Fayssal M. Farahat

IFN-α2a or IFN-β1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study

Abstract Objectives Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with significant mortality. We examined the utility of plasma MERS-CoV PCR as a prognostic indicator and compared the efficacies of IFN-α2a and IFN-β1a when combined with ribavirin in reducing MERS-CoV-related mortality rates. Methods We retrospectively analysed 32 patients with confirmed MERS-CoV infection, admitted between April 2014 and June 2014, by positive respiratory sample RT–PCR. Plasma MERS-CoV RT–PCR was performed at the time of diagnosis for 19 patients. Results The overall mortality rate was 69% (22/32). Ninety percent (9/10) of patients with positive plasma MERS-CoV PCR died compared with 44% (4/9) of those with negative plasma MERS-CoV PCR. Mortality rate in patients who received IFN-α2a was 85% (11/13) compared with 64% (7/11) in those who received IFN-β1a (P = 0.24). The mortality rate in patients with renal failure (14), including 8 on haemodialysis, was 100%. Age >50 years and diabetes mellitus were found to be significantly associated with mortality (OR = 26.1; 95% CI 3.58–190.76; P = 0.001 and OR = 15.74; 95% CI 2.46–100.67; P = 0.004, respectively). The median duration of viral shedding in patients who recovered was 11 days (range 6–38 days). Absence of fever was noted in 5/32 patients. Conclusions Plasma MERS-CoV RT–PCR may serve as an effective tool to predict MERS-CoV-associated mortality. Older age and comorbid conditions may have contributed to the lack of efficacy of IFN-α2a or IFN-β1a with ribavirin in treating MERS-CoV. Absence of fever should not exclude MERS-CoV.

Biomarkers of Chlorpyrifos Exposure and Effect in Egyptian Cotton Field Workers

Background Chlorpyrifos (CPF), a widely used organophosphorus pesticide (OP), is metabolized to CPF-oxon, a potent cholinesterase (ChE) inhibitor, and trichloro-2-pyridinol (TCPy). Urinary TCPy is often used as a biomarker for CPF exposure, whereas blood ChE activity is considered an indicator of CPF toxicity. However, whether these biomarkers are dose related has not been studied extensively in populations with repeated daily OP exposures. Objective We sought to determine the relationship between blood ChE and urinary TCPy during repeated occupational exposures to CPF. Methods Daily urine samples and weekly blood samples were collected from pesticide workers (n = 38) in Menoufia Governorate, Egypt, before, during, and after 9–17 consecutive days of CPF application to cotton fields. We compared blood butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) activities with the respective urinary TCPy concentrations in each worker. Results Average TCPy levels during the middle of a 1- to 2-week CPF application period were significantly higher in pesticide applicators (6,437 μg/g creatinine) than in technicians (184 μg/g) and engineers (157 μg/g), both of whom are involved in supervising the application process. We observed a statistically significant inverse correlation between urinary TCPy and blood BuChE and AChE activities. The no-effect level (or inflection point) of the exposure–effect relationships has an average urinary TCPy level of 114 μg/g creatinine for BuChE and 3,161 μg/g creatinine for AChE. Conclusions Our findings demonstrate a dose–effect relationship between urinary TCPy and both plasma BuChE and red blood cell AChE in humans exposed occupationally to CPF. These findings will contribute to future risk assessment efforts for CPF exposure.

Chlorpyrifos exposures in Egyptian cotton field workers

Neurobehavioral deficits have been reported in Egyptian pesticide application teams using organophosphorus (OP) pesticides, but whether these effects are related to OP pesticide exposures has yet to be established. In preparation for a comprehensive study of the relationship between OP pesticide dose and neurobehavioral deficits, we assessed exposure within this population. We conducted occupational surveys and workplace observations, and collected air, dermal patch and biological samples from applicators, technicians and engineers involved in chlorpyrifos applications during cotton production to test the hypotheses that: (1) dermal exposure was an important contributor to internal dose and varied across body regions; and (2) substantial differences would be seen across the three job categories. Applicators were substantially younger and had shorter exposure histories than did technicians and engineers. Applicators and technicians were observed to have relatively high levels of skin or clothing contact with pesticide-treated foliage as they walked through the fields. Both dermal patch loadings of chlorpyrifos and measurements of a chlorpyrifos-specific metabolite (TCPy) in urine confirmed substantial exposure to and skin absorption of chlorpyrifos that varied according to job category; and dermal patch loading was significantly higher on the thighs than on the forearms. These findings support our hypotheses and support the need for research to examine neurobehavioral performance and exposures in this population. More importantly, the exposures reported here are sufficiently high to recommend urgent changes in work practices amongst these workers.

HCV Infection among Saudi Population: High Prevalence of Genotype 4 and Increased Viral Clearance Rate

HCV is a major etiological agent of liver disease with a high rate of chronic evolution. The virus possesses 6 genotypes with many subtypes. The rate of spontaneous clearance among HCV infected individuals denotes a genetic determinant factor. The current study was designed in order to estimate the rate of HCV infection and ratio of virus clearance among a group of infected patients in Saudi Arabia from 2008 to 2011. It was additionally designed to determine the genotypes of the HCV in persistently infected patients. HCV seroprevalence was conducted on a total of 15,323 individuals. Seropositive individuals were tested by Cobas AmpliPrep/Cobas TaqMan HCV assay to determine the ratio of persistently infected patients to those who showed spontaneous viral clearance. HCV genotyping on random samples from persistently infected patients were conducted based on the differences in the 5′untranslated region (5′UTR). Anti-HCV antibodies were detected in 7.3% of the totally examined sera. A high percentage of the HCV infected individuals experienced virus clearance (48.4%). HCV genotyping revealed the presence of genotypes 1 and 4, the latter represented 97.6% of the tested strains. Evidences of the widespread of the HCV genotype 4 and a high rate of HCV virus clearance were found in Saudi Arabia.

Contributions of inhalation and dermal exposure to chlorpyrifos dose in Egyptian cotton field workers.

Abstract Objective: Chlorpyrifos exposures were assessed in 12 Egyptian cotton field workers. Methods: 3,5,6-trichloro-2-pyridinol (TCPy) was measured in 24-hour urine samples to estimate absorbed dose. Workshift air samples were used to calculate chlorpyrifos inhalation dose. Results: Patches on legs had the highest chlorpyrifos loading rates among body regions sampled. Geometric mean chlorpyrifos air concentrations were 5·1, 8·2, and 45·0 μg/m3 for engineers, technicians, and applicators, respectively; peak TCPy urinary concentrations were 75–129, 78–261, and 487–1659 μg/l, respectively; geometric mean doses were 5·2–5·4, 8·6–9·7, and 50–57 μg/kg, respectively, considering TCPy excretion half-life values of 27 and 41 hours. All worker doses exceeded the acceptable operator exposure level of 1·5 μg/kg/day. An estimated 94–96% of the dose was attributed to dermal exposure, calculated as the difference between total dose and inhalation dose. Discussion: Interventions to reduce dermal exposure are warranted in this population, particularly for the hands, feet, and legs.

Experimental strategy for translational studies of organophosphorus pesticide neurotoxicity based on real-world occupational exposures to chlorpyrifos

Translational research is needed to understand and predict the neurotoxic consequences associated with repeated occupational exposures to organophosphorus pesticides (OPs). In this report, we describe a research strategy for identifying biomarkers of OP neurotoxicity, and we characterize pesticide application workers in Egypts Menoufia Governorate who serve as our anchor human population for developing a parallel animal model with similar exposures and behavioral deficits and for examining the influence of human polymorphisms in cytochrome P450 (CYP) and paraoxonase 1 (PON1) enzymes on OP metabolism and toxicity. This population has previously been shown to have high occupational exposures and to exhibit a broad range of neurobehavioral deficits. In addition to observational studies of work practices in the field, questionnaires on demographics, lifestyle and work practices were administered to 146 Egyptian pesticide application workers applying pesticides to the cotton crop. Survey results indicated that the application workforce uses standard operating procedures and standardized equipment provided by Egypts Ministry of Agriculture, which provides a workforce with a stable work history. We also found that few workers report using personal protective equipment (PPE), which likely contributes to the relatively high exposures reported in these application workers. In summary, this population provides a unique opportunity for identifying biomarkers of OP-induced neurotoxicity associated with occupational exposure.

Predictors and outcomes of Candida bloodstream infection: eight-year surveillance, western Saudi Arabia.

OBJECTIVES To assess the epidemiological pattern of Candida bloodstream infection (BSI) over an 8-year period (2002-2009) in King Abdulaziz Medical City, western Saudi Arabia. METHOD A retrospective chart review was performed. RESULTS A total of 258 BSI were identified in 134 males (53.2%) and 118 females (46.8%). There were 86 (34.1%) cases of Candida albicans and 166 (65.9%) non-albicans Candida species. Malignancy was independently associated with the development of candidemia by non-albicans Candida species (odds ratio 3.24, 95% confidence interval 1.25-8.41). Fluconazole in vitro susceptibility was 38.5% for C. albicans and 52.5% for other Candida species. The overall, crude 12-month mortality rate was 50% for C. albicans and 57.8% for non-albicans Candida species. CONCLUSIONS The antifungal resistance coinciding with a change in the epidemiologic pattern of candidemia identified in this study is alarming and urges the need for a review of empiric antifungal therapy and potential contributing environmental factors.

Longitudinal assessment of occupational exposures to the organophosphorous insecticides chlorpyrifos and profenofos in Egyptian cotton field workers

Chlorpyrifos (CPF) and profenofos (PFF) are organophosphorus (OP) insecticides that are applied seasonally in Egypt to cotton fields. Urinary trichloro-2-pyridinol (TCPy), a specific CPF metabolite, and 4-bromo-2-chlorophenol (BCP), a specific PFF metabolite, are biomarkers of exposure, while inhibition of blood butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) activities are effect biomarkers that may be associated with neurotoxicity. Urinary TCPy and BCP and blood BChE and AChE activities were measured in 37 adult Egyptian Ministry of Agriculture workers during and after 9-17 consecutive days of CPF application followed by an application of PFF (9-11 days), and a second CPF application (5 days) in 2008. During the OP applications, urinary TCPy and BCP levels were significantly higher than baseline levels, remained elevated following the application periods, and were associated with an exposure related inhibition of blood BChE and AChE. Analysis of blood AChE levels before and after the PFF application period suggests that individual workers with peak BCP levels greater than 1000 μg/g creatinine exhibited further inhibition of blood AChE with PFF application, demonstrating that PFF exposure had a negative impact on AChE activity in this highly exposed worker population. While large interindividual differences in exposure were observed throughout this longitudinal study (peak urinary BCP and peak TCPy levels for individuals ranging from 13.4 to 8052 and 16.4 to 30,107 μg/g creatinine, respectively), these urinary biomarkers were highly correlated within workers (r=0.75, p<0.001). This suggests that the relative exposures to CPF and PFF were highly correlated for a given worker. The variable exposures between job classification and work site suggest that job title and work location should not be used as the sole basis for categorizing OP exposures when assessing neurobehavioral and other health outcomes in Egyptian cotton field workers. Together, these findings will be important in educating the Egyptian insecticide application workers in order to encourage the development and implementation of work practices and personal protective equipment to reduce their exposure to CPF and PFF.

Metabolism of profenofos to 4-bromo-2-chlorophenol, a specific and sensitive exposure biomarker

Profenofos is a direct acting phosphorothioate organophosphorus (OP) pesticide capable of inhibiting β-esterases such as acetylcholinesterase, butyrylcholinesterase, and carboxylesterase. Profenofos is known to be detoxified to the biologically inactive metabolite, 4-bromo-2-chlorophenol (BCP); however, limited data are available regarding the use of urinary BCP as an exposure biomarker in humans. A pilot study conducted in Egyptian agriculture workers, demonstrated that urinary BCP levels prior to application (3.3-30.0 μg/g creatinine) were elevated to 34.5-3,566 μg/g creatinine during the time workers were applying profenofos to cotton fields. Subsequently, the in vitro enzymatic formation of BCP was examined using pooled human liver microsomes and recombinant human cytochrome P-450s (CYPs) incubated with profenofos. Of the nine human CYPs studied, only CYPs 3A4, 2B6, and 2C19 were able to metabolize profenofos to BCP. Kinetic studies indicated that CYP 2C19 has the lowest Km, 0.516 μM followed by 2B6 (Km=1.02 μM) and 3A4 (Km=18.9μM). The Vmax for BCP formation was 47.9, 25.1, and 19.2 nmol/min/nmol CYP for CYP2B6, 2C19, and 3A4, respectively. Intrinsic clearance (Vmax/Km) values of 48.8, 46.9, and 1.02 ml/min/nmol CYP 2C19, 2B6, and 3A4, respectively, indicate that CYP2C19 and CYP2B6 are primarily responsible for the detoxification of profenofos. These findings support the use of urinary BCP as a biomarker of exposure to profenofos in humans and suggest polymorphisms in CYP 2C19 and CYP 2B6 as potential biomarkers of susceptibility.

Challenges facing female physicians in Egypt.

The number of female physicians all over the world has grown considerably, yet little is known about these women. This study was conducted to explore challenges faced by Egyptian female physicians as they pursue their careers and find different ways of coping with these challenges. The mean age of participants was 31.09 years (SD = 6.46 years). Most of them were married (76.7%), and 40% were part of dual-doctor families (both partners were physicians). In all, 53% of participants were clinicians, 22% academics, and 25% house officers. All academics had no shift work compared with all house officers and 75% of clinicians. Challenges reported by physicians were either work or family related. Although overt discrimination was rare, many participants complained of subtle forms of bias. All participants reported that balancing work and family was more difficult than they ever expected. Participating physicians have dealt with challenges in different ways: deciding on a small family size (82.3%), the recruitment of a babysitter/housekeeper (76.3%), and sharing in the family income (62.0%). Physician training programs, workforce policy, and public expectations should recognize and adapt to the diverse and changing needs of physicians.