Passive immunoprophylaxis with specific monoclonal antibody confers partial protection against Pneumocystis carinii pneumonitis in animal models.

Pneumocystis carinii is an important cause of pneumonitis in the immunosuppressed host. Little is known, however, about the biology of this organism. This report demonstrates that a MAb, M5E12, previously shown to be directed against a surface antigen that is present on rat-, rabbit-, ferret-, and human-derived P. carinii, is capable of hindering the development of P. carinii pneumonitis in animal models of this infection when administered throughout the period of immunosuppression. It appears that MAb M5E12 thus has identified a surface antigen of P. carinii that is important in host-parasite interactions.

Synergistic anti-Pneumocystis carinii effects of erythromycin and sulfisoxazole.

Pneumocystis carinii pneumonitis was effectively prevented in 90% of immunosuppressed rats by the administration of 100 mg of erythromycin and 300 mg/kg/day of sulfisoxazole. All of the untreated control and erythromycin-treated animals developed the infection and 80% of rats given sulfisoxazole alone had the pneumonitis. A similar pattern of response occurred when the drugs were used therapeutically for rats with established P. carinii pneumonitis. The erythromycin and sulfisoxazole ratio of 1:3 was the most effective of several dose combinations tested. The established safety record from three decades of clinical use of this drug combination plus the broad spectrum of coverage for other causes of diffuse pneumonitis such as Chlamydia, Mycoplasma, and Legionella warrant further study of erythromycin-sulfisoxazole in AIDS patients.

Nosocomial infections in immunocompromised children.

Within the last decade several advances in medicine have resulted in extended longevity of children with cancer, cystic fibrosis, certain congenital immunodeficiency disorders, chronic renal diseases and aplastic anemia. Forthwith, the population of such immunocompromised children has increased and accounts for a greater portion of the hospital census than heretofore. To avoid emotional, infectious and financial burdens of hospitalization, efforts have been successful in developing ambulatory outpatient programs within specialized centers. Although infection control policies have been reasonably well-established for the hospitalized inpatient, policies for the hospital outpatient are lacking. Investigations into the problems of "nosocomial outpatient infections" are needed. Accomplishments in recent years in the control of nosocomial infections include the development of preparations for passive immunization for varicella-zoster virus and hepatitis B virus exposures and the application of certain antibiotic regimens for prophylaxis. Currently a vaccine is under study for active immunization to varicella with possible efficacy for exposed susceptible persons. It is obvious that the proportion of children at increased risk for infection in the hospital environment will continue to increase.

Varicella in children with cancer: Seventy-seven cases.

The purpose of this study was to characterize varicella in childhood cancer patients. Seventeen of the 77 patients reviewed were in remission and off all therapy for 3 to 22 months. No one in this group died from varicella or had evidence of visceral dissemination. Among the remaining 60 patients, all of whom were receiving anticancer theapy when they developed varicella, 19 (32%) had visceral dissemination and 4 died, for a mortality rate of 7%. Each of the deaths was associated with primary varicella pneumonitis, with or without acute encephalitis. Visceral dissemination was not related to type or status of malignancy or to duration of specific anticancer therapy. Varicella was more likely to disseminate in children with absolute lymphopenia, less than 500 cells per cubic millimeter, than in patients with higher lymphocyte counts. Cessation of anticancer theapy prior to the onset of lesions appeared to lessen the risk of dissemination. These results show that varicella is more severe in cancer patients on therapy than the general population or in patients who have completed therapy, but is not highly fatal.

Pneumocystis carinii infection: evidence for high prevalence in normal and immunosuppressed children.

Using Pneumocystis carinii organisms propagated through three passages in embryonic chick epithelial lung cultures, specific antigens and antisera were prepared for use in counterimmunoelectrophoresis and indirect immunofluorescent antibody techniques. These methods proved to be specific and sensitive for the detection of P. carinii antigen and antibody, respectively, in sera, and were applied to the study of cancer patients with P. carinii pneumonitis (PCP), cancer patients without pneumonitis, and normal children. Antigenemia was detected in 95% of patients with PCP, in 15% of cancer patients without pneumonitis, and in none of the normal children tested. In cross-sectional and longitudinal studies of normal infants and children, acquisition of serum antibody to P. carinii was demonstrated to occur progressively with increase in age. By 4 years of age two thirds of the normal children were found to have antibody to P. carinii in titers of 1:16 or greater. These studies indicate that subclinical P. carinii infection is highly prevalent in normal children, analogous to other opportunistic infections where active disease is manifest predominantly in the compromised host.

Aspergillus osteomyelitis in an immunocompetent adolescent: a case report and review of the literature.

A black male adolescent with intact cellular and humoral immunity developed Aspergillus flavus-caused osteomyelitis involving the right tibial epiphysis following penetrating injury to that area. There was an apparent cure following amphotericin B therapy for six weeks. The clinical, pathologic, and therapeutic features of this case are described and compared with those in previously published cases. This case report represents the first well documented case of Aspergillus osteomyelitis in an immunocompetent host. The increasing incidence of invasive disease due to Aspergillus species and the increased awareness of the incidence of mycotic bone infections, particularly in pediatric patients, may allow further definition of pathogenesis and appropriate therapy.

Pneumocystis carinii pneumonitis in young immunocompetent infants.

Of 67 infants enrolled in a prospective study of infant pneumonia ten (14%) had evidence of Pneumocystis carinii infection. Diagnosis was achieved by demonstrating circulating P carinii antigens by counterimmunoelectrophoresis in all ten cases and by histopathology in the only infant who underwent an open lung biopsy. Antigenemia did not occur in 64 control infants (P = .003), nor in 57 patients of similar age who were hospitalized with pneumonitis due to Chlamydia trachomatis, respiratory syncytial virus, cytomegalovirus, adenovirus, and influenza A and influenza B viruses. None of the ten infants with P carinii pneumonitis had evidence of a primary immunodeficiency nor had any received immunosuppressive medication. These patients were hospitalized at a mean age of 6 weeks (range 2 to 12) and their illness was characterized by its afebrile course, presentation in crisis with severe respiratory distress, apnea, tachypnea, cough, increased IgM, and bilateral pulmonary infiltrates with hyperaeration. The clinical features of P carinii pneumonitis were indistinguishable from those of C trachomatis and cytomegalovirus pneumonia. Treatment with trimethoprim-sulfamethoxazole was associated wtih rapid disappearance of circulating antigens; however, the small number of patients studied did not permit an analysis of its clinical efficacy. These results indicate that P carinii singly or in combination with other infectious agents may be an important cause of pneumonitis in young, immunocompetent infants with no underlying illnesses.

Acute fulminating babesiosis in hamsters infected with Babesia microti.

In this study, Babesia microti (ATCC30222) from mice was adapted to golden hamsters. The parasite was passaged to immunosuppressed and then adapted to normal hamsters. When 30 normal hamsters were inoculated with this strain, parasitaemia increased to 74% of erythrocytes by day 7 and 70% of the hamsters died. By day 12, parasitaemia extended to 90%, with 97% mortality. Hearts and kidneys from infected animals were enlarged. Histopathology revealed acute myocarditis, hepatitis, pneumonitis, glomerulonephritis and splenomegaly. Giemsa, Acridine Orange and Rhodamine staining of the parasite were compared. Scanning electron microscopy of blood from infected hamsters revealed from 1 to 5 intra-erythrocytic parasites.

Pneumonitis due to Corynebacterium equi.

Corynebacterium equi, a known cause of pneumonitis in foals, calves, and swine, was isolated from the sputum and bronchial washings of a child with pneumonitis and leukemia. Clinical improvement followed the administration of chloramphenicol, and cultures of sputum specimens were sterile until relapse occurred after antibiotic therapy was terminated. Cure was achieved with a second course of chloramphenicol therapy. Corynebacterium equi was not isolated from 1,181 samples of sputum from other immunosuppressed children with cancer.

Presentation of Pneumocystis carinii pneumonia as unilateral hyperlucent lung.

Pneumocystis carinii pneumonia (PCP) presented as unilateral hyperlucent lung in a 27-month-old patient with a brain tumor who was receiving chemotherapy. Although unilateral pneumonia is an uncommon presentation of PCP in non-AIDS patients, PCP must be suspected in any pediatric cancer patient not receiving trimethoprim-sulfamethoxazole prophylaxis and receiving intensive chemotherapy.

Continuous negative chest-wall pressure as therapy for severe respiratory distress in older children.

Continuous negative chest-wall pressure (CNP) was used to treat five children, 4 to 11 years of age, who had progressively severe respiratory distress caused by Pneumocystis carinii penumonitis. After initial improvement, two patients developed progressive increases in respiratory rate, alveolar-arterial oxygen gradient, intrapulmonary right-to-left shunt, and hypoxia. The disease ended fatally in both. The remaining three patients continued to improve and recovered from their pulmonary disease. These results show that CNP therapy provides an effective means of improving arterial oxygenation in spontaneously breathing older children, just as in neonates, without the need for endotracheal intubation, prolonged sedation, and muscle relaxants.

Extrapulmonary cryptococcosis in children with acquired immunodeficiency syndrome.

There is a paucity of published information available on extrapulmonary cryptococcosis (EC) in children infected with human immunodeficiency virus, the etiologic agent of the acquired immunodeficiency syndrome. We surveyed investigators in pediatric acquired immunodeficiency syndrome around the country regarding their experience with EC. Investigators from 33 (87%) of 38 institutions responded and information on 13 patients from 11 institutions was analyzed. EC was the acquired immunodeficiency syndrome indicator disease in 9 (69%) of 13 patients. Median age was 8 years with a range of 2 to 17 years. Human immunodeficiency virus risk factors were transfusion (5 patients), hemophilia (4 patients) and perinatal exposure (4 patients). Meningitis, seen in 62% of patients, was the most common clinical manifestation. Although 2 patients with fulminant disease died before therapy was started, 10 (91%) of 11 had a clinical response to amphotericin B with or without flucytosine. Our study indicates a spectrum of EC in pediatric human immunodeficiency virus infection ranging from fulminant, fatal fungemia to chronic meningitis and fever of unknown origin. Cryptococcosis was generally not the cause of death in patients who initially responded to amphotericin B therapy. Optimal antifungal therapy, including the role of fluconazole, warrants further study.

Search for Pneumocystis carinii DNA in upper and lower respiratory tract of humans.

Recent studies suggest that Pneumocystis carinii DNA may be detected by PCR in oropharyngeal secretions in the majority of patients with P. carinii pneumonitis (PCP). However, the prevalence of P. carinii DNA in patients without PCP has not been well established. A prospective study of 258 nasal, pharyngeal, and salivary specimens from 86 individuals with AIDS, cancer or no underlying disease, and without respiratory infection, found no P. carinii DNA in any of the samples. Separately, to validate the PCR for detection of P. carinii DNA, 45 specimens from the lower respiratory tract (bronchoalveolar lavage [BAL] and sputum) from 31 patients with pneumonitis and AIDS or cancer were studied. Eleven had PCP by conventional stains and 20 did not. All patients with PCP, and none without PCP, had P. carinii DNA in BAL, sputum or both. The study indicates the prevalence of P. carinii DNA is low or absent in oropharyngeal secretions in the absence of PCP.

Candida tropicalis infections in children with leukemia.

The Candida species account for approximately three-fourths of fungal infections in patients with cancer. Although Candida albicans is the most frequent cause, C. tropicalis is increasingly implicated as an important pathogen. Over a 12 year period 19 children treated for leukemia at our institution developed C. tropicalis infections. We describe their clinical presentation, extent of fungal infection, treatment, and outcome. Fungemia without meningitis in 11 children was treated successfully, whereas C. tropicalis meningitis in 7 children was uniformly fatal. An additional patient had unsuspected, widespread infection detected at autopsy. Multiple sites, including the cerebrospinal fluid yielded C. tropicalis. Previously reported risk factors including neutropenia, broad-spectrum antibiotic usage, corticosteroid therapy, and total parenteral nutrition were observed in our cases. A high index of suspicion and the early use of aggressive antifungal therapy are critical to the successful management of C. tropicalis infections in children with leukemia.

Cytomegalovirus in tears from patients with normal eyes and with acute cytomegalovirus chorioretinitis.

Cytomegalovirus (CMV) was recovered from the tears in eight of 41 (19.5%) children excreting CMV in their urine or saliva. Tear excretors were all immunosuppressed children with acute lymphocytic leukemia. Three had active CMV chorioretinitis and five did not develop retinal disease in nine to 15 months of observation. To our knowledge this was the first report of the recovery of CMV from tears and of acquired CMV chorioretinitis in children. One patient with active chorioretinitis presented with a disciform elevation of the macula. Therapy with adenine arabinoside (ara-A) or idoxuridine was ineffective in two patients while a third patient treated with ara-Apossibly had a more rapid recovery. However, the significance is uncertain due to the unusual disease presentation and lack of data regarding the nature of cytomegalic inclusion disease chorioretinitis. Areas of retinal calcification were present at autopsy in one patient.

Pseudallescheria boydii in a patient with acute lymphoblastic leukemia.

Pseudallescheria boydii, a common soil organism, is best known as the causative agent of mycetoma. Isolation of the organism from sites other than the extremities is relatively uncommon. However, the use of corticosteroids and cancer chemotherapy has been associated with an increasing frequency of localized superinfection as well as disseminated disease. Recently, an increased number of disseminated P boydii infections, primarily associated with immunosuppressed patients, has been reported in the literature. We diagnosed an additional case of P boydii in a 16-year-old boy who had acute lymphoblastic leukemia and manifested a disseminated infection during reinduction chemotherapy. The unusual features of this case were the extent of organ involvement, which was more wide-spread than previously noted in the literature, and the presence of conidia in sections of an endocardial thrombus.

Pneumocystis carinii infection alters GTP-binding proteins in the lung.

The GTP-binding regulatory proteins (G proteins) in the membranes of the lung parenchyma from normal, uninfected ferrets were compared to those from immunosuppressed animals with and without Pneumocystis carinii pneumonitis. In lung membranes, pertussis toxin (PT) catalyzed ADP ribosylation of a 41-kDa protein; treatment with cholera toxin (CT) led to ribosylation of a 44-kDa polypeptide. Compared to that in the normal ferrets, the level of the 44-kDa protein was dramatically suppressed in the P. carinii-infected animals. Western blot analysis with specific antibodies to alpha s (which recognized CT substrates), alpha common (which reacted to PT substrates), the alpha q/11 epitope, and the beta subunit demonstrated that these proteins were decreased in animals with P. carinii pneumonitis (PCP). Western blotting of PCP-free membranes with a pan-Ras antibody revealed a 21-kDa polypeptide (corresponding to small G proteins). The level of the 21-kDa protein in membranes from PCP-affected animals was only 30% of that in membranes from PCP-free animals. Finally, analogous studies performed with rat lung membranes revealed similar findings. These data suggest that, independent of its exacerbation of immunosuppression, PCP leads to extensive changes in the GTP-binding proteins in the lung.

Search for extrapulmonary Pneumocystis carinii in an animal model.

Pneumocystis carinii-infected immunosuppressed ferrets and rats were searched for P. carinii cysts and trophozoites in extrapulmonary organs, including the heart, liver, stomach, kidney, and spleen. Foci of P. carinii were found in the liver or kidney of 4 (10%) of 40 ferrets but in no extrapulmonary sites of 30 rats with P. carinii pneumonitis. Attempts to identify P. carinii from immunosuppressed rat or ferret blood or propagate the organism intraorbitally in immunosuppressed rats were unsuccessful. Pneumocystis carinii was identified from aspirated stomach contents of ferrets but in none of the rats infected with P. carinii pneumonitis.

Fungal sinusitis in immunocompromised children with neoplasms.

This paper reviews the treatment and diagnosis of immunocompromised patients with fungal sinusitis at St Jude Children's Research Hospital. Sinusitis of all types was found to be more common in patients with hematopoietic neoplasms than in patients with solid tumors; 42% of patients with leukemia had abnormal sinus radiographs. Eight cases of pathologically proven fungal sinusitis were identified. All patients were undergoing chemotherapy for either acute myeloblastic leukemia or acute lymphoblastic leukemia and had neutrophil counts less than 100 cells/mm3. The most common findings were fever, facial pain, and abnormal sinus radiographs. Surveillance cultures of the upper aerodigestive system did not reliably predict sinus pathogens. An aggressive treatment approach consisting of early administration of amphotericin B (intravenously and via catheter irrigations of the sinuses) and surgical drainage is advocated. There was an 80% survival rate in patients in remission who were undergoing maintenance chemotherapy. All patients undergoing chemotherapy for relapse died.

Infrared, thermistor, and glass-mercury thermometry for measurement of body temperature in children with cancer.

Body temperature is often the sole determinant of whether or not the neutropenic cancer patient is admitted to the hospital for empiric antibiotic therapy. Recently developed infrared tympanic thermometers offer rapid readings, but their accuracy has not been established. We studied two infrared thermometers (FirstTemp and Thermoscan) and a thermistor (IVAC) in children with cancer. Mean infrared measurements did not differ significantly between right and left ear canals, and the mean IVAC temperature did not differ significantly from the left to the right axilla (P greater than 0.05, paired t test). IVAC predictive mode mean temperature was 0.2 degrees C lower than monitor mode mean temperature in the axilla (P less than 0.0001), but 0.1 degree C higher than monitor mode orally (P less than 0.0001). Aiming the infrared instrument at the tympanic membrane using an ear tug resulted in a 0.2 degree C higher mean temperature than casual placement in the ear canal (P less than 0.0001). After compensation for the mean difference in reference oral glass-mercury versus test instrument temperatures, the FirstTemp, Thermoscan, and oral and axillary predictive mode IVAC measurements yielded sensitivities for the detection of fever of 84%, 84%, 82%, and 86%; specificities of 100%, 99%, 100%, and 100%; positive predictive values of 100%, 93%, 100%, and 100%; and negative predictive values of 95%, 98%, 98%, and 98%, respectively. We conclude that each of these instruments detects fever with comparable reliability. Infrared instruments are especially attractive alternatives due to their time efficiency.