Chronic granulomatous disease: Clinical,functional, molecular,and genetic studies. The Israeli experience with 84 patients

Chronic granulomatous disease (CGD) is an innate immunodeficiency with a genetic defect of the nicotinamide adenosine dinucleotide phosphate, reduced, oxidase components. This leads to decreased reactive oxygen species (ROS) production, which renders patients susceptible to life‐threatening infections. Over the course of 30 years, we diagnosed CGD in 84 patients from 61 families using functional, molecular, and genetic studies. The incidence of CGD in Israel is 1.05 per 100,000 live‐births in the Jewish population and 1.49 in the Israeli Arab population. We diagnosed 52 patients (62%) with autosomal recessive inheritance (AR‐CGD) and 32 (38%) with X‐linked recessive inheritance (XLR‐CGD). Consanguinity was detected in 64% of AR‐CGD families (14% in Jews and 50% in Israeli Arabs). We found 36 different mutations (23 in XLR‐CGD and 13 in AR‐CGD patients), 15 of which were new. The clinical spectrum of CGD varied from mild to severe disease in both XLR and AR forms, although the AR subtype is generally milder. Further, residual ROS production correlated with milder clinical expression, better prognosis and improved overall survival. Patients with recurrent pyogenic infections developed fibrosis and hyperinflammatory states with granuloma formation. The management of CGD has progressed substantially in recent years, evolving from a fatal disease of early childhood to one of long‐term survival. Our present cohort displays an encouraging 81% overall long term survival. Early hematopoietic stem cell transplantation is advisable before tissue damage is irreversible. Successful transplantation was performed in 18/21 patients. Therapeutic gene modification could become an alternative cure for CGD. Am. J. Hematol. 92:28–36, 2017. © 2016 Wiley Periodicals, Inc.     

Trimethoprim-sulfamethoxazole prophylaxis in the management of chronic granulomatous disease

Long-term oral antimicrobial prophylaxis is accepted practice in the management of patients with chronic granulomatous disease (CGD). Reports of adverse outcome with trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis in other patient groups, and the recent occurrence of several severe fungal infections in patients followed at the National Institutes of Health (NIH), prompted a review of the NIH experience to examine the incidence of nonfungal and fungal infections in CGD patients with and without TMP-SMX prophylaxis. Prophylaxis decreased the incidence of nonfungal infections from 7.1 to 2.4 per 100 patient-months in patients with autosomal CGD (P less than .01) and from 15.8 to 6.9 infections per 100 patient-months (P = .06) in X-linked CGD patients. There was no significant change in the incidence of fungal infection in CGD patients on TMP-SMX (1.5-0.3 fungal infections/100 patient-months in autosomal CGD and 1.7-0.2 fungal infections/100 patient-months in X-linked CGD patients). TMP-SMX prophylaxis is indicated for the management of patients with CGD and decreases the incidence of non-fungal infections without increasing the incidence of fungal infections.     

Unrelated donor and HLA-identical sibling haematopoietic stem cell transplantation cure chronic granulomatous disease with good long-term outcome and growth

Chronic granulomatous disease (CGD) causes recurrent infection and inflammatory disease. Despite antimicrobial prophylaxis, patients experience frequent hospitalisations and 50% mortality by 30 years. Haematopoietic stem cell transplantation (HSCT) can cure CGD with resolution of infection and colitis. This study reports the survival and long-term outcome in 20 conditioned patients treated between 1998 and 2007, using 10 matched sibling (MSD) and 10 unrelated donors (URD). Age at HSCT, graft- versus -host disease (GvHD), growth, and outcome were analysed. Fourteen had ≥1 invasive infection, 10 had colitis and seven had growth failure before HSCT. Median age at transplantation was 75 months (range 15 months–21 years). Eighteen (90%) were alive 4–117 months (median 61) after HSCT with normal neutrophil function. Two died from disseminated fungal infection. Two experienced significant chronic GvHD, with continuing sequelae in 1. Colitis resolved within 8 weeks of HSCT. Mean weight and height for age Z scores on recovery from HSCT rose significantly ( P  < 0·001). HSCT with MSD or URD gave excellent engraftment and survival, remission of colitis and catch-up growth, with low incidence of significant GvHD. Transplant-associated complications were restricted to those with pre-existing infection or inflammation, supporting the argument for early HSCT for more CGD patients with a well matched donor.     

Modern management of chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytic cells resulting in failure to kill a characteristic spectrum of bacteria and fungi and in defective degradation of inflammatory mediators with concomitant granuloma formation. Current prophylaxis with trimethoprim-sulfamethoxazole, itraconazole and in selected cases additional interferon gamma is efficient, but imperfect. A significant recent progress towards new antibiotic (e.g. linezolid) and antifungal (e.g. voriconazole and posaconazole) therapy will allow survival of most patients into adulthood. Adolescent and adult CGD is increasingly characterized by inflammatory complications, such as granulomatous lung and inflammatory bowel disease, requiring immunosupressive therapy. Allogeneic haematopoietic stem cell transplantation from a human leucocyte antigen identical donor is currently the only proven curative treatment for CGD and can be offered to the selected patients. Gene-replacement therapy for patients lacking a suitable stem cell donor is still experimental and faces major obstacles and risks. However, it may offer some transitory benefits and has helped in a few cases to overcome life-threatening infections.     

Osteomyelitis due to Aspergillus spp. in patients with chronic granulomatous disease: comparison of Aspergillus nidulans and Aspergillus fumigatus.

OBJECTIVE: Chronic granulomatous disease (CGD) is a rare inherited disorder of NADPH oxidase in which phagocytes fail to generate reactive antimicrobial oxidants. Invasive fungal infections are an important cause of morbidity and mortality in CGD patients, with Aspergillus spp. being the most frequent fungal pathogens. We reviewed the reported cases of osteomyelitis in CGD patients due to Aspergillus nidulans and compared them with those due to Aspergillus fumigatus. METHODS: Twenty-four cases of osteomyelitis due to Aspergillus spp. in 22 male CGD patients were found in MEDLINE. RESULTS: Fourteen cases (58%) were due to Aspergillus nidulans and ten cases to Aspergillus fumigatus. No other aspergilli were reported as causes of osteomyelitis. Osteomyelitis due to Aspergillus nidulans was associated with pulmonary infection and involved 'small bones' more frequently than Aspergillus fumigatus osteomyelitis (p=0.032). Half of the CGD patients with Aspergillus nidulans osteomyelitis died compared with none of those with Aspergillus fumigatus osteomyelitis (p=0.019). In both Aspergillus nidulans and Aspergillus fumigatus cases, cure was achieved by prompt antifungal treatment combined with surgery and immunotherapy. CONCLUSION: Aspergillus nidulans causes osteomyelitis in CGD patients relatively frequently compared with Aspergillus fumigatus and may be accompanied by higher mortality. This contrasts with the low frequency with which Aspergillus nidulans causes osteomyelitis in patients with other types of immunodeficiency.     

Chronic granulomatous disease. Report on a national registry of 368 patients

A registry of United States residents with chronic granulomatous disease (CGD) was established in 1993 in order to estimate the minimum incidence of this uncommon primary immunodeficiency disease and characterize its epidemiologic and clinical features. To date, 368 patients have been registered; 259 have the X-linked recessive form of CGD, 81 have 1 of the autosomal recessive forms, and in 28 the mode of inheritance is unknown. The minimum estimate of birth rate is between 1/200,000 and 1/250,000 live births for the period 1980-1989. Pneumonia was the most prevalent infection (79% of patients; Aspergillus most prevalent cause), followed by suppurative adenitis (53% of patients; Staphylococcus most prevalent cause), subcutaneous abscess (42% of patients; Staphylococcus most prevalent cause), liver abscess (27% of patients; Staphylococcus most prevalent cause), osteomyelitis (25% of patients; Serratia most prevalent cause), and sepsis (18% of patients; Salmonella most prevalent cause). Fifteen percent of patients had gastric outlet obstruction, 10% urinary tract obstruction, and 17% colitis/enteritis. Ten percent of X-linked recessive kindreds and 3% of autosomal recessive kindreds had family members with lupus. Eighteen percent of patients either were decreased when registered or died after being registered. The most common causes of death were pneumonia and/or sepsis due to Aspergillus (23 patients) or Burkholderia cepacia (12 patients). Patients with the X-linked recessive form of the disease appear to have a more serious clinical phenotype than patients with the autosomal recessive forms of the disease, based on the fact that they are diagnosed significantly earlier (mean, 3.01 years of age versus 7.81 years of age, respectively), have a significantly higher prevalence of perirectal abscess (17% versus 7%), suppurative adenitis (59% versus 32%), bacteremia/fungemia (21% versus 10%), gastric obstruction (19% versus 5%), and urinary tract obstruction (11% versus 3%), and a higher mortality (21.2% versus 8.6%).     

Treatment of chronic granulomatous disease with myeloablative conditioning and an unmodified hemopoietic allograft: a survey of the European experience, 1985-2000

Treatment of chronic granulomatous disease (CGD) with myeloablative bone marrow transplantation is considered risky. This study investigated complications and survival according to different risk factors present at transplantation. The outcomes of 27 transplantations for CGD, from 1985 to 2000, reported to the European Bone Marrow Transplant Registry for primary immunodeficiencies were assessed. Most transplant recipients were children (n = 25), received a myeloablative busulphan-based regimen (n = 23), and had unmodified marrow allografts (n = 23) from human leukocyte antigen (HLA)-identical sibling donors (n = 25). After myeloablative conditioning, all patients fully engrafted with donor cells; after myelosuppressive regimens, 2 of 4 patients fully engrafted. Severe (grade 3 or 4) graft-versus-host disease (GVHD) disease developed in 4 patients: 3 of 9 with pre-existing overt infection, 1 of 2 with acute inflammatory disease. Exacerbation of infection during aplasia was observed in 3 patients; inflammatory flare at the infection site during neutrophil engraftment in 2: all 5 patients belonged to the subgroup of 9 with pre-existing infection. Overall survival was 23 of 27, with 22 of 23 cured of CGD (median follow-up, 2 years). Survival was especially good in patients without infection at the moment of transplantation (18 of 18). Pre-existing infections and inflammatory lesions have cleared in all survivors (except in one with autologous reconstitution). Myeloablative conditioning followed by transplantation of unmodified hemopoietic stem cells, if performed at the first signs of a severe course of the disease, is a valid therapeutic option for children with CGD having an HLA-identical donor.     

Invasive infection due to penicillium species other than P. marneffei

Infection caused by Penicillium spp. due to species other than P. marneffei is rare. We present three such cases of invasive disease. The first had chronic granulomatous disorder (CGD) with pulmonary infection caused by Penicillium spp. and he responded to amphotericin B therapy. Cases two and three were not known to be immunocompromised and both failed to respond to therapy. Case two had cerebral disease from an unknown source caused by P. chrysogenum. Case three probably acquired infection caused by P. decumbens peri-operatively and presented with paravertebral infection. The pertinent literature on invasive infections of Penicillium spp. other than P. marneffei is reviewed. From 1951 onwards, 31 reported cases of invasive disease included 12 cases of pulmonary infection (six in non-immunocompromised patients), four cases of prosthetic valve endocarditis, six cases of CAPD peritonitis, five cases of endophthalmitis, individual cases of fungemia and oesophagitis (both in AIDS), upper urinary tract infection and intracranial infection. Trauma, surgery or prosthetic material is commonly implicated in the non-pulmonary cases. Superficial infection (keratitis and otomycosis) is commonly caused by Penicillium spp. Allergic pulmonary disease, often occupational (such as various cheeseworkers' diseases), is also common. Optimal therapy for invasive infection is not established, but surgery may be advisable if possible. Amphotericin B may be the most effective antifungal drug.     

Antivirals key to MAC prevention regimen

Prophylaxis for Mycobacterium avium complex (MAC) should be considered standard treatment for all patients with advanced HIV disease. MAC is the most common bacterial infection that affects AIDS patients. There are three effective agents that significantly reduce the risk of MAC--rifabutin, clarithromycin, and azithromycin. MAC prophylaxis is cost-effective, improves the quality of a patient's life, and improves overall survival by 25 to 32 percent.     

Urinary tract infection caused by Corynebacterium group D2: report of 82 cases and review

Corynebacterium group D2 (CGD2) is a slow-growing, urea-splitting, multiantibiotic-resistant microorganism that is frequently isolated from urine samples and that, in certain circumstances, produces infection of the lower urinary tract (acute and chronic cystitis) and the upper urinary tract (pyelonephritis). This paper analyzes (by means of a retrospective and partially prospective clinical protocol) our experience with 82 patients with CGD2 bacteriuria. The infection was symptomatic in 62% of cases, and the clinical diagnoses included acute and chronic cystitis and pyelonephritis with or without bacteremia. Because CGD2 infection of the urinary tract may require specific antimicrobial treatment and because CGD2 is a fastidious microorganism, we recommend prolonged incubation of urine cultures (up to 48-72 hours), especially if the routine culture is negative, when patients are symptomatic, have alkaline urine, or have struvite crystals in the urine sediment.     

Prolonged recombinant interferon-gamma therapy in chronic granulomatous disease: evidence against enhanced neutrophil oxidase activity.

Recombinant interferon-gamma (rIFN-gamma) therapy has become an effective form of prophylaxis for patients with chronic granulomatous disease (CGD). Preliminary studies with CGD suggested that rIFN-gamma treatment enhanced phagocyte oxidase activity and increased superoxide (O2-) production. We evaluated several aspects of neutrophil NADPH oxidase activity in 19 CGD patients (representing all four known types of CGD) receiving prolonged rIFN-gamma therapy (6 to 27 months). In contrast to earlier studies, we failed to detect any improvement in neutrophil NADPH oxidase activity in 18 of the 19 CGD patients as determined by (1) intact cell O2- production (continuous assay), (2) nitroblue tetrazolium (NBT) staining, (3) cytochrome b558 spectroscopy, and (4) activity levels of cytosol and membrane oxidase components using a cell-free activation system. One patient with a variant form of X-linked CGD had a transient increase in neutrophil O2- production following 3 months of rIFN-gamma therapy. However, this was not sustained, and was not associated with any change in cytochrome b levels. In some patients, rIFN-gamma therapy was associated with the appearance of a small subset of circulating monocytes (1% to 20%) that were NBT-positive. Although the functional significance of this monocyte subpopulation needs to be determined, these results suggest that one possible mechanism by which rIFN-gamma may benefit CGD patients is by partially correcting the respiratory burst defect in a subset of monocytes. We conclude that the clinical benefit of prolonged rIFN-gamma therapy in the vast majority of CGD patients is not due to enhanced neutrophil NADPH oxidase activity. The mechanism of action of rIFN-gamma in most CGD patients remains unknown.     

Improvement of Leukocyte Bactericidal Activity in Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is characterized by an inability ofpatients’ leukocytes to generate hydrogen peroxide and to kill non-peroxide-forming bacteria, such as staphylococci and serratiae. We have introducedglucose oxidase into CGD leukocytes in order to generate peroxide and therebykill S. aureus and S. marcescens. These results support the concept that a leukocyte oxidative deficiency is primary to the pathogenesis of CGD.

Submitted on June 23, 1969 Accepted on September 8, 1969     

Prophylaxis with zidovudine (AZT) after exposure to human immunodeficiency virus: a brief discussion of the issues for emergency physicians.

Sound scientific information with which to determine the true efficacy of zidovudine for prophylaxis will probably not be available soon. Physicians should educate themselves thoroughly on the issues. It is highly recommended that thoughtful discussions of the issue of transmission of HIV from health personnel to patients as well as the key articles cited in this discussion be read. The details of a prophylaxis program, including laboratory evaluation, are provided in an article by Henderson and Gerberding and in greater detail in the article by Go et al. (Health care workers exposed to HIV can be enrolled in the Centers for Disease Control surveillance program by calling 404/639-1644. To enroll persons with large exposures to HIV in the zidovudine prophylaxis study, call 800/537-9978.) ED directors should work closely with local infectious disease specialists to determine if such a program is needed and how to implement it. Further details regarding the implementation of a prophylaxis program should be obtained from the literature and the Centers for Disease Control. All of the details of such a program should be worked out well in advance so that knowledgeable and immediate counseling can be provided to health care workers within one or two hours of exposure. Highly qualified individuals and institutions vary in their recommendations on prophylaxis, although most provide them. Zidovudine probably does not provide very effective protection, if it provides any. However, the medical, social, and economic consequences of HIV infection of health care workers are very real, and the serious irreversible adverse effects of zidovudine are very rare.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phosphorylation of the oxidase-related 48K phosphoprotein family in the unusual autosomal cytochrome-negative and X-linked cytochrome-positive types of chronic granulomatous disease

Activation of 32P-loaded neutrophils with phorbol myristate acetate causes the labeling of a family of three 48K proteins that focus near neutral pH. The relationship between these phosphoproteins and the activation of the respiratory burst has been supported by the previous finding that phosphorylation was defective in the two most common types of chronic granulomatous disease (CGD): X-linked cytochrome-negative (X/-) and autosomal cytochrome-positive (A/+). In this report, these studies have now been extended to the rare A/- and X/+ forms of the disease. In all three patients with A/- CGD examined, the two most acidic 48K proteins failed to undergo enhanced phosphorylation in response to phorbol stimulation, a finding similar to that seen in X/- patients. In contrast, neutrophils from two patients with X/+ CGD appeared to phosphorylate the neutral 48K proteins in a normal fashion. It thus appears that the different phosphorylation patterns seen in chronic granulomatous disease are a reflection of the genetic heterogeneity of this disorder. These findings lend further support to the conclusion that the 48K phosphoprotein family is related to the respiratory burst, although not necessarily in a straightforward manner.     

An evaluation of new prevention programs for tuberculous infection. II. BCG vaccination

Tuberculosis is an infectious disease produced by Mycobacterium tuberculosis in a 98-99% of the cases and by Mycobacterium bovis in a 1-2%. Its early diagnosis is of a great importance because permits to reduce the transmission of the infection. Until now, the diagnostic techniques used to discover the dissemination of the disease are indirect. We have the PPD skin test and, among them, Mantoux is the most common. Correctly used it has a great diagnostic and epidemiological value, because it permits to evaluate those patients who can obtain a benefit with the chemoprophylaxis when the skin test is positive. We analyse the actual via of chemoprophylaxis, when and how it must be used. We study not only the drugs for the prophylaxis, but also the good and bad utilisation of the BCG vaccine, that it starts to have its indications in other countries.     

Absence of both the 91kD and 22kD subunits of human neutrophil cytochrome b in two genetic forms of chronic granulomatous disease

Chronic granulomatous disease (CGD) is a group of inherited disorders in which phagocytic cells fail to generate antimicrobial oxidants. The various forms of CGD can be classified in terms of the mode of inheritance (either X-linked or autosomal recessive), and whether the neutrophils display the absorbance spectrum of a unique b-type cytochrome important for the function of the respiratory burst oxidase. The finding that purified neutrophil cytochrome b is a heterodimer consisting of a 91kD glycosylated and a 22kD nonglycosylated polypeptide has raised the question of which subunits are absent (or defective) in the various types of CGD. To address this question we have studied the expression of the cytochrome b subunits in three genetically distinct forms of CGD: X-linked/cytochrome b-negative (X-), autosomal recessive/cytochrome b-negative (A-), and autosomal recessive/cytochrome b-positive (A+). Using polyclonal antibodies to each of the two subunits, we prepared Western blots of lysates of intact neutrophils from ten CGD patients. In the controls and three patients with A+ CGD, both cytochrome subunits were easily detected. Consistent with the previously reported finding in five X- patients, neither subunit could be identified in neutrophils from three additional X- patients. Both subunits were also undetectable in four patients with A- CGD (three females, one male). This latter group of patients most likely bears a normal 91kD gene, since the patients are genetically distinct from the 91kD-defective X- group. The mutation in A- CGD, therefore, probably involves the 22kD gene and the eventual expression of the 22kD subunit. Furthermore, the expression of the 91kD subunit in this group of patients appears to be prevented due to the 22kD mutation in a manner converse to that seen in the X- CGD patients. Based on these studies, we hypothesize that the stable of expression of either of the two cytochrome subunits is dependent upon the other.     

Serologic Reactivity to the Emerging Pathogen Granulibacter bethesdensis

Background.?Granulibacter bethesdensis is a recently described member of the Acetobacteraceae family that has been isolated from patients with chronic granulomatous disease (CGD). Its pathogenesis, environmental reservoir(s), and incidence of infection among CGD patients and the general population are unknown. Methods.?Detected antigens were identified by mass spectroscopy after 2-dimensional electrophoresis and immunoaffinity chromatography. The prevalence of Granulibacter immunoreactivity was assessed through immunoblotting and enzyme-linked immunosorbent assay (ELISA). Results.?Methanol dehydrogenase (MDH) and formaldehyde-activating enzyme were recognized during analysis of sera from infected patients. Unique patterns of immunoreactive bands were identified in Granulibacter extracts, compared with extracts of other Acetobacteraceae species. By use of criteria based on these specific bands, specimens from 79 of 175 CGD patients (45.1%) and 23 of 93 healthy donors (24.7%) reacted to all 11 bands. An ELISA that used native MDH to capture and detect immunoglobulin G was developed and revealed high-titer MDH seroreactivity in culture-confirmed cases and 5 additional CGD patients. Testing of samples collected prior to culture-confirmed infection demonstrated instances of recent seroconversion, as well as sustained seropositivity. Infection of CGD mice with G. bethesdensis confirmed acquisition of high-titer antibody-recognizing MDH. Conclusions.?These serologic tests suggest that Granulibacter immunoreactivity is more common among CGD patients and, perhaps, among healthy donors than was previously suspected. This finding raises the possibility that clinical presentations of Granulibacter infection may be underappreciated.     

Bone marrow transplantation for chronic granulomatous disease: long-term follow-up and review of literature.

Chronic granulomatous disease (CGD) is a heterogeneous group of disorders with defective respiratory burst activity in phagocytes which results in recurrent pyogenic infections. We report an 8-year-old boy with X-linked CGD who received an HLA-identical BMT from his sister. The nitroblue tetrazolium test returned to normal 3 months post transplant. Neutrophil engraftment has been stable for 7 years post BMT. Our patient was the eighth case of CGD successfully treated by BMT. Conditioning regimens in these patients have consisted mainly of BU and CY. We suggest that BMT is a safe and effective method of cure for patients with CGD. BMT should be considered for patients with HLA-identical siblings.     

A community-based rheumatic fever/rheumatic heart disease cohort: twelve-year experience

BACKGROUND: A pilot rheumatic fever and rheumatic heart disease control porject was started in 1988 in blocks of district Ambala (Haryana) to test the feasibility of early detection, treatment and secondary prophylaxis for rheumatic fever/rheumatic heart disease cases. School teachers, students and health workers were trained to identify and refer suspected cases of rheumatic fever/rheumatic heart disease to the community health center where physicians examined the suspected cases and monthly secondary prophylaxis was provided to the confirmed cases. METHODS AND RESULTS: A survey of registered cases was done in 1999 to determine the compliance rate of secondary prophylaxis and to describe clinical and epidemiologic features of the registered cohort of rheumatic fever/rheumatic heart disease patients. A total of 257 patients had been registered till the end of 1999 with 1263 person-years of follow-up. Out of these registered patients, 132 were receiving secondary prophylaxis, 52 had died, 17 had migrated, 8 were lost to follow-up, 18 had stopped prophylaxis and 30 completed the prophylaxis course. The mean age at registration was 18 years. Half of the cases were in the 6-15 years age group at registration. Over half of the patients were registered with a history of rheumatic fever. Fever was the most common symptom (75.9%). Carditis was more common among cases with recurrent attacks of rheumatic fever than after a first attack. The mortality in rheumatic fever/rheumatic heart cases was 32.5/1000 person-years. The mean age at death was 24.4 years. Compliance with secondary prophylaxis was 92% during the past 12 years. CONCLUSIONS: A rheumatic fever/rheumatic heart disease control program can be sustained within the primary health care system and the case registry can be utilized not only for monitoring the program but also to gain insight into the epidemiology of the disease.     

Prevention of severe lower respiratory infections in patients with cystic fibrosis

Infection of the lower respiratory tract is the most frequent cause of death in patients with cystic fibrosis (CF). Pseudomonas aeruginosa is the predominant pulmonary pathogen; it establishes a chronic endobronchial infection and once acquired is rarely if ever eradicated. Although optimizing nutrition and pulmonary toilet improves the general health of patients with CF, bacterial respiratory infections are neither prevented nor cured. Likewise, attempts to prevent colonization and infection by means of antimicrobial prophylaxis have been generally unsuccessful. Since no effective radical cure for CF pulmonary infections has been found yet, means of preventing respiratory tract colonization have been sought. Immunization of patients who are already colonized with P aeruginosa has failed to eradicate colonization. Vaccines are therefore being sought that will forestall colonization by P aeruginosa, either by preventing adhesion to respiratory mucosa or by enhancing other immunological host defenses.