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.

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.

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.

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.

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.

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.

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.

CD71+ Erythroid Cells Exacerbate HIV-1 Susceptibility, Mediate trans-Infection, and Harbor Infective Viral Particles.

CD71+ erythroid cells (CECs) have a wide range of immunomodulatory properties. Here, we show that CECs are expanded in the peripheral blood of HIV patients, with a positive correlation between their frequency and the plasma viral load. CECs from HIV patients and human cord blood/placenta exacerbate HIV-1 infection/replication when cocultured with CD4+ T cells, and that preexposure of CD4+ T cells to CECs enhances their permissibility to HIV infection. However, mature red blood cells (RBCs) do not enhance HIV replication when cocultured with CD4+ T cells. We also found CECs express substantial levels of the NOX2 gene and via a mitochondrial reactive oxygen species (ROS)-dependent mechanism possibly upregulate NF-κB in CD4+ T cells once cocultured, which affects the cell cycle machinery to facilitate HIV-1 replication. The complement receptor-1 (CD35) and the Duffy antigen receptor for chemokines (DARC) as potential HIV target molecules are expressed significantly higher on CECs compared to mature red blood cells. Blocking CD35 or DARC substantially abolishes HIV-1 transmission by RBCs to uninfected CD4+ T cells but not by CECs. In contrast, we observed CECs bind to HIV-1 via CD235a and subsequently transfer the virus to uninfected CD4+ T cells, which can be partially blocked by the anti-CD235a antibody. More importantly, we found that CECs from HIV-infected individuals in the presence of antiretroviral therapy harbor infective viral particles, which mediate HIV-1 trans-infection of CD4+ T cells. Therefore, our findings provide a novel insight into the role of CECs in HIV pathogenesis as potential contributing cells in viral persistence and transmission.IMPORTANCE Immature red blood cells (erythroid precursors or CD71+ erythroid cells) have a wide range of immunomodulatory properties. In this study, we found that these erythroid precursors are abundant in the human cord blood/placental tissues, in the blood of HIV-infected and anemic individuals. We observed that these cells exacerbate HIV-1 replication/infection in target cells and even make HIV target cells more permissible to HIV infection. In addition, we found that HIV gets a free ride by binding on the surface of these cells and thus can travel to different parts of the body. In agreement, we noticed a positive correlation between the plasma viral load and the frequency of these cells in HIV patients. More importantly, we observed that infective HIV particles reside inside these erythroid precursors but not mature red blood cells. Therefore, these cells by harboring HIV can play an important role in HIV pathogenesis.

Galectin-9 Expression Defines a Subpopulation of NK Cells with Impaired Cytotoxic Effector Molecules but Enhanced IFN-γ Production, Dichotomous to TIGIT, in HIV-1 Infection.

NK cell functions are tightly regulated by the balance between the inhibitory and stimulatory surface receptors. We investigated the surface expression of galectin-9 (Gal-9) and its function in NK cells from HIV-infected individuals on antiretroviral therapy, long-term nonprogressors, and progressors compared with healthy controls. We also measured the expression of TIGIT and TIM-3 on different NK cell subpopulations and compared their functionality to Gal-9 + NK cells. Our data demonstrated significant upregulation of Gal-9 on NK cells in HIV-infected groups versus healthy controls. Gal-9 expression was associated with impaired expression of cytotoxic effector molecules granzyme B, perforin, and granulysin. In contrast, Gal-9 expression significantly enhanced IFN-γ expression in NK cells of HIV-1-infected individuals. We also found an expansion of TIGIT + NK cells in HIV-infected individuals; however, dichotomous to Gal-9 + NK cells, TIGIT + NK cells expressed significantly higher amounts of cytotoxic molecules but lower IFN-γ. Moreover, lower expression of cytotoxic effector molecules in Gal-9+ NK cells was associated with higher CD107a expression, which suggests indiscriminate degranulation. Importantly, a positive correlation between the plasma viral load and Gal-9+ NK cells was observed in progressors. Finally, we found that a cytokine mixture (IL-12, IL-15, and IL-18) can improve effector functions of Gal-9+ NK cells in HIV-infected individuals, although, such an effect was observed for Gal-9- NK cells, as well. Overall, our data highlight the important role of Gal-9 in dysfunctional NK cells and, more importantly, a dichotomy for the role of Gal-9 versus TIGIT and suggest a potential new avenue for the development of therapeutic approaches.

An atypical case of Whipple's disease presenting as fever of unknown origin: A brief review.

A 59-year-old woman with epilepsy was admitted to hospital with a 6-year history of fever of unknown origin (FUO). Computed tomography (CT) showed extensive low-attenuation mesenteric and retroperitoneal lymphadenopathy. Investigations for malignancy and infection were negative, including two separate excisional biopsies of lymph nodes. An ascending aortic aneurysm was seen on CT, and a diagnosis of large vessel vasculitis (LVV) was considered. A trial of prednisone for presumed LVV was initiated and then discontinued when positron emission tomography (PET) failed to show vasculitis. Repeat core biopsy of a mesenteric lymph node revealed non-necrotizing granulomatous inflammation and histiocytes with periodic acid-Schiff (PAS)-positive intracellular material. Electron microscopy and polymerase chain reaction (PCR) of the tissue confirmed Tropheryma whipplei. She was treated with ceftriaxone for 2 weeks, followed by long-term combination doxycycline and hydroxychloroquine. The patient's seizure control improved on therapy, raising the suspicion that the seizure disorder was due to Whipple's disease.

Résumé : Une femme de 59 ans atteinte d'épilepsie a été hospitalisée parce qu'elle faisait de la fièvre d'origine inconnue depuis six ans. La tomodensitométrie a révélé une lymphadénopathie mésentérique et rétropéritonéale étendue, à faible atténuation. Les explorations de tumeurs et d'infections ont été négatives, y compris deux biopsies-exérèses distinctes des ganglions lymphatiques. Les chercheurs ont observé un anévrisme aortique ascendant à la tomodensitométrie et ont envisagé un diagnostic de vasculite de gros vaisseaux (VGV). Ils ont amorcé un essai de prednisone pour traiter la VGV présumée, puis ont arrêté le traitement lorsque la tomographie par émission de positrons ne l'a pas confirmée. La reprise de la microbiopsie d'un ganglion lymphatique mésentérique a démontré une inflammation granulomateuse non nécrosante et des histiocytes positifs à du matériel intracellulaire par coloration PAS périodique. La microscopie par électrons et l'amplification en chaîne de la polymérase (PCR) des tissus a confirmé la personne d'un Tropheryma whipplei. La patiente a reçu un traitement de deux semaines à la ceftriaxone, suivi d'une association de doxycycline et d'hydroxychloroquine à long terme. Le contrôle de ses convulsions s'est amélioré grâce à la thérapie, laissant soupçonner que son trouble convulsif serait causé par la maladie de Whipple.

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.

A Step toward Tuberculosis Elimination in a Low-Incidence Country: Successful Diagnosis and Treatment of Latent Tuberculosis Infection in a Refugee Clinic.

Objectives. Approximately 65 percent of tuberculosis (TB) cases in Canada each year occur from reactivation in foreign-born individuals. Refugees are at high risk after immigration. Routine screening of this population for latent TB infection (LTBI) is generally considered infeasible. We evaluated the outcome of LTBI screening and treatment amongst refugees. Methods. Government-sponsored refugees in Edmonton are seen at the New Canadians' Clinic and screened for TB and LTBI. We reviewed records of patients between 2009 and 2011. Completeness of initial assessment, diagnosis of latent infection, and completion of LTBI treatment were evaluated. Treatment for LTBI was offered when patients had a positive Tuberculin Skin Test (TST) and risk factors for progression to TB. An Interferon-Gamma Release Assay (IGRA) was performed on all other TST positives; treatment is only offered if it was positive. Results. 949 refugees were evaluated. 746 TSTs were read, with 265 positive individuals. IGRA testing was performed in 203 TST positive individuals without other TB risk factors; 110 were positive. LTBI treatment was offered to 147 of 151 eligible patients, 141 accepted, and 103 completed a treatment course. Conclusion. We observed high proportions of patient retention, completion of investigations, and treatment. This care model promises to be a component of effective TB prevention in this high-risk population.

Delayed Hemolysis After Parenteral Artesunate Therapy for Severe Malaria in Two Returning Canadian Travelers.

Delayed hemolysis after parenteral artesunate has been described in Europe and Asia, but until recently had not been reported in patients receiving the artesunate product used in the United States and Canada. We report two cases of severe delayed hemolysis after the treatment with intravenous artesunate in Canada.