Rhodococcus equi infections of humans. 12 cases and a review of the literature.

Increased recognition of Rhodococcus equi as a human pathogen has occurred since 1983, when the first review article summarized the world's literature of 12 cases. In this article, we present 12 cases from the University of Oklahoma Health Sciences Center and review 60 from the literature. Most cases occur in immunocompromised hosts and present as chronic cavitary pneumonias. Associated extrapulmonary disease is seen at diagnosis in 7% of patients with pneumonia, and relapse occurs at extrapulmonary sites in 13%, often without reappearance of pulmonary disease. Relapse may follow a course of antimicrobial therapy that is too brief, but can also occur during treatment. Infections also occur in the gastrointestinal tract, causing enteritis and regional adenitis with abscesses. Contaminated wounds may become infected. Isolated bacteremias may be a manifestation of latent infection recurring during a period of immune suppression. A common feature of human R. equi infection is delay in diagnosis. The insidious course of disease contributes to delay, as does failure to identify the organism. R. equi is easily cultured on nonselective media but commonly mistaken for a diphtheroid or occasionally for a mycobacterium based on acid-fast appearance. Form and duration of treatment are closely related to host immune status. Immunocompromised patients require prolonged or indefinite therapy with multiple antibiotics. Infections in immunocompetent hosts are easily treated with short courses of single agents. Infections related to contaminated wounds are treated primarily by irrigation and debridement. Infections in immunocompromised hosts are increasing in frequency largely due the AIDS epidemic. Infections in immunocompetent hosts, reported rarely before this series, may be underdiagnosed, perhaps because R. equi resembles common commensals and has limited virulence in this population. This report demonstrates that R. equi infections, including community-acquired pneumonias, occur in immunocompetent hosts.

Use of aminoglycosides during cyclosporine A immunosuppression after liver transplantation in children.

To determine the frequency of renal dysfunction associated with the use of aminoglycosides with cyclosporine A (CyA) in children, the records of 26 consecutive children receiving CyA after liver transplantation were reviewed. Fourteen patients with normal baseline serum creatinine concentrations received an aminoglycoside postoperatively. These children received CyA and an aminoglycoside for 249 days (average, 17.8 days/patient). Forty of the 249 days included treatment with vancomycin or amphotericin B. Twelve children (86%) showed no evidence of renal dysfunction after aminoglycoside therapy. Two children developed renal dysfunction and eventually succumbed. In neither case could aminoglycoside nephrotoxicity be identified as the main cause of renal dysfunction. Multiple other factors, including ischemia and high CyA concentrations, probably contributed to renal deterioration. We conclude that aminoglycosides can be used safely in children receiving CyA following liver transplantation, provided serum CyA concentrations are followed closely and other risk factors for renal dysfunction are minimized.

Prevalence of Cryptosporidium parvum infection in children along the Texas-Mexico border and associated risk factors.

We examined the epidemiology of Cryptosporidium parvum in children aged 6 months to 13 years living in 1) colonias along the border (n = 105), 2) a clinic in an urban border community (n = 65), and 3) clinics in a large urban nonborder area (n = 109). Serum IgG and IgA anticryptosporidial antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Overall, 70.2% (196/279) of subjects had detectable C. parvum antibodies. Prevalence rates were higher (93/105 [89%]) in the colonias and urban border community (53/65 [82%]) compared to the urban nonborder community (50/109 [46%]). Within colonias, independent risk factors for C. parvum infection included consumption of municipal water instead of bottled water, older age, and lower household income. Children living along the Texas-Mexico border have a higher rate of infection with C. parvum compared to children living in a large nonborder urban area. Within colonias, C. parvum infection was associated with source of water supply, age, and socioeconomic status.

Analysis of false positive HIV-1 serologic testing in Kenya.

Sera of 95 mothers and 129 children from Nairobi, Kenya, collected in 1976, and of 466 adults and 193 children of Embu District, Kenya, collected in 1984 and 1985, were analyzed for the presence of human immunodeficiency virus type 1 (HIV-1) antibodies. Although no HIV-1 seropositivity was demonstrated by western blot analysis in both study groups, 7% of Nairobi mothers and 10% of adult females from Embu District had false positive results by enzyme immunoassay (EIA) compared with less than 1% seroreactivity rates observed in adult males and children. False positive results were not due to simian T lymphotropic virus type III (STLV-IIIAGM)/human T lymphotropic virus type IV (HTLV-IV) seropositivity. Sixty-one percent of the HIV-1 EIA reactive sera could not be explained by cytotoxic activity to lymphocytes bearing the HLA-DR4 or HLA-DQw3 phenotype. We conclude that false positive HIV EIA tests are frequently encountered in East Africa. Seroprevalence rates in rural Africa must be interpreted with caution due to the decreased specificity of HIV EIAs.

Experimental cryptosporidiosis in adult and neonatal rabbits.

Neonatal and adult New Zealand White rabbits were infected experimentally with Cryptosporidium parvum. No histologic evidence of infection was found in adult rabbits. However, increased levels of anti-cryptosporidial serum IgG were present, and multiple antigens were detected by serum on immunoblots. In neonates, variably severe, transient infection was present from Days 3 to 21 postinoculation. Serum IgG was initially elevated, decreased until Day 10 postinoculation, then progressively increased for the remainder of the study. A prominent 15 kilodalton antigen was detected on immunoblots using serum obtained on Days 14 until 28 postinoculation. Neonate anti-cryptosporidial fecal IgA were slightly elevated on Days 14 and 21 postinoculation.

Inability of interferon-gamma and aminoguanidine to alter Cryptosporidium parvum infection in mice with severe combined immunodeficiency.

Severe combined immunodeficiency (scid) mice have been useful in identifying specific host defense systems responsible for containing and eradicating Cryptosporidium parvum infection. Adult scid mice were given C. parvum oocysts and treated weekly with monoclonal antimurine interferon-gamma (anti-IFN-gamma). Anti-IFN-gamma-treated mice had more cryptosporidia seen in the intestines and had more severe morphologic changes associated with disease than control mice. To assess the mechanism of this effect, infected adult BALB/c and scid mice were treated with the nitric oxide synthase inhibitor, aminoguanidine. Infection in aminoguanidine-treated mice was not significantly different from that in control mice. Next, the effects of pharmacologic doses of IFN-gamma (10,000 IU) on the course of cryptosporidiosis in newborn scid mice were evaluated. IFN-gamma did not reverse the initial susceptibility of neonatal scid mice to cryptosporidiosis and continued treatment with IFN-gamma (10,000 IU weekly) did not alter survival. We conclude that IFN-gamma does not exert its anticryptosporidial effect by stimulation of nitric oxide production. Deficient IFN-gamma production by neonatal lymphocytes does not appear to be responsible for the increased severity of infection observed in neonatal animals. Also, IFN-gamma may not be useful in treating immunocompromised patients with cryptosporidiosis.

Cryptosporidium parvum infection after abrogation of natural killer cell activity in normal and severe combined immunodeficiency mice.

The role of natural killer (NK) cell activity in adult mice with severe combined immunodeficiency (scid mice) infected with Cryptosporidium parvum oocytes was evaluated. Adult BALB/c and scid mice were inoculated intragastrically with 10(6) C. parvum oocysts after the administration of anti-asialo-GM1 or control normal rabbit serum. Groups of animals were evaluated for splenic NK cell activity and examined histopathologically at 2, 4, and 6 wk postinfection. Virtual elimination of splenic NK cell activity by anti-asialo-GM1 treatment was demonstrated. Nonetheless, no differences in the occurrence of illness, death, or histopathologic evidence of infection were observed between anti-asialo-GM1-treated and control-treated BALB/c or scid mice. We conclude that NK cell activity, at least as measured in the spleen, does not play a significant role in murine host defense of cryptosporidial infection, even in the absence of functional B and T cells.

Cryptosporidiosis in adult and neonatal mice with severe combined immunodeficiency.

Cryptosporidium parvum causes protracted diarrhoea in immunodeficient hosts. To characterize the role that T and B lymphocytes play in the eradication of the parasite from the intestinal mucosa, the course of infection in mice with severe combined immunodeficiency (SCID) was studied. Twenty-nine SCID and 26 BALB/c adult mice received 10(6) oocysts intragastrically. The course of infection in the two strains was similar until 2 months after inoculation, when moderate numbers of organisms were identified in the villous and crypt mucosa of the ileum and proximal colon of SCID mice. Three months after inoculation, SCID mice developed wasting and progressive intestinal and biliary tract disease. At 5 months, mortality of 72 and 0 per cent, respectively, was observed in the SCID and BALB/c mice. Twenty-four SCID and 26 BALB/c neonatal mice were also inoculated with C. parvum. Cryptosporidiosis occurred in SCID and BALB/c mice within 2 weeks of inoculation. Subsequently, BALB/c, but not SCID mice, eradicated the parasite from their intestinal mucosa. SCID mice developed progressively severe cryptosporidiosis which killed all animals within 7 weeks. Responses mediated by B or T cells, or both, appeared to play a role in eradicating C. parvum from the intestinal mucosa, since SCID mice were more severely affected than BALB/c mice. The different course of infection in adult and neonatal SCID mice indicated that other age-related factors also played a role in containing C. parvum infection.

Severe mycoplasma pneumonia in young children with Down syndrome.

Three young children with Down syndrome developed fever, cough, wheezing, irritability, and tachypnea. They had bilateral infiltrates on their chest radiographs and developed respiratory distress, which required their hospitalization. Laboratory studies suggested that the children had mycoplasma pneumonia. These children may have experienced severe mycoplasma infections early in life because of their Down syndrome-associated immune abnormalities. When young children with Down syndrome develop pneumonia, physicians should consider Mycoplasma pneumoniae as the possible etiologic agent.

Diagnosis and treatment of the febrile child following hepatic portoenterostomy.

We report a retrospective analysis of 75 children with hepatic portoenterostomies hospitalized because of fever. Bacterial cholangitis was the most commonly defined cause of fever within 3 months of surgery. Pneumonia and upper respiratory infections were more common 3 months to 2 years following the procedure; however, cholangitis continued to occur during this time period. Twenty percent of hospitalizations were associated with bacteremia or fungemia. Streptococcus pneumoniae was the most common pathogen isolated from the blood. Three children with presumed cholangitis continued to have fever until effective antipseudomonal antibiotic coverage was implemented. The findings in this study lead to the following suggestions: vaccinate all children with pneumococcal vaccine at 2 years of age; a chest radiograph and dental evaluation should be obtained when evaluating the febrile child; empiric treatment for possible cholangitis should include an antipseudomonal penicillin derivative with an aminoglycoside; and if signs of peritonitis are present antibiotic treatment should also include antimicrobials effective against Haemophilus influenzae.

The management of health care workers' accidental parenteral exposures to biological specimens of HIV seropositive individuals.

Health care workers can reduce risks associated with caring for HIV seropositive individuals by strict adherence to routine infection control procedures. Educating personnel in infection control should be increasingly stressed in all health-related settings. When accidents occur, however, the health care industry must respond with appropriate care and follow-up of their employees. The outlined approach for the management of health care workers with needlestick injuries from HIV-contaminated biological specimens provides increased follow-up for workers at higher risk (those who develop illness in the months following an exposure) than current CDC guidelines; and less but sufficient follow-up of those who have a lower risk (no illness) of acquiring HIV infection. Overall, this protocol will provide a more economical, practical, and medically adequate method for follow-up of exposed health care personnel.

Septicemia and meningitis caused by Helicobacter cinaedi in a neonate.

Helicobacter cinaedi has been most frequently isolated from rectal swabs of homosexual men with proctocolitis. The microorganism is a normal intestinal inhabitant of hamsters. We report a case of septicemia and meningitis by H. cinaedi in a neonate whose mother cared for pet hamsters during the first two trimesters of her pregnancy. The isolate was detected after 3 days of incubation in a Bact/Alert pediatric blood culture vial and an enrichment broth culture of the cerebrospinal fluid. H. cinaedi should be added to the list of unusual fastidious organisms that cause sepsis and meningitis in the newborn.

Effects of carbohydrates and lectins on cryptosporidial sporozoite penetration of cultured cell monolayers.

Cryptosporidium parvum first interacts with enterocytes when sporozoites penetrate the host plasma membrane. We have developed a shell vial assay using human embryonic Intestine 407 cells and purified C. parvum sporozoites to study this process. Sporozoites were incubated in culture medium with various carbohydrates and lectins, and the suspensions were then added to the cell monolayers. Following incubation, the monolayers were fixed and stained and the number of schizonts were counted. No decreases in sporozoite motility or Intestine 407 cell viability were observed with carbohydrate or lectin treatment. N-Acetyl-D-glucosamine, chitobiose and chitotriose inhibited C. parvum infection, compared to 5 other tested carbohydrates. Wheat germ agglutinin reduced penetration and concanavalin A enhanced schizont formation, when compared to 8 other lectins. Next, we pretreated sporozoites or Intestine 407 cells with wheat germ agglutinin and concanaval in A prior to sporozoite inoculation. Wheat germ agglutinin treatment of sporozoites or cells equally caused a reduction in C. parvum infection, while enhancement was only observed when Intestine 407 cell were pretreated with concanavalin A. These data suggest that glycoproteins with terminal N-acetyl-D-glucosamine residues may play a role in C. parvum adhesion or penetration of enterocytes. Also, host glycoproteins with concanavalin A-like activity may play a role in these processes.

Seroprevalence of cryptosporidial antibodies during infancy, childhood, and adolescence.

Cryptosporidium parvum causes mild to moderately severe diarrhea in immunocompetent individuals. Cryptosporidial antibodies in the sera of 803 children seen at Children's Hospital of Oklahoma were measured by means of an ELISA. Thirteen percent of children younger than 5 years of age were seropositive for antibodies to C. parvum. The seropositivity rate for children who attended day-care facilities was higher than that for those who did not. In addition, children in this age group with a history of recent diarrhea were seropositive at a higher rate than were children without diarrhea. Thirty-eight percent of children (5-13 years of age) and 58% of adolescents (14-21 years of age) were seropositive for antibodies to C. parvum. Blacks and Native Americans in these age groups had higher seropositivity rates than did White non-Hispanics. There were no differences in seropositivity rates between sexes or between residents of the largest urban counties in Oklahoma and residents of the more rural counties. Exposure to C. parvum during childhood is common in Oklahoma. Socioeconomic factors may play a role in early exposure to this protozoal pathogen.

Bovine humoral immune response to Cryptosporidium parvum.

Cryptosporidiosis is a diarrheal disease predominantly affecting cattle and humans. Sera from experimentally infected calves and calves of various ages with no histories of exposure were evaluated for immunoglobulin G to Cryptosporidium parvum. An age-associated increase in immunoglobulin G was present in experimental calves and in calves with no histories of infection from 1 to 3, but not > 3, months of age.

Effect of abrogation of natural killer cell activity on the course of candidiasis induced by intraperitoneal administration and gastrointestinal candidiasis in mice with severe combined immunodeficiency.

Candida albicans CFU per gram of tissue recovered from livers, spleens, and kidneys of 12 severe combined immunodeficiency (scid) and 12 BALB/c mice 5 days after intraperitoneal (i.p.) administration of 10(7) C. albicans cells were not significantly different. Nine scid mice given normal rabbit serum (NRS) as a control and eight scid mice given anti-asialo-GM1 (alpha-ASGM1) had C. albicans CFU per gram recovered from livers and spleens 1 week after i.p. administration of C. albicans that were not significantly different, despite virtual elimination of natural killer (NK) cell activity in mice treated with alpha-ASGM1. At 2 weeks after i.p. administration, despite significantly increased NK cell activity in eight infected NRS-treated scid mice and virtual elimination of NK cell activity by alpha-ASGM1 treatment of eight scid mice, C. albicans CFU per gram recovered from livers and kidneys were not significantly different. At 2 weeks after intragastric administration of 2 x 10(6) C. albicans cells, eight NRS- and eight alpha-ASGM1-treated scid mice had identical proportions colonized with C. albicans and similar C. albicans CFU per gram recovered from feces. There was no evidence of hematogenous dissemination in either group. Similar results were seen 1 week after intragastric administration of 10(7) C. albicans cells. We conclude that NK cell activity is increased by i.p. administration of C. albicans in scid mice, but nontheless, abrogation of NK cell activity is not associated with enhanced susceptibility to candidiasis induced by i.p. administration and also is not associated with enhanced susceptibility to gastrointestinal colonization or hematogenous dissemination after intragastric administration of C. albicans.

Pneumonia caused by a newly recognized pseudomonad in a child with chronic granulomatous disease.

A pseudomonad was isolated from the pleural fluid and pulmonary decortication tissue of a 5-year-old child with chronic granulomatous disease. Although the isolate was phenotypically similar to Pseudomonas cepacia, its biochemical profile was more similar to that of Pseudomonas pickettii biovar 2. Its slow growth rate, ability to hydrolyze urea rapidly, and lateral and polar flagellar pattern were suggestive of Oligella ureolytica (formerly CDC group IVe). The cellular fatty acid composition was similar to that of P. cepacia and Pseudomonas gladioli, except for the presence of dodecanoic acid. Numerical analysis of the fatty acid data supported the interrelatedness of the isolate with other species of the pseudomallei group (rRNA homology group II) of Pseudomonas. The organism described in this report is an addition to the growing list of catalase-positive organisms which can potentially cause severe morbidity in patients with chronic granulomatous disease.