Unexplained Infections Research Articles

Newly diagnosed chronic granulomatous disease in a 53-year-old woman with Crohn disease

Chronic granulomatous disease (CGD) is characterized by defective bactericidal activity of white blood cells, specifically, a defect in superoxide production. Patients experience infections, predominantly caused by catalase-positive bacteria and fungal organisms, that may be severe and life-threatening. Most cases of CGD are diagnosed in children; however, it may rarely go undiagnosed until adulthood in individuals with unexplained infections and granulomatous inflammation. To describe an adult with Crohn disease and recurrent infections who was newly diagnosed as having CGD. A 53-year-old woman with a history of liver abscesses and Crohn disease presented with Burkholderia cepacia pneumonia and required a right middle lobe resection. Nitroblue tetrazolium test results confirmed the diagnosis of CGD, and Western blot analysis revealed the absence of the 47-phagocyte oxidase protein. Levels of Crohn-associated specific antibodies to Saccharomyces cerevisiae and Escherichia coli outer membrane porin C were elevated. The patient, newly diagnosed as having CGD, was given intravenous trimethoprim-sulfamethoxazole, after which she improved clinically and was discharged from the hospital in stable condition to receive daily oral trimethoprim-sulfamethoxazole treatment. The concomitant occurrence of Crohn disease and CGD, both characterized by granulomatous inflammation, is noteworthy. This case study demonstrates that CGD should be considered in adults with recurrent infections, especially those caused by catalase-positive organisms, such as B cepacia.

Does selected ecological evidence give a true picture of HIV transmission in Africa?

Current reconsideration of the contributions of various modes of transmission to HIV epidemics in sub-Saharan Africa has important implications for HIV prevention. In recent reviews, we argue that accumulated evidence supports the hypothesis that unsafe health care fuels Africa's HIV epidemics. In response, critics have presented selected ecological evidence - age and sex distribution of HIV infections and geographic distribution of hepatitis C virus infections - to support the conventional hypothesis that sexual contact accounts for most HIV infections. In this communication, we examine critics' evidence and arguments. Critics ignore or reject important evidence including, for example, large numbers of unexplained HIV infections in children, strong associations between incident HIV and injections, and genetically-linked infections in persons with no known sexual contact. We urge that research projects in Africa disclose unpublished relevant evidence on risks for incident HIV. In any case, because each iatrogenic infection causes subsequent linked infections, the impact of HIV transmission through health care has been underestimated. We commend the emerging consensus to improve the safety of health care delivery. In countries with generalized HIV epidemics, we urge public education about the risks for HIV acquisition from unsterile health care.

Chronic Granulomatous Disease: A Clinical Survey of 41 Patients from the Iranian Primary Immunodeficiency Registry

Background: Chronic granulomatous disease (CGD) represents a group of inherited disorders of the phagocytic system, involving recurrent infections at different sites, especially the respiratory system. The present study was accomplished in order to determine the clinical spectrum of Iranian patients with CGD. Methods: Forty-one patients (29 males and 12 females) with CGD, who had already been referred to two immunodeficiency referral centers in Iran, were reviewed during a 22-year period (1980–2002). Results: These patients belonged to 34 families, and 56% of them were consanguineous. The median age at the time of study was 12 years (3 months to 22 years). The median age at onset of symptoms was 4 months (1 month to 12 years), and the median diagnostic age was 5.5 years (2 months to 20 years), with a diagnostic delay of 3 years on average. The most common presenting complaint in our CGD patients was lymphadenopathy (seen in 11 patients, 26.8%). The most common manifestations of CGD (in descending order) were lymphadenopathy (75.6%), pulmonary infections (65.9%) and skin involvement (63.4%) during their illness, followed by gastrointestinal (56.1%), skeletal (29.3%), upper respiratory tract (26.8%) and central nervous system (2.4%) involvement. Conclusions: Early diagnosis of the disease is crucial. In view of the possibility of timely treatment, i.e. prophylactic treatment of infection, CGD should be excluded in any patient with unexplained infections or granulomas.

Mannose-Binding Lectin (MBL) in Health and Disease

Mannose-binding lectin (MBL) is the most intensively studied human collectin. It is recognized to be a versatile macro-molecule with many of the functional characteristics of IgM, IgG and Clq. In the presence of calcium the protein can bind to a wide spectrum of oligosaccharides through multiple lectin domains. Such binding to the repeating sugar arrays on microbial sur-faces may result in direkt uptake by one or more collectin receptors on phagocyte surface or may trigger the activation of a pro-serine protease complex (MASP 1 and MASP 2) leading to cleavage of C4 and C2 of the classical complement pathway. Although serum levels of MBL are normally rather low (1500 μg/litre) there is increasing evidence- that the protein plays an impor-tant role in immune defence, particularly during the phase of primary contact with a micro-organism. This is suggested by the observed association of an increased incidence of infections in individuals with structural mutations in exon 1 of the MBL gene. A cluster of such mutations in codons 52, 54 and 57 lead to secondary structural abnormalities of the collagenous triple helix and a failure to form biologically functional higher order oligomers. The codon 54 mutation has been identified in several Eurasian populations whereas the codon 57 mutation is characteristic of sub-Saharan populations. One intriguing paradox arising from the MBL genotyping studies is the observation that in many populations there are surprisingly high frequencies of either the codon 54 or codon 57 mutation, suggesting that there may be some biological advantage associ-ated with absence of the protein. Nevertheless, various groups have reported either low serum levels of MoL oraoincreased pected immunodeficiencies, those with frequent unexplained infections and those with systemic lupus erythematosus. There is also evidence that the rate of progression of AIDS in HIV positive men is faster in those with such mutations. A recently published study of a consecutive series of admissions to a paediatric unit suggests that children presenting with an infectious aetiology are significantly more likely to have a MBL mutation. Moreover, this association was independent of age. Prospective studies are underway to address the questions raised by these findings.

Chronic granulomatous disease in adults

Summary Background Chronic granulomatous disease (CGD), an inherited disorder of granulocyte function caused by failure of intracellular superoxide production, normally presents in the first years of life with severe recurrent bacterial and fungal infections. Methods From the files of two children's hospitals we identified 11 CGD patients who were remarkable for an unusually late diagnosis, at 13-43 years of age. Their clinical and laboratory features were examined. Findings The first clinical manifestation occurred at a median age of 3·6 years but CGD was not diagnosed until a median age of 22 years. Pneumonias and abscesses caused by Staphylococcus aureus and Aspergillus species were the most frequent infections. Granulomas, often leading to chronic complications, occurred in 7 of the patients. With 1·1 severe infections in 100 patient months, the 11 patients had a lower frequency of severe infections than patients with classic CGD; however, such infections could be equally life-threatening. 8 of the patients had X-linked CGD with small but detectable quantities of cytochrome b558, normally absent in X-linked CGD; and 3 had autosomal-recessive CGD. 9 patients had residual production of reactive oxygen metabolites, a feature that could explain the low incidence of infections. Interpretation CGD in adults may be more common than previously assumed. In view of the possibility of timely treatment, infection prophylaxis, and genetic counselling for affected families, CGD should be excluded in any patient with unexplained infections or granulomas.

A fatal case of systemic strongyloidiasis and review of the literature

Systemic strongyloidiasis is a rare but serious complication of intestinal strongyloidiasis. The condition occurs mainly in immunosuppressed patients and has a significant mortality rate. A case of systemic strongyloidiasis is described in a patient who received systemic steroid treatment, and a short review of the literature is given. The increased use of immunosuppressive and cytotoxic treatment necessitates increased awareness of this infection. HIV-infection, however, does not appear to increase the risk of developing systemic strongyloidiasis. Patients from endemic areas and travellers to such areas, even in the remote past, should be examined for strongyloidiasis before being given immunosuppressive treatment. Awareness of the possibility of systemic strongyloidiasis is essential if such a patient develops gastrointestinal or pulmonary symptoms or has repeated episodes of unexplained gram-negative infections while undergoing immunosuppressive treatment.

Defective Candida Opsonin and Procidin Function in Patients with Recurrent Pyogenic Infection: A Common Immunodeficiency

Polymorphonuclear cell function tests were performed in 340 patients with recurrent unexplained infections. Serum-dependent defects in phagocytosis and intracellular killing of Candida albicans (Candida opsonin and procidin defects) were specifically associated with susceptibility to recurrent pyogenic infections, Candida opsonin defects occurring in 12.7% and Candida procidin defects in 20.8% of patients compared with 3.7% of healthy controls. Saccharomyces cerevisiae opsonin deficiencies were also found frequently in patients with recurrent infections, being present in 18.2% compared with 7.4% controls, although not specifically in those with pyogenic infection.

Parapharyngeal abscess and torticollis

The combination of a parapharyngeal abscess and torticollis in an adult, due to a spastic contraction of the sterno-cleido-mastoid muscle is an extremely rare condition. We have recently been exposed to such case, in which it was very difficult to make the diagnosis and where CT of the neck gave us the answers without any difficulty. The indication for CT at an early stage in unexplained neck infections is stressed.

An epidemiological study of an outbreak of Q fever in a secondary school

Five cases of clinical Q fever were identified amongst students and staff of a Somerset secondary school between 23 October 1987 and 21 December 1987. Five goats which were kept at the school were found to have antibodies to Coxiella burnetii phase II. A cross-sectional study was conducted at the school in July 1988. A single CF test was used to identify evidence of prior infection, and a self-administered questionnaire was used to collect data on exposure variables and illness during 1987. Four hundred and ninety-nine eligible subjects took part in the study, and serological information was obtained from 461 of these. Eighty-seven subjects (18.9%) had CF titres of 20 or greater. It was estimated that only 1 in every 30 individuals with evidence of past C. burnetii infection had been recognized as a clinical case of Q fever. Antibody positive subjects were more likely to have been off school sick and to report having suffered chest pain than negative subjects. Contact with school animals, specifically cleaning the school poultry, collecting their eggs and visiting a school goat on the day of kidding, was associated with the presence of antibodies to C. burnetii. However, a large proportion of the antibody positives (24.2%) had no known contact with the school animals. Spread of organisms, either wind-borne or in straw or manure, may have been responsible for the high prevalence of unexplained infection.

Fungal Infections in AIDS Histoplasmosis and Coccidioidomycosis

Histoplasma capsulatum and Coccidioides immitis are two fungi that are regional in occurrence and cause opportunistic fungal infections in patients with AIDS. Many cases of histoplasmosis have been reported in patients months or years after they have been in an endemic area. These are obviously cases of reactivation of latent infections. With coccidioidomycosis, the cases have been reported from endemic areas, but some also appear to be reactivation infections, and we should anticipate such cases in nonendemic areas just as with histoplasmosis. The clinical presentations may be atypical, even mimicking acute bacterial sepsis. The diagnosis should be sought in any HIV-infected patient with an unexplained infection and residence or travel in an endemic area even in the remote past. Studies should include bone marrow examinations for histoplasmosis as well as skin biopsies with special strains and cultures for fungi for both infections. Sputum or bronchoscopy specimens have often been the source of a diagnosis in coccidioidomycosis. Serologic tests for antibody in both diseases yield inconsistently positive results in AIDS patients. Treatment of the acute infection should be with amphotericin B followed by maintenance suppressive therapy with ketoconazole or Amphotericin B.

Acquired Immunodeficiency Syndrome

The acquired immunodeficiency syndrome (AIDS) was recognized as a distinct clinical entity in 1981 and was characterized by unexplained opportunistic infections and an aggressive form of Kaposi's sarcoma. High risk groups for contracting AIDS include homosexual men, parenteral drug users, hemophiliacs, recipients of blood and blood products, and heterosexual contacts of such individuals. Immunologic abnormalities associated with AIDS include lymphopenia, functional T-cell deficits, B-lymphocyte defects, and various serologic abnormalities. The causative virus has been identified as the human T-lymphotropic virus/lymphadenopathy associated virus (HTLV-III/LAV). AIDS represents the severe end of the clinical spectrum of infection with HTLV-III/LAV. Other manifestations are asymptomatic carriage, generalized lymphadenopathy, and a set of non-specific symptoms, termed the AIDS-related-complex (ARC). Although seen predominantly in the United States, AIDS has a world-wide occurrence. No known therapy for AIDS exists. Research efforts are being directed at antiviral therapy, immunorestoration and the development of a vaccine.

Acquired immunodeficiency syndrome.

The acquired immunodeficiency syndrome (AIDS) was recognized as a distinct clinical entity in 1981 and was characterized by unexplained opportunistic infections and an aggressive form of Kaposi's sarcoma. High risk groups for contracting AIDS include homosexual men, parenteral drug users, hemophiliacs, recipients of blood and blood products, and heterosexual contacts of such individuals. Immunologic abnormalities associated with AIDS include lymphopenia, functional T-cell deficits, B-lymphocyte defects, and various serologic abnormalities. The causative virus has been identified as the human T-lymphotropic virus/lymphadenopathy associated virus (HTLV-III/LAV). AIDS represents the severe end of the clinical spectrum of infection with HTLV-III/LAV. Other manifestations are asymptomatic carriage, generalized lymphadenopathy, and a set of non-specific symptoms, termed the AIDS-related-complex (ARC). Although seen predominantly in the United States, AIDS has a world-wide occurrence. No known therapy for AIDS exists. Research efforts are being directed at antiviral therapy, immunorestoration and the development of a vaccine.

Reference ranges for IgG subclasses in preschool children.

A normal range for IgG1, IgG2, and IgG3 subclasses has been established for children aged 6 months to 5 years using commercially available monoclonal antisera. Of particular interest were the very low concentrations of IgG2 in some healthy children, a finding which casts doubt on the importance of IgG2 deficiency reported in some patients with otherwise unexplained infections. It was not possible to construct a normal range for IgG4 values probably because these segregate into two populations in normal subjects.

Retroperitoneal abscess: a presentation of colon carcinoma.

Retroperitoneal abscess as an initial manifestation of carcinoma of the colon is unusual. Inappropriate management of an unrecognized lesion is invariably fatal. Awareness of this uncommon presentation can lead to a precise preoperative diagnosis and appropriate therapy. The possibility of a perforated colon carcinoma should be considered in instances of unexplained retroperitoneal mass and infection, and a barium enema performed on all such patients. The authors report 3 cases and illustrate the radiological features of retroperitoneal abscesses due to perforated colon carcinoma.

Acquired Immune Deficiency Syndrome (AIDS)--A Pediatric Perspective

The number of reported cases of adults with acquired immune deficiency syndrome (AIDS) is increasing and concern is growing regarding the potential impact of this epidemic on the pediatric population. Male homosexuals were the initial group afffected by AIDS. Soon thereafter, the disease was encountered among intravenous drug abusers, Haitians, and hemophiliacs. Major defects in cellular immune function develop and leave AIDS patients vulnerable to serious, often fatal opportunistic infections or malignancies. In late 1982, the first evidence was provided to the Centers for Disease Control (CDC) indicating that infants and young children were victims of AIDS-like illness. Of five patients reported with otherwise unexplained immunodeficiency and opportunistic infection, one had received multiple blood transfusions for anemia and hyperbilirubinemia as a newborn.

IV. RESEARCH NEEDED TO LEARN HOW TO COPE WITH AIRBORNE INJECTION.

IT is unquestionably presumptuous to deal with the subject assigned to me, not only because it is a tremendously large topic whose solution has been the focus of many of our leading investigators, but also because of the nature of modern biological research. Since the growth of knowledge is stepwise with new concepts developing from previous experiments, it is not possible to spell out a program except in the broadest terms. However, it may be possible to relate what has been accomplished with some diseases to what needs be done in others, and in addition, since the situation is less than ideal, even among the best controlled diseases, to speculate about the future. As a framework for our thoughts we will use the familiar circular pathway, shown in Figure 1, often used for teaching these diseases. Since the principle focus of the topic is the method of spread, it is used as the starting point. Two types of spread are recognized based on the classification of Wells: droplet nuclei or true airborne particles which do not settle before ventilation and dustborne material, the residuals of particles which are large enough to settle before ventilation can remove them. The data obtained on the study of tuberculosis and measles, the two best studied true airborne diseases, indicate how different the gross epidemiologic pattern can be in spite of the common mechanisms. These differences depend on factors such as the density of infectious particles generated by the source case and the susceptibility of the exposed population, but illustrate that much research must be done in various populations before conclusions can be reached about the airborne spread of newly discovered agents. It is of interest, for example, that even though the superficial aspects of tuberculosis epidemiology suggest direct transmission by contact, and possibly indirectly by fomites and dust, it is probably rarely transmitted except by droplet nuclei, the prolonged contact being required because of the low density of infectious nuclei. This need for prolonged indoor proximity serves as a basis for much of the control work based upon case finding among close contacts. It is clear that since there is only one infectious unit in 20,000 cubic feet of air, several months of living in the environment are required on the average to infect a single individual. On the other hand, if the number of susceptibles exposed to the same volume of similarly infected air is markedly increased, as in schoolrooms, public eating places, public transportation, and so on, some will be infected much earlier. The patients with unexplained infections may come from a tremendously large population base and thus represent the very small percentage who become infected by short sojourn in infected air. As tuberculosis becomes more of a vagabond's disease, partly due to successful programs based on control of known contacts, the proportion of those with unknown source should increase. The fact that direct contact need not be used to explain the epidemiologic pattern of tuberculosis indicates the need for details about the portal of entry, hence the optimal size of the infectious quantum, their frequency in air, and so forth before definite decisions can be made about mode of spread. It is likely, however, that when the portal of entry re-

Ultraviolet radiation in the operating room. Intensities used and bactericidal effects.

Introduction From 1930 to 1936 in the Duke Hospital, unexplained infections, usually staphylococcal, were frequent, often severe, and occasionally fatal. They occurred most commonly in groups during the colder months when air contamination in the operating rooms was highest. This contamination was definitely proven at times to be associated with widespread dissemination of yellow staphylococci in the respiratory tracts of personnel and the general population. These infections were controlled by sanitizing the air and exposed surfaces in the operating rooms with ultraviolet radiation (2,537 A.) after all efforts by a more rigid application of the traditional aseptic and atraumatic technique had failed. Since the universal adoption of aseptic precautions for the of contact inoculations of wounds, many reports on procedures for control of unexplained operating-room infections by a more rigid technique have been made. A number of these may have been fallacious, the drop in the infection rate being

Primary Friedlander–Bacillus Peritonitis

PRIMARY unexplained infection of the peritoneum by the Friedlander bacillus (Klebsiella pneumoniae) is a condition of evident rarity. The case reported below (the second in the medical literature) describes a disease that is a distinct though little known clinical entity. Additional reports will aid in delineating possible similarity to the better known idiopathic pneumococcal and streptococcal peritonitides of infants and children. Case Report E. I., an 8-year-old girl of Irish descent, was referred to the hospital in April, 1943, by her family physician with the diagnosis of appendicitis with perforation. The immediate history dated to 4 days before . . .

THE IMPORTANCE OF AIR-BORNE PATHOGENIC BACTERIA IN THE OPERATING ROOM

During the first five and one-half years of the Duke Hospital, as a result of extensive studies carried out in an attempt to determine the cause of in clean wounds, we were forced to the conclusion that pathogenic bacteria floating in the air and sedimenting on the wound and sterile field were the cause of most of the unexplained infections in our operating rooms. We were unable to control this source of infection despite many changes in technic until ultraviolet radiation (predominantly 2,537 angstroms) was utilized to kill the bacteria (and fungi) in the air or after they sedimented on the sterile field. During the past five and one-half years since this technic of air sterilization was adopted the infection rate in clean wounds has been reduced to a small fraction of the previous level, and where it was used we have had no death from an infection