Nonhuman primates can be used as models for the study of immune-complex-associated diseases. Recognizing that very little is known about the levels of circulating immune complexes (CICs) in normal monkeys, we have used three assays to measure the levels in serum collected from 313 adult and 106 juvenile cynomolgus macaques (Macaca fascicularis). The prevalence was higher than expected. There was a strong statistical association between CIC levels and country of origin. Monkeys from Indonesia were more likely to have elevated CICs than those from Malaya or the Philippines. This relationship was observed with all three assays. Furthermore, juvenile macaques tended to have lower levels than did adults. This study indicates that it may be important to consider genetic factors, the country of origin, or both when selecting cynomolgus macaques for research on immune-complex-associated diseases.
Using an indirect immunofluorescence technique, sera from 113 cynomolgus monkeys (Macaca fascicularis), trapped in Peninsular Malaysia, were screened for the presence of antibody to six prototype strains of Rickettsia tsutsugamushi combined into three polyvalent groupings: I--Karp, TA716, and TA763; II--Gilliam; and III--TA678 and TH1817. Fifteen percent (17/113) of the monkeys had antibody titers greater than or equal to 1:50 to one or more of the antigenic groups. Although a titer greater than or equal to 1:150 is generally considered indicative or prior Rickettsia tsutsugamushi infection, we selected a less than 1:25 titer as a conservative standard to insure non-infected animals. Using this criterion, 62 (55%) of the 113 monkeys were accepted for use in scrub typhus studies. The high prevalence of antibody to scrub typhus in the semi-arboreal cynomolgus monkey is in marked contrast to the low prevalence reported in the strictly arboreal silvered leaf monkeys (Presbytis cristatus). The results of this study indicate that cynomolgus monkeys should be rigorously screened for evidence of prior infection before they are included in experimental scrub typhus studies.
This report summarizes the results of a comparative study of the virulence of the "S-M," H, and C strains of P. knowlesi for Indian rhesus monkeys (Macaca mulatta) and cynomolgus monkeys [M. irus (fascicularis)] of Malayan (West Malaysia) and Philippine origins. Each of the above strains produced fulminating, uniformly fatal infections in the rhesus monkey and mild, chronic infections, characterized by relatively low level parasitemias in cynomolgus monkeys of Philippine origin. In striking contrast, the H and C strains produced infections in cynomolgus monkeys of Malayan origin which were indistinguishable in severity from infections produced in M. mulatta. The circumstances of the study precluded evaluation of the virulence of the "S-M" strain for M. irus of Malayan origin. Even so, the available data make it necessary to qualify the long-held belief that infections with P. knowlesi in M. irus invariably follow a benign course.
Serum samples were obtained within 3 days of capture from 106 cynomolgus monkeys (Macaca fascicularis) in peninsular Malaysia. Fifty-two monkeys were trapped on the fringes of palm oil estates and 54 in dense primary jungle. Sera were tested for antibodies to hepatitis A virus (HAV) with a commercial radioimmunoassay. Twenty-four animals had detectable serum anti-HAV activity (6 of 52 from palm oil estate sites and 18 of 54 from primary jungle sites). Among monkeys at both sites, antibody prevalence was strongly correlated with animal weight: overall only four of 69 monkeys (6%) weighing less than 2.0 kg had serum anti-HAV antibodies, while 14 of 29 (48%) weighing 2.0 to 3.9 kg, and 6 of 8 (75%) weighing 4.0 kg or more, had serum anti-HAV antibodies. These data suggest that wild cynomolgus monkeys in Malaysian jungles become infected with HAV or an HAV-like virus at a rate comparable to that of humans in the same region, and raise the possibility of a sylvatic cycle for HAV.
A novel indirect fluorescent antibody test (IFAT) for detection of IgM against Nipah virus (NiV) was developed using HeLa 229 cells expressing recombinant NiV nucleocapsid protein (NiV-N). The NiV IFAT was evaluated using three panels of sera: a) experimentally produced sera from NiV-N-immunized/pre-immunized macaques, b) post-infection human sera associated with a Nipah disease outbreak in the Philippines in 2014, and c) human sera from a non-exposed Malaysian population. Immunized macaque sera showed a characteristic granular staining pattern of the NiV-N expressed antigen in HeLa 229 cells, which was readily distinguished from negative-binding results of the pre-immunized macaque sera. The IgM antibody titers in sequential serum samples (n = 7) obtained from three Nipah patients correlated well with previously published results using conventional IgM capture ELISA and SNT serology. The 90 human serum samples from unexposed persons were unreactive by IFAT. The IFAT utilizing NiV-N-expressing HeLa 229 cells to detect IgM antibody in an early stage of NiV infection is an effective approach, which could be utilized readily in local laboratories to complement other capabilities in NiV-affected countries.