Salmonella infections in immunocompromised adults

Clinical syndromes caused by Salmonella infection in humans are divided into typhoid fever, caused by Salmonella typhi and Salmonella paratyphi, and a range of clinical syndromes, including diarrhoeal disease, caused by a large number of non-typhoidal salmonella serovars (NTS). Typhoid is a human-restricted and highly adapted invasive disease, but shows little association with immunocompromise. In contrast, NTS have a broad vertebrate host range, epidemiology that often involves food animals, and have a dramatically more severe and invasive presentation in immunocompromised adults, in particular in the context of HIV. Immunocompromise among adults, including underlying severe or progressive disease, chronic granulomatous disease, defects or blockade of specific cytokines (particularly IL-12/IL-23/IL-17 and TNF), and HIV, is associated with suppurative foci and with primary bacteraemic disease, which may be recurrent. These patients have markedly increased mortality. Worldwide, invasive recurrent NTS bacteraemia associated with advanced HIV disease is a huge problem, and the epidemiology in this context may be more human-restricted than in other settings. This review will describe the presentation and pathogenesis of NTS in different categories of immunocompromised adults, contrasted to typhoid fever.     

Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa

Invasive strains of non-typhoidal salmonellae have emerged as a prominent cause of bloodstream infection in African adults and children, with an associated case fatality of 20-25%. The clinical presentation of invasive non-typhoidal salmonella disease in Africa is diverse: fever, hepatosplenomegaly, and respiratory symptoms are common, and features of enterocolitis are often absent. The most important risk factors are HIV infection in adults, and malaria, HIV, and malnutrition in children. A distinct genotype of Salmonella enterica var Typhimurium, ST313, has emerged as a new pathogenic clade in sub-Saharan Africa, and might have adapted to cause invasive disease in human beings. Multidrug-resistant ST313 has caused epidemics in several African countries, and has driven the use of expensive antimicrobial drugs in the poorest health services in the world. Studies of systemic cellular and humoral immune responses in adults infected with HIV have revealed key host immune defects contributing to invasive non-typhoidal salmonella disease. This emerging pathogen might therefore have adapted to occupy an ecological and immunological niche provided by HIV, malaria, and malnutrition in Africa. A good understanding of the epidemiology of this neglected disease will open new avenues for development and implementation of vaccine and public health strategies to prevent infections and interrupt transmission.     

Diagnosis of amoebic colitis by antigen capture ELISA in patients presenting with acute diarrhoea in Cairo, Egypt

We studied 84 consecutive patients presenting with acute diarrhoea (less than 1 week in duration) at an outpatient tropical medicine clinic in Cairo, Egypt. The diagnosis of amoebic colitis was established by the presence of Entamoeba histolytica galactose-inhibitable lectin antigen and the presence of occult blood in stool. Controls were 182 healthy regional people and 64 patients complaining of prolonged diarrhoea lasting more than 1 week. Entamoeba histolytica infection was found more frequently in patients with acute diarrhoea (57.1%) than in healthy controls (21.4%) or patients with prolonged diarrhoea (25%) (P < 0.001). There was a higher prevalence of Entamoeba dispar infection in the two control groups (24.2 and 20.3%, respectively, P=0.004 and 0.061) compared with those with acute diarrhoea (8.3%). Of the 84 patients with acute diarrhoea 32 had amoebic colitis (38%), and of these, 31 (97%) had at least one positive assay for serum amoebic antibodies (P < 0.001 compared with control groups). In summary, as determined by antigen-detection enzyme-linked immunosorbent assay, there is an unexpectedly high prevalence of amoebic colitis among patients presenting with acute diarrhoea to a tropical disease clinic in Cairo, Egypt.     

Non-thyphoidal salmonellosis in patients with systemic lupus erythematosus. A study of fifty patients and a review of the literature

The objective of this study was to characterize the clinical profile of lupus patients with non-typhoidal salmonellosis. A retrospective review of the clinical charts of lupus patients diagnosed with bacteriologically proven non-typhoidal salmonellosis over the last 20 y was undertaken, paying special attention to risk factors, clinical presentation and treatment outcome. Most episodes were bacteraemic without a localizing focus; and some patients were afebrile. They usually occurred in patients prone to opportunistic infections, and at times of increased immunosuppression given for lupus flares (especially nephritis). However, salmonellosis also occurred in some patients presenting with lupus. The C-reactive protein level was found to be significantly higher during the infective episodes compared to episodes of non-infective febrile lupus flare. All isolates were sensitive to the usual first-line antibiotics and eminently treatable with 3 weeks of appropriate antibiotics without recurrence/persistence or significant morbidity/mortality, the exceptions being spinal osteomyelitis and septic arthritis involving deformed joints requiring surgical debridement and prolonged antibiotic therapy for eradication. Mortality occurred in the setting of septic shock from mixed-microbial sepsis and major organ failure from active lupus. There is a high association of non-epidemic, non-typhoidal salmonellosis with SLE, especially in patients with active disease on intensified immunosuppression. The C-reactive protein value may be helpful in distinguishing between fever from a pure lupus flare and one complicated by infection.     

Clinical features and predictors of survival of AIDS-related non-Hodgkin's lymphoma in a population-based case series in Sydney, Australia

OBJECTIVES: To analyse clinical features and predictors of survival for AIDS-related non-Hodgkin's lymphoma (NHL) in the era of highly active antiretroviral therapy (HAART), compared to earlier in the HIV epidemic. METHODS: All AIDS-NHL cases diagnosed at three inner Sydney hospitals caring for people with AIDS during 1985-2001 were identified through medical record searches. Demographic, clinical, immunological and histopathological information was recorded. Year of NHL diagnosis was grouped into three periods, corresponding to whether monotherapy (1985-1991), dual therapy (1992-1995) or HAART (1996-2001) was the main treatment for HIV infection. Statistical comparisons were made between the pre-HAART and post-HAART eras. RESULTS: Three hundred cases of AIDS-NHL were identified. Divergent trends were identified for systemic and primary central nervous system (CNS) NHL. For systemic NHL, the CD4 count at NHL diagnosis increased markedly to 208 cells/microL in the post-HAART era (P=0.014) and there was a trend towards presentation as the first AIDS-defining illness (69%, P=0.053), and as earlier stage NHL disease (42%, P=0.048). Median survival time increased from 4.2 months in 1985-1991 to 19 months in the post-HAART era (P<0.001). In a multivariate model, predictors of poor survival from systemic NHL included: NHL diagnosis after another AIDS-defining illness (P<0.001), stage 4 NHL (P<0.001), presentation at extra lymphatic sites (P=0.001), and nonreceipt of chemotherapy (P=0.002). After adjusting for the factors, those diagnosed in the era of HAART had a significant 56% reduction in rate of death (P<0.001). In contrast, for CNS NHL, clinical features were little changed and survival did not improve in the era of HAART. CONCLUSIONS: Systemic NHL is presenting earlier in the course of HIV disease, and at a less advanced NHL stage. There has been a marked improvement in survival in the era of HAART even after adjustment for other prognostic variables. In contrast, primary CNS NHL remains a disease which presents late in the course of HIV infection and is associated with a very poor prognosis.     

A mycotic aneurysm of the ascending aorta and aortic arch induced by Salmonella Enteritidis

In very rare cases, salmonella infection may be associated with extra-intestinal manifestations. Of these, a mycotic aneurysm represents a life-threatening complication that is characterised by a high mortality rate. Prompt treatment with a combination of antibiotic therapy and surgical intervention is urgently required. We report on the case of a 60-year-old woman who presented with salmonella bacteraemia and the rare complication of an infected aneurysm of the ascending aorta and aortic arch.     

Normal chest radiography in pulmonary tuberculosis: implications for obtaining respiratory specimen cultures.

SETTING: Urban tuberculosis (TB) clinic, Nashville, Tennessee, USA. OBJECTIVE: Chest radiographs (CXRs) help in the diagnosis of pulmonary TB, but may be normal. Mycobacterium tuberculosis in culture is diagnostic of TB, but cultures are not routinely obtained in resource-poor settings. We examined rates and risk factors for pulmonary TB associated with normal CXR. DESIGN: An observational cohort study was performed among all respiratory culture-positive TB cases referred to the Nashville Health Department from October 1992 to July 2003. Clinical factors, demographics and underlying medical conditions were assessed. RESULTS: Of 601 study patients, 53 (9%) had normal CXRs: 31/138 (22%) were human immunodeficiency virus (HIV) infected and 22/463 (5%) were non-HIV-infected/unknown (P<0.001). Among HIV-infected patients, normal CXR was more likely in persons with renal failure (13% vs. 3%, P=0.048). Among non-HIV-infected/unknown patients, normal CXR was more likely in those who were asymptomatic at presentation (32% vs. 13%, P=0.022). In multivariable logistic regression analysis, HIV infection was associated with an increased risk of normal CXR (odds ratio [OR] 6.61, P<0.0001); factors associated with reduced risk were dyspnea (OR 0.24, P=0.026), positive sputum smear (OR 0.45, P=0.028) and cough (OR 0.48, P=0.038). CONCLUSIONS: The rate of normal CXR among persons with culture-confirmed pulmonary TB was high. Respiratory specimen cultures should be obtained in TB suspects with a normal CXR, particularly HIV-infected persons.     

Nosocomial enterococcal endocarditis: a serious hazard for hospitalized patients with enterococcal bacteraemia

OBJECTIVES: Enterococci are a major leading cause of infectious endocarditis and also a common cause of hospital-acquired bacteraemia, which is not believed to represent a serious hazard for the endocarditis. The incidence and risk factors for infectious endocarditis in patients with hospital-acquired enterococcal bacteraemia is determined. METHODS: Prospective analysis of 116 patients with enterococcal bacteraemia admitted to medical or surgical wards of a tertiary-care, university affiliated hospital during a period of 5 years. Echocardiography was performed when indicated by clinical criteria. RESULTS: Seventy-five (61.4%) episodes were hospital-acquired and 47 (38.5%) were community-acquired. Most patients had one or more underlying chronic diseases and major abdominal (58.6%) or genitourinary (38.6%) surgery. Seventeen patients (14.6%) developed enterococcal endocarditis. By univariate analysis the risk factors associated with endocarditis were community-acquired infection (P 0.012); monomicrobial bacteraemia (P 0.006); three or more positive blood cultures (P < 0.001); underlying valvulopathy (P < 0.001); presence of a prosthetic valve (P < 0.001) and age (P 0.012). Six patients (8%) developed nosocomial endocarditis. In this group of patients, three or more positive blood cultures (P < 0.01), bacteraemia as a result of Enterococcus faecalis (P 0.007); underlying valvulopathy (P < 0.001) and presence of a prosthetic valve (P < 0.001) were associated with endocarditis. By logistic regression, the presence of underlying valvulopathy and three or more positive blood cultures were associated with endocarditis (OR 21.0; CI 95% 1.65-26.9; P 0.019). CONCLUSIONS: The risk of developing infectious endocarditis in patients with hospital-acquired enterococcal bacteraemia is significant. Patients with underlying valvulopathy and three or more positive blood cultures with E. faecalis are prone to nosocomial enterococcal endocarditis.     

Non-cryptosporidial diarrhoea in human immunodeficiency virus (HIV) infected patients.

Thirty of 81 consecutive HIV antibody positive patients referred with non-cryptosporidial diarrhoea had no potential infectious cause; most had AIDS related complex rather than the full blown syndrome. Opportunistic infections with cytomegalovirus (CMV), mycobacterium avium-intracellulare (MAI), and herpes simplex virus (HSV), which allowed a diagnosis of AIDS to be made, were found in 19 patients and were the presenting features of AIDS in five. Other potential pathogenic species included entamoeba, giardia, campylobacter, and salmonella (without septicaemia). Cytomegalovirus infection was often accompanied by abdominal pain. Severe weight loss (greater than 10 kg) at presentation was found in patients with CMV infection and MAI. Bloody diarrhoea was confined to the group with HSV procitis. Malignant causes of diarrhoea were rare. Two patients developed a squamous carcinoma of the anorectal margin and one a non-Hodgkin's lymphoma. In only two of 12 patients who had Kaposi's sarcoma was this considered as a cause of diarrhoea. Rigid sigmoidoscopy showed macroscopic abnormalities in over a third (32) of the 81 patients with non-cryptosporidial diarrhoea. Most commonly this was severe inflammation (17) or discrete ulceration (four) [three of whom had CMV colitis]. Kaposi's sarcoma was identified in 11 patients. Non-specific inflammation was seen histologically in 40 of the 60 patients with no sigmoidoscopic inflammatory changes. Barium enema only revealed an abnormality in a minority of the patients and a colonoscopy only revealed information additional to rigid sigmoidoscopy in two patients--one with CMV ulcers in the transverse colon and the other with evidence of Kaposi's sarcoma not seen in the rectum. Ten patients had a rectal biopsy examined by electron microscopy as no infective cause of diarrhoea was uncovered. In four of these microtubular structures which are commonly seen in viral infections were found and two had prelymphomatous changes and in one of these frank lymphoma has developed. We recommend multiple stool analysis, sigmoidoscopy and rectal biopsy as the initial investigations in these patients reserving tests of malabsorption, colonoscopy, and barium enema for the small number of more difficult cases.     

Non-typhoidal salmonella bacteraemia among HIV-infected Malawian adults: high mortality and frequent recrudescence

OBJECTIVE: Non-typhoidal salmonella (NTS) bacteraemia is a common, recurrent illness in HIV-infected African adults. We aimed to describe the presentation and outcome of NTS bacteraemia, the pattern of recurrence, and to determine whether recurrence results from re-infection or recrudescence. DESIGN: One hundred consecutive adult inpatients with NTS bacteraemia in Blantyre, Malawi, were treated with chloramphenicol. Survivors were prospectively followed to detect bacteraemic recurrence. METHODS: Index and recurrent isolates were typed by antibiogram, pulsed-field gel electrophoresis and plasmid analysis to distinguish recrudescence from re-infection. RESULTS: Inpatient mortality was 47%, and 1-year mortality was 77%. A total of 77 out of 78 cases were HIV positive. Anaemia was associated with inpatient death, and several features of AIDS were associated with poor outpatient survival. Among survivors, 43% (19/44) had a first recurrence of NTS bacteraemia at 23-186 days. Among these, 26% (5/19) developed multiple recurrences up to 245 days. No recurrence was seen after 245 days, despite follow-up for up to 609 days (median 214). Suppurative infections were not found at presentation, and were only seen twice at recurrence. Index and recurrent paired isolates were identical by phenotyping and genotyping, consistent with recrudescence, rather than re-infection. CONCLUSION: NTS bacteraemia has a high mortality (47%) and recurrence (43%) rate in HIV-infected African adults. Recurrence is caused by recrudescence rather than re-infection. As focal infections were rarely found, recrudescence may often be a consequence of intracellular tissue sequestration. There is an urgent need for improved primary treatment and secondary prophylaxis in Africa.     

Epidemiological and clinical characteristics of bacteraemia caused by Aeromonas spp. as compared with Escherichia coli and Pseudomonas aeruginosa

We reviewed 75 episodes of Aeromonas spp. bacteraemia observed at our institution in 1979-2002, with special reference to episodes occurring in elderly patients (> or = 65 y) and to nosocomial episodes. In addition, we compared monomicrobial bacteraemic episodes caused by Aeromonas spp. (n = 54) with those caused by Escherichia coli (n = 108) and Pseudomonas aeruginosa (n = 108), to assess differences in clinical presentation and outcome. The 75 episodes of Aeromonas spp. bacteraemia occurred mainly in males (72%), suffering from chronic liver disease (36%) or neoplasm (33%). They had an abdominal origin in 52% of cases, were recorded as primary bacteraemia in 40%, and showed a 30-d case fatality rate of 36%. 22 episodes (29%) were nosocomial, 36 (48%) occurred in elderly patients and 21 (28%) were polymicrobial infections. In comparison with Aeromonas spp., E. coli bacteraemia was more often associated with less severe underlying conditions, a community-acquired infection (74%), and a urinary tract (52%) or abdominal (27%) origin and had a 30-d case fatality rate of 24%. P. aeruginosa bacteraemia occurred mainly in patients with severe underlying conditions, was associated with nosocomial infection (69%), and had a 30-d case fatality rate of 43%. In conclusion, Aeromonas spp. bacteraemia is a serious infection that should be considered in patients with chronic liver disease or neoplasm. It may occur in the elderly and as a nosocomial infection, and differs in clinical findings from bacteraemia due to other common pathogens.     

Fever of unknown origin in patients with HIV infection in Thailand: an observational study and review of the literature

Fever of unknown origin (FUO) is a common presentation for patients with advanced human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). We prospectively followed 72 patients, consecutively admitted to a Thai regional hospital with FUO and HIV infection to identify aetiologies and mortality in the era of available antiretroviral therapy (ART). Aetiologies of FUO were identified in 67 patients (93%), of whom 61(85%) had an infectious aetiology. The most common infectious aetiologies were Mycobacterium tuberculosis (n=30; 42%), Cryptococcus neoformans (n=17; 24%), Pneumocystis jiroveci (n=9; 13%), Toxoplasma gondii (n=5; 7%), and salmonella bacteraemia (n=5; 7%). Nineteen patients (26%) had co-infection with two or more pathogens. The median CD4 count was 120 cells/mm(3) (range, 1-581 cells/mm(3)), and the all-cause mortality was 22% (n=16). By multivariate analysis, inadequate antimicrobial treatment was the sole predictor of mortality (aOR=4.9; 95% CI=1.2-21.9; P=0.02). Overall, 58 of 72 patients (81%) had an opportunistic infection suggesting that guideline use of ART and prophylactic strategies remain unmet needs that will benefit individuals and populations with HIV/AIDS in Thailand.     

Recurrent non-typhoidal salmonella bacteremia in a patient with interleukin -12p40 deficiency

The South eastern region of Iran is an endemic area for salmonellosis. Sometimes bacteremia due to nontyphoidal salmonella occurs but certain patients are at increased risk for recurrent bacteremia. The risk of invasive salmonellosis and recurrent bacteremia is increased in the patients with immunosuppression, especially impaired cell-mediated immunity, lymphoproliferative diseases and in patients with IL-12 deficiency. In recent years, a series of inherited disorders of IL-12-IFN-gamma axis have been described that predispose affected individuals to disseminated disease caused by environmental mycobacteria and non-typhoidal salmonella. We report here the first such patient originating from and living in Iran. The patient was a 26-year-old man, suffering from IL-12p40 deficiency and presented with recurrent episodes of systemic salmonellosis. This report indicates that there are patients with inherited defects of the IL-12-IFN-gamma circuit in Iran. We recommended to consider this group of disorders in all patients with recurrent non-typhoidal salmonella bacteremia, wherever they are found.     

Clinical and social determinants of diarrhoeal disease in a rural HIV/AIDS clinic, South Africa: a case-control study

Diarrhoeal diseases are a common cause of morbidity and are associated with mortality in HIV-infected populations. Little is known about the contribution of clinical and socio-environmental factors to the risk of diarrhoea in these populations in rural sub-Saharan Africa. We conducted a case-control study of people attending a rural HIV clinic with an episode of diarrhoea in Bushbuckridge, South Africa. Cases were defined as HIV-positive adults with symptoms of diarrhoea before or after initiation of antiretroviral therapy (ART). Controls without diarrhoea were randomly selected from clinic attendees. Structured questionnaires and case-file reviews were undertaken to describe clinical and socioenvironmental risk factors. We recruited 103 cases of diarrhoea from 121 patients meeting case definitions. Cases were more likely to be women (P = 0.013), aged over 45 years (P = 0.002), divorced or separated (P = 0.006), have limited formal education (P = 0.003), have inadequate access to sanitation facilities (P = 0.045), have water access limited to less than three days per week (P = 0.032) and not yet initiated on ART (P < 0.001). In multivariate analysis, diarrhoea remained associated with female gender (adjusted odds ratio [aOR]: 2.02, 95% CI 1.10-3.73), older age (aOR: 6.31, 95% CI 1.50-26.50), limited access to water (aOR: 2.66, 95% CI 1.32-5.35) and pre-ART status (aOR: 5.87, 95% CI 3.05-11.27). Clinical and socio-environmental factors are associated with occurrence of diarrhoeal disease among rural HIV patients in South Africa. Further intervention research is urgently needed, combining community- and clinic-based approaches, to improve access to water, sanitation and ART for rural areas with high HIV prevalence, along with structural interventions to address gender inequities.     

Salmonella meningitis and infection with HIV

Patients infected with HIV demonstrate increased susceptibility to serious infections with non-typhoidal salmonellae. However, no cases of salmonella meningitis have been reported in this population. We now report three cases of salmonella meningitis which occurred in a population of 1800 patients with AIDS or AIDS-related complex at our hospitals. The incidence of meningitis complicating salmonella infection in our HIV-infected population appears to be much higher than that reported in non-AIDS patients (7.5 versus 0.15%). All had cerebrospinal fluid parameters consistent with bacterial meningitis, and two of three revealed organisms on cerebrospinal fluid Gram stain. Two presented with a fulminant illness and died despite therapy; the third developed a brain abscess associated with a relapse of meningitis. Salmonella meningitis should be considered as a cause of acute neurological deterioration in patients at risk for HIV-related disease. Relapses may occur, and mortality is high.     

HIV-1 co-infection in children hospitalised with tuberculosis in South Africa.

SETTING: Hospitals associated with the Department of Paediatrics at the University of the Witwatersrand, Johannesburg, South Africa. OBJECTIVES: To define the prevalence of human immunodeficiency virus (HIV) co-infection and differences in clinical presentation between HIV-infected and non-infected hospitalised children with tuberculosis. DESIGN: Children were prospectively enrolled between August 1996 and January 1997. RESULTS: Of 161 children enrolled, 42% were HIV-infected, including 67/137 with pulmonary tuberculosis (PTB) and 1/24 with extra-pulmonary disease (EPTB). Positive microscopy or bacteriology did not differ by HIV status for children with either PTB or EPTB. Although age did not differ between HIV-infected and non-infected children with PTB, non-HIV-infected children with EPTB were significantly older than those with PTB only (median age 32 months vs 14.5 months, P = 0.004). Chronic weight loss, malnutrition and the absence of BCG scarring were more common in HIV-infected children with PTB. HIV-infected children were also more likely to show cavitation (P = 0.001) and miliary TB (P = 0.01) on chest X-ray. Reactivity to tuberculin (> or = 5 mm and > or = 10 mm in HIV-infected and non-infected children, respectively) was significantly lower in HIV-infected children, as were CD4+ lymphocyte levels. The mortality rate during the study was 13.4% in HIV-infected children compared with 1.5% in non-HIV-infected children (P = 0.03). CONCLUSIONS: There is a high prevalence of HIV co-infection in children with TB. Progressive PTB and death are more common in HIV-infected children. Tuberculin skin testing is of limited use in screening for TB in HIV-infected children even when using a cut-point of > or = 5 mm.     

Presenting clinical features and C-reactive protein in the prediction of a positive stool culture in patients with diarrhoea

OBJECTIVES: To devise a scoring system by which clinical features and C-reactive protein (CRP) can be used to predict a positive stool culture in patients admitted with acute diarrhoea. METHODS: One hundred and thirty-two patients admitted to the Regional Infection Unit with diarrhoea thought to be due to bacterial gastroenteritis were included. Clinical features, CRP and outcome of stool culture were recorded, together with the final diagnosis. RESULTS: Forty-one patients had bacterial gastroenteritis characterized by the isolation of a bacterial enteropath (BGE). Sixty-three patients had non-specific gastroenteritis, defined as more than three loose stools per day with no bacterial enteropath isolated (NSGE). In 28 patients another diagnosis was made (Others). More of the patients with BGE (91%) had abdominal pain as compared with those with NSGE (67%) and Others (61%) (P=0.01). The mean duration of symptoms was longer in the Others group (6.14 days) as compared with patients with BGE (3.29) and NSGE (3.25) (P=0.01). The mean CRP was significantly higher in those with BGE (113.9mg/l) and Others (116.9mg/l) as compared to the NSGE patients (38.9mg/l) (P=0.001). A scoring system was devised which incorporated the presence or absence of abdominal pain (+10 or 0), the duration of symptoms (-10, for 5 or more days, 0 for less than 5 days of symptoms) and the CRP (CRP<50=0, CRP>50=5). A score of 15 or more predicted 79% of patients with BGE, while a score of <15 predicted 87% of those with NSGE and 86% of those with another diagnosis. CONCLUSIONS: This simple scoring system may be useful in predicting the positivity of stool culture, and therefore may be helpful in targeting those small number of patients who require antimicrobial therapy after hospital admission. We would not, however, favour reliance on this scoring system alone to choose whom to treat with antimicrobials.     

The changing demographics of women living with HIV/AIDS in southern Alberta from 1982 to 2006

INTRODUCTION:

Women account for a growing proportion of HIV infections in Canada. This has implications with respect to prevention, diagnosis and treatment.

OBJECTIVE:

To describe the female population presenting for HIV care in southern Alberta and to examine the impact of opt-out pregnancy screening.

METHODS:

A retrospective review of demographic and clinical characteristics of all patients presenting to the Southern Alberta HIV Clinic (SAC) care program from 1982 to 2006, was performed.

RESULTS:

The proportion of newly diagnosed patients who were female increased from 7.5% before 1998 to 21.5% after 1998. Women were more likely to be from vulnerable populations, such as intravenous drug users (31.3% versus 13.7%, P<0.001), aboriginals/Métis (21.5% versus 8.7%, P<0.001), blacks (28.9% versus 4.9%, P<0.001) and immigrants (36.6% versus 14.7%, P<0.001). Heterosexual intercourse was the main risk factor for HIV acquisition (43.7%). Women were less likely than men to have requested HIV testing (20.9% versus 37.8%, P<0.001). Opt-out pregnancy screening accounted for 12.7% of HIV-positive tests in women, following its introduction in 1998. Of the women diagnosed by pregnancy screening, 62.1% were from HIV-endemic countries. There was an association between reason for testing and CD4 count at presentation; women who requested their HIV test had higher median CD4 counts than those diagnosed because of illness (478 cells/mL, interquartile range [IQR]=370 cells/mL versus 174 cells/mL, IQR=328 cells/mL, P<0.001) or pregnancy screening (478 cells/mL, IQR=370 cells/mL versus 271 cells/mL, IQR=256 cells/mL, P=0.001).

CONCLUSIONS:

Women were less likely than men to have requested HIV testing and were more likely to be diagnosed by population-based screening methods. Women, especially vulnerable groups, account for a growing number and proportion of newly diagnosed HIV infections in Alberta. The implications of expanded screening in this population merit further consideration.     

Patients with non-viral liver disease have a greater tumor burden and less curative treatment options when diagnosed with hepatocellular carcinoma

AIM To assess the impact of underlying liver disease etiology on the presenting features and outcomes in a large cohort of patients with hepatocellular carcinoma(HCC). METHODS A prospective database of all patients with HCC was established from 1998 to March 2012. One thousand and seventy-eight patients were categorized into three groups, based on the etiology of their liver disease: hepatitis B virus(HBV), hepatitis C virus(HCV) and non-viral liver disease(NVLD). Overall survival was determined by Kaplan Meier analysis to time of death or last follow-up.RESULTS HCC patients with HCV(85%) were more likely to be diagnosed as part of a surveillance program, compared to HBV or NVLD(both 71%)(P 0.001). Patients with NVLD were more likely to receive best supportive care(29%) compared to those with HBV(21%) or HCV(20%)(P 0.02). Twelve percent of NVLD and 13% of HBV patients underwent liver transplantation compared to 21% of HCV patients(P = 0.001). Median survival from presentation was lowest in NVLD(1.7 years) when compared to HBV(2.8 years) and HCV(2.6 years)(P 0.05). In multivariate analysis, independent predictors of survival included Child Turcotte Pugh score, size of dominant lesion, absence of vascular invasion, and management with surgical resection or liver transplantation. Patient age and the etiology of the underlying liver disease were not independent predictors of survival CONCLUSION Patients with NVLD and HCC were less likely to be enrolled in a HCC surveillance program and are less likely to have curative therapies such as liver resection and transplantation after diagnosis with HCC, when compared to patients with Hepatitis B and Hepatitis C.     

Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration

CONTEXT: Thyroid nodules and goiter are common, and fine-needle aspiration biopsy (FNAB) is the first investigation of choice in distinguishing benign from malignant disease. OBJECTIVE: The objective of the study was to assess whether simple clinical and biochemical parameters can predict the likelihood of thyroid malignancy in subjects undergoing FNAB. DESIGN: The design was a prospective cohort. SETTING: The study was conducted at a single secondary/tertiary care clinic. PARTICIPANTS: One thousand five hundred consecutive patients without overt thyroid dysfunction (1304 females and 196 males, mean age 47.8 yr) presenting with palpable thyroid enlargement between 1984 and 2002 were evaluated by FNAB of the thyroid. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURES: Goiter type was assessed clinically and classified as diffuse in 183, multinodular in 456, or solitary nodule in 861 cases. Serum TSH concentration at presentation was measured in a sensitive assay in patients presenting after 1988 (n = 1183). The final cytological or histological diagnosis was determined after surgery (n = 553) or a minimum 2-yr clinical follow-up period (mean 9.5 yr, range 2-18 yr). RESULTS: The overall sensitivity and specificity of FNAB in predicting malignancy were 88 and 84%, respectively. The risk of diagnosis of malignancy rose in parallel with the serum TSH at presentation, with significant increases evident in patients with serum TSH greater than 0.9 mU/liter, compared with those with lower TSH. Binary logistic regression analysis revealed significantly increased adjusted odds ratios (AORs) for the diagnosis of malignancy in subjects with serum TSH 1.0-1.7 mU/liter, compared with TSH less than 0.4 mU/liter [AOR 2.72, 95% confidence interval (CI) 1.02-7.27, P = 0.046], with further increases evident in those with TSH 1.8-5.5 mU/liter (AOR 3.88, 95% CI 1.48-10.19, P = 0.006, compared with TSH < 0.4 mU/liter) and greater than 5.5 mU/liter (AOR 11.18, 95% CI 3.23-8.63, P < 0.001, compared with TSH < 0.4 mU/liter). Males (AOR 1.8, 95% CI 1.04-3.1, P = 0.04), younger patients (AOR 1.1, 95% CI 1.01-1.15, P = 0.025), and those with clinically solitary nodules (AOR 2.53, 95% CI 1.5-4.28, P = 0.001) were also at increased risk. Based on these findings, a formula to predict the risk of the diagnosis of thyroid malignancy in individual patients, taking into account their gender, age, goiter type determined clinically, and serum TSH, was calculated. CONCLUSIONS: The risk of malignancy in a thyroid nodule increases with serum TSH concentrations within the normal range. In addition to patient's gender, age, and goiter type, the serum TSH concentration at presentation is an independent predictor of the presence of thyroid malignancy. We propose that these simple clinical and biochemical factors can serve as an adjunct to FNAB in predicting risk of malignancy.