Objectives: The aim of this study was to develop a pharmacokinetic (PK) interaction model of intravenous (i.v.) and oral clindamycin when combined with rifampicin, and to determine whether appropriate clindamycin concentrations could be achieved for different doses and administration routes (oral, intermittent and continuous infusion) of clindamycin. Methods: Five hundred and eighteen plasma samples were prospectively obtained from 124 patients treated for bone and joint infections. Population pharmacokinetic analysis was performed using Monolix software. Monte Carlo simulations were run to determine the probability of achieving a minimal clindamycin plasma concentration equal to at least twice the MIC, or an unbound area under the curve/MIC >= 60. Results: A linear one-compartment model with first-order absorption and elimination was developed. Concomitant administration of rifampicin increased clindamycin clearance by an average factor of 3, whereas the impact on clindamycin bioavailability was dose dependent, with decreases from 56 to 11 and 4% for rifampicin doses of 600 mg and 900 mg q12 h, respectively. When administered simultaneously with rifampicin, satisfactory clindamycin concentrations could not be obtained when given orally. i.v. administration of a daily 3600 mg dose would be convenient for more than 80% of the patients, but doses of at least 4800 mg/d would be needed for a MIC equal to the 0.25 mg/L European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoint for Staphylococcus aureus. Intermittent i.v. administration every 6 hours is preferable to q8h regimens for the C-min/MIC criteria, but still performed poorly compared with continuous infusion. Discussion: : This model satisfyingly described the differential effect of rifampicin on the bioavailability and clearance of clindamycin. As previously described, this combination must not be taken orally. However, administration of clindamycin doses of at least 3600 mg/d by intermittent or, preferably, continuous infusion, can balance the impact of rifampicin. (c) 2025 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
Purpose: Neurological symptoms often prominent in post-acute sequelae of COVID-19 (PASC) necessitate deeper understanding. Our objective was to investigate brain metabolism in PASC and examine correlations with neurological symptoms during both the acute and chronic stages. Methods: Eighty-seven adults experiencing PASC with neurocognitive symptoms were recruited in the PERSICOR prospective study and examined using brain [F-18]FDG PET/CT. Comprehensive clinical variables including neurocognitive symptoms were evaluated. PET images were compared voxel-wise with SPM12 software ( P < 0.05, false discovery rate corrected) and volume-of-interest basis (BrainVisa software) with those of 55 healthy controls recruited before COVID-19 pandemic. We also investigated differences in brain metabolism according to the time interval after acute COVID-19. The correlation between brain metabolism and neurocognitive symptoms was assessed. Results: Frequently reported neurological symptoms included concentration difficulties (79%) and immediate/working memory impairments (66%). Significant hypometabolism was identified in regions previously identified in PASC: left fusiform gyrus (33% of patients), amygdala (23% on left, 28% on right), parahippocampal area (25% left, 24% right), and vermis (22%). The most substantial metabolism decreases were observed in the pons (5.5% decrease in the whole patient group vs controls) and right amygdala (-4.2%). Concentration and memory impairments correlated with decreased metabolism in prefrontal and mesial/inferior temporal areas, respectively ( P < 0.01 for both). A shorter interval between PET imaging and the acute phase of COVID-19 correlated with reduced glucose metabolism in the brainstem, thalamus, mesiotemporal lobe, frontobasal cortex, and olfactory bulb ( P < 10(-3)). Conclusions: This study underscores the links between neurological symptoms and cerebral hypometabolism in specific regions in PASC. These findings illuminate the complex neuropathophysiological mechanisms of PASC and pave the way for potential therapeutic interventions.
The International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC) is a multinational consortium of longitudinal cohorts of people with HIV who are at risk of hepatitis C virus (HCV) infection or infected with HCV.InCHEHC has been specifically designed to assess progress towards HCV elimination as a public health threat among people with HIV.• The first data merge includes 104 740 participants from 11 cohorts in Australia (n ¼ 22 033), Canada (n ¼ 2070), France (n ¼ 18 387), The Netherlands (n ¼ 24 785), Spain (n ¼ 16 725) and Switzerland (n ¼ 20 740), with data collected between 1987 and 2021.Participants include 86 132 males (81.4%), 19 514 females (18.4%) and 191 with unknown sex at birth (0.2%); 725 (1.0%) were known to be transgender across eight cohorts collecting data on this variable.At enrolment, the median age was 38 years (interquartile range: 30-46).Of the total 104 740 participants, 12 784 (12%) had an HCV antibody or RNA positive test at or up to 1 year prior to individual cohort enrolment; 32 360 (31%) did not have an HCV RNA or antibody test recorded at that time.• Clinical data are collected on all participants and behavioural and mortality data on a subset of them.Clinical data include HIV-related markers, HCV testing and treatment, liver health-related markers and sexually transmitted and blood-borne virus co-infections.Behavioural data include sexual and injecting risk behaviours and alcohol and drug use.Mortality data are collected using the International Classification of Diseases 9th or 10th revision (ICD-9/10) or Coding Causes of Death in HIV (CoDE) classification.
Background: Among people living with HIV and hepatitis C virus (HCV), people who inject drugs (PWID) have historically experienced higher mortality rates. Direct-acting antivirals (DAA), which have led to a 90 % HCV cure rate independently of HIV co-infection, have improved mortality rates. However, DAA era mortality trends among PWID with HIV/HCV remain unknown. Using data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC), we compared pre/post-DAA availability mortality changes in three groups: PWID, men who have sex with men (MSM), and all other participants. Methods: We included InCHEHC participants with HIV/HCV followed between 2010 and 2019 in Canada, France, the Netherlands, Spain, and Switzerland. All-cause mortality hazard was compared in the three groups, using Cox proportional hazards regression models adjusted for sex, age, advanced fibrosis/cirrhosis, and pre/post DAA availability. Results: Of the 11,029 participants, 76 % were men, 46 % were PWID, baseline median age was 46 years (interquartile range [IQR] = 40;51), and median CD4 T-cell count was 490 cells/mm3 (IQR = 327;689). Over the study period (median follow-up = 7.2 years (IQR = 3.7;10.0)), 6143 (56 %) participants received HCV treatment, 4880 (44 %) were cured, and 1322 participants died (mortality rate = 1.81/100 person-years (PY) [95 % confidence interval (CI)=1.72-1.91]). Overall, PWID had higher mortality rates than MSM (2.5/100 PY [95 % CI = 2.3-2.6] vs. 0.8/100 PY [95 % CI = 0.7-0.9], respectively). Unlike women with other transmission modes, those who injected drugs had a higher mortality hazard than men who did not inject drugs and men who were not MSM (adjusted Hazard-Ratio (aHR) [95 % CI] = 1.3[1.0-1.6]). Post-DAA availability, mortality decreased among MSM in the Netherlands, Spain, and Switzerland and increased among PWID in Canada (aHR [95 % CI] = 1.73 [1.15-2.61]). Conclusion: Post-DAA availability, all-cause mortality did not decrease in PWID. Determinants of cause-specific deaths (drug-related, HIV-related, or HCV-related) need to be identified to explain persistently high mortality among PWID in the DAA era.
Objectives: To report ophthalmological and microvascular findings in patients with post-acute COVID-19. Methods: In this prospective, monocentric cohort study, we included patients with post-acute COVID-19 who presented with ophthalmological symptoms. All patients underwent indocyanine green angiography (ICGA), OCT, OCT-angiography, adaptive optics, and GlycoCheck assessments. Results: We included 44 patients, predominantly female (81.8%), with a mean age of 47.5 ± 11.5 years. Key ICGA findings revealed hyperreflective dots in 32 eyes (36.4%) and hemangioma-like lesions in 7 eyes (8.0%). Capillary non-perfusion in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) was observed in 42 eyes (47.7%) and 21 eyes (23.9%), respectively. Eyes with hyperreflective dots exhibited a lower perfused boundary region (PBR), while those with superficial punctate keratitis showed a higher PBR (p = 0.02 and p = 0.002, respectively). Eyes with capillary non-perfusion in the SCP displayed lower capillary densities (CD4, CD5, and CD4-6; p = 0.001, 0.03, and 0.03, respectively), and eyes with non-perfusion in the DCP had lower CD4 (p = 0.03). A negative correlation was identified between capillary density and the wall-to-lumen ratio. Conclusions: Patients with post-acute COVID-19 demonstrate both retinal and choroidal vascular anomalies. Ocular pathology was associated with reduced capillary density. These injuries appear to stem more from microvascular disruptions than from persistent glycocalyx abnormalities.
Vaccine prevention strategies play a crucial role in the management of people living with HIV (PLWH). The aim of this study was to assess vaccination coverage and identify barriers to vaccine uptake in PLWH in the Paris region. A cross-sectional survey was conducted in PLWH in 16 hospitals in the Paris region. The vaccination status, characteristics, opinions, and behaviors of participants were collected using a face-to-face questionnaire and from medical records. A total of 338 PLWH were included (response rate 99.7 %). The median age of participants was 51 years (IQR: 41 -58). Vaccination coverage was 77.3 % for hepatitis B (95 % CI: 72.3 -81.8 %), 62.7 % for hepatitis A (57.3 -67.9 %), 61.2 % for pneumococcal vaccines (55.8 -66.5 %), 56.5 % for diphtheria/tetanus/poliomyelitis (DTP) (51.0 -61.9 %), 44.7 % for seasonal influenza (39.3 -50.1 %), 31.4 % for measles/mumps/rubella (26.4 -36.6 %) and 38.5 % for meningococcal vaccine (13.9 -68.4 %). The main reason for vaccine reluctance was related to the lack of vaccination proposals/reminders. The overall willingness to get vaccinated was 71.0 % (65.9 -75.8 %). In the multivariable analysis, several factors were associated with a higher vaccine uptake; for DTP vaccine: higher education level, having vaccination records, being registered with a general practitioner; for seasonal influenza vaccine: age > 60 years, higher education level, being employed. The overall vaccination coverage was suboptimal. Development of strategies reducing missed opportunity to offer vaccines is needed.
Purpose Neurological symptoms often prominent in post-acute sequelae of COVID-19 (PASC) necessitate deeper understanding. Our objective was to investigate brain metabolism in PASC and examine correlations with neurological symptoms during both the acute and chronic stages. Methods Eighty-seven adults experiencing PASC with neurocognitive symptoms were recruited in the PERSICOR prospective study and examined using brain [18F]FDG PET/CT. Comprehensive clinical variables including neurocognitive symptoms were evaluated. PET images were compared voxel-wise with SPM12 software (P < 0.05, false discovery rate corrected) and volume-of-interest basis (BrainVisa software) with those of 55 healthy controls recruited before COVID-19 pandemic. We also investigated differences in brain metabolism according to the time interval after acute COVID-19. The correlation between brain metabolism and neurocognitive symptoms was assessed. Results Frequently reported neurological symptoms included concentration difficulties (79%) and immediate/working memory impairments (66%). Significant hypometabolism was identified in regions previously identified in PASC: left fusiform gyrus (33% of patients), amygdala (23% on left, 28% on right), parahippocampal area (25% left, 24% right), and vermis (22%). The most substantial metabolism decreases were observed in the pons (5.5% decrease in the whole patient group vs controls) and right amygdala (−4.2%). Concentration and memory impairments correlated with decreased metabolism in prefrontal and mesial/inferior temporal areas, respectively (P < 0.01 for both). A shorter interval between PET imaging and the acute phase of COVID-19 correlated with reduced glucose metabolism in the brainstem, thalamus, mesiotemporal lobe, frontobasal cortex, and olfactory bulb (P < 10−3). Conclusions This study underscores the links between neurological symptoms and cerebral hypometabolism in specific regions in PASC. These findings illuminate the complex neuropathophysiological mechanisms of PASC and pave the way for potential therapeutic interventions.
Background: Among all studies describing COVID-19 clinical features during the first wave of the pandemic, only a few retrospective studies have assessed the correlation between olfac-tory dysfunction (OD) and the evolution of disease severity. The main aim was to assess whether OD is a predictive factor of COVID-19 severity based on the patient’s medical management (outpa-tient care, standard hospital admission, and ICU admission). Methods: A national, prospective, mul-ticenter cohort study was conducted in 20 public hospitals and a public center for COVID-19 screen-ing. During the first wave of the pandemic, from 6 April to 11 May 2020, all patients tested positive for COVID-19 confirmed by RT-PCR underwent two follow-up ENT consultations within 10 days of symptom onset. The main outcome measures were the evolution of medical management (out-patient care, standard hospital admission, and ICU admission) at diagnosis and along the clinical course of COVID-19 disease. Results: Among 481 patients included, the prevalence of OD was 60.7%, and it affected mostly female patients (74.3%) under 65 years old (92.5%), with fewer comor-bidities than patients with normal olfactory function. Here, 99.3% (290/292) of patients with OD presented with non-severe COVID-19 disease. Patients reporting OD were significantly less hospi-talized than the ones managed as outpatients, in either a standard medical unit or an ICU. Conclu-sions: As regards the clinical course of COVID-19 disease, OD could predict a decreased risk of hospitalization during the first wave of the pandemic.
OBJECTIVES:This study examines long COVID symptoms course over 12 months, their impact on daily life, and associated factors for symptom relief.METHODS:A prospective cohort study included 231 participants with long COVID at 12-month follow-up. Data on characteristics, symptom course, and remission were collected using a questionnaire and a remission scale. Poisson regression models were used to estimate the prevalence rate ratio (PRR) and 95% confidence intervals (CIs) for factors associated with symptom improvement.RESULTS:Of the 231 participants, 63.2% developed SARS-CoV-2 antibodies before COVID-19 vaccination. At 12 months, only 8.7% (95% CI: 5.4-13.1%) reported complete remission, while 28.6% noted significant improvement. Most symptoms remained prevalent: asthenia (83.1%), neurocognitive/neurological (93.9%), cardiothoracic (77.9%), Musculoskeletal (78.8%). During long COVID, 62.2% stopped working, and only 32.5% resumed full-time professional activities. Presence of SARS-CoV-2 antibodies before vaccination increased the probability of improvement (aPRR: 1.60, P = 0.028), while ageusia at initial long COVID phase decreased the probability (aPRR: 0.38, P = 0.007).CONCLUSIONS:Long-COVID symptoms persisted in the majority of participants after 12 months, with significant impacts on daily life and work. SARS-CoV-2 antibodies were associated with better prognosis, while persistent ageusia indicated a lower probability of improvement. These findings highlight the need for ongoing support and care for individuals with long COVID.
INTRODUCTION:HIV replication leads to a change in lymphocyte phenotypes that impairs immune protection against opportunistic infections. We examined current HIV replication as an independent risk factor for tuberculosis (TB). METHODS:We included people living with HIV from 25 European cohorts 1983-2015. Individuals <16 years or with previous TB were excluded. Person-time was calculated from enrolment (baseline) to the date of TB diagnosis or last follow-up information. We used adjusted Poisson regression and general additive regression models. RESULTS:We included 272,548 people with a median follow-up of 5.9 years (interquartile range [IQR] 2.3-10.9). At baseline, the median CD4 cell count was 355 cells/μL (IQR 193-540) and the median HIV-RNA level 22,000 copies/mL (IQR 1,300-103,000). During 1,923,441 person-years of follow-up, 5,956 (2.2%) people developed TB. Overall, TB incidence was 3.1 per 1,000 person-years (95% confidence interval [CI] 3.02-3.18) and was four times higher in patients with HIV-RNA levels of 10,000 compared with levels <400 copies/mL in any CD4 stratum. CD4 and HIV-RNA time-updated analyses showed that the association between HIV-RNA and TB incidence was independent of CD4. The TB incidence rate ratio for people born in TB-endemic countries compared with those born in Europe was 1.8 (95% CI 1.5-2.2). CONCLUSIONS:Our results indicate that ongoing HIV replication (suboptimal HIV control) is an important risk factor for TB, independent of CD4 count. Those at highest risk of TB are people from TB-endemic countries. Close monitoring and TB preventive therapy for people with suboptimal HIV control is important.
Background Reinfection after successful treatment with direct -acting antivirals is hypothesised to undermine efforts to eliminate hepatitis C virus (HCV) infection among people with HIV. We aimed to assess changes in incidence of HCV reinfection among people with HIV following the introduction of direct -acting antivirals, and the proportion of all incident cases attributable to reinfection. Methods We pooled individual -level data on HCV reinfection in people with HIV after spontaneous or treatment -induced clearance of HCV from six cohorts contributing data to the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC) in Australia, Canada, France, the Netherlands, Spain, and Switzerland between Jan 1, 2010, and Dec 31, 2019. Participants were eligible if they had evidence of an HCV infection (HCV antibody or RNA positive test) followed by spontaneous clearance or treatment -induced clearance, with at least one HCV RNA test after clearance enabling measurement of reinfection. We assessed differences in first reinfection incidence between direct -acting antiviral access periods (pre -direct -acting antiviral, limited access [access restricted to people with moderate or severe liver disease and other priority groups], and broad access [access for all patients with chronic HCV]) using Poisson regression. We estimated changes in combined HCV incidence (primary and reinfection) and the relative contribution of infection type by calendar year. Findings Overall, 6144 people with HIV who were at risk of HCV reinfection (median age 49 years [IQR 42-54]; 4989 [81%] male; 2836 [46%] men who have sex with men; 2360 [38%] people who inject drugs) were followed up for 17 303 person -years and were included in this analysis. The incidence of first HCV reinfection was stable during the period before the introduction of direct -acting antivirals (pre -introduction period; 4 center dot 1 cases per 100 person -years, 95% CI 2 center dot 8-6 center dot 0). Compared with the pre -introduction period, the average incidence of reinfection was 4% lower during the period of limited access (incidence rate ratio [IRR] 0 center dot 96, 95% CI 0 center dot 78-1 center dot 19), and 28% lower during the period of broad access (0 center dot 72, 0 center dot 60-0 center dot 86). Between 2015 and 2019, the proportion of incident HCV infections due to reinfection increased, but combined incidence declined by 34%, from 1 center dot 02 cases per 100 person -years (95% CI 0 center dot 96-1 center dot 07) in 2015 to 0 center dot 67 cases per 100 person -years (95% CI 0 center dot 59-0 center dot 75) in 2019. Interpretation HCV reinfection incidence and combined incidence declined in people with HIV following directacting antiviral introduction, suggesting reinfection has not affected elimination efforts among people with HIV in InCHEHC countries. The proportion of incident HCV cases due to reinfection was highest during periods of broad access to direct -acting antivirals, highlighting the importance of reducing ongoing risks and continuing testing in people at risk. Funding Australian National Health and Medical Research Council. Copyright (c) 2024 Elsevier Ltd. All rights reserved.
BACKGROUND Despite its important drug-drug interaction, combined clindamycin/rifampicin therapy may achieve effective plasma clindamycin concentrations, provided clindamycin is administered by continuous infusion. However, the precise clindamycin dose remains unknown. OBJECTIVES This study was undertaken to determine the daily clindamycin dose to be administered by continuous infusion in combination with rifampicin to achieve effective plasma clindamycin concentrations. PATIENTS AND METHODS Two plasma clindamycin concentrations were determined prospectively for 124 patients with bone-and-joint infections treated with continuously infused clindamycin. Twenty patients received clindamycin monotherapy, 19 clindamycin combined with rifampicin and 85 received clindamycin successively without and with rifampicin. A population pharmacokinetic model was developed using NONMEM 7.5. Monte Carlo simulations were run to determine which regimens obtained clindamycin concentrations of at least 3 mg/L. RESULTS A linear one-compartment model with first-order elimination accurately described the data. Clindamycin distribution volume was not estimated. Mean clindamycin clearances with rifampicin and without, respectively, were 33.6 and 10.9 L/h, with 12.8% interindividual variability. The lowest daily clindamycin dose achieving plasma concentrations of at least 3 mg/L in >90% of the patients, when combined with rifampicin, was 4200 mg/24 h. CONCLUSIONS Our results support continuous infusion of 4200 mg of clindamycin/24 h, in combination with rifampicin. This high-dose regimen requires therapeutic drug monitoring-guided dose adaptation.
Post-Covid is defined by persistent symptoms following a SARS-CoV-2 infection, after excluding other causes. The prevalence of post-Covid is estimated at around 30% in the general population after an infection. Some of the risk factors include female sex, the number of symptoms in the acute phase, and comorbidities. Vaccination and Omicron infection are associated with a lower prevalence. The pathophysiology of post-Covid is not known to date, with hypotheses including immune dysregulation, viral persistence, endothelial dysfunction, microthrombosis and their consequences. Current management is defined by an adaptation of daily activities, and a symptom-based approach reducing their severity, frequency and impact. Clinical trials are underway to offer potential treatments for those affected.
Introduction While COVID-19 is predominantly considered to be an acute self-remitting disease, it has been pointed out that a variety of symptoms can linger for several months, a phenomenon identified as long-COVID. Insomnia is particularly prevalent in long-COVID. In the present study, we aimed at confirming and characterising insomnia in long-COVID patients through polysomnography and to identify whether its parameters differ from patients with chronic insomnia and no long-COVID history. Materials and methods We conducted a case-control study, including 17 long-COVID patients with insomnia symptoms (cases), and 34 2:1 matched controls with a diagnostic of chronic insomnia and no history of long-COVID. All underwent a one-night polysomnography (PSG). Results First, we observed that long-COVID patients with insomnia complaints have altered PSG parameters, in favour of the diagnosis of chronic insomnia. Second, we show that insomnia related to long-COVID PSG parameters was not significantly different from regular chronic insomnia PSG parameters. Discussion Our results indicate that even though it is one of the most prevalent symptoms of long-COVID, its related insomnia resembles typical chronic insomnia, based on PSG studies. Even though additional studies are warranted, our results suggest that the pathophysiology and therapeutic options should be similar to those recommended for chronic insomnia.
Objective:It is unknown whether hepatitis C virus (HCV)-cured people with HIV (PWH) without cirrhosis reached the same mortality risk as HCV-uninfected PWH. We aimed to compare mortality in PWH cured of HCV by direct-acting antivirals (DAAs) to mortality in individuals with HIV monoinfection.Design:Nationwide hospital cohort.Methods:HIV-controlled participants without cirrhosis and HCV-cured by DAAs started between September 2013 and September 2020, were matched on age (+/- 5 years), sex, HIV transmission group, AIDS status, and body mass index (BMI) (+/- 1 kg/m(2)) to up to 10 participants with a virally suppressed HIV monoinfection followed at the time of HCV cure +/- 6 months. Poisson regression models with robust variance estimates were used to compare mortality in both groups after adjusting for confounders.Results:The analysis included 3961 HCV-cured PWH (G1) and 33 872 HCV-uninfected PWH (G2). Median follow-up was 3.7 years in G1 [interquartile range (IQR): 2.0-4.6], and 3.3 years (IQR: 1.7-4.4) in G2. Median age was 52.0 years (IQR: 47.0-56.0), and 29 116 (77.0%) were men. There were 150 deaths in G1 [adjusted incidence rate (aIR): 12.2/1000 person-years] and 509 (aIR: 6.3/1000 person-years) in G2, with an incidence rate ratio (IRR): 1.9 [95% confidence interval (CI), 1.4-2.7]. The risk remained elevated 12 months post HCV cure (IRR: 2.4 [95% CI, 1.6-3.5]). Non-AIDS/non-liver-related malignancy was the most common cause of death in G1 (28 deaths).Conclusions:Despite HCV cure and HIV viral suppression, after controlling on factors related to mortality, DAA-cured PWH without cirrhosis remain at higher risk of all-cause mortality than people with HIV monoinfection. A better understanding of the determinants of mortality is needed in this population.
Background Broad direct-acting antiviral (DAA) access may reduce hepatitis C virus (HCV) incidence through a "treatment as prevention" (TasP) effect. We assessed changes in primary HCV incidence following DAA access among people living with HIV (PLHIV). Methods We used pooled individual-level data from six cohorts from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). Follow-up started from the first recorded negative HCV antibody test date and ended at last negative antibody test or estimated infection date. Follow-up was restricted to 2010-2019. We used segmented Poisson regression to model trends across pre-, limited-(i.e., restrictions on access) and broad-DAA access periods. Findings Overall, 45,942 participants had at least one HCV antibody negative result and follow-up between 2010 and 2019. We observed 2042 incident HCV infections over 248,189 person-years (PY). Pooled incidence decreased from 0.91 per 100 PY in 2015 to 0.41 per 100 PY in 2019. Compared to the average pre-DAA period incidence (0.90 per 100 PY), average incidence was similar during the limited-DAA access period (Incidence rate ratio [IRR] = 0.98; 95% CI = 0.87, 1.11), and 52% lower during the broad-DAA access period (IRR = 0.48; 95%CI = 0.42, 0.52). The average annual decline in HCV incidence was 2% in the pre-DAA period; an additional 9% annual decline in incidence was observed during the limited-DAA access period (IRR = 0.91; 95%CI = 0.82, 1.00) and a further 20% decline in the broad-DAA access period (IRR = 0.80, 95%CI = 0.73, 0.89). Interpretation Our findings suggest that broad DAA access has a TasP effect on primary HCV incidence among PLHIV. Based on the initial years of DAA availability, the countries in the InCHEHC collaboration are on track to meet the World Health Organization's 80% HCV incidence reduction target for PLHIV by 2030. Copyright (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Appendicitis is a common clinical problem but is not specific to a parasite. A 43-year-old patient consulted for digestive troubles, mostly acute abdominal pain, in the right part. Taenia saginata was found in appendectomy. Different parasites were found in the histopathological evaluation of the appendix, mostly Enterobius vermicularis, but also Ascaris, Taenia, amoeba, and Schistosoma. Acute appendicitis was proven by submucosal fibrosis, active suppurative inflammation, and active granulomas surrounding eggs or larvae of parasites. However, parasites were detected by chance in uninflamed and histologically normal appendices or appendices with chronic inflammation removed during other surgical procedures. The role of parasites in the pathogenesis of acute appendicitis is unclear. An adapted antiparasitic treatment is always necessary after appendectomy following finding parasites.