Rhabdomyolysis, acute kidney injury, and mortality in Ebola virus disease: retrospective analysis of cases from Eastern Democratic Republic of the Congo, 2019.

BACKGROUND: Skeletal muscle injury in Ebola virus disease (EVD) has been reported, but its association with morbidity and mortality remains poorly defined. METHODS: Retrospective study of patients admitted to two EVD Treatment Units, over an eight-month period in 2019, during a large EVD epidemic in the Democratic Republic of the Congo. RESULTS: 333 patients (median age 30 years, 58% female) had at least one creatine kinase (CK) measurement (total 2,229 CK measurements, median 5 (IQR 1-11) per patient). 271 patients (81%) had an elevated CK (>380U/L), 202 (61%) had rhabdomyolysis (CK>1,000 IU/L), and 45 (14%) had severe rhabdomyolysis (≥5,000U/L). Among survivors, the maximum CK level was median 1,600 (IQR 550 to 3,400), peaking 3.4 days after admission (IQR 2.3 to 5.5) and decreasing thereafter. Among fatal cases, the CK rose monotonically until death, with maximum CK level of median 2,900 U/L (IQR 1,500 to 4,900). Rhabdomyolysis at admission was an independent predictor of AKI (aOR 2.2 [95%CI 1.2-3.8], p=0.0065) and mortality (aHR 1.7 [95%CI 1.03-2.9], p=0.037). CONCLUSIONS: Rhabdomyolysis is associated with AKI and mortality in EVD patients. These findings may inform clinical practice by identifying lab monitoring priorities and highlighting the importance of fluid management.

Neutrophils promote T-cell activation through the regulated release of CD44-bound Galectin-9 from the cell surface during HIV infection.

The interaction of neutrophils with T cells has been the subject of debate and controversies. Previous studies have suggested that neutrophils may suppress or activate T cells. Despite these studies, the interaction between neutrophils and T cells has remained a largely unexplored field. Here, based on our RNA sequencing (RNA-seq) analysis, we found that neutrophils have differential transcriptional and functional profiling depending on the CD4 T-cell count of the HIV-infected individual. In particular, we identified that neutrophils in healthy individuals express surface Galectin-9 (Gal-9), which is down-regulated upon activation, and is consistently down-regulated in HIV-infected individuals. However, down-regulation of Gal-9 was associated with CD4 T-cell count of patients. Unstimulated neutrophils express high levels of surface Gal-9 that is bound to CD44, and, upon stimulation, neutrophils depalmitoylate CD44 and induce its movement out of the lipid raft. This process causes the release of Gal-9 from the surface of neutrophils. In addition, we found that neutrophil-derived exogenous Gal-9 binds to cell surface CD44 on T cells, which promotes LCK activation and subsequently enhances T-cell activation. Furthermore, this process was regulated by glycolysis and can be inhibited by interleukin (IL)-10. Together, our data reveal a novel mechanism of Gal-9 shedding from the surface of neutrophils. This could explain elevated plasma Gal-9 levels in HIV-infected individuals as an underlying mechanism of the well-characterized chronic immune activation in HIV infection. This study provides a novel role for the Gal-9 shedding from neutrophils. We anticipate that our results will spark renewed investigation into the role of neutrophils in T-cell activation in other acute and chronic conditions, as well as improved strategies for modulating Gal-9 shedding.

Selective Upregulation of CTLA-4 on CD8+ T Cells Restricted by HLA-B*35Px Renders them to an Exhausted Phenotype in HIV-1 infection.

HLA-B*35Px is associated with HIV-1 disease rapid progression to AIDS. However, the mechanism(s) underlying this deleterious effect of this HLA allele on HIV-1 infection outcome has not fully understood. CD8+ T cells play a crucial role to control the viral replication but impaired CD8+ T cells represent a major hallmark of HIV-1 infection. Here, we examined the effector functions of CD8+ T cells restricted by HLA-B*35Px (HLA-B*35:03 and HLA-B*35:02), HLA-B*27/B57 and non-HLA-B*27/B57 (e.g. HLA-A*01, A*02, A*03, A*11, A*24, A*26, B*40, B*08, B*38, B*44). CD8+ T cells restricted by HLA-B*35Px exhibited an impaired phenotype compared with those restricted by HLA-B*27/B57 and even non-HLA-B*27/B57. CD8+ T cells restricted by non-HLA-B*27/B57 when encountered their cognate epitopes upregulated TIM-3 and thus became suppressed by regulatory T cells (Tregs) via TIM-3: Galectin-9 (Gal-9). Strikingly, CD8+ T cells restricted by HLA-B*35Px expressed fewer TIM-3 and therefore did not get suppressed by Tregs, which was similar to CD8+ T cells restricted by HLA-B*27/B57. Instead, CD8+ T cells restricted by HLA-B*35Px upon recognition of their cognate epitopes upregulated CTLA-4. The transcriptional and impaired phenotype (e.g. poor effector functions) of HIV-specific CD8+ T cells restricted by HLA-B*35 was related to persistent CTLA-4, elevated Eomes and blimp-1 but poor T-bet expression. As such, anti-CTLA-4 antibody, Ipilimumab, reversed the impaired proliferative capacity of antigen-specific CD8+ T cells restricted by HLA-B*35Px but not others. This study supports the concept that CD8+ T resistance to Tregs-mediated suppression is related to allele restriction rather than the epitope specificity. Our results aid to explain a novel mechanism for the inability of HIV-specific CD8+ T cells restricted by HLA-B*35Px to control viral replication.

Galectin-9 and VISTA Expression Define Terminally Exhausted T Cells in HIV-1 Infection.

We report significant upregulation of Galectin-9 (Gal-9) and VISTA on both CD4+ and CD8+ T cells in HIV-infected human patients. Gal-9 and VISTA expression was associated with impaired T cells effector functions. Although Gal-9 was coexpressed with other coinhibitory receptors such as TIGIT, CD160, CD39, and VISTA, it was simultaneously coexpressed with PD-1. Coexpression of Gal-9 with PD-1 was associated with a more terminally exhausted T cell phenotype in HIV-1 patients. This was marked by higher expression of EOMES, blimp1, and Glut1 in Gal-9+ versus Gal-9- T cells, which is consistent with an exhausted T cell phenotype. Gal-9+ T cells exhibited the phenotype characteristics of effector T cells (CD45RA+, CD45RO-/lo, CD62L-, CD27lo) with higher T-bet expression. A positive correlation between the plasma viral load with the plasma Gal-9 levels in treatment-naive HIV patients and an inverse correlation between CD4 count with the frequency of CD4+Gal-9+ T cells were observed. Increased percentages of Gal-9+ T cells was evident in HIV-treated patients. Enhanced expression of Gal-9 on T cells following PMA stimulation via protein kinase C suggests persistent TCR stimulation as a potential contributing factor in Gal-9 upregulation in HIV patients. This was supported by the constant degranulation of Gal-9+ T cells. Moreover, CD44 clustering by Gal-9 may influence cytoskeleton rearrangement and coclustering of CD3, which likely impact initiation of signal transduction via TCR. Our preliminary data also confirm upregulation of Gal-9 on T cells in hepatitis B virus and HPV infections. These results demonstrate a novel role for Gal-9 and VISTA in HIV pathogenesis.

A pilot study of Coxiella seroprevalence in occupationally exposed individuals in the Peace River region of Alberta and British Columbia.

A pilot seroprevalence study was performed among asymptomatic occupationally exposed individuals in June, 2016 in the Peace River region of Alberta and British Columbia. Five of 40 subjects - 3 of 24 small ruminant producers, 1 of 14 abattoir workers, and 1 of 2 veterinarians had evidence of Coxiella exposure. More systematic surveillance and more active promotion of biosecure husbandry methods should be considered.

Étude pilote sur la séroprévalence de Coxiella chez les personnes exposées en milieu de travail dans la région de la rivière de la Paix en Alberta et en Colombie-Britannique. Une étude pilote sur la séroprévalence a été réalisée parmi les personnes asymptomatiques exposées en milieu de travail en juin 2016 dans la région de la rivière de la Paix en Alberta et en Colombie-Britannique. Cinq des 40 sujets ­ 3 de 24 producteurs de petits ruminants, 1 de 14 travailleurs d'abattoir et 1 de 2 vétérinaires, présentaient des signes d'exposition à Coxiella. Une surveillance systématique accrue et une promotion plus active de méthodes d'élevage biosécuritaires devraient être considérées.(Traduit par Isabelle Vallières).

Burden of malaria is higher among children in an internal displacement camp compared to a neighbouring village in the Democratic Republic of the Congo.

BACKGROUND: In the Democratic Republic of the Congo (DRC), violent conflict has caused the displacement of millions of people into camps where they are exposed to poor living conditions and high rates of infectious diseases. Malaria, in particular, is a major cause of mortality in children under five; however, the burden of disease in displacement camps has not previously been described. METHODS: Two cross-sectional surveys were performed. First, prevalence of Plasmodium falciparum antigenemia was measured in a random sample of 200 children living in a displacement camp and 200 children from a nearby village (control group). Second, the proportion of febrile illness attributable to malaria was measured in a study of 100 children from the displacement camp and 100 children from the control village presenting to the same health clinic with fever. All participants were tested for P. falciparum with a rapid diagnostic test and additional demographic data, clinical characteristics, and malaria risk factors were determined using a parental questionnaire. RESULTS: In the community survey, children living in the displacement camp had a higher prevalence of P. falciparum infection (17 %) than controls (7.5 %) (OR 2.6; 95 % CI 1.3-4.1; P = 0.0095). In the clinic-based survey, the proportion of febrile illness attributable to malaria was higher among children from the displacement camp (78 %) than controls (39 %) (OR 5.5; 95 % CI 3.0-10.3; P < 0.001). Household bed net ownership and use was significantly lower in the displacement camp than control village in both surveys. Statistically significant differences in household wealth, maternal education, and exposure to community violence were also found. CONCLUSIONS: Population displacement due to violent conflict appears to be a risk factor for malaria, a major cause of child mortality. Children living in displacement camps are a relatively understudied population, but have a high burden of malaria, despite control programmes focused on bed net distribution.

Prevalence and correlates of HIV and hepatitis B virus coinfection in Northern Alberta.

BACKGROUND: HIV and hepatitis B virus (HBV) share transmission routes, and coinfection is associated with higher morbidity and mortality. To date, no Canadian studies have examined HIV-HBV coinfection. OBJECTIVES: To examine the prevalence and correlates of HIV and HBV coinfections in Northern Alberta. METHODS: The present study was a retrospective database review of all HIV-infected (HIV+) individuals in Northern Alberta from 1982 to 2010 and a chart review of HBV surface antigen-positive individuals for whom charts were available (46.2%). RESULTS: Of 2844 HIV+ patients, 2579 (90.7%) had been tested for HBV surface antigen, and 143 (5.5%) of these were HBV coinfected. Coinfected males were primarily Caucasian (70.8%), and coinfected females were primarily black (56.4%) or Aboriginal (31.3%). Coinfected individuals were more likely to be male (88.1% versus 71.3%; P<0.001) and to have died (34.3% versus 17.9%; P<0.001). CONCLUSIONS: The prevalence of coinfection with HBV in HIV-infected patients in Northern Alberta is lower than reported in other developed nations. The pattern of coinfections in Northern Alberta likely follows immigration trends. Recognition and management may be improving with time; however, further research and additional strategies are required to enhance the prevention, identification and management of HBV infection in HIV-infected individuals.

HISTORIQUE: Le VIH et le virus de l'hépatite B (VHB) partagent les mêmes voies de transmission, et la co-infection s'associe à un taux plus élevé de morbidité et de mortalité. Aucune étude canadienne ne porte sur la co-infection par le VIH et le VHB. OBJECTIFS: Examiner la prévalence et les corrélats de la co-infection par le VIH et le VHB dans le nord de l'Alberta. MÉTHODOLOGIE: La présente étude était une analyse rétrospective des bases de données de toutes les personnes infectées par le VIH (VIH+) dans le nord de l'Alberta entre 1982 et 2010 et une analyse des dossiers disponibles des personnes positives à l'antigène de surface du VHB (46,2 %). RÉSULTATS: Sur les 2 844 patients VIH+, 2 579 (90,7 %) avaient subi un test de dépistage de l'antigène capsidique du VHB, et 143 (5,5 %) étaient infectés par le VHB. Les hommes co-infectés étaient surtout de race blanche (70,8 %), et les femmes co-infectées, surtout noires (56,4 %) ou autochtones (31,3 %). Les personnes co-infectées étaient plus susceptibles d'être de sexe masculin (88,1 % par rapport à 71,3 %; P<0,001) et de mourir (34,3 % par rapport à 17,9 %; P<0,001). CONCLUSIONS: La prévalence de co-infection par le VHB chez les patients du nord de l'Alberta infectés par le VIH est moins élevée que celle qui est déclarée dans d'autres pays industrialisés. Le mode de co-infection dans le nord de l'Alberta suit probablement les tendances d'immigration. Le dépistage et le traitement s'améliorent peut-être au fil du temps. Cependant, d'autres recherches et des stratégies supplémentaires s'imposent pour améliorer la prévention, le dépistage et le traitement de l'infection par le VHB chez les personnes infectées par le VIH.

Exploring the Evidence for the Paradigms of Recovery and Social Work Converging in Mental Health Service Delivery Worldwide: Reflections from an Irish Case Study.

Recovery within mental health service delivery is no longer a new consideration in the Western world. However, it is well-documented how challenging its implementation and translation to practice and reality have been in contemporary mental health systems. In conjunction with this, mental health social work is continuously being challenged and debated in relation to its role, responsibilities, and identity in service delivery. This is largely the consequence of the continued dominance of the biomedical model in relation to service delivery. Yet, if we critically reflect on the philosophy and ethos of recovery, it becomes very clear that social work should be the key profession to lead the development and improvement of recovery-orientated services across the globe. To illustrate this argument, the authors first draw on empirical research undertaken by the lead author within the Republic of Ireland on how recovery is socially constructed within mental health service delivery. The key stakeholders involved in the Irish study included professionals, service users, family members, and policy influencers, with participants taking part in semi-structured interviews. Secondly, the authors reflect on some of the findings from this Irish study, presenting an argument for not only a more significant role for social work in an Irish mental health context but also making comparisons from an international perspective. This includes exploring the role of critical social work traditions for supporting services to move beyond a philosophy of recovery that has, to date, overlooked the intersectional injustices and inequalities faced by hard-to-reach populations. Finally, the authors conclude by providing some possibilities for how the paradigms of social work and recovery can and should continue to converge towards each other, opening a space for social work to become a more dominant perspective within mental health systems worldwide.

Flawed reports can harm: the case of supervised consumption services in Alberta.

Supervised consumption services have been scaled up within Canada and internationally as an ethical imperative in the context of a public health emergency. A large body of peer-reviewed evidence demonstrates that these services prevent poisoning deaths, reduce infectious disease transmission risk behaviour, and facilitate clients' connections to other health and social services. In 2019, the Alberta government commissioned a review of the socioeconomic impacts of seven supervised consumption services in the province. The report is formatted to appear as an objective, scientifically credible evaluation of these services; however, it is fundamentally methodologically flawed, with a high risk of biases that critically undermine its authors' assessment of the scientific evidence. The report's findings have been used to justify decisions that jeopardize the health and well-being of people who use drugs both in Canada and internationally. Governments must ensure that future assessments of supervised consumption services and other public health measures to address drug poisoning deaths are scientifically sound and methodologically rigorous. Health policy must be based on the best available evidence, protect the right of structurally vulnerable populations to access healthcare, and not be contingent on favourable public opinion or prevailing political ideology.

RéSUMé: Les services de consommation supervisée ont été établis au Canada et à l'étranger en tant qu'impératif éthique dans le contexte d'une urgence de santé publique. Un grand nombre d'études rigoureuses démontrent que ces services préviennent les décès par empoisonnement, réduisent les comportements à risque de transmission de maladies infectieuses, et facilitent les liens avec d'autres services sociaux et de santé. En 2019, le gouvernement de l'Alberta a commandé un examen des impacts socioéconomiques de sept services de consommation supervisée dans la province. La présentation du rapport donne l'impression que l'évaluation de ces services est objective et scientifiquement crédible; cependant, il présente des faiblesses importantes au plan méthodologique, notamment en raison de la présence de biais qui compromet l'évaluation des preuves scientifiques. Ses conclusions ont été utilisées pour justifier des décisions qui mettent en péril la santé et le bien-être des personnes qui consomment des drogues, tant au Canada qu'à l'étranger. Les gouvernements doivent s'assurer que les futures évaluations des services de consommation supervisée et d'autres mesures de santé publique pour lutter contre les décès par empoisonnement dû aux drogues sont scientifiquement fondées. Les politiques en matière de santé doivent être basées sur les meilleures données disponibles, protéger les droits des populations structurellement vulnérables à accéder aux soins de santé, et ne pas dépendre de l'opinion publique ou d'une idéologie politique dominante.

Mobile phone-based antiretroviral adherence support in Vietnam: feasibility, patient's preference, and willingness-to-pay.

Feasibility of using mobile phone for antiretroviral treatment adherence support was assessed in a multi-site survey. Of 1,016 respondents, 84.5 % used mobile phones; 78.6 % found it effective for adherence aid, 44.8 % had privacy concerns, and 63.5 % expressed willingness-to-use the service. Willingness-to-pay was US$ 2.5/month. Text messaging (41.8 %) and direct calls by health workers (35.4 %) were preferred. Expressed preference for specific support service included direct counseling with physician (43.1 %), automated reminder for pills taking (29.1 %), regular information messages (21.3 %), and booking of clinic visits (16.5 %). These findings inform the design of adherence interventions using mobile phone in the Vietnamese setting.

Cost-effectiveness of methadone maintenance treatment for HIV-positive drug users in Vietnam.

Methadone maintenance treatment (MMT) is efficacious in reducing drug use that may improve HIV/AIDS care and treatment outcomes. This study evaluated the incremental cost-effectiveness of MMT for HIV-positive drug users from the perspective of health service providers. A sample of 370 HIV-positive drug users (age: mean ± SD: 29.5 ± 5.9 years; 95.7% male) taking MMT in multi-sites was assessed at baseline, three, six and nine months. Costs of MMT services were analyzed and converted to the year 2009. Quality-adjusted life years (QALYs) were modeled from changes in health-related quality of life of patients using the modified World Health Organization Quality of Life - Brief Version (WHOQOL-BREF). Inverse probability-of-treatment weights, constructed using propensity score of non-responses, were applied to adjust for potential confounding. Over nine months, MMT substantially improved QALYs of HIV/AIDS patients (0.076 QALY [0.066-0.084]). The increments in QALY were large and stabilized in those patients taking antiretroviral treatment and abstinent to drug use. For one QALY gained, the MMT program would cost US$3745.3, approximately 3.2 times Vietnam GDP per capita in 2009. The cost-effectiveness of MMT intervention was robust against HIV advanced status or co-morbidity, e.g., TB treatment, but it might not be cost-effective for those patients who continued to use drug. Findings of this study indicate that providing MMT for HIV-positive drug users is a cost-effective intervention in Vietnam. Integrating MMT to HIV/AIDS care and treatment services would be beneficial in injection-driven HIV epidemics.

Changes in drug use are associated with health-related quality of life improvements among methadone maintenance patients with HIV/AIDS.

PURPOSE: This longitudinal study assessed the changes in drug use patterns and health-related quality of life (HRQL) among HIV-positive drug users in the first methadone maintenance treatment (MMT) cohort in Vietnam. METHODS: A secondary analysis was conducted on 370 HIV-positive drug users (age: mean ± SD: 29.5 ± 5.9 years; 95.7% men). Modified WHOQOL-BREF, self-report, and opioid confirmatory urine tests were used to assess HRQL and drug use behaviours at baseline, 3, 6, and 9 months. Generalized estimating equations (GEE) models were constructed to adjust for intra-individual correlations. RESULTS: MMT response rate after 9 months was 89.9%. Rates of positive heroin urine tests rapidly decreased at the first trimester (18.1%) and then stabilized during the next 2 trimesters (11.8 and 14.4%). Among patients with continued drug use, frequency of use decreased from 3.4 to 0.7 time/day. Improvements in HRQL were large over the course of the study and highest in the psychological domain. Adjusting for propensity score in GEE models, ongoing heroin use during MMT resulted in large decrements in all HRQL domains. CONCLUSIONS: MMT improved the outcomes of treatment for drug users in ways that might facilitate success of antiretroviral therapy. Integrating MMT to HIV care and treatment services could be beneficial in injection-driven HIV epidemics in resource-scare settings.

All-cause and HIV-related mortality rates among HIV-infected patients after initiating highly active antiretroviral therapy: the impact of Aboriginal ethnicity and injection drug use.

BACKGROUND: Aboriginals are over-represented in Canada's HIV epidemic and are commonly infected with HIV via injection drug use (IDU); however, little is known about the impact of Aboriginal ethnicity on mortality after starting highly active antiretroviral therapy (HAART). Therefore, we compared mortality rates between Aboriginal and non-Aboriginal HIV patients and between IDU and non-IDU HIV patients after they initiated HAART. METHODS: We conducted a retrospective cohort study of antiretroviral-naïve patients starting HAART January 1999-June 2005 (baseline), followed until December 2005. We constructed two Cox proportional hazards models, one to estimate all-cause and one to estimate HIV-related mortality hazard ratios (HRs), considering sex, and baseline age, CD4 cell count, HIV RNA level, calendar year, and HAART regimen as potential confounders. RESULTS: The 548 study patients were followed for 1,889.8 person-years; 194 (35%) were Aboriginal, 255 (46%) were IDUs. We observed 55 deaths; 47% were HIV-related. In multivariable models, Aboriginals experienced higher all-cause (HR = 1.85, 95% CI = 1.05-3.26, p = 0.034) and HIV-related (HR = 3.47, 95% CI = 1.36-8.83, p = 0.009) mortality rates compared to non-Aboriginals; and, compared to patients with other exposures, IDUs experienced higher all-cause (HR = 2.45, 95% CI = 1.31-4.57, p = 0.005) but similar HIV-related (p = 0.27) mortality rates. CONCLUSIONS: Compared to non-Aboriginals, Aboriginal HIV patients suffer higher all-cause and HIV-related mortality rates after starting HAART. The strongest and most significant predictor of higher all-cause mortality was IDU. Future research should examine reasons for the observed poorer survival of Aboriginal and IDU HIV patients after initiating HAART to develop interventions to improve the prognosis for these vulnerable populations.

Pregnancy Among HIV-Serodiscordant Couples: Case Report of Vertical Transmission and Retrospective Case Series.

BACKGROUND: HIV transmission during pregnancy and breastfeeding among serodiscordant heterosexual couples represents an ongoing barrier to the elimination of vertical transmission of HIV-1 infection in Canada. OBJECTIVE: To report a case of vertical HIV transmission during breastfeeding and examine the prevalence of risk factors for HIV transmission in the pregnancy and postpartum periods among serodiscordant couples where the male partner is HIV positive and female partner HIV negative. METHODS: Case report and retrospective chart review of HIV-serodiscordant pregnant couples over an eight-year period in Edmonton, Canada. RESULTS: We report a case of maternal primary HIV infection during the postpartum period and vertical transmission to a nursing infant that went undetected until the infant presented with AIDS. We also report a series of 41 serodiscordant pregnant couples identified by our public health nurse between 2008 and 2016. Among HIV-infected male partners, 20 (49%) had a detectable viral load (VL) during their partner's pregnancy and during breastfeeding, with median peak VL 4,700 copies/mL (range 49-120,000) and 5,100 copies/mL (range 40-120,000) during pregnancy and breastfeeding, respectively. None of the female partners seroconverted during pregnancy, but three seroconverted at 1.8, 2.4, and 6.9 years after delivery. No vertical transmission occurred. CONCLUSION: Despite concerted attempts to minimize HIV transmission during pregnancy and breastfeeding in our well-resourced setting, residual transmission risk remains due to non-suppressed viral load within many HIV-serodiscordant pregnant couples.

Epidemiological and Clinical Characteristics of Alveolar Echinococcosis: An Emerging Infectious Disease in Alberta, Canada.

Human alveolar echinococcosis (AE) is a zoonotic cestode infection which is usually fatal in the absence of treatment. Treatment involves major surgery or indefinite antiparasitic therapy. The incidence is rising in Europe and Asia, with an increased risk observed in immunocompromised individuals. Previously, AE acquisition in North America was extremely rare, except for one remote Alaskan Island. Recent studies have demonstrated a new European-like strain of Echinococcus multilocularis (Em) in wildlife and in human AE in western Canada. We report the experience of all AE patients diagnosed in Alberta. Each was diagnosed by histopathology, serology, and PCR-confirmed by a reference laboratory. Seventeen cases of human AE, aged 19-78 years, nine females, were diagnosed between 2013 and 2020: all definitely or probably acquired in Alberta. Six lived in urban areas, and 14 had kept dogs. In eight, the lesions were found incidentally on abdominal imaging performed for other indications. Six were immunocompromised to varying degrees. Six were first diagnosed at surgery. All have been recommended benzimidazole therapy. One died of surgical complications. Clinicians should be aware of this diagnostic possibility in patients presenting with focal nonmalignant hepatic mass lesions. Greater urbanization of coyotes, the predominant definitive host of Em in Alberta, and growing numbers of immune suppressed individuals in the human population may lead to increasing recognition of AE in North America.

Prenatal screening and perinatal HIV transmission in Northern Alberta, 1999-2006.

OBJECTIVES: We evaluated the effectiveness of a program that includes routine opt-out prenatal HIV screening, combination antiretroviral therapy (ART), and a multidisciplinary team in preventing perinatal HIV transmission. METHODS: A retrospective analysis was performed on HIV-infected pregnant women in northern Alberta, Canada, who delivered between January 1, 1999, and February 28, 2006. RESULTS: Ninety-eight women had 113 deliveries. Forty-three percent were diagnosed with HIV infection through prenatal screening. Approximately 60% of HIV-infected pregnant women were Aboriginal, with 45% reporting alcohol use and 42% illicit drug use during pregnancy. The use of combination ART during pregnancy increased throughout the study period; 89% or more received combination ART from 2004 through 2006. Only 1 of the 111 infants (0.9%) was confirmed to be HIV infected, and that infant was born to a woman with no prenatal care. CONCLUSIONS: High rates of HIV testing using an opt-out approach, combined with efforts by a multidisciplinary team, resulted in a low rate of perinatal HIV transmission in our cohort. The added value of retesting high-risk women late in pregnancy or with rapid HIV tests at the time of delivery should be explored.

Drug-drug interaction between itraconazole and the protease inhibitor lopinavir/ritonavir.

OBJECTIVE: To report the results of therapeutic drug monitoring of lopinavir/ritonavir and itraconazole concentrations in an HIV-infected male who was treated for histoplasmosis. CASE SUMMARY: A 34-year-old HIV-infected man who had recently initiated efavirenz-based antiretroviral therapy was diagnosed with disseminated Histoplasma capsulatum infection. In the hospital, lopinavir/ritonavir 400 mg/100 mg twice daily replaced efavirenz to avoid efavirenz-itraconazole interactions. After 14 days of liposomal amphotericin B therapy, itraconazole solution was initiated at 150 mg twice daily for 3 days, followed by 200 mg daily. Prior to itraconazole initiation, lopinavir trough concentration was 7.4 mg/L. The lopinavir trough concentration 15 days later, after 14 days of itraconazole, was 6.8 mg/L. An itraconazole concentration measured 2 hours post-dose on day 15 of oral therapy was 1.9 microg/mL. After 2 weeks of liposomal amphotericin, urine Histoplasma antigen was 27.23 ng/mL; after 5 months of oral itraconazole therapy, it decreased to 5.24 ng/mL. Plasma HIV RNA decreased 4.26 log(10) in 5 months to less than 40 copies/mL. The patient has demonstrated marked clinical improvement. DISCUSSION: In this case, dosing recommendations of itraconazole 200 mg daily with lopinavir/ritonavir were appropriate. Lopinavir trough concentrations were not significantly different following the addition of itraconazole and were above the minimum target of 1 mg/L in treatment-naïve patients. The itraconazole concentration was above the recommended concentration of at least 1 microg/mL. CONCLUSIONS: The dose of itraconazole was reduced to 200 mg daily as recommended by current guidelines, and therapeutic drug monitoring of both itraconazole and lopinavir concentrations confirmed that no further dosage adjustments were necessary.