Enteral administration of crushed rilpivirine in a patient with HIV: A case report.

Antiretroviral therapy administration is challenging in patients with HIV requiring enteral nutrition. There are limited pharmacokinetic data available regarding the absorption of crushed rilpivirine (RPV) and its impact on drug bioavailability, plasma concentrations and, consequently, the efficacy of treatment. We present the case of a 60-year-old woman with HIV diagnosed with squamous cell carcinoma who needed enteral administration of antiretroviral therapy following the insertion of a gastrotomy tube in September 2018. Initially, the patient was treated with a daily dose of RPV 25 mg, dolutegravir 50 mg and emtricitabine 200 mg. The treatment was later intensified with darunavir boosted with ritonavir. RPV and dolutegravir were crushed, dissolved in water and administered via a percutaneous endoscopic gastrostomy tube. Therapeutic drug and viral load monitoring determined the adequacy of enteral antiretroviral dosing. RPV plasma concentrations remained within the expected therapeutic range of 43-117 ng/mL, with only 1 below the currently used 50 ng/mL efficacy threshold. After the treatment intensification with darunavir boosted with ritonavir, the patient achieved an undetectable viral load. While we observed satisfactory RPV plasma concentrations, it is essential to maintain strict monitoring of administration method, plasma concentrations and virological responses when initiating treatment with crushed RPV. Hence, additional pharmacokinetic data are necessary to ensure the effective enteral administration of RPV and to establish the best antiretroviral dosing regimens.

Effect of open-lung vs conventional perioperative ventilation strategies on postoperative pulmonary complications after on-pump cardiac surgery: the PROVECS randomized clinical trial.

PURPOSE: To evaluate whether a perioperative open-lung ventilation strategy prevents postoperative pulmonary complications after elective on-pump cardiac surgery. METHODS: In a pragmatic, randomized, multicenter, controlled trial, we assigned patients planned for on-pump cardiac surgery to either a conventional ventilation strategy with no ventilation during cardiopulmonary bypass (CPB) and lower perioperative positive end-expiratory pressure (PEEP) levels (2 cm H2O) or an open-lung ventilation strategy that included maintaining ventilation during CPB along with perioperative recruitment maneuvers and higher PEEP levels (8 cm H2O). All study patients were ventilated with low-tidal volumes before and after CPB (6 to 8 ml/kg of predicted body weight). The primary end point was a composite of pulmonary complications occurring within the first 7 postoperative days. RESULTS: Among 493 randomized patients, 488 completed the study (mean age, 65.7 years; 360 (73.7%) men; 230 (47.1%) underwent isolated valve surgery). Postoperative pulmonary complications occurred in 133 of 243 patients (54.7%) assigned to open-lung ventilation and in 145 of 245 patients (59.2%) assigned to conventional ventilation (p = 0.32). Open-lung ventilation did not significantly reduce the use of high-flow nasal oxygenotherapy (8.6% vs 9.4%; p = 0.77), non-invasive ventilation (13.2% vs 15.5%; p = 0.46) or new invasive mechanical ventilation (0.8% vs 2.4%, p = 0.28). Mean alive ICU-free days at postoperative day 7 was 4.4 ± 1.3 days in the open-lung group vs 4.3 ± 1.3 days in the conventional group (mean difference, 0.1 ± 0.1 day, p = 0.51). Extra-pulmonary complications and adverse events did not significantly differ between groups. CONCLUSIONS: A perioperative open-lung ventilation including ventilation during CPB does not reduce the incidence of postoperative pulmonary complications as compared with usual care. This finding does not support the use of such a strategy in patients undergoing on-pump cardiac surgery. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02866578. https://clinicaltrials.gov/ct2/show/NCT02866578.

Antibiotic use for respiratory infections among Hajj pilgrims: A cohort survey and review of the literature.

BACKGROUND: To evaluate the occurrence and determinants associated with antibiotic use for respiratory tract infections (RTIs) among Hajj pilgrims. METHODS: Prospective cohort surveys were conducted among French pilgrims from 2012 to 2017. We also conducted a systematic review about available evidence for antibiotic consumption in relation with RTIs during the Hajj. RESULTS: 783 pilgrims were included in the survey. During the Hajj, 85.3% presented respiratory symptoms and 47.6% used antibiotics. Pilgrims with productive cough or fever were three times and twice as likely to have used antibiotics. Dry cough, sore throat and voice failure were also associated with increased antibiotic use. 26.3% of pilgrims presented symptoms compatible with a lower tract respiratory infection. According to the French recommendations, only 39.6% of pilgrims who used an antibiotic actually had an indication for it. Antibiotic intake was associated with an increased frequency of persistent symptoms post-Hajj (aRR = 1.31, 95%CI [1.04-1.66]). The review included 14 articles. The use of antibiotic for respiratory tract infections during the Hajj varied from 7% to 58.5%. In 9 studies, the antibiotic consumption rate was >30%. CONCLUSION: Respiratory tract infections are common during the Hajj, leading to high prevalence of inappropriate antibiotic intake.

Acquisition of respiratory and gastrointestinal pathogens among health care workers during the 2015 Hajj season.

BACKGROUND: Data on the risk of transmission of infection to health care workers (HCWs) serving ill pilgrims during the Hajj is scarce. METHODS: Two cohorts of HCWs, the first serving Hajj pilgrims in Mecca and the second serving patients in Al-Ahsa, were investigated for respiratory and gastrointestinal symptoms and pathogen carriage using multiplex polymerase chain reaction before and after the 2015 Hajj. RESULTS: A total of 211 HCWs were enrolled of whom 92 were exposed to pilgrims (Mecca cohort), whereas 119 were not exposed (Al-Ahsa cohort). Symptoms were observed only in HCWs from the Mecca cohort, with 29.3% experiencing respiratory symptoms during the Hajj period or in the subsequent days and 3.3% having gastrointestinal symptoms. Acquisition rates of at least 1 respiratory virus were 14.7% in the Mecca cohort and 3.4% in the Al-Ahsa cohort (P = .003). Acquisition rates of at least 1 respiratory bacterium were 11.8% and 18.6% in the Mecca and Al-Ahsa cohorts, respectively (P = .09). Gastrointestinal pathogens were rarely isolated in both cohorts of HCWs and acquisition of pathogens after the Hajj was documented in only a few individuals. CONCLUSIONS: HCWs providing care for pilgrims both acquire pathogens and present symptoms (especially respiratory symptoms) more frequently than those not working during Hajj.

The Presence of Acinetobacter baumannii DNA on the Skin of Homeless People and Its Relationship With Body Lice Infestation. Preliminary Results.

The presence of Acinetobacter baumannii was demonstrated in body lice, however, little is known about the mechanism of natural lice infection. In 2013 and 2014, cross-sectional one-day studies were therefore performed within two Marseille homeless shelters to assess the presence of A. baumannii DNA on human skin, blood and in body lice collected from the same homeless individuals. All 332 participants completed questionnaires, were examined for dermatologic signs, and provided four skin samples (hair, neck, armpits, and pelvic belt), blood samples and body lice (if any). We developed a new real-time PCR tool targeting the ompA/motB gene for the detection of A. baumannii for all collected samples. Blood culture was also performed. Body lice were found in 24/325 (7.4%) of subjects. We showed a prevalence of A. baumannii DNA skin-carriage in 33/305 (10.8%) of subjects. No difference was found in A. baumannii DNA prevalence according to body sites. A strong association between body lice infestation (OR = 3.07, p = 0.029) and A. baumannii DNA skin-carriage was noted. In lice, A. baumannii DNA was detected in 59/219 arthropods (26.9%). All blood cultures and real-time PCR on blood samples were negative for A. baumannii. Lice probably get infected with A. baumannii while biting through the colonized skin and likely transmit the bacteria in their feces. We found no evidence that lice facilitate the invasion of A. baumannii into the blood stream. Further investigations are needed to compare phenotypic and genotypic features of A. baumannii isolates from human skin and lice from the same individuals.

Clinical respiratory infections and pneumonia during the Hajj pilgrimage: A systematic review.

BACKGROUND: The Islamic Hajj pilgrimage to Mecca is one of the world's largest annual mass gatherings. Inevitable overcrowding during the pilgrims' stay greatly increases the risk of acquiring and spreading infectious diseases, especially respiratory diseases. METHOD: The MEDLINE/PubMed and Scopus databases were searched for all relevant papers published prior to February 2018 that evaluated the prevalence of clinical symptoms of respiratory infections, including pneumonia, among Hajj pilgrims, as well as their influenza and pneumococcal vaccination status. RESULTS: A total of 61 papers were included in the review. Both cohort- and hospital-based studies provide complementary data, and both are therefore necessary to provide a complete picture of the total burden of respiratory diseases during the Hajj. Respiratory symptoms have been common among Hajj pilgrims over the last 15 years. In cohorts of pilgrims, cough ranged from 1.9% to 91.5%. However, the prevalence rates of the most common symptoms (cough, sore throat, and subjective fever) of influenza-like illness (ILI) varied widely across the included studies. These studies have shown variable results, with overall rates of ILI ranging from 8% to 78.2%. These differences might result from differences in study design, study period, and rates of vaccination against seasonal influenza that ranged from 1.1% to 100% among study participants. Moreover, the definition of ILI was inconsistent across studies. In hospitalized Hajj pilgrims, the prevalence of pneumonia, that remains a major concern in critically ill patients, ranged from 0.2% to 54.8%. CONCLUSIONS: Large multinational follow-up studies are recommended for clinic-based syndromic surveillance, in conjunction with microbiological surveillance. Matched cohorts ensure better comparability across studies. However, study design and data collection procedures should be standardized to facilitate reporting and to achieve comparability between studies. Furthermore, the definition of ILI, and of most common symptoms used to define respiratory infections (e.g., upper respiratory tract infection), need to be precisely defined and consistently used. Future studies need to address potential effect of influenza and pneumococcal vaccine in the context of the Hajj pilgrimage.

A systematic review of emerging respiratory viruses at the Hajj and possible coinfection with Streptococcus pneumoniae.

BACKGROUND: The annual Hajj to the Kingdom of Saudi Arabia attracts millions of pilgrims from around the world. International health community's attention goes towards this mass gathering and the possibility of the development of any respiratory tract infections due to the high risk of acquisition of respiratory viruses. METHOD: We searched MEDLINE/PubMed and Scopus databases for relevant papers describing the prevalence of respiratory viruses among Hajj pilgrims. RESULTS: The retrieved articles were summarized based on the methodology of testing for these viruses. A total of 31 studies were included in the quantitative/qualitative analyses. The main methods used for the diagnosis of most common respiratory viruses were polymerase chain reaction (PCR), culture and enzyme-linked immunosorbent assay (ELISA). Influenza, rhinovirus and parainfluenza were the most common viruses detected among pilgrims. Coronaviruses other than MERS-CoV were also detected among pilgrims. The acquisition of MERS-CoV remains very limited and systematic screening of pilgrims showed no infections. CONCLUSIONS: Well conducted multinational follow-up studies using the same methodology of testing are necessary for accurate surveillance of respiratory viral infections among Hajj pilgrims. Post-Hajj cohort studies would further evaluate the impact of the Hajj on the acquisition of respiratory viruses.

Mass Gatherings and the Spread of Respiratory Infections. Lessons from the Hajj.

The mass gathering of people is a potential source for developing, propagating, and disseminating infectious diseases on a global scale. Of the illnesses associated with mass gatherings, respiratory tract infections are the most common, the most easily transmitted, and the most likely to be spread widely beyond the site of the meeting by attendees returning home. Many factors contribute to the spread of these infections during mass gatherings, including crowding, the health of the attendees, and the type and location of meetings. The annual Hajj in the Kingdom of Saudi Arabia is the largest recurring single mass gathering in the world. Every year more than 10 million pilgrims attend the annual Hajj and Umrah. Attendees assemble in confined areas for several days. People with a wide range of age, health, susceptibility to illness, and hygiene sophistication come in close contact, creating an enormous public health challenge. Controlling respiratory infections at the Hajj requires surveillance, rapid diagnostic testing, and containment strategies. Although the Hajj is without equal, other mass gatherings can generate similar hazards. The geographic colocalization of the Zika virus epidemic and the 2016 Summer Olympic Games in Brazil is a current example of great concern. The potential of international mass gatherings for local and global calamity calls for greater global attention and research.

The spectrum of respiratory pathogens among returning Hajj pilgrims: myths and reality.

Enhanced surveillance systems have been implemented recently in many countries in order to rapidly detect and investigate any possible cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection among travellers returning from the Middle East, including notably Hajj pilgrims. According to the available surveillance data, only a few sporadic travel-associated MERS-CoV cases have been reported outside the Arabian Peninsula so far, mainly in Europe, North Africa, and Asia. These have resulted in no cases, or limited numbers of secondary cases except in Korea. The vast majority of viral respiratory infections in pilgrims returning home have been due to seasonal influenza viruses, rhinoviruses, and other known coronaviruses distinct from the MERS coronavirus. Influenza vaccination should be a priority for all Hajj pilgrims, as recommended by experts.

Hajj-associated viral respiratory infections: A systematic review.

Respiratory tract infections (RTI) are the most common infections transmitted between Hajj pilgrims. The aim of this systematic review was to determine the prevalence of virus carriage potentially responsible for RTI among pilgrims before and after participating in the Hajj. A systematic search for relevant literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. 31 studies were identified. Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS) were never isolated in Hajj pilgrims. The viruses most commonly isolated from symptomatic patients during the Hajj by PCR were rhinovirus (5.9-48.8% prevalence), followed by influenza virus (4.5-13.9%) and non-MERS coronaviruses (2.7-13.2%) with most infections due to coronavirus 229E; other viruses were less frequently isolated. Several viruses including influenza A, rhinovirus, and non-MERS coronaviruses had low carriage rates among arriving pilgrims and a statistically significant increase in their carriage rate was observed, following participation in the Hajj. Further research is needed to assess the role of viruses in the pathogenesis of respiratory symptoms and their potential role in the severity of the symptoms.

The inevitable Hajj cough: Surveillance data in French pilgrims, 2012-2014.

BACKGROUND: Respiratory tract infections are the most common infection affecting Hajj pilgrims, and the ''Hajj cough'' is considered by pilgrims almost de rigueur. METHODS: French pilgrims were recruited between January 2012-December 2014 and information on demographics, medical history, compliance with preventive measures and health problems during travel were collected. RESULTS: A total of 382 pilgrims were included with 39.3% aged ≥65 years and 55.1% suffering from a chronic disease, most frequently hypertension and diabetes. The prevalence of cough was 80.9% and a high proportion presented with associated sore throat (91.0%), rhinitis (78.7%) and hoarseness (63.0%). Myalgia was reported in 48.3% of cases and subjective fever in 47.3%. The incubation time of respiratory symptoms was 7.7 days (range 0-25 days) and 51.9% of pilgrims presenting with a cough during their stay were still symptomatic on return. Among pilgrims with a cough, 69.4% took antibiotics. The prevalence of cough was significantly higher among females than men, but age, chronic conditions and preventive measures had no significant effect. CONCLUSIONS: The Hajj cough is highly common, likely a result of crowded conditions at religious places. Pilgrims should be advised to carry symptomatic relief for the Hajj cough such as cough suppressant, soothing throat lozenges and paracetamol. Use of antibiotics should be discouraged.

Epidemiology of Injuries Caused by Mammals Treated in Emergency Departments in Marseille, France.

A total of 304 patients with mammal-related injuries were included over the 2-year survey period (1.5% of total admissions) at the emergency departments of a large city in southern France. Admissions peaked during the summer months. Dogs accounted for 75.3% and cats for 16.8% of cases. Dog injuries were significantly more common in younger individuals. Overall, signs of infection were observed in 17.9% of cases and were more likely to occur in patients injured by cats and in patients injured more than 1 day before consulting. The majority of patients received an antibiotic prophylaxis, independent to the delay between injury and consultation. Only 1 out of 10 injured patients who consulted an emergency department were seen at the rabies treatment center. Emergency department surveillance data offers an effective and efficient method for conducting animal bite surveillance to monitor trends and characterize animal bite victims.

French Hajj pilgrims' experience with pneumococcal infection and vaccination: A knowledge, attitudes and practice (KAP) evaluation.

BACKGROUND: Transmission of respiratory infections poses a major public health challenge during the Hajj and Umrah in the Kingdom of Saudi Arabia. Acquisition of Streptococcus pneumoniae during Hajj has been studied in the past and recommendations for vaccination against S. pneumoniae have been made for high risk groups. METHODS: The purpose of this study was to assess the knowledge and attitudes of French Hajj pilgrims towards pneumococcal vaccination. Adult pilgrims departing from Marseille, France to Mecca for the 2014 Hajj season were administered a face-to-face questionnaire to ascertain their knowledge and attitudes towards pneumococcal vaccination before departing for Hajj. RESULTS: A total of 300 participants took part. Their overall knowledge about the severity of pneumonia and the existence of the vaccine was very low. Out of 101 participants who had an indication for pneumococcal vaccination, irrespective of their travel status, only 7% were advised to have the vaccine by their general practitioner. CONCLUSIONS: These results reinforce the need for better dissemination of information either before or during the pre-travel counselling. The visit to the travel clinic for receiving the mandatory meningococcal vaccination for Hajj is a good opportunity to update routine immunizations, including pneumococcal vaccination.

Diarrhea at the Hajj and Umrah.

This systematic review aims to summarize the incidence and etiology of diarrheal illness among pilgrims attending the Hajj and Umrah. Gastroenteritis and diarrhea have been potential threats during previous Hajj pilgrimages. The last cases of Hajj related cholera were reported in 1989. Currently, respiratory tract infections account for the majority of health problems during the Hajj. This shift in epidemiology reflects the improvement of sanitary conditions in Saudi Arabia in general, and at religious sites in particular. Nevertheless, gastrointestinal diseases, food-poisoning outbreaks, and diarrhea continue to occur among pilgrims. Available studies about diarrhea among Hajj pilgrims indicate a mean prevalence of 2% with the highest prevalence of 23% among a group of French pilgrims in 2013. There is an obvious lack of information about the etiology of diarrheal disease at the Hajj. Further studies addressing this issue in hospitalized patients as well as prospective cohort studies would be of interest. During the Hajj, hand washing is regularly carried out by pilgrims under a ritual purification, often called ablution. We recommend implementation of effective hand hygiene practices focusing on the regular use of alcohol-based hand rubs, as they require less time than traditional hand washing, act more rapidly, and contribute to sustained improvement in compliance associated with decreased infection rates.

Acquisition of extended-spectrum cephalosporin- and colistin-resistant Salmonella enterica subsp. enterica serotype Newport by pilgrims during Hajj.

Gatherings like the Hajj involving many people who travel from different parts of the world represent a risk for the acquisition and dissemination of infectious diseases. In this study, acquisition of multidrug-resistant (MDR) Salmonella spp. in 2013 Hajj pilgrims from Marseille, France, was investigated. In total, 267 rectal swabs were collected from 129 participants before their departure and after their return from the pilgrimage as well as during the pilgrimage from patients with diarrhoea. Samples were screened for the presence of Salmonella using quantitative real-time PCR and culture. Whole-genome sequencing was performed to characterise one of the isolates, and the mechanism leading to colistin resistance was investigated. Six post-Hajj samples and one sample collected during a diarrhoea episode in Hajj were positive for Salmonella by real-time PCR, with five Salmonella enterica belonging to several serotypes recovered by culture, whereas no pre-Hajj sample was positive. Two of the isolates belonged to the epidemic Newport serotype, were resistant to cephalosporins, gentamicin and colistin, and harboured the bla(CTX-M-2) gene and a 12-nucleotide deletion in the pmrB gene leading to colistin resistance. This study shows that pilgrims acquired Salmonella bacteria, including a novel MDR clone, during the Hajj pilgrimage. This calls for more improved public health surveillance during Hajj because Salmonella is one of the most common diarrhoea-causing bacteria worldwide. Therefore, returning pilgrims could disseminate MDR bacteria worldwide upon returning to their home countries.

Foot ailments during Hajj: A short report.

A study of ailments of the feet in pilgrims of Hajj revealed that 31% of them suffered from blisters, and the prevalence was five times higher in females. The presence of comorbidity (diabetes, obesity and advanced age) warrants immediate attention to them to avoid serious complications.

Respiratory viruses and bacteria among pilgrims during the 2013 Hajj.

Pilgrims returning from the Hajj might contribute to international spreading of respiratory pathogens. Nasal and throat swab specimens were obtained from 129 pilgrims in 2013 before they departed from France and before they left Saudi Arabia, and tested by PCR for respiratory viruses and bacteria. Overall, 21.5% and 38.8% of pre-Hajj and post-Hajj specimens, respectively, were positive for ≥1 virus (p = 0.003). One third (29.8%) of the participants acquired ≥1 virus, particularly rhinovirus (14.0%), coronavirus E229 (12.4%), and influenza A(H3N2) virus (6.2%) while in Saudi Arabia. None of the participants were positive for the Middle East respiratory syndrome coronavirus. In addition, 50.0% and 62.0% of pre-Hajj and post-Hajj specimens, respectively, were positive for Streptococcus pneumoniae (p = 0.053). One third (36.3%) of the participants had acquired S. pneumoniae during their stay. Our results confirm high acquisition rates of rhinovirus and S. pneumoniae in pilgrims and highlight the acquisition of coronavirus E229.

Non-pharmaceutical interventions for the prevention of respiratory tract infections during Hajj pilgrimage.

Overcrowding during the yearly Hajj mass gatherings is associated with increased risk of spreading infectious diseases, particularly respiratory diseases. Non-pharmaceutical interventions (e.g., hand hygiene, wearing face masks, social distancing) are known to reduce the spread of respiratory viruses from person to person and are therefore recommended to pilgrims by public health agencies. The implementation of effective public health policies and recommendations involves evaluating the adherence to and effectiveness of these measures in the specific context of the Hajj. This review summarizes the evidence related to the effectiveness of non-pharmaceutical interventions in preventing the spread of respiratory infectious diseases during the Hajj. Overall, although hand hygiene compliance is high among pilgrims, face mask use and social distancing remain difficult challenges. Data about the effectiveness of these measures at the Hajj are limited, and results are contradictory, highlighting the need for future large-scale studies.