Primate Hosts Research Articles

Immune Response in Primates Vaccinated with Duck Embryo Cell Culture Rabies Vaccine

Adult rhesus monkeys (Macaca mulata) were vaccinated with four inactivated rabies vaccines, including two cell culture vaccines, one zonal purified cell culture vaccine, and a 10% extracted duck embryo vaccine. The vaccines were potency tested by both National Institutes of Health (NIH) and Habel methods and passed one or both tests. However, a vaccine having acceptable potency by one method frequently failed or was marginal by the other procedure. Groups of three monkeys were inoculated with each vaccine by one of two schedules. The first consisted of four weekly 1-ml doses followed by a 1-ml booster dose at 6 months, and the second consisted of seven daily 1-ml doses of vaccine with no booster. Both zonal purified and extracted duck embryo vaccines induced detectable neutralizing antibody by day 7 with either schedule, and antibody titers elicited by the cell culture vaccine remained high through 210 days. However, antibody titers produced by the 10% duck embryo vaccine dropped sharply after their 28-day peak. Duck embryo cell culture vaccines with low or marginal potency as measured by Habel or NIH tests still produced rapid, high levels of serum-neutralizing antibody in primates. LD(50) or NIH and Habel tests as measured in mice were not necessarily good indices of antibody response in the primate host. The need for a cell culture potency test that will yield a more predictable correlation with the definitive host's antibody response is discussed.

Properties of DNA from some malarial parasites.

The base compositions of DNA from some species of malarial parasite have been estimated by measurement of density in CsCl gradients and of thermal denaturation temperatures. Species from avian (Plasmodium gallinaceum) and rodent (P. bergheiandP. vinckei) hosts – often used as model systems in malarial studies – contain single DNA components with base compositions of about 20% G + C. By contrast, species from primate hosts (P. knowlesiandP. falciparum) contain major DNA components of about 40% G + C and minor ones of about 20% G + C. These differences could be reflexions of markedly different genomes within these two groups of the genusPlasmodium.Apart from differences in base composition, the physico-chemical properties of the main components of DNA from primate and rodent malarial parasites are very similar to those of DNA from mammalian cells. DNA from avian malarial parasites appears to have some unusual properties.One of us (P.I.T.) received financial assistance from the World Health Organization. We thank Dr F. Hawking and Dr J. Williamson for many helpful discussions, Dr W. H. G. Richards, Dr A. Voller and Dr D. C. Warhurst for the provision of some of the strains and Miss Jane Dunnett, Mrs A. C. Gutteridge and Mr T. Scott-Finnigan for technical assistance.

Schistosoma mansoni Infections in Cercopithecus sabaeus Monkeys

Cercopithecus sabaeus (green) monkeys discharged eggs up to 3.5 years after initial exposure and for a comparable period after reexposure. The number and development of worms from challenge infections were similar to initial infections, but excretion of eggs was delayed after challenge. Monkeys exposed repeatedly to moderate or small numbers of cercariae tolerated a burden of worms that would have been lethal as a single initial infection. There was evidence that worms lived for 5 years, and without regression in size. Large accumulations of eggs still occurred in the liver and intestine after 5 years, and the relative numbers of immature, mature, and degenerate eggs were similar to early stages of first infections. The response of the green monkey to S. mansoni is in marked contrast to that of Macaca mulatta, which suppresses excretion of eggs after 6 to 9 months and quickly acquires strong resistance to challenge infections. The longer output of eggs by the green monkey is more like what occurs in man. A corresponding comparison of acquired resistance is not possible because too little is known about resistance imposed against schistosomes in the human host. The rhesus and the green monkeys may provide a valuable experimental model for investigating the immune mechanism against schistosomes. The green monkey may be useful in the evaluation of schistosomicidal drugs. The need for experimental hosts of human schistosomes that react to the infections more like man than the commonly used Macaca mulatta (rhesus) monkey was emphasized by Sadun et al. (1966a). Their studies and those of Sadun and Bruce (1964) on the biology and pathology of schistosomiasis in 10 species of primates showed that worm recovery rates were highest in three species of Macaca, but self-cure occurred within a few months. The baboon and chimpanzee discharged eggs for much longer periods, but worm recovery was relatively low. For other species, the infections were abortive from the beginning. Only the chimpanzee developed pipe-stem fibrosis of the liver. The need for information on other primate hosts was noted by the above authors. Information on acquired resistance among primate hosts is essentially limited to the rhesus monkey. For man, too little is known to recognize a suitable model. The current study is concerned with another primate, Cercopithecus sabaeus, the green Received for publication 22 May 1967. * Assigned to Walter Reed Army Institute of Research, Washington, D. C. (20012), with duty station at the Department of Preventive and Social Medicine, University of Ibadan, Ibadan, Nigeria. t Present address: Tropical Disease Section, Ecological Investigations Program, Communicable Disease Center, U. S. Public Health Service, San Juan, Puerto Rico. monkey, and includes observations on the length of the prepatent period, duration and pattern of egg discharge, life-span of the infection, distribution and condition of eggs in tissues, and acquired resistance. These objectives were not all completed as originally planned, due to closing of this laboratory. A number of investigators have exposed the green monkey to human schistosomes for limited objectives, and only a few animals were involved, or the infections were of short duration (Archibald, 1923; Black, 1932; Vogel and Minning, 1953; Kuntz, 1955; Vogel, 1962; Hsii and Hsii, 1962; Meisenhelder and Thompson, 1963; and Ritchie et al., 1964). The green monkey was found to discharge eggs for relatively long periods. In contrast to M. mulatta, challenge infections developed to maturity in animals that had been infected

Immunogenicity of experimental trachoma vaccines in baboons: III. Experiments with inactivated vaccines

Heating at 37° C. for 5 days completely abolished the capacity of a trachoma/inclusion conjunctivitis (TRIC) vaccine to protect baboons against conjunctival infection. Treatment with formalin also impaired or abolished immunogenicity.The rate of inactivation of TRIC agent by ultraviolet light was exponential, and was about 7 times faster than that of a suspension of vaccinia virus of comparable turbidity. By contrast with vaccinia, irradiation of TRIC agent with twice the dose of ultraviolet light needed to destroy infectivity resulted in loss of immunogenicity.The deleterious action of these inactivation procedures on the potency of TRIC vaccines may be explained in terms of damage to a protective antigen; alternatively, live vaccines may be more immunogenic because TRIC agents are capable of multiplying within primate hosts after parenteral injection.Unlike the same type of variant of another strain of inclusion conjunctivitis, the ‘fast-killing’ variant of MRC-4 was still pathogenic for the baboon conjunctiva.

Effect of aerosol age on the infectivity of airborne Pasteurella tularensis for Macaca mulatta and man.

Sawyer, William D. (U.S. Army Medical Unit, Fort Detrick, Frederick, Md.), Joseph V. Jemski, Arthur L. Hogge, Jr., Henry T. Eigelsbach, Elwood K. Wolfe, Harry G. Dangerfield, William S. Gochenour, Jr., and Dan Crozier. Effect of aerosol age on the infectivity of airborne Pasteurella tularensis for Macaca mulatta and man. J. Bacteriol. 91:2180-2184. 1966.-In aging aerosols of Pasteurella tularensis SCHU-S4, the respiratory infectivity for man and Macaca mulatta decreased more rapidly than the viability of the organisms. Infectivity was diminished after 120 min, and was reduced 10-fold after 180 min. These findings confirmed previous observations made in mice and guinea pigs, and also revealed that smaller losses of infectivity were detectable in the primate hosts.

Biology and Distribution of the Rat Lungworm, Angiostrongylus cantonensis, and its Relationship to Eosinophilic Meningoencephalitis and other Neurological Disorders of Man and Animals

Publisher Summary This chapter outlines the importance of the rat lungworm as the most likely etiological agent of cerebral angiostrongylosis of man. The important information that has been discussed concerning Angiostrongylus cantonensis includes (1) the ability of the parasite to migrate, develop, and produce eosinophilic meningoencephalitis in man and simian hosts; (2) the existence of a parallel relationship between the geographical distribution of human cases of eosinophilic meningoencephalitis and distribution of the parasite in the rodent host; (3) the ability of the parasite to utilize, under natural conditions, a variety of land mollusks as intermediate hosts, and to utilize freshwater prawns, land planarians, land crabs, pigs, and calves as carrier hosts; and (4) the apparent transmission of the parasite to man by ingestion of uncooked carrier hosts and molluscan intermediate hosts. Many gaps remain to be investigated in the fields of biology, epidemiology, immunology, pathology, and chemotherapy. Some of the urgent research needs include (1) determination of a simple technique for the diagnosis of human angiostrongylosis, which includes the possible use of purified worm antigen suitable for cutaneous testing; (2) more information on animals, which serve as carrier hosts for the infective larval parasite, and the methods of human infection; and (3) more information on the effects of the parasite in the primate and other mammalian hosts, with special reference to neurological and related disorders.

Characterization of Agents Isolated from Market Chickens in a Quest for Enteric Viruses

The difficulties of studying human enteroviruses in other than primate hosts instigated a search for similar agents in common laboratory animals. It was hoped that an easily manipulated virushost system might be found which would provide a model of behavior analogous to that of the enteroviruses in humans. The search was initiated in chickens since these animals were readily available under conditions which might be expected to favor the wide dissemination of multiple strains. In addition, they could be reared for experimental purposes in complete isolation from others of their kind.

Acanthocephalans and Cestodes of South American Monkeys and Marmosets

Records for cestodes and acanthocephalans resulting from an endoparasite survey of Peruvian and Colombian monkeys and marmosets are presented and discussed. Thirty-four of 65 animals harbored Prosthenorchis elegans or P. spirula; 11 animals were hosts for Atriotaenia megastoma, Raillietina (R.) trinitatae, or Hymenolepis cebidarum. New host records noted in this paper are as follows: P. spirula-Cebuella pygmaea; P. elegansTamarinus nigricollis, Cebuella pygmaea, Saimiri boliviensis; Hymenolepis cebidarum-Tamarinus nigricollis; Atriotaenia megastoma-Tamarinus nigricollis, Saimiri sciurea, Saimiri boliviensis. Previous host records for these helminths are reviewed and discussed. Many scientific names recorded in the literature for hosts of these parasites are synonyms of one another or have been superseded as a result of nomenclatural changes; an attempt is made to bring some order into the confused host record for several of the parasites. Host-parasite patterns are related to host diet and to probable modes of transmission. These patterns are shown to be consistent with the suspected transmission routes. The parasitologic record also provides data bearing on the natural diet of some of the primate hosts. The early papers in this series on endoparasites of Neotropical primates have been based on a survey of newly imported Peruvian and Colombian monkeys and marmosets carried out in San Francisco from 1960 to 1962. The methods and importing procedures have been discussed in several of the previous papers (Dunn and Lambrecht, 1963a, b; Dunn, Lambrecht, and du Plessis, 1963). In the present contribution some records are supplied for cestodes and for acanthocephalans of the genus Prosthenorchis, and present knowledge of the host-parasite patterns for these helminths in South and Central American primates is reviewed. The records presented below are based on the results of dissections of 65 animals of nine species. The hosts, countries of origin, and numbers examined are listed in Received for publication 14 June 1963. * The George Williams Hooper Foundation and Division of Parasitology, Department of Medicine, San Francisco Medical Center, University of California. Current address: Medical Zoology Laboratory, Institute for Medical Research, Kuala Lumpur, Federation of Malaya. This study was supported in part by U. S. Public Health Service Grant Al 04189-02 from the ICMRT Program, Office of International Research, National Institutes of Health. This paper is No. 6 in a series on the endoparasites of Neotropical primates. Table I. Common names for the hosts under consideration are as follows: Tamarinus nigricollis (Spix, 1823)-black-and-red tamarin; Oed pomidas oedipus (L., 1758)-pinche marmoset; Cebuella pygmaea (Spix, 1823)-pygmy marmoset; Callicebus cupreus (Spix, 1823) -red titi monkey; Aotes trivirgatus Humboldt, 1811-night-monkey; Saimiri sciurea (L., 1758)-common squirrel-monkey; Saimiri boliviensis d'Orbigny, 1834-black-headed squirrel-monkey; Lagothrix cana (Geoffroy) 1812Amazonian woolly monkey (in earlier papers of this series this animal was referred to as L. infumata); Ateles paniscus (L., 1758)black spider-monkey. THE GENUS Prosthenorchis

Comparative Observations on Experimental Schistosoma mansoni Infections in African Green and Rhesus Monkeys

The pattern of egg excretion and the number of schistosomes are compared in five African green (Cercopithecus aethiops pygerythrus and C. aethiops sabaeus) and five rhesus monkeys. Egg excretion in the green monkey was lower during the acute phase and declined more slowly thereafter. The green monkeys maintained a significantly higher number of worms over a period of many months. The number of eggs passed by green monkeys during chronic infections was much less than would be expected from the number of live worms recovered at autopsy. Although primate hosts are valuable in schistosomiasis research, rhesus monkeys, which have been used mostly, rapidly develop strong immunity to schistosomes which reduces the worm burden and egg excretion (Meleney and Moore, 1954; Vogel, 1958; Naimark et al., 1960; Meisenhelder, Olszewski, and Thompson, 1960; Sadun et al., 1961; Thompson, Meisenhelder, and Najarian, 1962). Although improvisations permit the evaluation of drugs against Schistosoma mansoni infection in the rhesus monkey (Thompson et al., 1962), acquired immunity limits its value for this and many other purposes. The importance of searching for a primate host better than the rhesus monkey has been emphasized in a report to the World Health Organization (1959). Vogel (1958) stated, without elaboration, that the survival of S. mansoni and the duration of its egg excretion is much longer in African green monkeys than in the rhesus. These considerations stimulated the present observations dealing with the course of S. mansoni infection in African green monkeys relative to rhesus monkeys. MATERIALS AND METHODS The animals infected during this work included three Cercopithecus aethiops pygerythrus (the East African green monkey) and two C. aethiops sabaeus (the West African green monkey). Four of these were studied in parallel as pairs with a monkey of each subspecies in each pair, i.e., numbers 25 and 138, 38 and 39. Received for publication 9 January 1963. As detailed accounts appear elsewhere (Najarian and Thompson, 1958; Thompson et al., 1962), the materials and techniques will be described only briefly. The monkeys were anesthetized intravenously with sodium thiamylal (Surital ?, Parke, Davis and Co.) and exposed percutaneously for 45 min to S. mansoni cercariae (Puerto Rican strain) collected from 30 or more Australorbis glabratus. The course of infection was followed by semiquantitative stool examinations for eggs; acidether preparations of 1 ml of feces were examined twice weekly from the 5th week after exposure until autopsy. Egg counts were not adjusted for the water content of the feces. Infections were assessed terminally by the number of live worms found at autopsy; following perfusion, the mesenteric and portal veins, the ground liver, and the perfusate were examined for schistosomes.

Papio doguera (dog face baboon), a primate reservoir host of Schistosoma mansoni in East Africa

1. 1) A prevalence of natural infection with Schistosoma mansoni of 23.9 per cent. was found in 134 Papio doguera (dog face baboons) classified as children or older. These findings were based upon the examination of tissue removed at autopsy from the liver and intestine. 2. 2) The demonstration of natural infection in baboons indicates that P. doguera is a reservoir host for S. mansoni in East Africa.

The chemotherapy of experimental plague in the primate host.

The chemotherapy of experimental plague in the primate host.

Experimental Studies on Human and Primate Species of Strongyloides

Summary and Conclusions 1. This paper presents experimental evidence showing the behavior of strains of Strongyloides obtained from primate hosts and from human hosts. 2. Previous studies by the writer have demonstrated the different capacities of macaque, ateles and human strains of Strongyloides to establish themselves in autochthonous and reciprocal hosts. This investigation presents evidence based on inoculation of man, the macaque and the dog with chimpanzee, macaque, capuchin and human strains. 3. Repeated passage of pure type human strains through canine hosts invariably produced alterations. These tended to simplify themselves into the direct type of development. Passage of the chimpanzee strain through dogs failed to modify it from the original indirect type, but in man the stability was reduced. The organism bred true to type in the macaque but after this passage was unable to develop in dogs. 6. Change from the hyperinfective and indirect types to the direct type was accompanied by a decrease in the virulence of the organism and increased failure to establish itself in the canine host. This is in direct contrast with the increased virulence and greater ease of establishing itself in the case of the unmodified chimpanzee strain during successive passages through dogs. 5. The data established by this investigation provide proof as to the instability and variability of the several strains of Strongyloides studied.