Whole genome transcriptomic reveals heat stroke molecular signatures in humans.

An evolutionary heat shock response (HSR) protects most living species, including humans, from heat-induced macromolecular damage. However, its role in the pathogenesis of heat stroke is unknown. We examined the whole genome transcriptome in peripheral blood mononuclear cells of a cohort of subjects exposed to the same high environmental heat conditions, who developed heat stroke (n = 19) versus those who did not (n = 19). Patients with heat stroke had a mean rectal temperature at admission of 41.7 ± 0.8°C, and eight were in deep coma (Glasgow Coma Score = 3). The transcriptome showed that genes involved in more than half of the entire chaperome were differentially expressed relative to heat stress control. These include the heat shock protein, cochaperone, and chaperonin genes, indicating a robust HSR. Differentially expressed genes also encoded proteins related to unfolded protein response, DNA repair, energy metabolism, oxidative stress, and immunity. The analysis predicted perturbations of the proteome network and energy production. Cooling therapy attenuated these alterations without complete restoration of homeostasis. We validated the significantly expressed genes by a real-time polymerase chain reaction. The findings reveal the molecular signature of heat stroke. They also suggested that a powerful HSR may not be sufficient to protect against heat injury. The overwhelming proteotoxicity and energy failure could play a pathogenic role. KEY POINTS: Most living species, including humans, have inherent heat stress response (HSR) that shields them against heat-induced macromolecular damage. The role of the HSR in subjects exposed to environmental heat who progressed to heat stroke versus those that did not is unknown. Our findings suggest that heat stroke induces a broad and robust HSR of nearly half of the total heat shock proteins, cochaperones, and chaperonin genes. Heat stroke patients exhibited inhibition of genes involved in energy production, including oxidative phosphorylation and ATP production. Significant enrichment of neurodegenerative pathways, including amyloid processing signalling, the Huntington's and Parkinson's disease signalling suggestive of brain proteotoxicity was noted. The data suggests that more than a powerful HSR may be required to protect against heat stroke. Overwhelming proteotoxicity and energy failure might contribute to its pathogenesis.

Classic heat stroke in a desert climate: A systematic review of 2632 cases.

BACKGROUND: Although classic heat stroke (HS) is one of the most ancient conditions known to humans, the description of its early clinical manifestations, natural course, and complications remains uncertain. OBJECTIVES: A systematic review of the demographics, clinical characteristics, biomarkers, therapy, and outcomes of HS during the Muslim (Hajj) pilgrimage in the desert climate of Mecca, Saudi Arabia. METHODS: We searched the MEDLINE, Embase, Web of Science Core Collection, SCOPUS, and CINAHL databases from inception to April 2022. We summarized the data from eligible studies and synthesized them in narrative form using pooled descriptive statistics. RESULTS: Forty-four studies, including 2632 patients with HS, met the inclusion criteria. Overweight or obesity, diabetes, and cardiovascular disease were prevalent among cases of HS. Evidence suggests that extreme hyperthermia (pooled mean = 42.0°C [95% confidence interval (CI): 41.9, 42.1], range 40-44.8°C) with hot and dry skin (>99% of cases) and severe loss of consciousness (mean Glasgow Coma Scale <8 in 53.8% of cases) were the dominant clinical characteristics of classic HS. Hypotension, tachypnea, vomiting, diarrhea, and biochemical biomarkers indicating mild-to-moderate rhabdomyolysis, acute kidney, liver, heart injury, and coagulopathy were frequent at the onset. Concomitantly, stress hormones (cortisol and catecholamines) and biomarkers of systemic inflammation and coagulation activation were increased. HS was fatal in 1 in 18 cases (pooled case fatality rate = 5.6% [95%CI: 4.6, 6.5]). CONCLUSIONS: The findings of this review suggest that HS induces an early multiorgan injury that can progress rapidly to organ failure, culminating in death, if it is not recognized and treated promptly.

Undiagnosed and missed active pulmonary tuberculosis during mass gatherings: a prospective cross-sectional study from the Hajj pilgrimage.

Mass gatherings increase the risk of infectious diseases transmission including tuberculosis (TB). The Hajj pilgrimage to Mecca, Saudi Arabia, is attended by over 2 million pilgrims many of whom are from high TB-burden countries, and has been linked to increased risk of TB acquisition among travellers. We investigated the burden of undiagnosed and missed active pulmonary TB (PTB) among Hajj pilgrims symptomatic for cough. The study was conducted among hospitalised and non-hospitalised travellers attending the Hajj pilgrimage in 2016 and 2017. Questionnaires were used to collect relevant data and sputum samples were collected from participants and processed using the Xpert MTB-RIF assay. Non-hospitalised pilgrims (n = 1510) originating from 16 high and medium TB-burden countries were enrolled. Undiagnosed, rifampicin-sensitive, active PTB was identified in 0.7%. Comorbidities (adjOR = 5.9 [95% CI = 1.2-27.8]), close contact with a TB case (adjOR = 5.9 [95% CI = 1.2-27.8]), cough in household (adjOR = 4.46 [95% CI = 1.1-19.5]), and previous TB treatment (adjOR = 10.1 [95% CI = 4.1-98.1]) were independent risk factors for TB. Of the hospitalised pilgrims (n = 304), 2.9% were positive for PTB, and 2.3% were missed, including a rifampicin-resistant case. History of TB treatment was associated with increased risk of TB (adjOR = 8.1 [95% CI = 1.3-48.7]). International mass gatherings may play an important role in the global epidemiology of TB. Preventive measures should be directed to reducing the risk of TB importation and transmission during Hajj and other similar events.

Pattern of utilization, disease presentation, and medication prescribing and dispensing at 51 primary healthcare centers during the Hajj mass gathering.

BACKGROUND: The majority of pilgrims seeking healthcare during Hajj are seen at primary healthcare centers (PHCCs). Data on the utilization of these facilities during Hajj can aid in directing optimal health services delivery and allocation of resources during the pilgrimage. METHOD: We investigated the pattern of disease presentation, caseload, and medication prescribing and dispensing at 51 PHCCs during the 2019 Hajj. Data on patients' demographics, diagnoses, and prescribed medications were retrieved from each PHCC's electronic records and analyzed. Data were also used to calculate six of the World Health Organization (WHO) indicators for drug use at these facilities. RESULTS: Data were captured for 99,367 patients who were mostly Hajj pilgrims (95.4%), male (69.1%) from the Eastern Mediterranean (60.8%) and had a mean age of 46.6 years (SD = 14.9). Most patients (85.2%) were seen in Mina and towards the end of Hajj. The majority of patients (96.0%) had a single diagnosis; most commonly, respiratory (45.0%), musculoskeletal (17.2%), and skin (10.5%) diseases. Patients were prescribed 223,964 medications, mostly analgesics (25.1%), antibacterials for systemic use (16.5%), anti-inflammatory and antirheumatic products (16.4%), and cough and cold preparations (11.9%). On average, 2.25 (SD = 0.94) medications were prescribed per consultation, with low (1.3%) prevalence of polypharmacy. An antibiotic and an injectable were prescribed in 43.6 and 2.67% of patient encounters, respectively. Most (92.7%) of the prescribed drugs were actually dispensed, in an average time of 8.06 min (SD = 41.4). All PHCCs had a copy of the essential drugs list available, on which all the prescribed drugs appeared. CONCLUSION: Respiratory illnesses are the main reason for PHCCs visits during Hajj, and analgesics and antibiotics are the most common medications prescribed to pilgrims. Our results, including the calculated WHO drug use indicators, contribute to evidence-based optimization of primary healthcare services during Hajj.

Respiratory pathogens among ill pilgrims and the potential benefit of using point-of-care rapid molecular diagnostic tools during the Hajj.

We investigated respiratory pathogens among ill Hajj pilgrims from Marseille. We also discuss the potential role of point-of-care (POC) rapid molecular diagnostic tools for this purpose. Clinical data were collected using a standardised questionnaire. Influenza A and B viruses, human rhinovirus and human coronaviruses, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae were investigated using real-time PCR in respiratory samples obtained during travel, at the onset of symptoms. 207 participants were included. A cough, expectoration, rhinitis and a sore throat were the most frequent respiratory symptoms, followed by loss of voice and dyspnoea. 38.7% and 25.1% of pilgrims reported a fever and influenza-like symptoms, respectively. 59.4% pilgrims received antibiotics. Rhinovirus (40.6%) was the most frequent pathogen, followed by S. aureus (35.8%) and H. influenzae (30.4%). Virus and bacteria co-infections were identified in 28.5% of participants. 25.1% pilgrims who were positive for respiratory bacteria did not receive antibiotic treatment. In the context of the Hajj pilgrimage, it is important to detect infections that can be easily managed with appropriate treatment, and those that can affect prognosis, requiring hospitalisation. POC rapid molecular diagnostic tools could be used for patient management at small Hajj medical missions and to rationalise antibiotic consumption among Hajj pilgrims.

Interferon-induced transmembrane protein-3 genetic variant rs12252 is associated with COVID-19 mortality.

Interferon-induced membrane proteins (IFITM) 3 gene variants are known risk factor for severe viral diseases. We examined whether IFITM3 variant may underlie the heterogeneous clinical outcomes of SARS-CoV-2 infection-induced COVID-19 in large Arab population. We genotyped 880 Saudi patients; 93.8% were PCR-confirmed SARS-CoV-2 infection, encompassing most COVID-19 phenotypes. Mortality at 90 days was 9.1%. IFITM3-SNP, rs12252-G allele was associated with hospital admission (OR = 1.65 [95% CI; 1.01-2.70], P = 0.04]) and mortality (OR = 2.2 [95% CI; 1.16-4.20], P = 0.01). Patients less than 60 years old had a lower survival probability if they harbor this allele (log-rank test P = 0.002). Plasma levels of IFNγ were significantly lower in a subset of patients with AG/GG genotypes than patients with AA genotype (P = 0.00016). Early identification of these individuals at higher risk of death may inform precision public health response.

Gastrointestinal symptoms and the acquisition of enteric pathogens in Hajj pilgrims: a 3-year prospective cohort study.

The acquisition of enteric pathogens and risk factors for Hajj-associated diarrhea in Hajj pilgrims is poorly documented. Pilgrims from Marseille participating in the Hajj in 2016-2018 underwent successive systematic rectal swabbing before and after their travel. Carriage of the main enteric pathogens was assessed by real-time PCR. Baseline demographics, adherence to individual preventive measures, gastrointestinal symptoms, and treatments were recorded. A total of 376 pilgrims were included. The median age was 62.0 years. During the Hajj, 18.6% presented at least one gastrointestinal symptom, 13.8% had diarrhea, and 36.4% had acquired at least one enteric pathogen. Enteropathogenic Escherichia coli (EPEC) and Enteroaggregative E. coli (EAEC) were the pathogens most frequently acquired by pilgrims (17.6% and 14.4%, respectively). Being female was associated with increased frequency of gastrointestinal symptoms during the pilgrimage (aOR = 2.38, p = 0.004). Enterohemorrhagic Escherichia coli (EHEC) acquisition was associated with a four-fold higher risk of reporting at least one gastrointestinal symptom and diarrhea (aOR = 3.68 and p = 0.01 and aOR = 3.96 and p = 0.01, respectively). Pilgrims who suffered from diarrhea were more likely to wash their hands more often (aOR = 2.07, p = 0.03) and to be either overweight (aOR = 2.71, p = 0.03) or obese (aOR = 2.51, p = 0.05). Enteric bacteria such as E. coli that are frequently associated with traveler's diarrhea due to the consumption of contaminated food and drink were frequently found in pilgrims. Respecting strict measures regarding food and water quality during the Hajj and adherence to preventive measures such as good personal hygiene and environmental management will help reduce the burden of gastrointestinal infections at the event.

Acquisition of multidrug-resistant bacteria and encoding genes among French pilgrims during the 2017 and 2018 Hajj.

The objective of this study is to determine the acquisition of multidrug-resistant (MDR) bacteria and antibiotic resistance-encoding genes by French Hajj pilgrims and associated risk factors. Pilgrims traveling during the 2017 and 2018 Hajj were recruited. All pilgrims underwent two successive systematic nasopharyngeal and rectal swabs, pre- and post-Hajj. Specific culture media were used to screen for MDR bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant bacteria, and extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E). qPCR was used to identify antibiotic resistance-encoding genes from cultured isolates. Direct screening of genes encoding for colistin resistance (mcr-1, 2, 3, 4, 5, and 8) from nasopharyngeal and rectal swabs was performed using qPCR, and positive qPCR results were simultaneously tested by sequencing. There were 268 pilgrims included. The percentage of pilgrims acquiring MDR bacteria during the Hajj was 19.4%. A total of 81 strains were isolated (1 carbapenem-resistant Acinetobacter baumannii, 12 MRSA, and 68 ESBL-E). ESBL-E strains were found in rectal samples of 6.0% pilgrims pre-Hajj and of 16.4% pilgrims post-Hajj. Only 0.4% pilgrims were positive for CARB post-Hajj and 1.9% carried nasal MRSA pre- and post-Hajj. In addition, 23 (8.6%) post-Hajj rectal swabs were positive for mcr genes (19 mcr-1 gene and 4 mcr-4 gene). No significant association was found between co-factors and acquisition of MDR bacteria or mcr genes. MDR bacteria and genes are acquired by pilgrims during the Hajj mass gathering. Rationalization of antibiotic consumption and implementation of measures to prevent transmission of bacteria among pilgrims during the event are of paramount importance.

Gastrointestinal symptoms and knowledge and practice of pilgrims regarding food and water safety during the 2019 Hajj mass gathering.

BACKGROUND: Food and water-borne diseases (FWBDs) are a health risk at the Hajj mass gathering. The current study documented the prevalence and management of gastrointestinal (GI) symptoms among pilgrims during the 2019 Hajj and assessed their knowledge and practice concerning food and water safety. METHOD: An analytical cross-sectional study was conducted in Macca, Saudi Arabia, among adult Hajj pilgrims from 28 countries. Data was collected from 15th-20th August 2019 by facer-to-face interviews using an anonymous structured questionnaire. Basic demographic data as well as information regarding pilgrims' knowledge and practice relating to food and water safety and any GI symptoms experienced during the Hajj was collected and analyzed. RESULTS: The study enrolled 1363 pilgrims with a mean age of 50.1 years (SD = 12.3) and 63.4% (n = 845) were male. At least 9.7% (n = 133) of pilgrims experience GI symptoms and 5.1% (69/1363) suffered diarrhea. Most respondents drunk bottled water (99.4%, n = 1324) and obtained their food from their hotel /Hajj mission (> 86%). In general, pilgrims had good knowledge and practice in relation to food and water safety, although risky practices were noted concerning keeping food at unsafe temperatures and hazardous sharing of food and water. Gender, nationality and suffering GI symptoms during Hajj were significantly associated with good knowledge and good practice. There was a moderate but statistically significant positive correlation between knowledge and practice scores (rs = 0.41, p < 0.0001). CONCLUSION: Despite overall good knowledge and self-reported practice, risky behaviors relating to food and water safety were identified among pilgrims, many of whom suffered from GI symptoms during Hajj. Our results can form the basis for developing tailored, targeted and effective interventions to improve pilgrims' knowledge and behavior and reduce the burden of FWBDs at the Hajj and beyond.

Medication utilization pattern among outpatients during the Hajj mass gathering.

BACKGROUND: The Kingdom of Saudi Arabia (KSA) provides free healthcare, including medications, for the over 2 million Muslim pilgrims who attend Hajj every year. Information on drug utilization patterns at the Hajj is important to strengthen the supply chain for medicines, avert stock-outs, identify inappropriate use, and support public health planning for the event. METHOD: We investigated drug utilization pattern among outpatients in eight seasonal Holy sites hospitals in Makkah, KSA, during the 2018 Hajj. Data on medication prescribed and dispensed were retrieved from the hospitals' electronic records. Data were also used to calculate six of the WHO indicators for drug use at these facilities. RESULTS: A total of 99,117 medications were prescribed for 37,367 outpatients during 37,933 encounters. Outpatients were mainly older males and originated from 134 countries. Twenty medications accounted for 72.8% of the 323 different medications prescribed. These were mainly nonsteroidal anti-inflammatory drugs, analgesics and antipyretics, and antibacterial medicines for systemic use. Outpatients were prescribed an average of 2.6 (SD = 1.2) drugs per consultation and polypharmacy (≥5 medications) was observed in 4.8% of the encounters. Antibiotics and an injection were prescribed in 46.9% and 6.5% of encounters, respectively. Nearly 90% of the prescribed drugs were actually dispensed. On average, medications were dispensed 16.4 (SD = 119.8) minutes from the time they were prescribed for the patient. All hospitals had a copy of the essential drugs list available and all of the prescribed drugs appeared on that list. CONCLUSION: Nonsteroidal anti-inflammatory drugs, analgesics and antibiotics are the most common medications prescribed to outpatient during Hajj. Our results, including the calculated WHO drug use indicators, can form a basis for further investigations into appropriate drug use at the Hajj and for planning purposes. These results could also guide the development of reference values for medications prescribing and use indicators at mass gatherings.

Seroprevalence of Herpes Simplex Virus Type 1 and Type 2 and Coinfection With HIV and Syphilis: The First National Seroprevalence Survey in Saudi Arabia.

BACKGROUND: Herpes simplex virus (HSV) infection is one of the most common viral infections worldwide. Genital herpes is associated with other sexually transmitted infections (STIs) including HIV. Data on prevalence of HSV infections and other STIs in the Kingdom of Saudi Arabia are limited. METHODS: We conducted the first national seroprevalence survey to determine the prevalence and epidemiology of HSV infection among adult Saudis and coinfection with other STIs. Serology was used to detect HSV-1, HSV-2, HIV, and syphilis infections among 4985 participants recruited from across the Kingdom. RESULTS: The overall prevalence of HSV-1 and HSV-2 in the enrolled population was 88.8% and 1.26%, respectively. Although not significant for HSV-2, HSV infection was more prevalent among females, those working, and those who were married (married, divorced, or widowed), especially those married at a younger age. Prevalence of both viruses was statistically significantly higher among those with low education and increased with age. Prevalence of Treponema pallidum antibodies and HIV in the sampled population was very low (0.55% and 0.06%, respectively), as was their prevalence among HSV-2-positive participants (1.6% for both). The correlation between HSV-2 infection and other STIs was significant for HIV (P < 0.0001) but not for T. pallidum antibodies (P = 0.25). CONCLUSIONS: Herpes simplex virus type 1 infection is highly prevalent in Saudi Arabia and mostly acquired before adulthood. Herpes simplex virus type 2 prevalence is very low, acquired in adulthood, and increased with age. Monitoring the prevalence of HSV infection can help inform targeted strategies to prevent new infections, neonatal transmission, and the spread of other STIs in the Kingdom.

Prevalence of MERS-CoV nasal carriage and compliance with the Saudi health recommendations among pilgrims attending the 2013 Hajj.

BACKGROUND: Annually, Saudi Arabia is the host of the Hajj mass gathering. We aimed to determine the Middle East respiratory syndrome coronavirus (MERS-CoV) nasal carriage rate among pilgrims performing the 2013 Hajj and to describe the compliance with the Saudi Ministry of Health vaccine recommendations. METHOD: Nasopharyngeal samples were collected from 5235 adult pilgrims from 22 countries and screened for MERS-CoV using reverse transcriptase-polymerase chain reaction. Information regarding the participants' age, gender, country of origin, medical conditions, and vaccination history were obtained. RESULTS: The mean age of the screened population was 51.8 years (range, 18-93 years) with a male/female ratio of 1.17:1. MERS-CoV was not detected in any of the samples tested (3210 pre-Hajj and 2025 post-Hajj screening). According to the vaccination documents, all participants had received meningococcal vaccination and the majority of those from at-risk countries were vaccinated against yellow fever and polio. Only 22% of the pilgrims (17.5% of those ≥65 years and 36.3% of diabetics) had flu vaccination, and 4.4% had pneumococcal vaccination. CONCLUSION: There was no evidence of MERS-CoV nasal carriage among Hajj pilgrims. While rates of compulsory vaccinations uptake were high, uptake of pneumococcal and flu seasonal vaccinations were low, including among the high-risk population.

Escalating climate-related health risks for Hajj pilgrims to Mecca.

BACKGROUND: Global temperatures are on the rise, leading to more frequent and severe heatwaves with associated health risks. Heat-related illnesses (HRIs) are an increasing threat for travellers to hot climate destinations. This study was designed to elucidate the interplay between increasing ambient temperatures, incidence of HRIs and the effectiveness of mitigation strategies during the annual Hajj mass gathering over a 40-year period. METHODS: An observational study was conducted utilizing historical records spanning four decades of meteorological data, and the rates of heat stroke (HS) and heat exhaustion (HE) during the Hajj pilgrimage in Mecca, Saudi Arabia. With an annual population exceeding 2 million participants from over 180 countries, the study analysed temporal variations in weather conditions over two distinct Hajj hot cycles and correlated it with the occurrence of HS and HE. The effectiveness of deployed mitigation measures in alleviating health vulnerabilities between the two cycles was also assessed. RESULTS: Throughout the study period, average dry and wet bulb temperatures in Mecca escalated by 0.4°C (Mann-Kendall P < 0.0001) and 0.2°C (Mann-Kendall P = 0.25) per decade, respectively. Both temperatures were strongly correlated with the incidence of HS and HE (P < 0.001). Despite the intensifying heat, the mitigation strategies including individual, structural and community measures were associated with a substantial 74.6% reduction in HS cases and a 47.6% decrease in case fatality rate. CONCLUSION: The study underscores the escalating climate-related health risks in Mecca over the study period. The mitigation measures' efficacy in such a globally representative setting emphasizes the findings' generalizability and the importance of refining public health interventions in the face of rising temperatures.

Invasive meningococcal disease in older adults: current perspectives and call for action.

PURPOSE: Invasive meningococcal disease (IMD) is a devastating condition. While most attention is directed towards disease in children and adolescents, IMD poses an important cause of morbidity and mortality in adults ≥60 years. While immunization is a critical component of healthy ageing strategies, meningococcal immunization is not routinely offered to older adults. The aim of this review was to summarize clinical and epidemiological aspects of IMD and available immunization strategies, with a particular focus on disease in older individuals, to emphasize the importance of this rather neglected area. METHODS: An expert working group was established to evaluate clinical and epidemiological data to raise awareness of IMD in older individuals, and develop suggestions to improve the existing burden. RESULTS: Routine child and adolescent meningococcal immunization has substantially reduced IMD in these targeted populations. Consequently, prevalence and proportion of IMD among those ≥60 years, mostly unvaccinated, is increasing in developed countries (accounting for up to 25% of cases). IMD-related mortality is highest in this age-group, with substantial sequelae in survivors. IMD due to serogroups W and Y is more prevalent among older adults, often with atypical clinical features (pneumonia, gastrointestinal presentations) which may delay timely treatment. CONCLUSIONS: IMD in older adults remains overlooked and greater awareness is required at clinical and societal levels. We encourage clinicians and immunization policy makers to reconsider IMD, with a call for action to remedy existing inequity in older adult access to protective meningococcal immunization.

Original Article--Mid-term Clinical and Hemodynamic Outcomes in Middle Age Patients Post Trifecta™ (Abbott) Aortic Valve Replacement: A Single-center Study.

Background: Trifecta™ is an externally wrapped bovine pericardial aortic valve with a favorable hemodynamic performance and acceptable rate of freedom from structural valve degeneration. However, recent reports of early Trifecta valve failure question its durability. Rheumatic valve disease in young population is predominant, there is no data on the Trifecta performance, durability or safety available worldwide over the middle age population, as well as there are no previous similar reports from Middle East region. We report on mid-term clinical and hemodynamic performance of Trifecta valve in middle age population with small aortic annuls, a single center report. Methods: A retrospective study of all patients who underwent Trifecta™ SAVR between June 2014 and December 2019 at a cardiac center in Riyadh, Saudi Arabia. Hemodynamic performance was analyzed by longitudinal Doppler echocardiography. Results: During a 5.5-year period, a total of 24 patients underwent SAVR with Trifecta™ valves at our heart center. Patients had a median age of 47.1 years (IQR = 37) and male:female ratio of 1:1. Patients had a median EuroScoreII of 2 (IQR = 1). The 19 mm valve was the most frequently used (29.2%) followed by the 21 mm and 23 mm (both 25.0%). Concomitant procedure was (54.2%). All patients survived their operations and most (87.0%) had their symptoms relieved. A 30-day mortality rate of 4.2%. Patients were followed up for a median of 58.5 months (IQR = 38), during which 8.3% required re interventions, giving an overall freedom from re-intervention of 91.7%. The re-intervention after valve implantation was recorded in two (8.3%). These re-interventions were performed 3 years post initial surgery and were due to structural valve deterioration (SVD). The mean gradient reduced significantly from 43.6 ± 23.9 mmHg (median = 41, IQR = 21) at baseline to 13.0 ± 7.4 mmHg (median = 11, IQR = 5) one-week post intervention (p < 0.001). The average mean gradients were stable from post-operation to follow-up (13.0 ± 7.4 vs 14.1 ± 6.4 mmHg). Conclusion: Our study confirms excellent mid-term durability, clinical and hemodynamic performance of the Trifecta™ valve in middle age population, despite the fact of non-statically significant trend-up of transvalvular gradient over the follow up period. Further long-term studies with larger sample-size are warranted to confirm these results.

Meningococcal disease in the Middle East: A report from the Global Meningococcal Initiative.

This review details recent findings from the Global Meningococcal Initiative's (GMI) recent meeting on the surveillance and control strategies for invasive meningococcal disease in the Middle East. The nature of case reporting and notification varies across the region, with many countries using bacterial meningitis as an IMD case definition in lieu of meningitis and septicaemia. This may overlook a significant burden associated with IMD leading to underreporting or misreporting of the disease. Based on these current definitions, IMD reported incidence remains low across the region, with historical outbreaks mainly occurring due to the Hajj and Umrah mass gatherings. The use of case confirmation techniques also varies in Middle Eastern countries. While typical microbiological techniques, such as culture and Gram staining, are widely used for characterisation, polymerase chain reaction (PCR) testing is utilised in a small number of countries. PCR testing may be inaccessible for several reasons including sample transportation, cost, or a lack of laboratory expertise. These barriers, not exclusive to PCR use, may impact surveillance systems more broadly. Another concern throughout the region is potentially widespread ciprofloxacin resistance since its use for chemoprophylaxis remains high in many countries.

Risk factors for heat-related illnesses during the Hajj mass gathering: an expert review.

Human exposure to a hot environment may result in various heat-related illnesses (HRIs), which range in severity from mild and moderate forms to life-threatening heatstroke. The Hajj is one of the largest annual mass gatherings globally and has historically been associated with HRIs. Hajj attracts over two million Muslim pilgrims from more than 180 countries to the holy city of Makkah, Kingdom of Saudi Arabia. Several modifiable and non-modifiable factors render Hajj pilgrims at increased risk of developing HRIs during Hajj. These include characteristics of the Hajj, its location, population, and rituals, as well as pilgrims' knowledge of HRIs and their attitude and behavior. Makkah is characterized by a hot desert climate and fluctuating levels of relative humidity. Pilgrims are very diverse ethnically and geographically, with different adaptations to heat. Significant proportions of the Hajj population are elderly, obese, and with low levels of fitness. In addition, many have underlying health conditions and are on multiple medications that can interfere with thermoregulation. Other factors are inherent in the Hajj and its activities, including crowding, physically demanding outdoor rituals, and a high frequency of infection and febrile illness. Pilgrims generally lack awareness of HRIs, and their uptake of preventive measures is variable. In addition, many engage in hazardous behaviors that increase their risk of HRIs. These include performing rituals during the peak sunshine hours with no sun protection and with suboptimal sleep, nutrition, and hydration, while neglecting treatment for their chronic conditions. HRIs preventive plans for Hajj should incorporate measures to address the aforementioned factors to reduce the burden of these illnesses in future Hajj seasons. Lessons from the Hajj can be used to inform policy making and HRIs preventive measures in the general population worldwide.

Diagnosing and managing heat exhaustion: insights from a systematic review of cases in the desert climate of Mecca.

Heat exhaustion (HE) is a common, yet obscure, heat-related illness that affects millions of people yearly and its burden is projected to rise due to climate change. A comprehensive literature synthesis is lacking despite previous studies on various HE aspects. This systematic review aims to fill this gap by identifying and synthesizing available evidence on the risk factors, symptoms, biomarkers, treatment options, and outcomes for HE. The review focused on HE during the Muslim (Hajj) pilgrimage where the condition is endemic. We conducted a structured search of MEDLINE/PubMed, Embase, Web of Science Core Collection, SCOPUS, and CINAHL databases. We summarized the data from eligible studies and synthesized them in narrative form using pooled descriptive statistics. Ten studies were included between 1980 and 2019, reporting over 1,194 HE cases. HE cases presented with elevated core temperature (up to 40°C) and mainly affected older males from the Middle East and North Africa region, with overweight individuals at a higher risk. Clinical symptoms included hyperventilation, fatigue, dizziness, headaches, nausea, and vomiting, but not central nervous system disturbances. HE was associated with cardiac stress, and with water, electrolyte, and acid-base alterations. Cooling and hydration therapy were the primary management strategies, leading to a low mortality rate (pooled case fatality rate=0.11 % [95 % CI: 0.01, 0.3]). Most cases recovered within a few hours without complications. HE is associated with cardiac stress and changes in homeostasis, leading to distinct clinical symptoms. Early diagnosis and treatment of HE are crucial in reducing the risk of complications and mortality. The review provides insights into the pathophysiology and outcomes of HE, adding to the scarce literature on the subject. Prospero registration number: CRD42022325759.

Association of Ambient Temperature with Mortality in Resident and Multiethnic Transient Populations in a Desert Climate, 2006-2014.

BACKGROUND: Although the association between ambient temperature and mortality in local populations is evident, this relationship remains unclear in transient populations (e.g., due to immigration, mass gatherings, or displacement). The holy city of Mecca annually shelters two populations comprising its residents and the transitory Hajj pilgrims (>2 million people from >180 countries). Both live side by side in a hot desert climate, rendering the development of evidence-based heat-protective measures challenging. OBJECTIVES: We aimed to characterize the ambient temperature-mortality relationship and burden for the Mecca resident and Hajj transient populations, which have distinct levels of adaptation to ambient temperature. METHODS: We analyzed daily air temperature and mortality data for Mecca residents and pilgrims over nine Hajj seasons between 2006 and 2014, using a fitted standard time-series Poisson model. We characterized the temperature-mortality relationship with a distributed lag nonlinear model with 10 d of lag. We determined the minimum mortality temperature (MMT) and attributable deaths for heat and cold for the two populations. RESULTS: The median average daily temperature during the Hajj seasons was 30°C (19°C-37°C). There were 8,543 and 10,457 nonaccidental deaths reported during the study period among Mecca residents and pilgrims, respectively. The MMT was 2.5°C lower for pilgrims in comparison with the MMT for Mecca residents (23.5°C vs. 26.0°C). The temperature-mortality relationship shape varied from inverted J to U shape for the Mecca and pilgrim populations, respectively. Neither hot nor cold temperatures had a statistically significant association with mortality in Mecca residents. In contrast, for pilgrims, elevated temperatures were associated with significantly high attributable mortality of 70.8% [95% confidence interval (CI): 62.8, 76.0]. The effect of heat on pilgrims was immediate and sustained. DISCUSSION: Our findings indicate that pilgrims and Mecca residents exposed to the same hot environmental conditions exhibited distinct health outcomes. This conclusion suggests that a precision public health approach may be warranted to protect against high environmental temperature during mass gatherings of diverse populations. https://doi.org/10.1289/EHP9838.

Human tolerance to extreme heat: evidence from a desert climate population.

BACKGROUND: Ambient temperatures exceeding 40 °C are projected to become common in many temperate climatic zones due to global warming. Therefore, understanding the health effects of continuous exposure to high ambient temperatures on populations living in hot climatic regions can help identify the limits of human tolerance. OBJECTIVE: We studied the relationship between ambient temperature and non-accidental mortality in the hot desert city of Mecca, Saudi Arabia, between 2006 and 2015. METHODS: We used a distributed lag nonlinear model to estimate the mortality-temperature association over 25 days of lag. We determined the minimum mortality temperature (MMT) and the deaths that are attributable to heat and cold. RESULTS: We analyzed 37,178 non-accidental deaths reported in the ten-year study period among Mecca residents. The median average daily temperature was 32 °C (19-42 °C) during the same study period. We observed a U-shaped relationship between daily temperature and mortality with an MMT of 31.8 °C. The total temperature-attributable mortality of Mecca residents was 6.9% (-3.2; 14.8) without reaching statistical significance. However, extreme heat, higher than 38 °C, was significantly associated with increased risk of mortality. The lag structure effect of the temperature showed an immediate impact, followed by a decline in mortality over many days of heat. No effect of cold on mortality was observed. IMPACT STATEMENT: High ambient temperatures are projected to become future norms in temperate climates. Studying populations familiar with desert climates for generations with access to air-conditioning would inform on the mitigation measures to protect other populations from heat and on the limits of human tolerance to extreme temperatures. We studied the relationship between ambient temperature and all-cause mortality in the hot desert city of Mecca. We found that Mecca population is adapted to high temperatures, although there was a limit to tolerance to extreme heat. This implies that mitigation measures should be directed to accelerate individual adaptation to heat and societal reorganization.