Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome.

BACKGROUND: Whether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear. METHODS: We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results. RESULTS: A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group. CONCLUSIONS: A combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).

Longevity of Middle East Respiratory Syndrome Coronavirus Antibody Responses in Humans, Saudi Arabia.

Understanding the immune response to Middle East respiratory syndrome coronavirus (MERS-CoV) is crucial for disease prevention and vaccine development. We studied the antibody responses in 48 human MERS-CoV infection survivors who had variable disease severity in Saudi Arabia. MERS-CoV-specific neutralizing antibodies were detected for 6 years postinfection.

A rickettsia infection from Saudi Arabia.

We here present a young patient who developed fever, headache, maculopapular skin rash and an eschar 3 days following a tick bite. Serology for Rickettsia was consistent with acute spotted fever group (SFG) infection. He had a dramatic response to doxycycline. Vectors for rickettsia transmission are shown in a number of studies from Saudi Arabia while human serological studies from Oman revealed that these infections are common among the rural population. Surprisingly, despite the existence of potential vectors, this disease is rarely reported from the Arab Gulf countries. To the best of our knowledge this is the first case report of SFG acquired within Saudi Arabia. SFG should be considered in the differential diagnosis of febrile illness and exposure history.

Isolation and deisolation of patients admitted with presumptive pulmonary tuberculosis. Can it be shortened?

OBJECTIVES: To determine the ideal number of sputum acid-fast bacilli (AFB) smears and polymerase chain reaction (PCR) required for discontinuing TB isolation among patients with suspected pulmonary TB.  Methods: This was a single-center, record-based retrospective study of all admitted patients diagnosed with culture-proven pulmonary TB between 2010 and 2018. The study was conducted at Prince Sultan Military Medical City (PSMMC) in Riyadh, Saudi Arabia, a large tertiary care center consisting of 1,200 beds. Data were obtained from our TB notification records. Patients with smear-positive TB were investigated. Only the first 3 sputum smears for AFB were included in the analysis. The  PCR results for Mycobacterium tuberculosis (MTB) were also included in the study. The incremental yield of the second and third smears was assessed.  Results: Overall, 240 patients were MTB-culture positive. A total of 126 (52.5%) patients were smear and culture positive, whereas 114 were culture positive but smear negative. Of 126 patients who were AFB smear positive, 98 (77.8%) were detected in the first specimen, 13 (10.3%) in the second specimen, and only 9 (7.1%) in the third specimen. Polymerase chain reaction for MTB was positive in 122 (96.8%) smear-positive patients. Four patients did not undergo a PCR test.  Conclusion:  A single Xpert MTB/resistance to rifampicin test detected all smear-positive patients, whereas the third smear did not significantly contribute to MTB isolation.

Characteristics and outcome of viral pneumonia caused by influenza and Middle East respiratory syndrome-coronavirus infections: A 4-year experience from a tertiary care center.

BACKGROUND: After the emergence of new influenza viruses, the morbidity and mortality of viral pneumonia have received a great attention. OBJECTIVES: The objective of this study is to describe the epidemiologic, clinical and laboratory changes, and outcomes of viral pneumonia caused by influenza and the Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. METHODS: In a retrospective cohort study, the medical records of all patients diagnosed with viral pneumonia at Prince Sultan Military Medical City, Riyadh, Saudi Arabia, during the period from January 2012 to December 2015 were screened. Cases who were > 18 years old and were confirmed by a respiratory viral panel to have viral pneumonia either MERS-CoV or influenza viruses were included in the analysis. Sociodemographic, clinical, laboratory, and outcome data were extracted from patients' medical files. The data were analyzed descriptively and inferentially to identify the predictors of poor outcome. RESULTS: A total of 448 patients with confirmed viral pneumonia were included, of those, 216 (48.2%) were caused by influenza A (non H1N1)/influenza B, 150 (33.5%) by H1N1, and 82 (18.3%) by MERS-CoV. The majority of patients presented with fever (82%), shortness of breath (64%), and flu-like symptoms (54.9%), particularly in MERS-CoV infected cases (92%). The peak incidence of viral pneumonia was in early spring and autumn. The mortality rate was 13.8%, and it was significantly higher among MERS-CoV cases. The predictors of death were age > 65 years, male gender, and associated comorbidities particularly diabetes mellitus, hypertension, and chronic kidney diseases. The number of comorbid illnesses was directly related to the increase in mortality in this group of patients. CONCLUSION: Viral pneumonia caused by influenza and MERS-CoV carries a high mortality rate, particularly among MERS-CoV infected cases. Old age, male gender, and comorbid illnesses are predictors of poor outcome. Routine testing for newly emergent viruses is warranted for adults who have been hospitalized with pneumonia.

Ten-year experience of Q fever endocarditis in a tertiary cardiac center in Saudi Arabia.

BACKGROUND: Q fever endocarditis (QFE) is considered rare in the Middle East, with only a few cases reported in Saudi Arabia. The aim of this study is to report on the experience of our centre on QFE. METHODS: We searched the medical records for cases of QFE at our cardiac center from 2009-2018. Demographic data, clinical features, serology and echocardiography results, treatments, and outcomes were assessed. RESULTS: Five hundred and two cases of infective endocarditis were detected over the 10 years period. Among the 234 patients with blood culture-negative endocarditis (BCNE), 19 (8.10%) had QFE. All patients had a previously diagnosed congenital heart disease except for one patient with rheumatic heart disease. Eleven patients had received a bovine jugular vein-related implant, e.g., a Melody valve (seven patients) or Contegra conduit (four patients). Coinfection was detected in three patients, and immunologic and embolic phenomena were observed in five patients. All patients received a combination of hydroxychloroquine and doxycycline, with good outcomes. Only two patients required surgery while on treatment. Two patients died several months after treatment; the cause of death was not identified. CONCLUSION: This study indicates that Q fever exists in our population. The majority of the patients had congenital heart disease (CHD) and underwent bovine jugular vein implants. Patients with CHD are at increased risk of infective endocarditis. Bovine jugular vein implants increase the risk of infective and possibly QFE. Proper exclusion of Q fever is warranted in all BCNE and possibly in culture-positive endocarditis cases in areas endemic to Q fever. KEY POINTS: We presented the largest series of Q fever endocarditis cases in Saudi Arabia. We showed that Q fever is not rare in the Middle East and suggest that it should be considered in all blood culture-negative endocarditis cases.

Brucellosis accompanied by haemophagocytic lymphohistiocytosis and multiple splenic abscesses in a patient with depression.

A 39-year-old woman was being treated for depression in our clinic. She subsequently developed a fever and was diagnosed with pancytopenia and moderate splenomegaly. Laboratory and bone marrow results, including markedly increased serum ferritin levels, suggested haemophagocytic lymphohistiocytosis. CT showed multiple splenic abscesses and ovarian vein thrombosis. All laboratory values returned to normal after treatment for culture-positive brucellosis.

Total knee prosthesis infected with Mycobacterium tuberculosis.

Mycobacterium tuberculosis (MTB) infection of a prosthetic joint is rarely reported in developed countries.1 Typically, MTB infection involves the hips or knees, and the infection can occur secondary to crushing and degradation of the granuloma during surgery or, less commonly, from distant foci spreading through the blood. In the present case, MTB infection likely resulted from haematogenous spread since multiple hot spots suggestive of MTB infection were noted in other sites. Early diagnosis allows for antitubercular therapy with retention of the prosthesis, while late diagnosis frequently results in removal and reimplantation of the joint. To avoid major surgery, a high index of suspicion is required to diagnose prosthetic joint tuberculosis.

Streptococcus bovis prosthetic valve endocarditis associated with silent colonic carcinoma.

A 75-year-old woman was admitted to our hospital with a 3-month history of fever. Of note, she had a bioprosthetic mitral valve replacement 1 year prior to admission. Streptococcus bovis was isolated from three sets of blood cultures. An echocardiogram showed a flickering mass attached to the bioprosthesis. Her blood culture became sterile by the fourth day of ceftriaxone therapy. In spite of the absence of gastrointestinal symptoms, screening colonoscopy revealed an invasive colonic adenocarcinoma. The association linking S. bovis endocarditis and colonic tumours is well recognised. However, despite early reports of this association by Klein et al in 1979, a large number of practising physicians remain unaware of this phenomenon. This lack of awareness results in lost opportunities for early diagnosis and, consequently, improved outcome in such patients. Our report emphasises this association in an area with a low incidence of S. bovis endocarditis.