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Biomedical subjects

Rana A Hajjeh

Publications and source records attributed to Rana A Hajjeh.

At least 19 recordsLinked to original sources

Population-based surveillance for cryptococcosis in an antiretroviral-naive South African province with a high HIV seroprevalence.

OBJECTIVES: To measure the burden of disease and describe the epidemiology of cryptococcosis in Gauteng Province, South Africa. DESIGN AND METHODS: The study was an active, prospective, laboratory-based, population-based surveillance. An incident case of cryptococcosis was defined as the first isolation by culture of any Cryptococcus species from any clinical specimen, a positive India ink cryptococcal latex agglutination test or a positive histopathology specimen from a Gauteng resident. Cases were identified prospectively at all laboratories in Gauteng. Case report forms were completed using medical record review and patient interview where possible. RESULTS: Between 1 March 2002 and 29 February 2004, 2753 incident cases were identified. The overall incidence rate was 15.6/100 000. Among HIV-infected persons, the rate was 95/100 000, and among persons living with AIDS 14/1000. Males and children under 15 years accounted for 49 and 0.9% of cases, respectively. The median age was 34 years (range, 1 month-74 years). Almost all cases (97%) presented with meningitis. Antifungal therapy was given to 2460 (89%) cases of which 72% received fluconazole only. In-hospital mortality was 27% (749 cases). Recurrences occurred in 263 (9.5%) incident cases. Factors associated with death included altered mental status, coma or wasting; factors associated with survival included employment in the mining industry, visual changes or headache on presentation. CONCLUSIONS: This study demonstrates the high disease burden due to cryptococcosis in an antiretroviral-naive South African population and emphasizes the need to improve early recognition, diagnosis and treatment of the condition.

AIDS-Related Opportunistic Infections↗

Cryptococcus gattii infection: characteristics and epidemiology of cases identified in a South African province with high HIV seroprevalence, 2002-2004.

We describe 46 Cryptococcus gattii-infected persons identified by population-based surveillance conducted in South Africa. Most patients with C. gattii infection presented with meningitis. The mortality rate during hospitalization was 36%. We found no significant differences between persons with and persons without C. gattii infection with regard to clinical presentation, acquired immunodeficiency syndrome diagnosis, concomitant conditions, or prior opportunistic infections. C. gattii isolates had low MICs to the tested antifungal drugs.

Adolescent↗

Differentiation of tuberculous meningitis from acute bacterial meningitis using simple clinical and laboratory parameters.

Tuberculous meningitis (TBM) is still a major cause of serious illness in many parts of the world. The newer diagnostic tests and neuroimaging methods are unlikely to be available in many developing countries. We attempt to identify simple parameters for early diagnosis. A retrospective study was performed to compare the clinical and laboratory features of cultured-confirmed, TBM (134) and other bacterial meningitis (709). Features independently predictive of TBM were studied by multivariate logistic regression to develop a diagnostic rule. Six features were found predictive: length of clinical history >5 days, headache, total cerebrospinal fluid (CSF) white blood cell count of <1000/mm3, clear appearance of CSF, lymphocyte proportion of >30%, and protein content of >100 mg/dL. Application of 3 or more parameters revealed 93% sensitivity and 77% specificity. Applying this diagnostic rule can help in the early diagnosis of TBM, in both children and adults.

Adolescent↗

Evaluation of amphotericin B interpretive breakpoints for Candida bloodstream isolates by correlation with therapeutic outcome.

One hundred seven Candida bloodstream isolates (51 C. albicans, 24 C. glabrata, 13 C. parapsilosis, 13 C. tropicalis, 2 C. dubliniensis, 2 C. krusei, and 2 C. lusitaniae strains) from patients treated with amphotericin B alone underwent in vitro susceptibility testing against amphotericin B using five different methods. Fifty-four isolates were from patients who failed treatment, defined as death 7 to 14 days after the incident candidemia episode, having persistent fever of >or=5 days' duration after the date of the incident candidemia, or the recurrence of fever after two consecutive afebrile days while on antifungal treatment. MICs were determined by using the Clinical Laboratory Standards Institute (formally National Committee for Clinical Laboratory Standards) broth microdilution procedure with two media and by using Etest. Minimum fungicidal concentrations (MFCs) were also measured in two media. Broth microdilution tests with RPMI 1640 medium generated a restricted range of MICs (0.125 to 1 microg/ml); the corresponding MFC values ranged from 0.5 to 4 microg/ml. Broth microdilution tests with antibiotic medium 3 produced a broader distribution of MIC and MFC results (0.015 to 0.25 microg/ml and 0.06 to 2 microg/ml, respectively). Etest produced the widest distribution of MICs (0.094 to 2 microg/ml). However, none of the test formats studied generated results that significantly correlated with therapeutic success or failure.

Adolescent↗

Rapid enzyme-linked immunosorbent assay for the diagnosis of human brucellosis in surveillance and clinical settings in Egypt.

OBJECTIVE: To optimize and standardize an enzyme-linked immunosorbent assay (ELISA) for rapid diagnosis of human brucellosis in clinical cases identified during a surveillance study for acute febrile illness (AFI). METHODS: Serum samples from patients presenting with AFI at 13 fever hospitals across Egypt between 1999 and 2003 were kept frozen at NAMRU-3 and used in this study. The assay was evaluated in 5 subject groups: brucellosis cases confirmed by blood culture (group I, n=202) 87% positive by standard tube agglutination test (TA), brucellosis cases exclusively confirmed by TA (group II, n=218), blood cultures from AFI cases positive for bacterial species other than Brucella (group III, n=103), AFI cases with unexplained etiologies (group IV, n=654), and healthy volunteers (group V, n=50). All members of groups III-V were negative for brucellosis by TA. RESULTS: Sensitivity and specificity of ELISA for total specific antibodies were >=96% versus 87% for TA as compared to microbial culture, the current gold standard method for Brucella identification. Assessment of Brucella antibody classes by ELISA in random subsets of the 5 groups showed significantly high (p>0.001) levels of anti Brucella IgG (>=81%) and IgM (>=90%) in groups I and II only. CONCLUSION: The obtained sensitivity and specificity results indicate that our ELISA is more suitable for AFI surveillance and clinical settings than blood culture and TA. The developed assay is also cost-effective, easier to use, faster, and the coated plates can be stocked for at least 8 months, providing a potential for field use and automation.

Adolescent↗

An epidemic of coccidioidomycosis in Arizona associated with climatic changes, 1998-2001.

BACKGROUND: Reports of coccidioidomycosis cases in Arizona have increased substantially. We investigated factors associated with the increase. METHODS: We analyzed the National Electronic Telecommunications System for Surveillance (NETSS) data from 1998 to 2001 and used Geographic Information Systems (GIS) to map high-incidence areas in Maricopa County. Poisson regression analysis was performed to assess the effect of climatic and environmental factors on the number of monthly cases; a model was developed and tested to predict outbreaks. RESULTS: The overall incidence in 2001 was 43 cases/100,000 population, a significant (P<.01, test for trend) increase from 1998 (33 cases/100,000 population); the highest age-specific rate was in persons > or =65 years old (79 cases/100,000 population in 2001). Analysis of NETSS data by season indicated high-incidence periods during the winter (November-February). GIS analysis showed that the highest-incidence areas were in the periphery of Phoenix. Multivariable Poisson regression modeling revealed that a combination of certain climatic and environmental factors were highly correlated with seasonal outbreaks (R2=0.75). CONCLUSIONS: Coccidioidomycosis in Arizona has increased. Its incidence is driven by seasonal outbreaks associated with environmental and climatic changes. Our study may allow public-health officials to predict seasonal outbreaks in Arizona and to alert the public and physicians early, so that appropriate preventive measures can be implemented.

Adult↗

Excess mortality, hospital stay, and cost due to candidemia: a case-control study using data from population-based candidemia surveillance.

OBJECTIVE: To determine the mortality, hospital stay, and total hospital charges and cost of hospitalization attributable to candidemia by comparing patients with candidemia with control-patients who have otherwise similar illnesses. Prior studies lack broad patient and hospital representation or cost-related information that accurately reflects current medical practices. DESIGN: Our case-control study included case-patients with candidemia and their cost-related data, ascertained from laboratory-based candidemia surveillance conducted among all residents of Connecticut and Baltimore and Baltimore County, Maryland, during 1998 to 2000. Control-patients were matched on age, hospital type, admission year, discharge diagnoses, and duration of hospitalization prior to candidemia onset. RESULTS: We identified 214 and 529 sets of matched case-patients and control-patients from the two locations, respectively. Mortality attributable to candidemia ranged between 19% and 24%. On multivariable analysis, candidemia was associated with mortality (OR, 5.3 for Connecticut and 8.5 for Baltimore and Baltimore County; P < .05), whereas receiving adequate treatment was protective (OR, 0.5 and 0.4 for the two locations, respectively; P < .05). Candidemia itself did not increase the total hospital charges and cost of hospitalization; when treatment status was accounted for, having received adequate treatment for candidemia significantly increased the total hospital charges and cost of hospitalization ($6,000 to $29,000 and $3,000 to $22,000, respectively) and the length of stay (3 to 13 days). CONCLUSION: Our findings underscore the burden of candidemia, particularly regarding the risk of death, length of hospitalization, and cost associated with treatment.

Adolescent↗

Determining risk factors for candidemia among newborn infants from population-based surveillance: Baltimore, Maryland, 1998-2000.

BACKGROUND: Our objective was to determine risks factors for late onset candidemia, independent of birth weight, in newborn infants. METHODS: We performed a matched case-control study. Cases were identified through active, population-based surveillance for candidemia, conducted in Baltimore City and County during 1998-2000, and were defined as the incident isolation of any Candida species from the bloodstream of an infant 3 months old or younger. Four controls, matched by age, hospital, birth weight category, hospital stay and admission date, were selected for each case. Potential risk factors included clinical, demographic and maternal prenatal data. RESULTS: Of the 35 cases, 19 (54%) infections were with Candida albicans, 9 (26%) were with Candida parapsilosis and 5 (14%) were with Candida glabrata. Cases had a median birth weight of 680 g (range, 430-3200 g); median gestational ages of cases and controls were 25 and 27 weeks, respectively. Compared with controls, cases had significant higher mortality (20% versus 4%; P = 0.004). No maternal factors were associated with increased risk of disease; cases were as likely as controls to be of black race. Multivariable conditional logistic regression analysis revealed that gestational age younger than 26 weeks [adjusted odds ratio, 6.5; 95% confidence interval (95% CI), 1.3-32], vaginal delivery (adjusted odds ratio, 4.3; 95% CI 1.3-14.2) and abdominal surgery (adjusted odds ratio, 10.9; 95% CI 1.9-62) were independently associated with increased risk of candidemia. CONCLUSIONS: Independent of birth weight, infants born at <26 weeks or those who have had abdominal surgery are at a significantly increased risk of candidemia. This study helps define a subgroup of preterm infants at high risk of developing bloodstream infections with Candida species.

Baltimore↗

A large histoplasmosis outbreak among high school students in Indiana, 2001.

BACKGROUND: A histoplasmosis outbreak occurred in an Indiana high school in November-December 2001. METHODS: To describe the risk factors for this outbreak, we conducted a cohort study of all available students and staff (N = 682) and an environmental investigation. RESULTS: Of the 523 (77%) persons who displayed serologic evidence of recent Histoplasma capsulatum infection, 355 (68%) developed symptoms consistent with acute pulmonary histoplasmosis. Rototilling of soil in a school courtyard known to be a bird roosting site had been performed during school hours on November 12, 2001, 14 days before both the peak of the onset of illness and a rise in student absenteeism. Being a student (odds ratio, 3.3; 95% confidence interval, 2.2-5.0) and being a student in a classroom near the courtyard during the rototilling (odds ratio, 3.1; 95% confidence interval, 1.8-5.2) were independently associated with infection and symptomatic illness. H. capsulatum was isolated from environmental samples, including soil from the courtyard and dust collected from a filter of a heating, ventilating and air-conditioning system. CONCLUSIONS: Soil-disrupting activities within a school courtyard caused the largest outbreak to date of histoplasmosis among adolescents. Improved efforts are needed to educate the community in endemic areas about histoplasmosis to prevent the occurrence of such outbreaks in the future. In addition, increased awareness among health care providers of this disease would facilitate appropriate diagnosis and treatment.

Adolescent↗

Epidemiologic and molecular characterization of an outbreak of Candida parapsilosis bloodstream infections in a community hospital.

Candida parapsilosis is an important cause of bloodstream infections in the health care setting. We investigated a large C. parapsilosis outbreak occurring in a community hospital and conducted a case-control study to determine the risk factors for infection. We identified 22 cases of bloodstream infection with C. parapsilosis: 15 confirmed and 7 possible. The factors associated with an increased risk of infection included hospitalization in the intensive care unit (adjusted odds ratio, 16.4; 95% confidence interval, 1.8 to 148.1) and receipt of total parenteral nutrition (adjusted odds ratio, 9.2; 95% confidence interval, 0.9 to 98.1). Samples for surveillance cultures were obtained from health care worker hands, central venous catheter insertion sites, and medical devices. Twenty-six percent of the health care workers surveyed demonstrated hand colonization with C. parapsilosis, and one hand isolate was highly related to all case-patient isolates by tests with the DNA probe Cp3-13. Outbreak strain isolates also demonstrated reduced susceptibilities to fluconazole and voriconazole. This largest known reported outbreak of C. parapsilosis bloodstream infections in adults resulted from an interplay of host, environment, and pathogen factors. Recommendations for control measures focused on improving hand hygiene compliance.

Adult↗

Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program.

To determine the incidence of Candida bloodstream infections (BSI) and antifungal drug resistance, population-based active laboratory surveillance was conducted from October 1998 through September 2000 in two areas of the United States (Baltimore, Md., and the state of Connecticut; combined population, 4.7 million). A total of 1,143 cases were detected, for an average adjusted annual incidence of 10 per 100,000 population or 1.5 per 10,000 hospital days. In 28% of patients, Candida BSI developed prior to or on the day of admission; only 36% of patients were in an intensive care unit at the time of diagnosis. No fewer than 78% of patients had a central catheter in place at the time of diagnosis, and 50% had undergone surgery within the previous 3 months. Candida albicans comprised 45% of the isolates, followed by C. glabrata (24%), C. parapsilosis (13%), and C. tropicalis (12%). Only 1.2% of C. albicans isolates were resistant to fluconazole (MIC, > or = 64 microg/ml), compared to 7% of C. glabrata isolates and 6% of C. tropicalis isolates. Only 0.9% of C. albicans isolates were resistant to itraconazole (MIC, > or = 1 micro g/ml), compared to 19.5% of C. glabrata isolates and 6% of C. tropicalis isolates. Only 4.3% of C. albicans isolates were resistant to flucytosine (MIC, > or = 32 microg/ml), compared to < 1% of C. parapsilosis and C. tropicalis isolates and no C. glabrata isolates. As determined by E-test, the MICs of amphotericin B were > or = 0.38 microg/ml for 10% of Candida isolates, > or =1 microg/ml for 1.7% of isolates, and > or = 2 microg/ml for 0.4% of isolates. Our findings highlight changes in the epidemiology of Candida BSI in the 1990s and provide a basis upon which to conduct further studies of selected high-risk subpopulations.

Adolescent↗

Coccidioidomycosis among workers at an archeological site, northeastern Utah.

In 2001, an outbreak of acute respiratory disease occurred among persons working at a Native American archeological site at Dinosaur National Monument in northeastern Utah. Epidemiologic and environmental investigations were undertaken to determine the cause of the outbreak. A clinical case was defined by the presence of at least two of the following symptoms: self-reported fever, shortness of breath, or cough. Ten workers met the clinical case definition; 9 had serologic confirmation of coccidioidomycosis, and 8 were hospitalized. All 10 were present during sifting of dirt through screens on June 19; symptoms began 9-12 days later (median 10). Coccidioidomycosis also developed in a worker at the site in September 2001. A serosurvey among 40 other Dinosaur National Monument workers did not find serologic evidence of recent infection. This outbreak documents a new endemic focus of coccidioidomycosis, which extends northward its known geographic distribution in Utah by approximately 200 miles.

Adolescent↗

Candida parapsilosis characterization in an outbreak setting.

Candida parapsilosis is an important non-albicans species which infects hospitalized patients. No studies have correlated outbreak infections of C. parapsilosis with multiple virulence factors. We used DNA fingerprinting to determine genetic variability among isolates from a C. parapsilosis outbreak and from our clinical database. We compared phenotypic markers of pathogenesis, including adherence, biofilm formation, and protein secretion (secretory aspartic protease [SAP] and phospholipase). Adherence was measured as colony counts on silicone elastomer disks immersed in agar. Biofilms formed on disks were quantified by dry weight. SAP expression was measured by hydrolysis of bovine albumin; a colorimetric assay was used to quantitate phospholipase. DNA fingerprinting indicated that the outbreak isolates were clonal and genetically distinct from our database. Biofilm expression by the outbreak clone was greater than that of sporadic isolates (p < or =0.0005). Adherence and protein secretion did not correlate with strain pathogenicity. These results suggest that biofilm production plays a role in C. parapsilosis outbreaks.

Aspartic Acid Endopeptidases↗

Histoplasmosis associated with exploring a bat-inhabited cave in Costa Rica, 1998-1999.

Between October 1998 and April 1999, 51 persons belonging to two separate groups developed acute pulmonary histoplasmosis after visiting a cave in Costa Rica. The first group consisted of 61 children and 14 adults from San Jose, Costa Rica; 44 (72%) were diagnosed with acute histoplasmosis. The second group comprised 14 tourists from the United States and Canada; 9 (64%) were diagnosed with histoplasmosis. After a median incubation time of 14 days, the most common symptoms were headache, fever, cough, and myalgias. Risk factors for developing histoplasmosis included crawling (odds ratio [OR] = 17.5, 95% confidence interval [CI] = 2.3-802) and visiting one specific room (OR = 3.4, 95% CI = 1.0-12.3) in the cave. Washing hands (OR = 0.1, 95% CI = 0.01-0.6) after exiting the cave was associated with a decreased risk of developing histoplasmosis. Histoplasma capsulatum was isolated from bat guano collected from inside the cave. Persons who explore caves, whether for recreation or science, should be aware of the risk bat-inhabited caves pose for developing histoplasmosis, especially if they are immunocompromised in any way.

Adolescent↗

Outbreak of invasive aspergillosis among renal transplant recipients.

Invasive aspergillosis (IA) is rare among renal transplant recipients (RTRs). We investigated a cluster of IA among RTRs at a California hospital from January to February 2001, when construction was ongoing. We conducted a cohort study among RTRs who were hospitalized between January 1 and February 5, 2001, to determine risk factors for IA. IA was defined using established guidelines. Four IA cases occurred among 40 RTRs hospitalized during the study period. Factors associated with an increased risk of IA included prolonged hemodialysis, lengthy corticosteroid treatment posttransplant, and use of sirolimus alone or with mycophenolate (P<0.05). After the study period, three additional RTRs developed IA; two Aspergillus isolates recovered from these patients had indistinguishable profiles by DNA fingerprinting, suggesting common-source exposure. This study suggests that immunosuppressed RTRs can be at an increased risk for IA. Measures to prevent IA in these patients should be taken during hospital construction.

Adult↗

The changing epidemiology of cryptococcosis: an update from population-based active surveillance in 2 large metropolitan areas, 1992-2000.

To examine trends in the incidence and epidemiology of cryptococcosis, active, population-based surveillance was conducted during 1992-2000 in 2 areas of the United States (the Atlanta, Georgia, and Houston, Texas, metropolitan areas; combined population, 7.4 million). A total of 1491 incident cases were detected, of which 1322 (89%) occurred in HIV-infected persons. The annual incidence of cryptococcosis per 1000 persons with AIDS decreased significantly during the study period, from 66 in 1992 to 7 in 2000 in the Atlanta area, and from 24 in 1993 to 2 in 1994 in the Houston area. Poisson regression analysis revealed that African American persons with AIDS were more likely than white persons with AIDS to develop disease. Less than one-third of all HIV-infected persons with cryptococcosis were receiving antiretroviral therapy before diagnosis. Our findings suggest that HIV-infected persons who continue to develop cryptococcosis in the era of highly active antiretroviral therapy (HAART) in the United States are those with limited access to health care. More efforts are needed to expand the availability of HAART and routine HIV care services to these persons.

AIDS-Related Opportunistic Infections↗

Human immunodeficiency virus type 1 subtype and other factors associated with extrapulmonary Cryptococcosis among patients in Thailand with AIDS.

Delineating factors associated with extrapulmonary cryptococcosis (EPC), a major disease burden among Thailand's AIDS patients, can clarify its pathogenesis and guide preventive interventions. From November 1993 through June 1996, enhanced surveillance of 2261 human immunodeficiency virus (HIV)-seropositive patients in a hospital near Bangkok showed EPC among 561 of 1553 AIDS patients (36.1%). Univariate analysis results were confirmed by multivariate analyses of data on 1259 patients. Logistic regression models identified factors significantly associated with EPC to be male sex (adjusted odds ratio [aOR], 2.0; 95% confidence interval [CI], 1.3-2.9), age <33 years (aOR, 1.5; 95% CI, 1.2-1.9), severe immunosuppression (aOR, 1.8; 95% CI, 1.3-2.6), not injecting drugs (aOR, 3.0; 95% CI, 1.7-5.5), and infection with HIV-1 circulating from CRF01_AE (formerly subtype E) versus subtype B (aOR, 2.3; 95% CI, 1.2-4.5). The association with CRF01_AE may result from undetermined markers of exposure or viral subtype effects on host immune responses. Better understanding of the epidemiology of EPC may reduce EPC incidence through targeted primary prevention and treatment.

AIDS-Related Opportunistic Infections↗

Stability of allelic frequencies and distributions of Candida albicans microsatellite loci from U.S. population-based surveillance isolates.

Allelic distributions and frequencies of five Candida albicans microsatellite loci have been determined for strains isolated from the bloodstream and obtained through active population-based surveillance in two U.S. metropolitan areas between 1998 and 2000. These data were compared to data for isolates obtained from two other U.S. regions in 1992 to 1993. In a majority of pairwise combinations between sites, no evidence was seen for shifts in microsatellite allelic frequencies. One to three alleles were highly predominant and correlated with major genotypes. These data both support the concepts of allelic stability and genetic equilibria and suggest that, in the United States, strains of C. albicans isolated from the bloodstream may form a defined, genetically homogeneous population across geographical distance and time.

Candida albicans↗