Efficacy, durability, and tolerability of bictegravir/emtricitabine/tenofovir alafenamide for the treatment of HIV in a real-world setting in Belgium.

OBJECTIVES: Our objective was to evaluate the efficacy, durability, and tolerability of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in a real-world setting in Belgium. METHODS: This was a retrospective, multicentre cohort study involving adult treatment-naïve (TN) and treatment-experienced (TE) people living with HIV receiving BIC/FTC/TAF between 1 January 2019 and 30 September 2020. The primary outcome was rate of virological suppression (plasma HIV-1 viral load <50 copies/mL; on-treatment analysis) at weeks 24 and 48. The main secondary outcomes included loss of virological suppression (LVS; two consecutive viral loads of >200 copies/mL after being virologically suppressed) by week 48 and analysis of resistance-associated mutations at time of LVS; tolerability of BIC/FTC/TAF over the 48-week study period; and change in weight and proportion of participants reporting a >10% weight gain at week 48. RESULTS: Overall, 2001 participants were included. Through 48 weeks, overall rate of virological suppression was 93.5%, with similar results observed in the following subgroups: age ≥50 years (92.7%), women (92.8%), Black sub-Saharan African (91%), TN (94%), TE (93.2%), and non-suppressed at baseline (86.6%). LVS was observed in 0.7% (n = 14) of participants, with one participant developing resistance-associated mutations to nucleoside reverse transcriptase inhibitors (184 V) and integrase strand transfer inhibitors (263KR). Of the 131 (6.5%) treatment discontinuations, the most common reason was an adverse event (2.4%), with the most frequent being central nervous system/psychiatric (0.4%) and gastrointestinal (0.4%) toxicity. Median weight gain at week 48 was 2 kg (interquartile range -1 to 5), and a >10% weight increase was observed in 11.6% of participants. CONCLUSION: In this large real-world cohort, BIC/FTC/TAF showed excellent virological efficacy in a diverse population of patients with HIV. Rare occurrence of emergent drug resistance was observed, and treatment was well tolerated.

Efficacy, durability, and tolerability of dolutegravir/lamivudine and dolutegravir/rilpivirine for the treatment of HIV in a real-world setting in Belgium.

OBJECTIVES: A paradigm shift from three-drug regimens to two-drug regimens (2DRs) is currently taking place in real-world clinical practice. This study aimed to describe the efficacy, durability, and tolerability of dolutegravir (DTG)/lamivudine (3TC) and DTG/rilpivirine (RPV) in a real-world setting. METHODS: This was a retrospective, observational, multicentre (ten centres in Belgium) study involving adult treatment-naïve and treatment-experienced people living with HIV on DTG/3TC or DTG/RPV between 1 January 2019 and 30 September 2020. The primary endpoint was rate of virological suppression (VS; plasma HIV-1 viral load [VL] <50 copies/ml) using an on-treatment analysis. Main secondary endpoints included the proportion of people that experienced loss of VS (LVS; defined as two consecutive HIV-1 VLs of >200 copies/ml after initially achieving VS) and a resistance analysis at the time of LVS; rate, incidence, and reasons for discontinuation of treatment (stopping treatment or changing any component of the 2DR); and change in weight, along with the proportion of people reporting a >10% weight gain. Ordinal logistic regression analysis examined associations between baseline variables and >10% on-treatment weight gain. RESULTS: Overall, 948 people were included, of whom 734 (77%) were on DTG/3TC and 214 (23%) were on DTG/RPV. Baseline characteristics included 54% aged ≥50 years, 31% female, 31% Black sub-Saharan African, 95% treatment-experienced, and 8% with HIV-1 VL ≥50 copies/ml. Through 48 weeks, the rate of VS for the overall cohort was 98.3% (99.1% with 3TC; 96.2% with RPV). LVS was observed in 0.5% (n = 5) of the overall population (n = 1 [3TC group], n = 4 [RPV group]). There were 40 treatment discontinuations (4.2%, n = 27 [3TC group]; n = 13 [RPV group]), corresponding to an incidence of 4.7 per 100 patient-years. The most common reason for discontinuation was an adverse event (1.4%), with neurotoxicity the most frequent (0.5%). Median on-treatment weight gain at week 48 was 1 kg (interquartile range [IQR] -1-3) overall, 1 kg (IQR -1-3) in the 3TC group, and 2 kg (IQR 0-4) in the RPV group. A >10% weight increase was observed in 6.3% of people. Regression analysis showed that being on a tenofovir disoproxil fumarate-based regimen prior to 2DR initiation was the only variable associated with a >10% increase in weight from baseline (odds ratio 3.48; 95% confidence interval 1.13-10.68; p = 0.038). CONCLUSION: In this real-world analysis, the 2DRs analysed were effective, durable, and safe for those who were treatment-naive and treatment-experienced. A slight increase in weight was associated with these regimens.

Impact of collaborative physician-pharmacist stewardship strategies on prophylactic antibiotic practices: a quasi-experimental study.

BACKGROUND: An effective use of surgical antibiotic prophylaxis (SAP) appears essential to prevent the development of infections linked to surgery while inappropriate and excessive prescriptions of prophylactic antibiotics increase the risk of adverse effects, bacterial resistance and Clostridium difficile infections. In this study, we aimed to analyze SAP practices in an acute secondary hospital in Belgium during the years 2016-2021 in order to evaluate the impacts of combined stewardship interventions, implemented thanks to a physician-pharmacist collaboration. METHODS: A quasi-experimental study on SAP practices was conducted during 5 years (2016-2021) in a Belgian University Hospital. We first performed a retrospective observational transversal study on a baseline group (2016.1-2016.4). Then, we constituted a group of patients (2017.1-2017.4) to test a combined intervention strategy of stewardship which integrated the central role of a pharmacist in antibiotic stewardship team and in the pre-operative delivery of nominative kits of antibiotics adapted to patient factors. After this test, we collected patient data (2018.1-2018.4) to evaluate the sustained effects of stewardship interventions. Furthermore, we evaluated SAP practices (2019.1-2019.4) after the diffusion of a computerized decision support system. Finally, we analyzed SAP practices in the context of the COVID-19 pandemic (2020.1-2020.4 and 2021.1-2021.4). The groups were compared from year to year in terms of compliance to institutional guidelines, as evaluated from seven criteria (χ2 test). RESULTS: In total, 760 surgical interventions were recorded. The observational study within the baseline group showed that true penicillin allergy, certain types of surgery and certain practitioners were associated with non-compliance (p < 0.05). Compared with the baseline group, the compliance was significantly increased in the test group for all seven criteria assessed (p < 0.05). However, the effects were not fully sustained after discontinuation of the active interventions. Following the diffusion of the computerized decision support system, the compliance to guidelines was not significantly improved. Finally, the COVID-19 pandemic did not appear to affect the practices in terms of compliance to guidelines. CONCLUSIONS: This study shows that optimization of SAP practices is achievable within a proactive multidisciplinary approach including real-time pharmaceutical interventions in the operating area and in the care units practicing SAP.

A public health value-based healthcare paradigm for HIV.

BACKGROUND: HIV patients face considerable acute and chronic healthcare needs and battling the HIV epidemic remains of the utmost importance. By focusing on health outcomes in relation to the cost of care, value-based healthcare (VBHC) proposes a strategy to optimize quality of care and cost-efficiency. Its implementation may provide an answer to the increasing pressure to optimize spending in healthcare while improving patient outcomes. This paper describes a pragmatic value-based healthcare framework for HIV care. METHODS: A value-based HIV healthcare framework was developed during a series of roundtable discussions bringing together 16 clinical stakeholder representatives from the Belgian HIV reference centers and 2 VBHC specialists. Each round of discussions was focused on a central question translating a concept or idea to the next level of practical implementation: 1) how can VBHC principles be translated into value-based HIV care drivers; 2) how can these value-based HIV care divers be translated into value-based care objectives and activities; and 3) how can value-based HIV care objectives and activities be translated into value-based care indicators. Value drivers were linked to concrete objectives and activities using a logical framework approach. Finally, specific, measurable, and acceptable structure, process and outcomes indicators were defined to complement the framework. RESULTS: Our framework identifies 4 core value areas where HIV care would benefit most from improvements: Prevention, improvement of the cascade of care, providing patient-centered HIV care and sustaining a state-of-the-art HIV disease management context. These 4 core value areas were translated into 12 actionable core value objectives. For each objective, example activities were proposed. Indicators are suggested for each level of the framework (outcome indicators for value areas and objectives, process indicators for suggested activities). CONCLUSIONS: This framework approach outlines how to define a patient- and public health centered value-based HIV care paradigm. It proposes how to translate core value drivers to practical objectives and activities and suggests defining indicators that can be used to track and improve the framework's implementation in practice.

Corrigendum: CSF HIV RNA Escape in Opsoclonus-Myoclonus-Ataxia Syndrome: Case Report and Review of the Literature.

[This corrects the article DOI: 10.3389/fneur.2020.585527.].

CSF HIV RNA Escape in Opsoclonus-Myoclonus-Ataxia Syndrome: Case Report and Review of the Literature.

Background: Human immunodeficiency viruses (HIV) infection is associated with a broad range of neurological manifestations, including opsoclonus-myoclonus ataxia syndrome (OMAS) occurring in primary infection, immune reconstitution syndrome or in case of opportunistic co-infection. Case: We report the exceptional case of a 43-year-old female under HIV treatment for 10 years who presented initially with suspected epileptic seizure. Although the clinical picture slightly improved under anti-epileptic treatment, it was rapidly attributed to OMAS. The patient exhibited marked opsoclonus, mild dysarthria, upper limbs intermittent myoclonus, ataxia in 4 limbs, truncal ataxia, and a severe gait ataxia (SARA score: 34). The diagnostic work-up showed radiological and biological signs of central nervous system (CNS) inflammation and cerebral venous sinus thromboses. The HIV viral load was higher in cerebrospinal fluid (CSF) than in the blood (4,560 copies/ml vs. 76 copies/ml). She was treated for 5 days with pulsed corticotherapy. Dolutegravir and anticoagulation administration were initiated. Follow-ups at 2 and 4 months showed a dramatic improvement of clinical neurologic status (SARA score at 4 months: 1), reduction of CNS inflammation and revealed undetectable CSF and serum viral loads. Conclusion: This case underlines the importance of the evaluation of the CSF viral load in HIV patients developing OMAS and suggests CSF HIV RNA escape as a novel cause for OMAS.

Impact of solid cancer on in-hospital mortality overall and among different subgroups of patients with COVID-19: a nationwide, population-based analysis.

BACKGROUND: Cancer seems to have an independent adverse prognostic effect on COVID-19-related mortality, but uncertainty exists regarding its effect across different patient subgroups. We report a population-based analysis of patients hospitalised with COVID-19 with prior or current solid cancer versus those without cancer. METHODS: We analysed data of adult patients registered until 24 May 2020 in the Belgian nationwide database of Sciensano. The primary objective was in-hospital mortality within 30 days of COVID-19 diagnosis among patients with solid cancer versus patients without cancer. Severe event occurrence, a composite of intensive care unit admission, invasive ventilation and/or death, was a secondary objective. These endpoints were analysed across different patient subgroups. Multivariable logistic regression models were used to analyse the association between cancer and clinical characteristics (baseline analysis) and the effect of cancer on in-hospital mortality and on severe event occurrence, adjusting for clinical characteristics (in-hospital analysis). RESULTS: A total of 13 594 patients (of whom 1187 with solid cancer (8.7%)) were evaluable for the baseline analysis and 10 486 (892 with solid cancer (8.5%)) for the in-hospital analysis. Patients with cancer were older and presented with less symptoms/signs and lung imaging alterations. The 30-day in-hospital mortality was higher in patients with solid cancer compared with patients without cancer (31.7% vs 20.0%, respectively; adjusted OR (aOR) 1.34; 95% CI 1.13 to 1.58). The aOR was 3.84 (95% CI 1.94 to 7.59) among younger patients (<60 years) and 2.27 (95% CI 1.41 to 3.64) among patients without other comorbidities. Severe event occurrence was similar in both groups (36.7% vs 28.8%; aOR 1.10; 95% CI 0.95 to 1.29). CONCLUSIONS: This population-based analysis demonstrates that solid cancer is an independent adverse prognostic factor for in-hospital mortality among patients with COVID-19. This adverse effect was more pronounced among younger patients and those without other comorbidities. Patients with solid cancer should be prioritised in vaccination campaigns and in tailored containment measurements.

Long-term treatment with atazanavir (ATV) in real life in Belgium: a retrospective observational cohort of 2264 HIV patients.

OBJECTIVES: This 5-year follow-up study aimed to assess clinical outcomes of HIV-1 infected adults treated with atazanavir (ATV) in clinical practice in Belgium, to describe patient profiles and characteristics, as well as treatment safety. METHODS: A multicenter, non-interventional, non-comparative, retrospective cohort study was performed in HIV-1 positive adult patients treated with ATV between 2006 and 2012. Data were collected from 8 AIDS reference centers' databases. All analyses were on-treatment. Sub-analyses were carried out in unboosted ATV treated patients and in females. The primary endpoint was defined as the time-to-treatment-discontinuation. Furthermore, virological suppression, immunological response, time to loss of virological response, reasons for ATV initiation, and discontinuation were also assessed. RESULTS: 2264 ARV-naive and ARV-experienced patients (median age: 41 years) were included. Females and non-Caucasians were broadly represented (40 and 45%, respectively). The probability to remain on treatment was 0.78 (CI: 0.76; 0.78) for the first and 0.69 (CI: 0.66; 0.71) for the second year and was similar between males and females. Overall, 771 patients (34.1%) discontinued ATV over time, the median (Q1-Q3) time to discontinuation being 0.8 (0.3-1.5) year. In unboosted ATV-treated patients, results were comparable to the overall ATV population, except for a higher rate of discontinuation-over-time (45.1%). CONCLUSIONS: Clinical and safety data from this 5 year-cohort study show that the vast majority of patients remained on ATV treatment for the first and second years, overall as well as patients treated with unboosted ATV and females.

High uptake of pre-exposure prophylaxis (PrEP) during early roll-out in Belgium: results from surveillance reports.

Background Since 1 June 2017, oral pre-exposure prophylaxis (PrEP) could be prescribed and reimbursed in Belgium as prophylactic medication for people who are at increased risk of HIV acquisition. The aim of this study was to determine the uptake of daily and event-driven PrEP in Belgium during the first 9 months of roll-out. METHODS: Routine aggregated data on the number of reimbursement requests and the number of boxes of Truvada (Gilead Sciences, Cambridge, UK) delivered for PrEP through the Belgian pharmacies were obtained from the National Institute for Health and Disability Insurance. We also collected aggregated data from seven Aids Reference Centres (ARCs) currently providing most of the PrEP care in Belgium. RESULTS: From 1 June 2017 to 28 February 2018, 1352 requests for reimbursement were approved by the National Institute for Health and Disability Insurance. Almost 98% of those who bought at least one box of 30 tablets of emtricitabine 200mg/tenofovir disoproxil fumarate 300mg (FTC/TDF) in a Belgian pharmacy were male, and most (67%) were between 30 and 50 years of age. According to data obtained from ARCs, the proportion of those choosing event-driven PrEP initially ranged between 29% and 73%. CONCLUSIONS: The uptake of PrEP in Belgium since the start of the roll-out in June 2017 has been high, and almost entirely limited to men who have sex with men, of whom 43% initially prefer a non-daily regimen. A better understanding is needed as to why other populations, such as sub-Saharan African migrants, are not accessing PrEP, as well as the development of a more sustainable PrEP delivery model.

Long-term use of darunavir/ritonavir-containing regimens in daily practice in Belgium: retrospective observational cohort data of 1701 HIV-patients.

Background Once daily (QD) ritonavir or cobicistat-boosted darunavir (DRV/b), in combination with other antiretrovirals (ARVs), is recommended as a first-line option for human immunodeficiency virus-infected patients in European and USA guidelines. The objective of this study was to analyse the outcomes of DRV/r QD-based antiretroviral therapy (ART) regimens in real-life settings. Methods This is an observational, non-interventional, non-comparative, retrospective, multicentre cohort study. Data were collected from the databases of eight Belgian AIDS Reference Centres. All patients who received at least one dose of DRV/r QD, regardless of background ARV regimen, with a minimum follow-up of 6 months were included. Results Data from 1701 subjects were collected. Most were male (66.5%) with a mean age of 42.9 years, 33.1% were treatment-naïve and 66.9% were ART experienced. During a median follow-up of 2.45 years (95% CI: 1.50-3.34), the probability to remain on treatment was 87% for the first year, 79% for the second year. DRV/r was well tolerated with few discontinuations due to adverse events (6.9%) or virological failure (0.8%). Among the 1138 treatment-experienced patients, 111 (9.8%) patients received DRV/r QD monotherapy. Conclusions This retrospective cohort analysis confirms the long-term effectiveness and good tolerability of DRV/r QD in a real-life setting. No unexpected adverse events were reported.

Belgian guidelines for non-occupational HIV post-exposure prophylaxis 2017.

We present the updated Belgian guidelines for the use of non-occupational HIV post-exposure prophylaxis (NONOPEP). This document is inspired by UK guidelines 2015, adapted to the Belgian situation and approved by all AIDS reference centers in Belgium. When recommended, NONOPEP should be initiated as soon as possible, preferably within 24 h of exposure but can be offered up to 72 h. The duration of NONOPEP should be 28 days. These current guidelines include epidemiologic estimations, which can be used to calculate the risk of infection after a potential exposure and help to decide whether or not to start prophylaxis. We review which medications to use in the context of the last Belgian NONOPEP convention, provide a checklist for initial assessment, and make recommendations for monitoring individuals receiving NONOPEP.

Factors associated with the continuum of care of HIV-infected patients in Belgium.

INTRODUCTION: We studied factors associated with the continuum of HIV care in Belgium. METHODS: Data of the national registration of new HIV diagnosis and of the national cohort of HIV-infected patients in care were combined to obtain estimates of and factors related with proportions of HIV-infected patients in each step of the continuum of care from diagnosis to suppressed viral load (VL). Factors associated with ignorance of HIV seropositivity were analyzed among patients co-infected with HIV and STI in the Belgian STI sentinel surveillance network. Associated factors were identified by multivariate logistic regression. RESULTS: Among 4038 individuals diagnosed with HIV between 2007 and 2010, 90.3% were linked to care. Of 11684 patients in care in 2010, 90.8% were retained in care up to the following year, 88.3% of those were on ART, of whom 95.3% had suppressed VL (<500 cp/ml) (Figure 1). In multivariate analyses, factors associated with ignoring HIV+ status were being younger (p<0.001), being heterosexual compared to MSM, and of a region of origin other than Belgium, Sub-Saharan Africa and Europe. Non-Belgian regions of origin were associated with lower entry and retention in care (p<0.001 for both). Preoperative HIV testing was associated with lower entry in care (p=0.003). MSM had a higher retention in care (p<0.001), whilst IDU had lower retention (p=0.004). Low CD4 at first clinical contact and clinical reasons for HIV testing were independently associated with being on ART (p<0.001 for both); whilst prenatal HIV diagnosis was associated with lower proportion on ART (p=0.016) and lower proportion with suppressed VL among those on ART (p=0.005). Older age was associated with both being on ART and having suppressed VL among those on ART (p=0.007 and p<0.001 respectively), independently of time since HIV diagnosis (Table 1). CONCLUSIONS: Regions of origin and risk groups (MSM/heterosexual/IDU) are the main factors associated with ignorance of HIV seropositivity, entry and retention in care, but once the HIV patient is retained in care, no effect of these factors on the proportions on ART and with suppressed VL are observed. The association of prenatal HIV diagnosis and proportions on ART and with suppressed VL could be biased by transitory CD4 disturbances during pregnancy and ART discontinuation after pregnancy. The higher probabilities of older patients to be on ART and have suppressed VL once retained in care could be influenced by factors not studied here like comorbidities, adherence or duration on ART.

Prevalence and European AIDS Clinical Society (EACS) criteria evaluation for proximal renal tubular dysfunction diagnosis in patients under antiretroviral therapy in routine setting.

INTRODUCTION: Tenofovir (TDF) is an antiretroviral drug often used in combination regimen in HIV-positive patients. Adverse effects affecting kidneys consist in an increase or a new onset proteinuria, a decrease of glomerular filtration rate (GFR), and/or a proximal renal tubular dysfunction (PRTD) that rarely leads to Fanconi's syndrome. EACS guidelines propose to screen PRTD in patients with chronic renal insufficiency, with a sudden decrease of eGFR, with hypophosphataemia (if non-renal causes such as vitamin D deficiency are excluded) and with a new onset proteinuria. We aim to evaluate the prevalence of PRTD by comparing the group of patients under TDF to the group free of TDF, in our cohort of 300 patients. We also aim to evaluate the accuracy of EACS criteria for screening PRTD in routine settings and to assess the utility of urinary samples in PRTD diagnosis. MATERIALS AND METHODS: During two consecutive years, we collected annually blood and urine samples at the same time in our outpatient clinic. We assessed kidney function, plasma levels and fractional excretion of phosphate, uric acid, potassium, plasma glucose and proteinuria. PRTD was defined by the presence of at least two out of the five following criteria: fractional excretion (FE) of phosphate >20% (or >10% when serum phosphate <0.8 mmol/L), non-diabetic glycosuria (positive urine glucose with plasma glucose <70 mg/dL), renal tubular acidosis (urinary pH >5.5 and serum bicarbonate <21 mmol/L), uric acid FE >10% or potassium FE >10%. After the first year, patients with TDF regimen who were diagnosed with PRTD were shifted to TDF-free regimen and included again in the study. RESULTS: For PRTD (first line), they are expressed in number of diagnoses/total number of patients in this group. The second line resumes the number of PRTD diagnose patients who should have been screened according to EACS criteria. CONCLUSIONS: PRTD screening according to EACS criteria is not sufficient to diagnose every case, especially minor PRTD, mainly because the prevalence is low and its diagnosis remains difficult in routine settings. We recommend performing a urine test including proteinuria every year for patients undergoing TDF treatment. The next step will be to follow PRTD patients to evaluate the time laps until full recovery after TDF shift.

HIV positive asylum seekers receiving the order to leave the Belgian territory.

INTRODUCTION: In a human rights based approach, the Parliamentary Assembly of the Council of Europe has recently released a resolution about migrants and refugees and the fight against HIV (1). It states that "an HIV positive migrant should never be expelled when it is clear that he will not receive adequate health care and assistance in the country to which he is being sent back. To do otherwise would amount to a death sentence for that person." Nevertheless, in Belgium, for the last 2 years, none of the HIV-infected migrants in care in the AIDS Reference Centers (ARC) received the right to stay in Belgium for medical reasons. METHODS: We identified all HIV-infected asylum seekers in care between 1 July 2012 and 1 July 2014 in the ARC of Charleroi, Belgium, and we analyzed their medical and social files. RESULTS: Among the 302 patients in active follow up in our ARC, 45 HIV positive asylum seekers were in care during the last 2 years. Male/female ratio was 0/96. Mean age was 35 years. Countries of origin and reasons for migration are detailed in the Table 1. 18% (8/45) knew their seropositivity before arriving in Europe. All the patients introduced an asylum request, 29 (64%) have received a negative answer and an order to leave the territory, 4 (9%) were regularized for non-medical reasons (see Table 1), 4 (9%) are waiting for an answer and for 8 (18%) outcome is unknown due to lost follow up (LFU). 31 (69%) patients have also introduced a request to stay for medical reasons: 18 (58%) have received a refusal, 7 (23%) are still waiting for an answer, and 6 (19%) are LFU. Only 23 (51%) patients are still in care in our ARC on 1 July 2014 (see Table 1). The immigration office bases its decisions on availability of the treatment in the country even if accessible only to a limited number of patients. CONCLUSIONS: Decisions taken by the Belgian authorities for the last two years concerning HIV-infected asylum seekers do not guarantee the continuity of care of those patients and push them towards illegality. Such decisions ignore the international commitments of Belgium in the fight against HIV (2) and are contradictory with the recommendations of the recent resolution of the Council of Europe (1). An approach more respectful of Human Rights in the decisions concerning the seropositive asylum seekers patients taken by the authorities is urgently needed in Belgium. We invite our European colleagues to describe the situation of the HIV asylum seekers in their countries.

Prospective multicenter evaluation of the expert system "KABISA TRAVEL" in diagnosing febrile illnesses occurring after a stay in the tropics.

BACKGROUND: KABISA TRAVEL is a clinical decision support system developed by the Institute of Tropical Medicine of Antwerp, Belgium, for the diagnosis of febrile illnesses after a stay in the tropics. This study aimed to compare the diagnostic accuracy of KABISA TRAVEL with that of expert travel physicians. METHODS: From December 2007 to April 2009, travelers with fever after a stay in the tropics were included in a multicenter trial conducted in travel referral centers in the Netherlands, Italy, Spain, and Belgium. Physicians were asked (1) to rank their first assessment diagnoses, (2) to enter in KABISA TRAVEL clinical and laboratory data available within 36 hours, and (3) to interact with the tutor until its final diagnostic ranking. Both physicians and KABISA TRAVEL rankings were then compared with the final diagnosis confirmed by reference methods. The clinical utility was also surveyed. RESULTS: A total of 205 cases with confirmed diagnosis were evaluated (male/female ratio: 1.85; mean age: 35 y). Most patients were western travelers or expatriates (60%) and were returning from sub-Saharan Africa (58%). Travel physicians and KABISA TRAVEL ranked the correct diagnosis in the first place for 70 and 72% of the cases, respectively, and within the top five both for 88% of them. Travel physicians reported having been suggested useful further investigations in 16% of the cases, and having been helped for obtaining the diagnosis in 24%. This was reported more frequently when they had initially missed the diagnosis (suggestion: 48% in missed vs 12% in found diagnoses, p < 0.001; helpful: 48% in missed vs 21% in found diagnoses, p = 0.005). CONCLUSIONS: KABISA TRAVEL performed as well as expert travel physicians in diagnosing febrile illnesses occurring after a tropical stay. Clinicians perceived the system as more helpful when they had not immediately considered the correct diagnosis.

Diversity of life-threatening complications due to Mediterranean spotted fever in returning travelers.

BACKGROUND: Mediterranean spotted fever (MSF) is a tick-borne infection caused by Rickettsia conorii conorii mainly endemic in the Mediterranean Basin. Although usually considered as a benign disease, severe forms of MSF have been sporadically reported. METHODS: We report on three patients who developed severe MSF complications after a stay in Morocco. Literature was reviewed to assess the frequency and pattern of MSF complications in the largest reported case series in endemic countries. RESULTS: Each of our three patients diagnosed with MSF presented with a different complicated course: one with meningoencephalitis, one with lung embolism and one with septic shock and multi organ failure. In published series, rate of complications (defined as severe organ involvement) ranged from 1% to 20%. However, study designs and settings were highly variable and did not allow for relevant comparisons. Meningoencephalitis and shock with multi organ failure were the most frequently observed complications. Mortality of severe course was up to 20% in some series. CONCLUSION: Severe organ involvement is not infrequent in patients with Mediterranean spotted fever and fatal outcome is regularly reported. Because presentations of complicated course may be extremely diverse, a high index of suspicion is required in febrile patients with potential exposure, in particular if skin rash and/or eschar are found. Early appropriate antibiotherapy is crucial to improve outcome.

Acute increase in goiter size during a normal pregnancy: an exceptional case report.

This case report illustrates an exceptional clinical situation in which a pregnant woman abruptly presented, at 5 months' gestation, with major swelling of the thyroid gland that led to respiratory symptoms and emergency hospitalization. The medical condition was shown to be caused by acute intrathyroidal hemorrhage within a preexisting-albeit until then unnoticed-multinodular goiter. The cause of the intrathyroidal hemorrhage could not be firmly delineated, although it remains possible that an unusual extraneous cause constituted a "trauma" that triggered this rare medical condition.