HIV transmission at a Saudi Arabia hemodialysis unit.

BACKGROUND: Hemodialysis is associated with increased risk of healthcare-associated infections but considered a low-risk setting for human immunodeficiency virus (HIV) transmission. We investigated 3 hemodialysis unit (HDU) patients with new HIV infections to determine whether transmission was hemodialysis-associated and to correct factors that contributed to transmission. METHODS: Each patient was evaluated for HIV risk factors. Blood samples were tested to determine relatedness of HIV strains. Clinical data (gathered over 18 months) was reviewed to identify seroconversions at 12 HDUs. Infection prevention and control practices were evaluated at 14 HDUs. FINDINGS: No other HIV seroconversions were identified during the study. HIV gag, pol, and env gene sequences were consistent with a clonal relationship. HIV and hepatitis C virus prevalence rates at one HDU 1 (5.7% and 6.5%, respectively) were higher than for 11 other HDUs (0% and 0.15%, respectively). CONCLUSIONS: Sequencing supports either patient-to-patient or common-source transmission. Infections occurred despite Saudi Arabia's low HIV prevalence and national dialysis policies that emphasize stringent infection prevention and control practices.

Family cluster of Middle East respiratory syndrome coronavirus infections.

A human coronavirus, called the Middle East respiratory syndrome coronavirus (MERS-CoV), was first identified in September 2012 in samples obtained from a Saudi Arabian businessman who died from acute respiratory failure. Since then, 49 cases of infections caused by MERS-CoV (previously called a novel coronavirus) with 26 deaths have been reported to date. In this report, we describe a family case cluster of MERS-CoV infection, including the clinical presentation, treatment outcomes, and household relationships of three young men who became ill with MERS-CoV infection after the hospitalization of an elderly male relative, who died of the disease. Twenty-four other family members living in the same household and 124 attending staff members at the hospitals did not become ill. MERS-CoV infection may cause a spectrum of clinical illness. Although an animal reservoir is suspected, none has been discovered. Meanwhile, global concern rests on the ability of MERS-CoV to cause major illness in close contacts of patients.

Recovery from severe novel coronavirus infection.

We describe the third confirmed case of novel coronavirus infection in a resident of the Arabian Peninsula. Our patient presented, as did 2 prior cases, with severe pneumonia and renal dysfunction requiring intensive care support including assisted ventilation. However, unlike the earlier cases, and despite underlying chronic disease and a single kidney, he survived his infection and has been discharged home. The Ministry of Health continues active surveillance for additional cases. As this case report goes to press, 2 additional confirmed cases have been identified in Riyadh, Saudi Arabia. Contact investigations are in progress. Future work will focus not only on the origin of the virus and mechanisms of transmission, but also the host factors that influence pathogenesis and prognosis.

HIV case notification rates in the Kingdom of Saudi Arabia over the past decade (2000-2009).

OBJECTIVE: To study trends in HIV case notification rates in the Kingdom of Saudi Arabia. DESIGN: A ten year retrospective review of annual HIV case notification returns to the Ministry of Health, Kingdom of Saudi Arabia. METHODS: Annual Registry statistics covering the period 2000 to 2009 were reviewed. Annual incidence trends were stratified according to the following demographics: age, nationality, geographical region of residence, gender, and mode of disease acquisition. RESULTS: 10,217 new HIV cases (2,956 in Saudi nationals and 7,261 in non-Saudis) were reported. Africans of Sub-Saharan Africa origin accounting for 3,982/7,261 (53%) of non-Saudi cases constituted: Ethiopians (2,271), Nigerians (1,048), and Sudanese nationals (663). The overall average annual incidence was <4 cases per 100,000; 1.5 cases per 100,000 for Saudis (range 0.5-2.5), and 13.2 per 100,000 for non-Saudis (range 5.7-19.0). Notifications increased yearly from 2000 for both groups until a plateau was reached in 2006 at 1,390 new cases. Case notification in Saudi nationals increased from 20% in the early 2001 to 40% in 2009. 4% (124/2,956) of cases were reported in Saudi children. The male to female ratio was 1.6:1 for non-Saudi nationals (43.8% male, 27.3% female) and 4.4:1 for Saudis (23.5% male, 5.4% female). CONCLUSIONS: Whilst the numbers of reported HIV cases have stabilised since 2006, HIV/AIDS remains an important public health problem in KSA, both in migrants and Saudi nationals. HIV transmission to Saudi children is also of concern. Optimization of data collection, surveillance, and pro-active screening for HIV is required.

Detection of respiratory viruses among pilgrims in Saudi Arabia during the time of a declared influenza A(H1N1) pandemic.

BACKGROUND: The objectives of this study were to determine whether pilgrim attendance at the Hajj was associated with an increased risk of acquiring influenza, and other respiratory viruses, and to evaluate the compliance of pilgrims with influenza vaccination and other recommended preventive measures. METHODS: A cross-sectional survey was conducted among pilgrims as they arrived at the King Abdulaziz International Airport in Jeddah for the 2009 Hajj and as they departed from the same airport during the week after the Hajj. Nasopharyngeal and throat swabs were tested for 18 respiratory virus types and subtypes using the xTAG Respiratory Viral Panel FAST assay. RESULTS: A total of 519 arriving pilgrims and 2,699 departing pilgrims were examined. Their mean age was 49 years and 58% were male. In all, 30% of pilgrims stated that they had received pandemic influenza A(H1N1) vaccine before leaving for the Hajj and 35% of arriving pilgrims reported wearing a face mask. Only 50% of arriving pilgrims were aware of preventive measures such as hand hygiene and wearing a mask. The prevalence of any respiratory-virus infection was 14.5% (12.5% among arriving pilgrims and 14.8% among departing pilgrims). The main viruses detected (both groups combined) were rhinovirus-enterovirus (N = 414, 12.9%), coronaviruses (N = 27, 0.8%), respiratory syncytial virus (N = 8, 0.2%), and influenza A virus (N = 8, 0.2%) including pandemic influenza A(H1N1) (N = 3, 0.1%). The prevalence of pandemic influenza A(H1N1) was 0.2% (N = 1) among arriving pilgrims and 0.1% (N = 2) among departing pilgrims. The prevalence of any respiratory virus infection was lower among those who said they received H1N1 vaccine compared to those who said they did not receive it (11.8% vs 15.6%, respectively, p = 0.009). CONCLUSION: We found very low pandemic influenza A(H1N1) prevalence among arriving pilgrims and no evidence that amplification of transmission had occurred among departing pilgrims.

Emergence of medicine for mass gatherings: lessons from the Hajj.

Although definitions of mass gatherings (MG) vary greatly, they consist of large numbers of people attending an event at a specific site for a finite time. Examples of MGs include World Youth Day, the summer and winter Olympics, rock concerts, and political rallies. Some of the largest MGs are spiritual in nature. Among all MGs, the public health issues, associated with the Hajj (an annual pilgrimage to Mecca, Saudi Arabia) is clearly the best reported-probably because of its international or even intercontinental implications in terms of the spread of infectious disease. Hajj routinely attracts 2·5 million Muslims for worship. WHO's global health initiatives have converged with Saudi Arabia's efforts to ensure the wellbeing of pilgrims, contain infectious diseases, and reinforce global health security through the management of the Hajj. Both initiatives emphasise the importance of MG health policies guided by sound evidence and based on experience and the timeliness of calls for a new academic science-based specialty of MG medicine.

Seroprevalence of Alkhurma and other hemorrhagic fever viruses, Saudi Arabia.

A 2009 deployment of military units from several Saudi Arabian provinces to Jazan Province, Saudi Arabia, enabled us to evaluate exposure to Alkhurma, Crimean-Congo, dengue, and Rift Valley hemorrhagic fever viruses. Seroprevalence to all viruses was low; however, Alkhurma virus seroprevalence was higher (1.3%) and less geographically restricted than previously thought.

Inappropriate antimicrobial use and potential solutions: a Middle Eastern perspective.

Addressing the many challenges posed by escalating antimicrobial resistance requires a strategy at institutional, community, national, regional and international levels. Partners in the development of such a strategy should include representatives from clinical and veterinary medicine, public health, microbiology, animal husbandry, the pharmaceutical and agriculture industries as well as behavioral sciences. In the Middle East, antimicrobial resistance is a crisis at the present time. It stems from a wide range of problems; however, there are few studies from this region about factors associated with proliferating resistance. In this article, we explore inappropriate antimicrobial use in this part of the world and suggest possible solutions to mitigate the problem.

Rapid and fatal meningococcal disease due to a strain of Neisseria meningitidis containing the capsule null locus.

BACKGROUND: Neisseria meningitidis continues to be an important cause of invasive bacterial disease among children and young adults worldwide. In Canada, N. meningitidis strains that bear serogroups B and C polysaccharide capsules predominate. We report the first documented case of invasive meningococcal disease in an immunocompetent host caused by an acapsular strain of N. meningitidis containing the capsule null locus (cnl). METHODS: Analysis of the isolate was performed with use of serological and molecular methods, including multilocus sequence typing and cnl gene identification. Analysis of 16S ribosomal RNA (rRNA) and porA genes was also performed to confirm the identity of the bacterium. RESULTS: The patient was a healthy, immunocompetent 13-year-old child, and N. meningitidis was recovered from a sample of her cerebrospinal fluid before death. The isolate was nontypeable by both conventional antisera and indirect whole-cell enzyme-linked immuosorbent assay methods using antibodies to serogroups B, C, Y, and W135. The isolate was further identified as a cnl strain, serotype 15 (ST-198). N. meningitidis-specific DNA was identified in the isolate and in the pre- and postmortem specimens by 16S rRNA and porA gene analysis. CONCLUSIONS: This is the first reported case of fatal meningococcal disease caused by an acapsular cnl strain of N. meningitidis that was isolated from an immunocompetent host. Routine molecular diagnostic methods targeted at the cnl locus failed to detect this organism, indicating a need to determine the incidence of infection with cnl strains among patients with culture-negative invasive disease.

The role of the cytomegalovirus antigenemia assay in the detection and prevention of cytomegalovirus syndrome and disease in solid organ transplant recipients: A review of the British Columbia experience.

BACKGROUND: The pp65 cytomegalovirus (CMV) antigenemia assay has been used as a means of guiding the pre-emptive therapy of CMV disease in solid organ transplant (SOT) recipients. Recently, concerns have been raised regarding the utility of the test to accurately and precisely detect viral activity early enough to reduce the morbidity and mortality associated with CMV OBJECTIVE: To determine the performance characteristics of the method of antigenemia testing of SOT recipients used at Vancouver General Hospital, Vancouver, British Columbia. METHODS: All SOT recipients between January 1, 1999, and June 30, 2000, were retrospectively reviewed for six months following transplantation. Physical examination results, laboratory parameters, antigenemia results and treatment information were reviewed. RESULTS: A total of 134 kidney, liver, lung and kidney-pancreas transplant recipients were included in the analysis. The overall performance characteristics of the antigenemia assay in predicting CMV disease included a sensitivity of 64%, a specificity of 81%, a positive predictive value of 76% and a negative predictive value of 71%. A mean of 18 days passed between the onset of signs and symptoms of CMV disease/syndrome and the first recorded positive antigenemia result, and only 26% of patients had a positive test result before the onset of symptoms. It was found that an antigenemia test breakpoint of at least one positive cell for defining a positive test provided the most sensitive and specific prediction, with increased odds of developing CMV disease. CONCLUSIONS: Based on performance characteristics, the Vancouver General Hospital's current method of antigenemia testing to guide pre-emptive ganciclovir therapy in SOT patients is not optimal for the early detection of disease. Further study is needed on new molecular testing methods to determine if our ability to predict CMV disease can be improved.

Potential capsule switching from serogroup Y to B: The characterization of three such Neisseria meningitidis isolates causing invasive meningococcal disease in Canada.

Three group B Neisseria meningitidis isolates, recovered from meningococcal disease cases in Canada and typed as B:2c:P1.5, were characterized. Multilocus sequence typing showed that all three isolates were related because of an identical sequence type (ST) 573. Isolates typed as 2c:P1.5 are common in serogroup Y meningococci but rare in isolates from serogroups B or C. Although no serogroup Y isolates have been typed as ST-573, eight isolates showed five to six housekeeping gene alleles that were identical to that of ST-573. This suggested that the B:2c:P1.5 isolates may have originated from serogroup Y organisms, possibly by capsule switching.

A Francisella tularensis pathogenicity island required for intramacrophage growth.

Francisella tularensis is a gram-negative, facultative intracellular pathogen that causes the highly infectious zoonotic disease tularemia. We have discovered a ca. 30-kb pathogenicity island of F. tularensis (FPI) that includes four large open reading frames (ORFs) of 2.5 to 3.9 kb and 13 ORFs of 1.5 kb or smaller. Previously, two small genes located near the center of the FPI were shown to be needed for intramacrophage growth. In this work we show that two of the large ORFs, located toward the ends of the FPI, are needed for virulence. Although most genes in the FPI encode proteins with amino acid sequences that are highly conserved between high- and low-virulence strains, one of the FPI genes is present in highly virulent type A F. tularensis, absent in moderately virulent type B F. tularensis, and altered in F. tularensis subsp. novicida, which is highly virulent for mice but avirulent for humans. The G+C content of a 17.7-kb stretch of the FPI is 26.6%, which is 6.6% below the average G+C content of the F. tularensis genome. This extremely low G+C content suggests that the DNA was imported from a microbe with a very low G+C-containing chromosome.

Assessment of partial sequencing of the 65-kilodalton heat shock protein gene (hsp65) for routine identification of Mycobacterium species isolated from clinical sources.

We assessed the ability of an in-house database, consisting of 111 hsp65 sequences from putative and valid Mycobacterium species or described groups, to identify 689 mycobacterial clinical isolates from 35 species or groups. A preliminary assessment indicated that hsp65 sequencing confirmed the identification of 79.4% of the isolates from the 32 species examined, including all Mycobacterium tuberculosis complex isolates, all isolates from 13 other species, and 95.6% of all M. avium-M. intracellulare complex isolates. Identification discrepancies were most frequently encountered with isolates submitted as M. chelonae, M. fortuitum, M. gordonae, M. scrofulaceum, and M. terrae. Reexamination of isolates with discrepant identifications confirmed that hsp65 identifications were correct in a further 40 isolates. This brought the overall agreement between hsp65 sequencing and the other identification methods to 85.2%. The remaining 102 isolates had sequence matches below our acceptance criterion, had nondifferential sequence matches between two or more species, were identified by 16S rRNA sequencing as a putative taxonomic group not contained in our database, or were identified by hsp65 and 16S rRNA gene sequencing as a species not in our biochemical test database or had conflicting identifications. Therefore, to incorporate the unconfirmed isolates it was necessary to create 29 additional entries in our hsp65 identification database: 18 associated with valid species, 7 indicating unique sequences not associated with valid or putative species or groups, and 4 associated with unique, but currently described taxonomic groups. Confidence in the hsp65 sequence identification of a clinical isolate is best when sequence matches of 100% occur, but our data indicate that correct identifications can be confidently made when unambiguous matches exceeding 97% occur, but are dependent on the completeness of the database. Our study indicates that for hsp65 sequencing to be an effective means for identifying mycobacteria a comprehensive database must be constructed. hsp65 sequencing has the advantage of being more rapid and less expensive than biochemical test panels, uses a single set of reagents to identify both rapid- and slow-growing mycobacteria, and can provide a more definitive identification.

Complete DNA sequence analyses of the first two varicella-zoster virus glycoprotein E (D150N) mutant viruses found in North America: evolution of genotypes with an accelerated cell spread phenotype.

Varicella-zoster virus (VZV) is considered to be one of the most genetically stable of all the herpesviruses. Yet two VZV strains with a D150N missense mutation within the gE glycoprotein were isolated in North America in 1998 and 2002. The mutant strains have an accelerated cell spread phenotype, which distinguishes them from all wild-type and laboratory viruses. Since the VZV genome contains 70 additional open reading frames (ORFs), the possibility existed that the phenotypic change was actually due to an as-yet-undiscovered mutation or deletion elsewhere in the genome. To exclude this hypothesis, the entire genomes of the two mutant viruses were sequenced and found to contain 124,883 (VZV-MSP) and 125,459 (VZV-BC) nucleotides. Coding single-nucleotide polymorphisms (SNPs) were identified in 14 ORFs. One missense mutation was discovered in gH, but none was found in gB, gI, gL, or gK. There were no coding SNPs in the major regulatory protein ORF 62. One polymorphism was discovered which could never have been anticipated based on current knowledge of herpesvirus genomics, namely, the origins of replication differed from those in the prototype strain but not in a manner expected to affect cell spread. When the two complete mutant VZV sequences were surveyed in their entirety, the most reasonable conclusion was that the increased cell spread phenotype was dependent substantially or solely on the single D150N polymorphism in glycoprotein gE. The genomic results also expanded the evolutionary database by identifying which VZV ORFs were more likely to mutate over time.

New variant of varicella-zoster virus.

In 1998, a varicella-zoster virus glycoprotein E (gE) mutant virus (VZV-MSP) was isolated from a child with chickenpox. VZV-MSP, representing a second VZV serotype, was considered a rarity. We isolated another VZV-MSP-like virus from an elderly man with herpes zoster. These gE mutant viruses may have arisen through independent mutation or may represent a distinct VZV subpopulation that emerged more than 50 years ago.