Plasmodium falciparum merozoite vaccine in Aotus monkeys. An evaluation of the tolerableness of three types of adjuvants.

Eight Aotus trivirgatus monkeys were included in a comparative study of adverse reactions caused by 3 types of malarial vaccine. The antigen consisted of late schizonts and merozoites combined with each of 3 adjuvants, a lipoidal amine CP-20,961, a muramyl dipeptide derivative [B30]-MDP, or Freund's complete adjuvant (FCA); 3 monkeys received CP-20,961 and 3 [B30]-MDP, whereas the FCA vaccine was given to 2 animals. All the vaccine combinations caused some adverse reactions, but their nature and intensity varied. Oedema, petechiae and/or ecchymosis, induration, and formation of fluctuating masses at the injection site were the local reactions observed, but except for the FCA group, all reactions disappeared without notable sequelae. Fever was the commonest general reaction, being mildest in the [B30]-MDP group. A transient increase (about 50%) in leukocyte count and a decrease (15-20%) in red blood cell count were observed in all animals, regardless of the type of adjuvant or whether it was a primary or booster injection in question. However, because the vaccine using [B30]-MDP evoked the mildest reactions, this may be the one most promising for future human studies if its protective efficacy is proven.

The occurrence of an adverse reaction to chloroquine in Dirofilaria immitis-infected dogs.

The occurrence of an adverse reaction in Dirofilaria immitis-infected dogs following an intramuscular injection of chloroquine is described. The manifestations of this adverse reaction were characteristic of a neurologic disorder rather than the hypovolemic, shock-like state of the post-DEC adverse reaction previously described in dogs. In 3 of the 12 dogs the adverse reaction was of sufficient severity as to be fatal. Alterations in serum fibrinogen, serum transaminase levels and platelet numbers occurred but the magnitude of changes were not as great as that in the post-DEC adverse reaction. Following the injection of chloroquine the microfilaremia increased to a degree that was greater than the increase following DEC administration in the dog.

Reactogenicity of a malaria merozoite antigen in Aotus monkeys compared with the effects caused by two new adjuvants, CP-20,961 and [B30]-MDP.

Six Aotus trivirgatus monkeys were included in a clinical study to compare the adverse reactions caused by a Plasmodium falciparum antigen and 2 adjuvants, a lipoidal amine, CP-20,961, and a muramyl dipeptide derivative, [B30]-MDP. Two monkeys were given 2 intramuscular injections, 3 weeks apart, of 1 of these vaccine components. Both the antigen and the two adjuvants caused local and general reactions as well as hematological and biochemical changes. Except for an up to 60% rise in leukocyte count, the antigen caused reactions least, followed by [B30]-MDP. CP-20,961 evoked more vigorous reactions and changes, but none of them reached such an extent that it would contraindicate its potential use in forthcoming vaccine studies. We conclude that both adjuvants are to be considered as relatively safe when combined with an appropriate P. falciparum antigen.

Inhibition of the adverse reaction to diethylcarbamazine in Dirofilaria immitis-infected dogs by lodoxamide ethyl.

Lodoxamide ethyl, a new oral anti-allergy drug, was tested for its ability to inhibit the post-treatment adverse reaction to diethylcarbamazine (DEC) in Dirofilaria immitis-infected dogs. Lodoxamide was highly effective, as judged by the absence of both overt signs and characteristic post-DEC changes in platelet numbers, serum fibrinogen level, and serum transaminase (SGOT, SGPT) levels, in blocking the reaction in dogs with a microfilaremia level that would make them moderately reactive. Lodoxamide was less effective in blocking the reaction in dogs with microfilaremias greater than approximately 10,000 mf/ml, a level which is regularly associated with a severe post-DEC adverse reaction. Some dogs with this level of microfilaremia were fully protected, others partially protected, and others were afforded no protection. Two other agents tested, indomethacin and homochlorocyclizine, were found to have comparatively little or no blocking activity.

Plasmodium falciparum merozoite vaccination in Aotus monkeys recovered spontaneously from P. falciparum infection: a clinical study.

6 Aotus trivirgatus monkeys, which had all spontaneously recovered from an experimentally induced Plasmodium falciparum infection, were included in a clinical study concentrating on possible adverse reactions caused by a vaccine using late schizonts and merozoites as an antigen a synthetic compound, CP-20,961, as an adjuvant. Two monkeys in the study were vaccinated once, 2 twice, 1 received adjuvant alone and 1 served as a saline control. Local and general inflammatory reactions as indicated by local oedema, induration, femoral lymphadenopathy, fever and leukocytosis, were observed in all vaccinated animals and in the one monkey after the second adjuvant injection. Serum albumin and transaminase enzyme levels increased in all animals whereas plasma fibrinogen, protamine sulfate and ethanol gelation titers rose only inthe vaccinated monkeys. A transient increase of alkaline phosphatase and erythrocyte sedimentation rate was noticed in half of them. We conclude that this type of malaria vaccine causes moderate adverse reactions in Aotus but they are transitory and seem not to lead to permanent damage.

Observations on the adverse reaction to diethylcarbamazine in Dirofilaria immitis-infected dogs.

The severity of the adverse reaction, as assessed by clinical, haematological, and biochemical abnormalities, following treatment of Dirofilaria immitis-infected dogs with diethylcarbamazine (DEC) was found to be related to the level of microfilaraemia. The magnitude of change in the blood constituents studied was proportional to the severity of the side reaction. The most notable alterations in dogs experiencing a moderate or severe adverse reaction were a decrease in platelet numbers and fibrinogen level, a rise in serum transaminases, and the appearance of fibrin monomers. The practical value of qualitatively and quantitatively characterizing the post DEC adverse reaction is discussed.

A comparative study of rosette formation in 12 species of nonhuman primates.

Lymphocytes, isolated from the peripheral blood of 12 species of nonhuman primates, were tested for the ability to form rosettes with antibody-complement-coated erythrocytes (EAC rosettes) and with erythrocytes from various animal species. In general, New World primates (wooly, spider colobus, capuchin and owl monkeys) had a greater number of EAC rosette-forming cells (30-44%) than did Old World monkeys (baboons, gibbons, rhesus, cynomolgus, pigtailed, stumptailed and Japanese macaques) (22-30%). All possessed lymphocytes capable of forming rosettes with sheep erythrocytes. Lymphocytes from some primate species formed rosettes with canine, equine, goat or porcine erythrocytes.

Rapid decrease of precipitating and reaginic antibodies in Dirofilaria immitis-infected dogs which develop severe adverse reactions following treatment with diethylcarbamazine.

Dirofilaria immitis-infected dogs were treated with diethylcarbamazine. Measurement of the level of IgG precipitating antibody was carried out by counterimmunoelectrophoresis and that of IgE by passive cutaneous anaphylaxis in pre-treatment and post-treatment serum samples. In dogs showing severe to moderate adverse reactions to the drug there were pronounced decreases of both antibodies to a "metabolic" antigen prepared from the medium in which adult female worms had been incubated. These antibody levels did not decline in non-reacting dogs. Precipitating antibody levels to somatic antigens extracted from adult worms and microfilariae remained unaltered in both reactive and non-reactive animals.

Experimental infection of cats with the liver fluke Platynosomum concinnum,.

The severity of Platynosomum concinnum infection in cats experimentally infected with 125 flukes (small dose) and 1,000 flukes (large dose) was determined by monitoring clinical signs and hematologic, serum biochemical, and pathologic changes during the infection. All cats (8/8) with a small fluke burden and 3 of 8 cats with a large burden remained clinically asymptomatic, whereas 60% of the cats given large doses had mild signs of inappetence and lethargy. Eosinophilia, peaking 4 to 5 months after infection, was present in all parasitized cats. During the early stages of platynosomiasis, a transient but substantial increase in aspartate aminotransferase and alanine aminotransferase activities was observed in cats given small and large doses. These observations agreed with gross and histopathologic observations, which included enlargement of the gallbladder and biliary ducts, with leukocyte infiltration, adenomatous hyperplasia, and fibrosis of the ductal areas.

A simple restraining device for use with neonatal and small nonhuman primates.

A simple and inexpensive restraining device was designed for use with neonatal and small nonhuman primates weighing less than 2 kg. With this device a technician working alone can collect blood samples, fecal or vaginal smears, nasal or oral swabs, or perform a variety of routine procedures including physical examination and administration of medication.

Evaluation of fecal technics for the diagnosis of cat liver fluke infection.

The comparative efficiency of 5 standard technics for the detection of feline liver fluke ova in feces was evaluated. The formalin-ether technic proved superior to direct smear, sugar flotation, zinc sulfate flotation, or detergent sedimentation technics. The formalin-ether technic correctly diagnosed all Platynosomum concinnum-infected cats studied, as confirmed by necropsy findings.

Differentiating feline T and B lymphocytes by rosette formation.

The number of bone marrow-derived and thymus-dependent lymphocytes in the peripheral blood of felines was assessed. Feline bone marrow-derived lymphocytes were determined by erythrocyte antibody complement (EAC)-rosette formation and membrane immunofluorescence. A good correlation was observed between the cells forming EAC-rosettes (mean of 40.2 +/- 9.7%) and those possessing membrane immunoglobulins (mean of 45.3 +/- 4.1%). Feline thymus-dependent lymphocytes form non-immune (E)-rosettes with rodent erythrocytes (mouse, rat, guinea pig) but not with erythrocytes from humans, monkeys, dogs, mongooses, chickens, rabbits, sheep, and hamsters. An average of 32.3 +/- 992% of the peripheral blood lymphobytes of cats formed rosettes with guinea pig erythrocytes. Antibody blocking, cytotoxicity, and mix-rosette studies demonstrated that guinea pig red blood cells bind specifically to T lymphocytes. Of feline peripheral blood lymphocytes, 41.0 +/- 7.5% showed fluorescent staining with fluorescein-labeled rabbit anti-cat thymus antiserum.

Guinea pig percutaneous femoral blood sampling technic using a new restraining device.

A new method was described for repetitive blood sampling of guinea pigs via percutaneous puncture of the femoral vessels. Either manual immobilization of the animal or a specially designed restraining board was used. This method did not endanger the animal and required neither anesthesia, surgical skill, nor special equipment.