Echinococcosis in a non-endemic country - 20-years' surgical experience from a Norwegian tertiary referral Centre.

BACKGROUND: In Scandinavia, the incidence of cystic echinococcosis (CE) and alveolar echinococcosis (AE) is low and almost exclusively an imported disease following the trends of immigration. The aim of the study was to review available data on clinical management and outcome for patients treated at Oslo University Hospital, a referral centre for echinococcosis in Norway, with special emphasis on surgical treatment. METHODS: All patients admitted with echinococcosis between January 2000 and December 2020 were identified. Medical records were reviewed retrospectively concerning patient demographics, treatment strategy, surgical procedures, complications and outcomes. RESULTS: A total of 92 patients with median age 37 years (range 4-85) were identified. Sixty-eight patients (74%) were symptomatic. All patients, except for two, were immigrants to Norway and born in endemic areas. Ninety patients were diagnosed with CE and two with AE. Location of the cysts was most commonly in the liver (86%) followed by peritoneum, lungs, and spleen. All patients with active cysts were treated with albendazole. Surgical treatment was performed in 51 (56%) patients. The most common reason for abstaining from surgical treatment was that the diagnostic work-up revealed inactive cysts or interventional radiology was performed. Of the 51 patients who underwent surgery, a radical procedure was performed in 32 (64%) cases, a conservative procedure in 12 (24%), and a combination in six (12%). Clavien Dindo grade ≥3 complications occurred in 30%, and 90-day mortality was 2%. Bile leakage occurred in seven patients and was treated successfully with endoscopic retrograde cholangiopancreatography with biliary stent placement in all patients. CONCLUSION: In a low-endemic area like Norway, management of echinococcus includes medical therapy, surgery, and/or interventional radiology. Surgical intervention seems to be effective, and is associated with acceptable morbidity rates.

Transition to PCR diagnosis of cryptosporidiosis and giardiasis in the Norwegian healthcare system: could the increase in reported cases be due to higher sensitivity or a change in the testing algorithm?

Cryptosporidiosis has been a notifiable infection in Norway since 2012 and giardiasis since 1977. For both infections, there has been an increase in notified cases. We used a questionnaire to explore whether this may be associated with implementation of molecular diagnostic methods. We received responses from 14 of 16 laboratories, most of which had implemented molecular diagnostic methods for these parasites. Algorithms for testing had also been modified, and several laboratories now test more faecal samples than previously for both parasites. The increase in reported cases may reflect not only higher sensitivity of diagnostic methods, but also more sample testing.

Imported visceral leishmaniasis and immunosuppression in seven Norwegian patients.

BACKGROUND: Visceral leishmaniasis (VL) is a protozoal disease that may be aggravated by immunosuppression. In recent years, a growing number of patients with chronic diseases use biological treatment. When such immunosuppressed patients travel to endemic areas, they are facing the risk of VL. Increased incidence of leishmaniasis is reported in endemic areas like the Mediterranean basin, an area frequently visited by Norwegian tourists. This may lead to an increased number of patients, many presenting to health personnel unfamiliar with the disease, in their home countries. METHODS: We reviewed the files of seven immunosuppressed patients with VL, admitted to Oslo and Haukeland University Hospitals in Norway in the period 2009-2018. RESULTS: The patients were 41-83 (median 66) years of age; four had rheumatic disease all of whom used methotrexate; one had advanced HIV infection, one had inflammatory bowel disease and one had myelofibrosis. Leishmania infantum was confirmed in five patients by polymerase chain reaction (PCR) and sequencing. In the remaining two patients, a definite Leishmania species could not be identified. All patients had a history of recent recreational travel to Spain. Most patients underwent extensive diagnostic work-up before diagnosed with VL. All received treatment with liposomal amphotericin B and all were cured; albeit two after re-treatment due to relapse. CONCLUSIONS: Visceral leishmaniasis is a potentially life-threatening but usually treatable condition. It is endemic in Southern Europe, including popular tourist destinations such as the Mediterranean basin. It is relatively unknown to most medical practitioners in non-endemic areas and clinical vigilance is required to identify those who are infected.

Donor-derived strongyloidiasis after organ transplantation in Norway.

Strongyloides stercoralis is an intestinal helminth which in humans can cause asymptomatic chronic infection maintained for decades through its auto-infective cycle. During solid organ transplantation, recipients may unintentionally receive an organ infected with strongyloides. This is a very rare complication but may have deadly outcome if not detected. We hereby report two transplant recipients whom developed Strongyloides hyperinfection syndrome after organ transplantation from the same deceased donor. Recipient 1 was kidney transplanted and presented at day 65 post engraftment with diarrhea and subsequent septicemia and gastric retention. Larvae were detected in gastric aspirate. Recipient 2 was simultaneously kidney and pancreas transplanted and presented at day 90 post engraftment also with gastric retention and septicemia. Larvae were demonstrated on duodenal biopsy and stool sample. The clinical course was complicated with severe duodenal bleedings, gastric retention, meningitis, and prolonged hospitalization. Retrospective testing of pre-transplant donor serum was positive for Strongyloides stercoralis antibodies. As a result of disease severity and gastric retention albenazole was administered via a jejunal tube and ivermectin subcutaneously in both recipients. S stercoralis was successfully eradicated and the transplants ended up with unaffected graft function. Following these two cases, we started systematic screening of all deceased donors for serum Strongyloides IgG in October 2016. After having screened 150 utilized donors one tested positive for Strongyloides, which initiated prophylactic ivermectin treatment to organ recipients. No symptoms or disease developed. Our center will continue to screen all donors as prophylactic treatment may avert this potentially lethal complication in cases of donor-derived Strongyloides infection.

High MIP-1ß Levels in Plasma Predict Long-Term Immunological Nonresponse to Suppressive Antiretroviral Therapy in HIV Infection.

BACKGROUND: HIV-infected patients who fail to reconstitute their CD4 T-cell counts during suppressive antiretroviral therapy (ART) have increased risk of both AIDS-related and non-AIDS-related morbidity and mortality. Improved understanding of immunological nonresponse (INR) is necessary to enable earlier clinical intervention. METHODS: In a cohort of 112 HIV-infected patients starting ART, we performed a serial analysis of 32 plasma-soluble markers, assessed by multiplex cytokine and enzyme immunoassay. Samples were drawn pre-ART and during the first 3 years of treatment, with a final observation time of 8.4 years (interquartile range, 7.0-10.7 years) on ART. Long-term INR (LT-INR) was defined as failure to reach a CD4 T-cell count >350 cells per microliter. Marker stability was evaluated by parallel analysis of samples from ART-naïve and HIV-seronegative controls. RESULTS: Baseline CD4 T-cell counts predicted subsequent LT-INR (n = 15) [odds ratio, 1.10 (95% confidence interval: 1.01 to 1.19) pr. 10 cells/µL reduction in CD4 count, P = 0.030] in the cohort as a whole, but not in patients with baseline CD4 counts <200 cells per microliter (n = 78). LT-INR was best characterized by elevated plasma levels of the CC chemokine macrophage inflammatory protein 1ß (MIP-1ß), both at baseline (pre-ART) and during ART. In patients with baseline CD4 counts <200 cells per microliter, baseline MIP-1ß predicted LT-INR [odds ratio 1.23 (95% confidence interval: 1.02 to 1.47) per 10 pg/mL increase in MIP-1ß, P = 0.029]. CONCLUSIONS: Elevated pre-ART levels of MIP-1ß identified LT-INR patients who started ART at CD4 counts <200. INR was characterized by persistently high MIP-1ß during suppressive ART. Thus, MIP-1ß may be of use for early identification of LT-INR.

An exploratory trial of cyclooxygenase type 2 inhibitor in HIV-1 infection: downregulated immune activation and improved T cell-dependent vaccine responses.

Chronic HIV infection is characterized by chronic immune activation and dysfunctional T cells with elevated intracellular cyclic AMP (cAMP), which inhibits the T cell activation capability. cAMP may be induced by prostaglandin E(2) following lipopolysaccharide (LPS)-induced upregulation of cyclooxygenase type 2 (COX-2) in monocytes due to the elevated LPS levels in patients with chronic HIV infection. This hypothesis was tested using celecoxib, a COX-2 inhibitor, for 12 weeks in HIV-infected patients without antiretroviral treatment in a prospective, open, randomized exploratory trial. Thirty-one patients were randomized in the trial; 27 completed the study, including 13 patients on celecoxib. Celecoxib reduced chronic immune activation in terms of CD38 density on CD8(+) T cells (-24%; P = 0.04), IgA levels (P = 0.04), and a combined score for inflammatory markers (P < 0.05). Celecoxib further reduced the inhibitory surface receptor programmed death 1 (PD-1) on CD8(+) T cells (P = 0.01), including PD-1 on the HIV Gag-specific subset (P = 0.02), enhanced the number of CD3(+) CD4(+) CD25(+) CD127(lo/-) Treg or activated cells (P = 0.02), and improved humoral memory recall responses to a T cell-dependent vaccine (P = 0.04). HIV RNA (P = 0.06) and D dimers (P = 0.07) tended to increase in the controls, whereas interleukin-6 (IL-6) possibly decreased in the treatment arm (P = 0.10). In conclusion, celecoxib downmodulated the immune activation related to clinical progression of chronic HIV infection and improved T cell-dependent functions in vivo.

Interleukin-10-secreting T cells define a suppressive subset within the HIV-1-specific T-cell population.

Recent studies have indicated that Treg contribute to the HIV type 1 (HIV-1)-related immune pathogenesis. However, it is not clear whether T cells with suppressive properties reside within the HIV-1-specific T-cell population. Here, PBMC from HIV-1-infected individuals were stimulated with a 15-mer Gag peptide pool, and HIV-1-specific T cells were enriched by virtue of their secretion of IL-10 or IFN-gamma using immunomagnetic cell-sorting. Neither the IL-10-secreting cells nor the IFN-gamma-secreting cells expressed the Treg marker FOXP3, yet the IL-10-secreting cells potently suppressed anti-CD3/CD28-induced CD4(+) as well as CD8(+) T-cell proliferative responses. As shown by intracellular cytokine staining, IL-10- and IFN-gamma-producing T cells represent distinct subsets of the HIV-1-specific T cells. Our data collectively suggest that functionally defined HIV-1-specific T-cell subsets harbor potent immunoregulatory properties that may contribute to HIV-1-associated T-cell dysfunction.