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Pneumocystis carinii infections have been detected both serologically and histologically in untreated, germ-free and conventional rats killed immediately upon arrival from two commercial sources. Pneumocystis antigenemia was detected by counterimmunoelectrophoresis (CIE) and antibody was titered by indirect immunofluorescence. The data suggest that 1) P. carinii is enzootic in certain rat colonies; 2) in utero transmission is a distinct possibility; and 3) paucity of cysts does not rule out P. carinii, as trophozoites predominate in early or sub-clinical infections. Histologic data support the validity of CIE for noninvasive detection of P. carinii antigen. Infection with this agent may be missed by basing diagnosis upon the presence of cyst forms alone, and it may be more common than previously supposed. These data have significant implications for the natural history, diagnosis, and epidemiology of P. carinii with regard to the human host.

Over the past decade, P carinii has become an important cause of pneumonia in the compromised host. Progress has been made in clinical awareness of the organism, in methods of diagnosis, and in developing new forms of treatment. However, there is still a lack of basic knowledge about the biology, taxonomy, and epidemiology of P carinii; of specific host immune factors involved in the pathogenesis of the infection; and of a clinically reliable serologic test. With recent advances in P carinii research, progress hopefully will be made in these areas in the future.

An experiment was carried out exposing immunosuppressed mice to the atmosphere to determine if transmission of Pneumocystis carinii occurred in Kenya. Mice were killed at weekly intervals for four months and the lungs examined histologically for the presence of these parasites. None of the mice contracted even light infections and this, together with the lack of clinical evidence of this disease in immunosuppressed or neonatal cases, suggests that this parasite does not occur in Kenya. Possible reasons for this are discussed.

Pneumocystis carinii (Pc) derived from nude mice (MPc) and hypercorticonized rats (RPc) was subjected to transmission experiments via intranasal (i.n.) route into athymic nu/nu mice (BALB/c background) and run/rnu rats (Rowett hooded strain) and their euthymic heterozygotes rnu/+ rats. Although all these recipient animals received intensive cortisone treatment, MPc propagated only in nu/nu mice. In contrast, RPc strains from three different sources were transmitted successfully to both rats and mice irrespective of their athymicity. The MPc strain could not be transmitted to the other three rat strains used. When RPc organisms were successively propagated in nu/nu mice they lost their pathogenicity to rats after five passages. An antigenic difference between MPc and RPc was suggested by cross reaction of rabbit-raised antiMPc and antiRPc sera against MPc and RPc organisms. An absorption experiment of the sera with both MPc and RPc revealed cross reactivity as well as specific reactivity. The mouse passaged RPc seemed to change the antigenic characteristic to that of MPc.

Experimental infection with both human- and rat-derived Pneumocystis carinii has been produced in nude mice by intrapulmonary injection of lung homogenates that contained P. carinii and by environmental transmission. Most infected mice did not appear ill, and their lungs exhibited a mild and nonspecific inflammatory response. Thus, P. carinii can be transmitted from one animal species to another, and this result suggests that a defect in thymic-dependent lymphocytes is important in the development of the infection. Experimental work with P. carinii in the nude mouse should be performed in isolators because of the communicability of the organism.

Discussed are incidence, predisposing factors, presenting symptoms, diagnostic and isolation procedures, and therapy of Pneumocystis carinii pneumonia in renal transplant recipients. A case is reported of a 46-year-old recipient of a cadaveric kidney, who develop P. carinii infection and was successfully treated with pentamidine isethionate.

Studies were reviewed on attempts to apply serologic methods for the laboratoary diagnosis of pneumocystis pneumonia and for epidemiologic surveillance in outbreaks of this disease. At autopsy the parasite was found in 7.7% of patients with a clinically latent infection. In this series of patients, parasitologic findings were not correlated with the results of a complement fixation (CF) test or with those of an indirect fluorescent antibody test. The high incidence of serologic reactivity in the CF test in chronic obstructive lung disease was not related with special clinical symptoms. Longitudinally performed parasitologic and serologic observations will be needed to find out if Pneumocystis carinii is a pathogen and fulfills Koch's criteria. Preliminary data are given for such an experimental approach in a colony of rats.

Axenic rats maintained in germfree isolators were found to be free of Pneumocystis carinii after three months of immunosuppression with dexamethasone. This P. carinii-free rat model was used to identify the mode of acquisition of P. carinii from the natural environment. Germfree were exposed in selective manner to potential sources of P.carinii, including air, water, and food. Animals exposed in the isolator with filtered (sterile) air and to regular (unsterile) water and food did not acquire P. carinii. Rats exposed in open cages to room air but maintained on sterile water and food acquired the infection. Animals fed lung tissue infected with P. carinii did not acquire the infection. These findings show that P. carinii is naturally acquired as an airborne organism in a de novo infection.

Thirty-five male Sprague-Dawley rats were divided into 3 groups, including 1 control and 2 experimental groups, in order to compare the efficacy of using cortisone acetate alone or in addition to intranasal inoculation of Pneumocystis carinii organisms for the purpose of inducing acute P. carinii pneumonia. The presence of P. carinii was monitored in nasal secretions on a weekly basis and in lungs at autopsy. Titers of IgG antibody were also monitored by enzyme-linked immunosorbent assay. No rat receiving cortisone acetate injections alone and only 2 of the rats receiving both cortisone and intranasal inoculation of P. carinii organisms showed Pneumocystis organisms in the lungs. However, Pneumocystis cysts did appear in the nasal secretions of 3 of the 5 control rats, all 8 rats receiving cortisone acetate injections only, and 12 of 18 rats receiving both cortisone acetate injections and an intranasal inoculum. IgG titers of both cortisonized groups remained less than 1:4 throughout the course of the experiment. The titer of the control group increased from negative to 13 (geometric mean).

A chronic pulmonary disease was encountered in nude mice of a barrier sustained colony, and Pneumocystis carinii was identified as the causative agent histopathologically as well as on impression smear preparations in the affected lungs. Fatal infection was seen only in old nude mice aged more than 6 months, while focal pulmonary lesions were developed without clinical signs in young adult nudes 2 to 3 months of age. The lesions produced in aged nude mice were characterized by propagation of mononuclear cells with the presence of foamy masses of P. carinii. Heterozygous littermates were much less susceptible to the infection but pneumocystic lesions could be produced readily by multiple treatment with immunosuppressants. The infection could be transmitted without immunosuppressant to non-infected nudes but not to heterozygous littermates after intranasal inoculation of affected tissue emulsion or by cage mating with severely affected nudes.

Fourteen of 156 renal-transplant recipients treated with cyclosporine and steroids developed Pneumocystis carinii-related pneumonia (PCP) over a 19-month period. This was a significant change from past experience with this disease in renal-transplant patients receiving azathioprine and steroids (six cases among 179 patients from 1977 to 1981). Epidemiological investigation failed to implicate either person-to-person or nosocomial spread of infection. Cases of PCP occurred more frequently in males. Twelve patients (86%) had onset of disease in the third or fourth months after transplantation. Comparison of cases to matched controls revealed that the cases had received lower doses of steroids and had a higher incidence of cytomegalovirus infection. This suggested that the cases may have been more effectively immunosuppressed than the controls. After institution of prophylaxis with trimethoprim-sulfamethoxazole, no further cases of PCP developed.