592 cynomolgus monkeys of newly-imported 14 different groups, sero-epidemiological follow-up surveys of natural infections with SV5, measles (MV) and herpes simplex (HSV) were conducted both at the time of arrival and at the end of the 9-week quarantine period at Tsukuba Primate Center for Medical Science (TPC). At the time of arrival, the positive rate of antibodies against these viruses greatly varied with different countries of origin. As regards SV5, the positive rate ranged widely from 0 to 94.9% among different import-groups, being markedly low in the Philippine monkey groups. The positive rate of MV antibody was generally very high, varying from 11.1 to 78.2% in almost all import-groups except two groups from Indonesia in which no positive case was detected. Concerning HSV, every import-group had a very high positive rate though the average antibody titer was not so high. Generally, the positive rates of SV5 and MV markedly increased by the end of quarantine period. Especially, MV positive rate reached 100% in almost all of the import-groups. However, two Indonesian groups showed no increase of SV5 and MV positive rates during the quarantine period. No increase of SV5 positive rate was detected either with any of three Philippine groups. As for HSV, the positive rate remained unchanged or rather decreased during the quarantine period in almost all groups except two Indonesian groups having shown a significant increase.

The measles virus is known to infect several species of monkeys. A group of 87 cynomolgus monkeys (Macaca fascicularis) was screened to observe whether there was an association between measles and the cold symptoms seen in most of the animals. Another 23 monkeys were vaccinated with attenuated measles vaccine and their antibody titres monitored to ascertain whether the vaccine would protect them against measles.

Tamarins (Saguinus mystax and Saguinus labiatus) were experimentally infected with two strains of measles virus. One of the strains (JM) spread readily among the animals with a high fatality rate. The second strain (Edmonston) appeared to be less pathogenic and less transmissible than strain JM. Aerosol was considered the most probable mode of infection.

The pathological changes found in four Abyssinian Colobus monkeys (Colobus guereza) dying of measles are described. Warthin-Finkeldey giant cells were plentiful in the lymphoid tissue and spleen, in the mucosa of the alimentary tract and in the lungs, where they accompanied a non-suppurative pneumonia. In the alimentary tract they were most frequent in the colon when an associated colitis was present. Measles virus was recovered from the lung tissue of one animal, the virus being neutralised by both human and rhesus monkey anti-sera. This together with the close similarity between the pathological changes in human and monkey measles, supports the contention that the two diseases are one and due to the same virus.

Serologic testing revealed that 17/84 (20.2%) of bought-in Aotus and 1/31 (3.2%) of colony-born Aotus had haemagglutination-inhibition antibody. Clinically-inapparent measles infections were detected in 3 monkeys by increased antibody titres. Following the detection of a recent infection, antibody titre persisted at a high level for at least 240 days. Although 84% of the monkeys were sero-susceptible, no further serological evidence of measles infection occurred.

Of 21 newly-imported rhesus monkeys, 11 showed a typical macular rash and 13 developed a 4-fold or greater rise in antibody titre to measles. 5 animals died, 4 of them with extensive pneumonia, pleurisy and pericarditis. Although measles was involved in each case, there were contributory causes of death, namely Diplococcus pneumoniae and Staphylococcus aureus infection, and infestation with Oesophagostomum (nodular worm) larvae.

Morbillivirus derived from diseased harbour seals (Phoca vitulina) has characteristics of acute virulent canine distemper virus infection in mink. The infection induced a disease resembling the acute systemic and nervous form of canine distemper.

The various species of marmosets are susceptible to a wide variety of infectious agents of which only a few have been fully characterized. Little is known concerning spontaneous disease in their natural habitat, and often deaths in the laboratory go unexplained. In captivity, Herpesvirus-T infection appears to be the most important viral infection, but serious disease may also follow infection with measles virus (rubeola) and an unidentified paramyxovirus. Bacterial diseases are multiple, but rarely occur as epizootics. Various species of Salmonella, Yersinia, Klebsiella, and Diplococcus are among the more frequent pathogens. Mycoses and parasitic infections are also numerous, but most do not result in major losses.

An epizootic of measles occurred in a group of 31 silvered leaf-monkeys (Presbytis cristatus) that had been in captivity for 4-12 months. Twenty-four of the monkeys exhibited a maculopapular rash that persisted for 6-9 days. A serous to mucopurulent nasal discharge and conjunctivitis were seen in some animals. Eight monkeys died during the epizootic; however, their deaths could not be directly attributed to measles. Serum samples from the surviving monkeys collected 1-2 months prior to, and 5 weeks after, the epizootic were examined by the complement-fixation and hemagglutination-inhibition tests for antibodies to measles virus. The preepizootic complement-fixation titers were all less than 1:4 and hemagglutination-inhibition titers, less than 1:10. The postepizootic complement-fixation titers in 21 of 23 surviving monkeys ranged from 1:8 to 1:128, and hemagglutination-inhibition titers in 22 of 23 monkeys ranged from 1:40 to 1:80 or greater.

Peste des petits ruminants (PPR) is a virus disease of sheep and goats in West Africa. When first described, the virus was considered a variant of rinderpest virus. The biological and physicochemical characteristics of the virus indicate that it is closely related to measles, rinderpest and canine distemper viruses. These three viruses form the genus Morbillivirus of the Paramyxoviridae. PPR virus is sufficiently distinct from these 3 viruses to justify considering it as the fourth member of the Morbillivirus genus.

Two female rhesus macaques (Macaca mulatta) and one female pigtailed macaque (M. nemestrina) developed acute neurological signs including ataxia, muscular incoordination, and seizures. Light microscopy showed Cowdry Type A intranuclear inclusion bodies in astrocytes and neurons of the cerebral cortex and Purkinje's cells of the cerebellum. Many cells also had intracytoplasmic inclusion bodies. Electron microscopy identified paramyxoviral nucleocapsids in the intranuclear and intracytoplasmic inclusions in two monkeys. We believe these monkeys had measles encephalitis because measles virus is the only paramyxovirus known to cause inclusion bodies in macaques and because the lesions in these monkeys resembled measles encephalitis in man.