Abstract Objectives Antimicrobial resistance of Mycoplasma genitalium (MG) is a growing concern worldwide. Because reliable data on the burden of resistant MG in Belgium are missing, an additional prospective surveillance program was implemented in 2022 to estimate the real burden of resistant MG in Belgium. Methods Belgian laboratories (n=21) provided frozen remnants of MG positive samples to the National Reference Centre of Sexually Transmitted Infections from July to November 2022. The presence of macrolide and fluoroquinolones resistance associated mutations (RAMs) was assessed using Sanger sequencing of the 23SrRNA and parC gene. Differences in resistance patterns were correlated with surveillance methodology, socio-demographic and behavioral variables via Fisher’s exact test and logistic regression analysis. Results Sequencing for both macrolide and fluoroquinolone RAMs was successful for 232/244 MG positive samples. Over half of the samples were resistant to macrolides (55.2%). All MG in samples from men who have sex with men (MSM) (24/24) were resistant to macrolides. The presence of fluoroquinolone RAMs was estimated to be 26% and did not differ with socio-demographic and sexual behaviour characteristics. Conclusions Given the considerable cost of macrolide resistance testing, our data suggest that the use of macrolide resistance testing in MSM does not seem justified in Belgium. However, the lower prevalence of macrolide resistance in other population groups, combined with further emergence of fluoroquinolone resistance provides evidence for macrolide resistance testing in these groups. Continued surveillance of resistance in MG in all groups will be crucial to guide national testing- and treatment strategies.
Abstract Objectives The aim of this retrospective study was to collect epidemiological, clinical, laboratory, imaging, management, and follow-up data on cases of alveolar echinococcosis (AE) diagnosed and/or followed up within the Namur Hospital Network (NHN) in order to gather information on the challenges, pitfalls, and overall experience in the diagnosis and treatment of AE. Methods EchiNam was a multicenter retrospective study. Patients diagnosed and/or treated for probable or confirmed AE in the NHN between 2002 and 2023 were included in the study. Patient selection was based on diagnosis codes, laboratory results, and albendazole (ABZ) dispensing. Results A total of 22 AE cases were retrieved, of which four were classified as probable and 18 as confirmed cases. Nine patients were either asymptomatic or had symptoms attributed to another disease. Clinical examination yielded pathologic findings in 10 patients. The median duration from the first AE-suggestive laboratory abnormalities to diagnosis was 176 days, and the median duration from the first AE-related imaging abnormalities to diagnosis was 133 days. Overall, 12 patients underwent surgical resection, with only four achieving complete lesion resection. Nine patients experienced ABZ-related adverse effects, with temporary ABZ discontinuation in five. Conclusion Due to various factors such as a long incubation period and a lack of awareness among Belgian physicians, AE is often diagnosed at advanced disease stages. Treatment then becomes more complex or even suboptimal, resulting in prolonged therapy, higher risk of adverse effects, significantly impaired quality of life, poor prognosis, and higher mortality rates. Measures should be taken to achieve early diagnosis in endemic areas.
Mouse islets were used to study the effects of inhibitors of cyclooxygenase and lipoxygenase pathways on insulin release, ionic fluxes, and β-cell membrane potential. The cyclooxygenase inhibitors, Na-salicylate and Na-acetylsalicylate, potentiated glucose-induced insulin release, despite a decrease in Ca influx evidenced by inhibition of the Ca-dependent electrical activity in β-cells and 45Ca efflux from islets perifused with a medium containing Ca. This paradox can probably be explained by a mobilization of intracellular Ca (acceleration of 45Ca efflux in the absence of Ca) with subsequent activation of K+ channels (acceleration of 86Rb efflux) and repolarization of the membrane. These effects of salicylate could not be ascribed to a change in intracellular pH because they were not mimicked by 2-Cl-benzoate, which has a similar pK as salicylate but increased insulin release by stimulating Ca influx in β-cells. Among the other cyclooxygenase inhibitors tested, indomethacin caused a slight potentiation of insulin release accompanied by marginal increases in 45Ca efflux and electrical activity, whereas flurbiprofen and ibuprofen were ineffective. Among the lipoxygenase inhibitors, compound BW 755c reversibly decreased glucose-induced insulin release by inhibiting Ca influx in β-cells, but nordihydroguaiaretic acid had no effect. Inhibitors of arachidonic acid metabolism have effects on ionic fluxes and β-cell membrane potential, which may explain some of the changes in insulin release they produce.
Background Antimicrobial resistance (AMR) of Mycoplasma genitalium (MG) is a growing concern worldwide and surveillance is needed. In Belgium, samples are sent to the National Reference Centre of Sexually Transmitted Infections (NRC-STI) on a voluntary basis and representative or robust national AMR data are lacking. Aim We aimed to estimate the occurrence of resistant MG in Belgium. Methods Between July and November 2022, frozen remnants of MG-positive samples from 21 Belgian laboratories were analysed at the NRC-STI. Macrolide and fluoroquinolone resistance-associated mutations (RAMs) were assessed using Sanger sequencing of the 23SrRNA and parC gene. Differences in resistance patterns were correlated with surveillance methodology, socio-demographic and behavioural variables via Fisher’s exact test and logistic regression analysis. Results Of the 244 MG-positive samples received, 232 could be sequenced for macrolide and fluoroquinolone RAMs. Over half of the sequenced samples (55.2%) were resistant to macrolides. All sequenced samples from men who have sex with men (MSM) (24/24) were macrolide-resistant. Fluoroquinolone RAMs were found in 25.9% of the samples and occurrence did not differ between socio-demographic and sexual behaviour characteristics. Conclusion Although limited in sample size, our data suggest no additional benefit of testing MG retrieved from MSM for macrolide resistance in Belgium, when making treatment decisions. The lower occurrence of macrolide resistance in other population groups, combined with emergence of fluoroquinolone RAMs support macrolide-resistance testing in these groups. Continued surveillance of resistance in MG in different population groups will be crucial to confirm our findings and to guide national testing and treatment strategies.
From early 2020, a high demand for SARS-CoV-2 tests was driven by several testing indications, including asymptomatic cases, resulting in the massive roll-out of PCR assays to combat the pandemic. Considering the dynamic of viral shedding during the course of infection, the demand to report cycle threshold (Ct) values rapidly emerged. As Ct values can be affected by a number of factors, we considered that harmonization of semi-quantitative PCR results across laboratories would avoid potential divergent interpretations, particularly in the absence of clinical or serological information. A proposal to harmonize reporting of test results was drafted by the National Reference Centre (NRC) UZ/KU Leuven, distinguishing four categories of positivity based on RNA copies/mL. Pre-quantified control material was shipped to 124 laboratories with instructions to setup a standard curve to define thresholds per assay. For each assay, the mean Ct value and corresponding standard deviation was calculated per target gene, for the three concentrations (107, 105 and 103 copies/mL) that determine the classification. The results of 17 assays are summarized. This harmonization effort allowed to ensure that all Belgian laboratories would report positive PCR results in the same semi-quantitative manner to clinicians and to the national database which feeds contact tracing interventions.
We report the case of a 22-month-old African boy with cutaneous lesions as the predominant feature of disseminated cryptococcosis (positive blood and cerebrospinal fluid cultures) and as the presenting manifestation of severe vertically acquired HIV infection (CDC C3 category). To our knowledge these cutaneous lesions have never been reported as the initial manifestation of AIDS in children. Disseminated cryptococcosis is an uncommon complication in HIV-infected children. Its prevalence has recently been estimated at ∼1% compared with a prevalence of 6 to 10% in the adult AIDS population. 1 In the same study the mean age of cryptococcosis in vertically infected children was 9.7 years, and the median CD4 cell count at the time of diagnosis was 54/μl. The most common manifestation of disseminated cryptococcosis is meningoencephalitis; the skin may be secondarily involved. We report the case of a 22-month-old African boy with disseminated cryptococcosis. The clinical presentation was predominantly cutaneous and was associated with severe vertically acquired HIV infection (CDC C3 category). We believe that cutaneous cryptococcosis as the presenting manifestation of severe HIV infection has not been previously reported in children. Case report. FK, a 22-month-old African boy living in Burkina Faso, was referred to our department in Yvoir, Belgium, for evaluation of cutaneous nodules associated with poor feeding, failure to thrive and irritability. He was the first child of nonconsanguineous parents, born at term after a normal pregnancy. His birth weight was 3.25 kg and his height was 53 cm. There was no known history of HIV infection in the parents. His medical history was unremarkable until the age of 19 months when he weighed 12 kg (50th percentile). From then he began to feed poorly with failure to thrive. No investigation was undertaken. At 21 months painful ulcerated nodules and papules appeared on his face and limbs. On clinical examination at admission he was febrile (rectal temperature, 38.5°C), emaciated with a weight of 8.6 kg (below the 3rd percentile) for a height of 84 cm (10th percentile) and a cranial circumference of 48 cm (10th percentile). Numerous excoriated, umbilicated, painful nodules were visible on his face and limbs associated with generalized lymphadenopathy and firm hepatosplenomegaly (Fig. 1). Neurologic examination revealed severe irritability and neck stiffness.Fig. 1: Excoriated, umbilicated, painful nodules on the leg.On admission the following investigations were performed: erythrocyte sedimentation rate 121 mm/h; C-reactive protein 2 mg/dl (normal, <0.5 mg/dl); white blood cell count of 2.9 × 109/l with 68% polymorphonuclear cells, 27% lymphocytes; hemoglobin 5.5 g/l; and platelet count 62 × 109/l. The T cell subsets analyses showed a selective defect in helper cells (OKT4, 4 cells/μl) with a helper:suppressor ratio of 0.05. The cerebrospinal fluid (CSF) contained 2 cells/μl, a glucose of 12 mg/dl (0.66 mmol/l; serum glucose, 91 mg/dl or 5 mmol/l) and a protein of 0.5 mg/l (normal, <0.4 mg/l). Direct examination of CSF disclosed encapsulated yeasts. Cryptococcal capsular polysaccharide antigens were detected in CSF and serum. Cultures from CSF and blood yielded a Cryptococcus neoformans var. neoformans (serotype D) which was resistant to flucytosine. The skin biopsy specimen showed numerous small yeast-like organisms. Severe cortical atrophy and diffuse white matter abnormalities were observed on a cerebral computerized tomography scan. The diagnosis of HIV infection was confirmed by positive HIV antibodies (enzyme-linked immunosorbent assay) on two separate serum samples and by a positive HIV-1 p24 antigen. The viral burden performed with a quantitative PCR assay (Amplicor HIV-1 Monitor) was 161 000 copies/ml. His mother had positive HIV antibodies, which retrospectively supported the diagnosis of HIV-vertically acquired infection. The boy was treated with amphotericin B (1 mg/kg/day) in combination with fluconazole (12 mg/kg/day). With this regimen cutaneous lesions and neurologic symptoms gradually improved, and there was a weight gain of 1 kg. After 4 weeks of treatment serum and CSF cryptococcal antigens were still positive (CSF titer, 1/160) and CSF culture grew for C. neoformans which indicated treatment failure. Five weeks later he had to return to his country without antiretroviral therapy. His outcome is unknown. Discussion. Disseminated cryptococcosis is defined as recovery of C. neoformans from blood, sterile body fluids or tissues other than pulmonary tissue. The main pathogen is C. neoformans var. neoformans (serotypes A and D) which is ubiquitous in soil, grasses and pigeon feces. C. neoformans var. gattii (serotypes B and C) is more common in tropical and subtropical areas. Invasive infection by C. neoformans is a major complication in adults with advanced HIV infection. Cryptococcal meningoencephalitis has been reported to occur in 6 to 10% of the adult AIDS population. 2 In contrast available data suggest that disseminated cryptococcosis is very uncommon in HIV-infected children, with a reported frequency between 0.6 and 1.4%. 1, 3, 4 Disseminated cryptococcosis was the first sign of AIDS disease in 27% (8 of 30 patients) to 69% (9 of 13 patients) of the children in the two largest reports. 1, 4 The interval between HIV infection and development of cryptococcosis is unknown in most cases associated with transfusion but is estimated to be 9.7 years in children vertically infected. 1 This finding supports the concept that cryptococcal infection occurs late in the disease process of children infected with HIV, which may reflect either the lower exposure to sources of C. neoformans in children or the need for a minimal level of exposure to be reached before the disease appears. The theory of low exposure to C. neoformans is confirmed by seroepidemiologic studies showing a low seroprevalence against this yeast in healthy children in contrast to adults. 5 Skin lesions usually represent metastases to the skin of a disseminated infection and are difficult to diagnose clinically because of their polymorphism. These lesions were the predominant feature of disseminated cryptococcosis in our patient and to our knowledge have never been reported as the initial manifestation of AIDS in children and only rarely in adult patients. 6, 7
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