Case characteristics among Middle East respiratory syndrome coronavirus outbreak and non-outbreak cases in Saudi Arabia from 2012 to 2015.

OBJECTIVES: As of 1 November 2015, the Saudi Ministry of Health had reported 1273 cases of Middle East respiratory syndrome (MERS); among these cases, which included 9 outbreaks at several hospitals, 717 (56%) patients recovered, 14 (1%) remain hospitalised and 543 (43%) died. This study aimed to determine the epidemiological, demographic and clinical characteristics that distinguished cases of MERS contracted during outbreaks from those contracted sporadically (ie, non-outbreak) between 2012 and 2015 in Saudi Arabia. DESIGN: Data from the Saudi Ministry of Health of confirmed outbreak and non-outbreak cases of MERS coronavirus (CoV) infections from September 2012 through October 2015 were abstracted and analysed. Univariate and descriptive statistical analyses were conducted, and the time between disease onset and confirmation, onset and notification and onset and death were examined. RESULTS: A total of 1250 patients (aged 0-109 years; mean, 50.825 years) were reported infected with MERS-CoV. Approximately two-thirds of all MERS cases were diagnosed in men for outbreak and non-outbreak cases. Healthcare workers comprised 22% of all MERS cases for outbreak and non-outbreak cases. Nosocomial infections comprised one-third of all Saudi MERS cases; however, nosocomial infections occurred more frequently in outbreak than non-outbreak cases (p<0.001). Patients contracting MERS during an outbreak were significantly more likely to die of MERS (p<0.001). CONCLUSIONS: To date, nosocomial infections have fuelled MERS outbreaks. Given that the Kingdom of Saudi Arabia is a worldwide religious travel destination, localised outbreaks may have massive global implications and effective outbreak preventive measures are needed.

An outbreak of Middle East Respiratory Syndrome (MERS) due to coronavirus in Al-Ahssa Region, Saudi Arabia, 2015.

Between 19 April and 23 June 2015, 52 laboratory-confirmed cases of Middle East Respiratory Syndrome due to coronavirus (MERS) were reported from Al-Ahssa region, eastern Saudi Arabia. The first seven cases occurred in one family; these were followed by 45 cases in three public hospitals. The objectives of this investigation were to describe the epidemiological characteristic of the cluster and identify potential risk factors and control measures to be instituted to prevent further occurrence of MERS. We obtained the medical records of all confirmed cases, interviewed the members of the affected household and reviewed the actions taken by the health authorities. All the cases were connected. The index case was a 62-year-old man with a history of close contact with dromedary camels; three of the seven infected family members and 18 people in hospitals died (case-fatality rate, 40.4%). The median incubation period was about 6 days. The cluster of cases appeared to be due to high exposure to MERS, delayed diagnosis, inadequate risk communication and inadequate compliance of hospital health workers and visitors with infection prevention and control measures.

An outbreak of Middle East Respiratory Syndrome (MERS) due to coronavirus in Al-Ahssa Region, Saudi Arabia, 2015

Between 19 April and 23 June 2015, 52 laboratory-confirmed cases of Middle East Respiratory Syndrome due to coronavirus [MERS] were reported from Al-Ahssa region, eastern Saudi Arabia. The first seven cases occurred in one family; these were followed by 45 cases in three public hospitals. The objectives of this investigation were to describe the epidemiological characteristic of the cluster and identify potential risk factors and control measures to be instituted to prevent further occurrence of MERS. We obtained the medical records of all confirmed cases, interviewed the members of the affected household and reviewed the actions taken by the health authorities. All the cases were connected. The index case was a 62-year-old man with a history of close contact with dromedary camels; three of the seven infected family members and 18 people in hospitals died [case-fatality rate, 40.4%]. The median incubation period was about 6 days. The cluster of cases appeared to be due to high exposure to MERS, delayed diagnosis, inadequate risk communication and inadequate compliance of hospital health workers and visitors with infection prevention and control measures

Entre le 19 avril et le 23 juin 2015, 52 cas confirmés en laboratoire de syndrome respiratoire du Moyen-Orient [MERS] causé par le coronavirus ont été notifiés dans la région d'Al-Ahssa, partie orientale de l'Arabie saoudite. Les sept premiers cas sont survenus dans une seule famille ; ils ont été suivis de 45 cas déclarés dans trois hôpitaux publics. Cette investigation avait pour objectifs de détailler les caractéristiques épidémiologiques de ce groupe de cas et d'identifier les facteurs de risque potentiels ainsi que les mesures de lutte à mettre en place afin d'empêcher la survenue de nouveaux cas de MERS. Nous avons consulté les dossiers médicaux de l'ensemble des cas confirmés, avons interrogé les membres des foyers touchés et passé en revue les interventions entreprises par les autorités sanitaires. Tous les cas étaient reliés entre eux. Le cas indicateur était un homme de 62 ans ayant eu des contacts étroits avec des dromadaires ; trois des sept membres infectés de la famille et 18 patients hospitalisés sont décédés [taux de létalité : 40,4%]. La période d'incubation médiane était d'environ 6 jours. Le groupe de cas était vraisemblablement dû à une forte exposition au MERS, associée à un diagnostic tardif, une communication sur les risques inappropriée et une mauvaise observance des mesures de prévention et de lutte contre les infections par les personnels de santé de l'hôpital et les visiteurs

Presentation and reasons for HIV-1 testing in Saudi Arabia.

Clinical presentation, CD4+ T lymphocyte count at diagnosis, and reasons for HIV-1 testing reflect the attitudes towards HIV testing and also the ability of the health-care system to diagnose HIV early. In a cross-sectional study from the HIV database in a large HIV-referral centre in Saudi Arabia, all 410 HIV-infected patients were included, 276 men and 134 women. Women were younger at diagnosis (mean age 25.5 compared with 29 years for men, P < 0.04) and had higher CD4+ T lymphocytes (mean 461 for women and 223 for men, P < 0.001). Out of 276 men, 90 (33%) were identified as HIV infected when they presented with AIDS. Fifty-five percent of the infected women were tested for HIV-1 because of contact with an infected person compared with 8% of the infected men, odds ratio (OR) 13.8 (95% confidence interval [CI]: 7.7-24.9). AIDS remains the main presentation for HIV-infected men. Women are diagnosed earlier and younger than men.

Successful therapy of cerebral phaeohyphomycosis due to Ramichloridium mackenziei with the new triazole posaconazole.

Cerebral phaeohyphomycosis caused by Ramichloridium mackenziei is universally fatal. All reported cases with long-term follow-up have indicated 100% mortality despite antifungal therapy and surgical intervention. We describe the case of a 62-year-old patient who underwent renal transplantation and had a cerebral abscess caused by R. mackenziei. The infection progressed despite surgical evacuation and therapy with liposomal amphotericin B, itraconazole, and 5-flucytosine. The patient was subsequently treated with the investigational triazole posaconazole oral suspension, 800 mg/day, in divided doses. Treatment with posaconazole resulted in progressive clinical and radiologic improvement. The patient is alive four years after diagnosis and maintained on posaconazole therapy. This case supports the potential role of this extended-spectrum azole in the treatment of this serious fungal infection of the central nervous system.

Fungal endocarditis: evidence in the world literature, 1965-1995.

We analyzed 270 cases of fungal endocarditis (FE) that occurred over 30 years. Vascular lines, non-cardiac surgery, immunocompromise and injection drug abuse are increasing risk factors. Delayed or mistaken diagnosis (82% of patients), long duration of symptoms before hospitalization (mean +/- standard deviation, 32+/-39 days) and extracardiac manifestations were characteristic. From 1988 onwards, 72% of patients were diagnosed preoperatively, compared with 43% before 1988 (P=.0001). The fungi most commonly isolated were Candida albicans (24% of patients), non-albicans species of Candida (24%), Apergillus species (24%), and Histoplasma species (6%); recently-emerged fungi accounted for 25% of cases. The mortality rate was 72%. Survival rates were better among patients who received combined surgical-antifungal treatment, were infected with Candida, and had univalvular involvement. Improvement in the survival rate (from <20% before 1974 to 41% currently) coincided with the introduction of echocardiography and with improved diagnostic acumen. Fungal endocarditis recurs in 30% of survivors. It is recommended that fungal endocarditis be diagnosed early through heightened diagnostic acumen; that patients be treated with combined lipid-based amphotericin B and early surgery; and that patients be followed up for > or =4 years while on prophylactic antifungal therapy.

Disseminated Mycobacterium simiae infection in patients with AIDS.

OBJECTIVES: To report our experience with disseminated Mycobacterium simiae disease in patients with AIDS, and review other cases reported in the literature. METHODS: We retrospectively reviewed all cases of M. simiae that were isolated from sterile body sites over a 9-year period at the University Health System Hospital at San Antonio, Texas, U.S.A. Data included patient demographics, clinical features, other accompanying opportunistic infections, in vitro susceptibility, therapy and outcome. RESULTS: Ten cases of M. simiae disseminated disease were identified. All of them were inpatients with AIDS. Another nine cases of disseminated infection in AIDS patients were reported in the literature. Advanced AIDS with absolute CD4 counts of less than 50 and an associated AIDS-defining illness characterized all cases. Persistent fever and debilitation without localizing signs were the most common clinical features. Our patients responded poorly to antimycobacterial drugs and died within 6 months of diagnosis. The only reported successful therapy was in patients who responded well to highly active antiretroviral therapy and antimycobacterial regimens containing clarithromycin, ethambutol and ciprofloxacin. CONCLUSIONS: Clinical presentation of M. simiae infection mimics Mycobacterium avium complex, with fever and progressive debilitation, but is less responsive to therapy. Immuno-reconstitution with potent antiretroviral therapy may be the best therapy for such resistant disease.

SCH 56592, amphotericin B, or itraconazole therapy of experimental murine cerebral phaeohyphomycosis due to Ramichloridium obovoideum ("Ramichloridium mackenziei").

Ramichloridium obovoideum ("Ramichloridium makenziei") is a rare cause of lethal cerebral phaeohyphomycosis. It has been, so far, geographically restricted to the Middle East. BALB/c mice were inoculated with two strains of R. obovoideum intracranially. Therapy with amphotericin B, itraconazole, or the investigational triazole SCH 56592 was conducted for 10 days. Half the mice were monitored for survival and half were killed for determination of the fungal load in brain tissue. Recipients of SCH 56592 had significantly prolonged survival and lower brain fungal burden, and this result was found for mice infected with both of the fungal strains tested. Itraconazole reduced the brain fungal load in mice infected with one strain but not the other, while amphotericin B had no effect on brain fungal concentrations. This study indicates a possible role of SCH 56592 in the treatment of the serious cerebral phaeohyphomycosis due to R. obovoideum.

Investigation and control of aspergillosis and other filamentous fungal infections in solid organ transplant recipients.

Filamentous fungal infections are associated with high morbidity and mortality in solid organ transplant patients, and prevention is warranted whenever possible. An increase in invasive aspergillosis was detected among solid organ transplant recipients in our institution during 1991-92. Rates of Aspergillus infection (18.2%) and infection or colonization (42%) were particularly high among lung transplant recipients. Epidemiologic investigation revealed cases to be both nosocomial and community-acquired, and preventative efforts were directed at both sources. Environmental controls were implemented in the hospital, and itraconazole prophylaxis was given in the early period after lung transplantation. The rate of Aspergillus infection in solid organ transplant recipients decreased from 9.4% to 1.5%, and mortality associated with this disease decreased from 8.2% to 1.8%. The rate of Aspergillus infection or colonization among lung transplant recipients decreased from 42% to 22.5%; nosocomial Aspergillus infection decreased from 9% to 3.2%. Cases of aspergillosis in lung transplant recipients were more likely to be early infections in the pre-intervention period. Early mortality in lung transplant recipients decreased from 15% to 3.2%. Two cases of dematiaceous fungal infection were detected, and no further cases occurred after environmental controls. The use of environmental measures that resulted in a decrease in airborne fungal spores, as well as antifungal prophylaxis, was associated with a decrease in aspergillosis and associated mortality in these patients. Ongoing surveillance and continuing intervention is needed for prevention of infection in high-risk solid organ transplant patients.

Efficacy of the triazole SCH 56592 against Leishmania amazonensis and Leishmania donovani in experimental murine cutaneous and visceral leishmaniases.

Current therapy for leishmaniasis is unsatisfactory. Efficacious and safe oral therapy would be ideal. We examined the efficacy of SCH 56592, an investigational triazole antifungal agent, against cutaneous infection with Leishmania amazonensis and visceral infection with Leishmania donovani in BALB/c mice. Mice were infected in the ear pinna and tail with L. amazonensis promastigotes and were treated with oral SCH 56592 or intraperitoneal amphotericin B for 21 days. At doses of 60 and 30 mg/kg/day, SCH 56592 was highly efficacious in treating cutaneous disease, and at a dose of 60 mg/kg/day, it was superior to amphotericin B at a dose of 1 mg/kg/day. The means of tail lesion sizes were 0.32 +/- 0.12, 0.11 +/- 0.06, 0.17 +/- 0.07, and 0.19 +/- 0.08 mm for controls, SCH 56592 at 60 and 30 mg/kg/day, and amphotericin B recipients, respectively (P = 0.0003, 0.005, and 0.01, respectively). Parasite burden in draining lymph nodes confirmed these efficacy findings. In visceral leishmaniasis due to L. donovani infection, mice treated with SCH 56592 showed a 0.5- to 1-log-unit reduction in parasite burdens in the liver and the spleen compared to untreated mice. Amphotericin B at 1 mg/kg/day was superior to SCH 56592 in the treatment of visceral infection, with a 2-log-unit reduction in parasite burdens in both the liver and spleen. These studies indicate very good activity of SCH 56592 against cutaneous leishmaniasis due to L. amazonensis infection and, to a lesser degree, against visceral leishmaniasis due to L. donovani infection in susceptible BALB/c mice.

Efficacies of KY62 against Leishmania amazonensis and Leishmania donovani in experimental murine cutaneous leishmaniasis and visceral leishmaniasis.

Current therapy for leishmaniasis is unsatisfactory because parenteral antimonial salts and pentamidine are associated with significant toxicity and failure rates. We examined the efficacy of KY62, a new, water-soluble, polyene antifungal, against cutaneous infection with Leishmania amazonensis and against visceral infection with Leishmania donovani in susceptible BALB/c mice. Mice were infected with L. amazonensis promastigotes in the ear pinna and in the tail and were treated with KY62 or amphotericin B. The cutaneous lesions showed a remarkable response to therapy with KY62 at a dose of 30 mg per kg of body weight per day. At this dose, the efficacy of KY62 was equivalent to or better than that of amphotericin B at 1 to 5 mg/kg/day. Mice infected intravenously with 10(7) L. donovani promastigotes and treated with KY62 showed a 4-log reduction in the parasite burden in the liver and spleen compared to untreated mice. These studies indicate potent activity of KY62 against experimental cutaneous leishmaniasis caused by L. amazoniensis and against experimental visceral leishmaniasis caused by L. donovani.

Markedly elevated serum lactate dehydrogenase levels are a clue to the diagnosis of disseminated histoplasmosis in patients with AIDS.

Disseminated histoplasmosis is a common late manifestation of AIDS, but the diagnosis may be unsuspected in some patients because the clinical presentation of histoplasmosis may mimic other opportunistic infections. High serum lactate dehydrogenase (LDH) levels have been associated with disseminated histoplasmosis. We therefore evaluated whether markedly increased LDH levels were useful for making a diagnosis of disseminated histoplasmosis by comparing admission LDH levels for 15 patients with culture-proven disseminated histoplasmosis with those for 30 patients with advanced AIDS who were admitted to the hospital for evaluation of pulmonary infiltrates and fever. The mean admission LDH level in patients with disseminated histoplasmosis was 1,356 IU/L (range, 145-5,410 IU) whereas it was 332 (range, 77-832 IU) in the patients with other pulmonary processes. Admission LDH levels were >600 IU in 11 (73%) of the 15 patients with disseminated histoplasmosis vs. 3 (10%) of controls (P < .001). We conclude that markedly elevated admission LDH levels may be a clinical clue to the diagnosis of disseminated histoplasmosis in patients with AIDS.

Breast abscess caused by Brucella melitensis.

Cutaneous and soft tissue lesions are uncommon manifestations of brucellosis. Though breast involvement in animal brucellosis is not uncommon, involvement of the breast in human brucellosis is extremely rare. We report a case of breast abscess in a 39-year-old female caused by Brucella melitensis. Treatment with combination of trimethoprim/sulphamethoxazole (TMP/ SMX; cotrimoxazole) and doxycycline for 3 months resulted in clinical cure.

Impaired elimination of atenolol in a nephropathic patient with self-medication overdose.

A case of intoxication with atenolol (plasma concentration of 2.71 mg/L) caused by an improper self-medication combined with impaired renal function is presented. The patient was supported with atropine, isoproterenol, dopamine, and dobutamine, and a thorough pharmacokinetic monitoring of atenolol was conducted. As the serum creatinine concentration returned slowly to baseline with good diuresis, the concentration of atenolol decreased (biologic half-life = 2.95 days) and the blood pressure gradually recovered. The patient improved and was subsequently discharged in good health. Had pharmacokinetic monitoring of atenolol not been performed, hemodialysis would have been indicated.