Replacement of previously circulating respiratory syncytial virus subtype B strains with the BA genotype in South Africa

Respiratory Syncytial Virus (RSV) is a major cause of bronchiolitis and pneumonia in infants, immunocompromised and the elderly in both developed and developing countries. Re-infections are common and G protein variability is one mechanism to overcome herd immunity. This is illustrated by the appearance of the BA genotype with a 60 nucleotide duplication dominating the subtype B genotypes in epidemics worldwide. To investigate the evolution of subtype B in South Africa (SA) since 2002 the genetic variability of the G protein was analyzed in all recent strains isolated over four years (2006-2009) in SA hospitals. Bayesian analysis revealed a replacement of all subtype B genotypes previously identified in SA with the BA genotype since 2006, while subtype A genotypes identified in previous years are still circulating. Compared to BA strains from other countries, the evolutionary rate of the SA BA genotype was shown to be 2.305 x 10-3 nucleotide substitutions/site/year and drift was evident. The most recent common ancestor (MRCA) of the SA BA viruses was determined to date back to 1996. All SA BA isolates clustered with the BA-IV sub genotype and the appearance of new sub-genotypes within this branch may occur if drift continues. Sequencing of the complete G protein of selected SA strains revealed an additional 6 nucleotide deletion. Acquisition of the 60 nucleotide duplication appeared to have improved the fitness of this virus and more recent subtype B strains may need to be included in experimental vaccines to evaluate their efficacy in the current setting of evolved circulating strains.Poliomyelites Research Foundationhttp://jvi.asm.or

Pathology of fatal lineage 1 and 2 West Nile virus infections in horses in South Africa

Since 2007, West Nile virus (WNV) has been reported in South African horses, causing severe neurological signs. All cases were of lineage 2, except for one case that clustered with lineage 1 viruses. In the present study, gross and microscopic lesions of six South African lineage 2-infected horses and the one lineage 1 case are described. Diagnoses were confirmed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) of central nervous system (CNS) tissue and one by RT-PCR of a brain virus isolate. The CNS of all cases was negative by RT-PCR or immunohistochemistry (IHC) for African horse sickness (AHS), equine encephalosis virus, equine herpes viruses 1 and 4, other zoonotic flaviviruses, alphaviruses, and shunivirus, and either by immunofluorescence or IHC for rabies. Gross visceral lesions were nonspecific but often mimicked those of AHS. The CNS histopathology of WNV lineage 2 cases resembled the nonsuppurative polioencephalomyelitis reported in the Northern Hemisphere lineage 1 and recent Hungarian lineage 2 cases. Occasional meningitis, focal spinal ventral horn poliomalacia, dorsal and lateral horn poliomyelitis, leucomyelitis, asymmetrical ventral motor spinal neuritis and frequent olfactory region involvement were also seen. Lineage 2 cases displayed marked variations in CNS lesion severity, type and distribution, and suggested various viral entry routes into the CNS, based on findings in experimental mice and hamsters. Lineage 1 lesions were comparable to the milder lineage 2 cases. West Nile virus IHC on CNS sections with marked lesions from all cases elicited only two antigen-positive cells in the olfactory cortex of one case. The presence in the CNS of T-lymphocytes, B-lymphocytes, plasma cells and macrophage-monocytes was confirmed by cluster of differentiation (CD) 3, CD20, multiple myeloma oncogene 1 (MUM1) and macrophage (MAC) 387 IHC.http://www.jsava.co.zaam201

Fatal neurologic disease and abortion in mare infected with lineage 1 West Nile virus, South Africa

In 2010, lineage 1 West Nile virus was detected in South Africa in the brain of a pregnant mare that succumbed to neurologic disease and in her aborted fetus, suggesting an association with abortion in horses. All West Nile virus strains previously detected in horses and humans in South Africa were lineage 2.This study was funded by the National Research Foundation of South Africa.http://www.cdc.gov/ei

Zoonotic alphaviruses in fatal and neurologic infections in wildlife and nonequine domestic animals, South Africa

Alphaviruses from Africa, such as Middelburg virus (MIDV), and Sindbis virus (SINV), were detected in horses with neurologic disease in South Africa, but their host ranges remain unknown. We investigated the contribution of alphaviruses to neurologic infections and death in wildlife and domestic animals in this country. During 2010– 2018, a total of 608 clinical samples from wildlife and nonequine domestic animals that had febrile, neurologic signs or unexplained deaths were tested for alphaviruses. We identified 32 (5.5%) of 608 alphavirus infections (9 SINV and 23 MIDV), mostly in neurotissue of wildlife, domestic animals, and birds. Phylogenetic analysis of the RNA-dependent RNA polymerase gene confirmed either SINV or MIDV. This study implicates MIDV and SINV as potential causes of neurologic disease in wildlife and nonequine domestic species in Africa and suggests a wide host range and pathogenic potential.https://wwwnc.cdc.gov/eidpm2020Medical Virolog

Influenza vaccination of pregnant women and protection of their infants

BACKGROUND There are limited data on the efficacy of vaccination against confirmed influenza in pregnant women with and those without human immunodeficiency virus (HIV) infection and protection of their infants. METHODS We conducted two double-blind, randomized, placebo-controlled trials of trivalent inactivated influenza vaccine (IIV3) in South Africa during 2011 in pregnant women infected with HIV and during 2011 and 2012 in pregnant women who were not infected. The immunogenicity, safety, and efficacy of IIV3 in pregnant women and their infants were evaluated until 24 weeks after birth. Immune responses were measured with a hemagglutination inhibition (HAI) assay, and influenza was diagnosed by means of reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays of respiratory samples. RESULTS The study cohorts included 2116 pregnant women who were not infected with HIV and 194 pregnant women who were infected with HIV. At 1 month after vaccination, seroconversion rates and the proportion of participants with HAI titers of 1:40 or more were higher among IIV3 recipients than among placebo recipients in both cohorts. Newborns of IIV3 recipients also had higher HAI titers than newborns of placebo recipients. The attack rate for RT-PCR–confirmed influenza among both HIV-uninfected placebo recipients and their infants was 3.6%. The attack rates among HIV-uninfected IIV3 recipients and their infants were 1.8% and 1.9%, respectively, and the respective vaccine-efficacy rates were 50.4% (95% confidence interval [CI], 14.5 to 71.2) and 48.8% (95% CI, 11.6 to 70.4). Among HIV-infected women, the attack rate for placebo recipients was 17.0% and the rate for IIV3 recipients was 7.0%; the vaccine-efficacy rate for these IIV3 recipients was 57.7% (95% CI, 0.2 to 82.1). CONCLUSIONS Influenza vaccine was immunogenic in HIV-uninfected and HIV-infected pregnant women and provided partial protection against confirmed influenza in both groups of women and in infants who were not exposed to HIV. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov numbers, NCT01306669 and NCT01306682.)The Bill and Melinda Gates Foundation (OPP1002747), the National Institutes of Health, National Center for Advancing Translational Sciences Colorado Clinical and Translational Sciences Institute (UL1 TR000154, for REDCap), the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation in Vaccine-Preventable Diseases, and the Respiratory and Meningeal Pathogens Research Unit of the Medical Research Council.http://www.nejm.org/am201

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Association of respiratory syncytial virus glyco- and non-structural proteins with disease severity in infected children

Respiratory Syncytial Virus (RSV) is a major cause of bronchiolitis and pneumonia in infants, immunocompromised and the elderly in both developed and developing countries. Re-infections are common and G protein variability is one mechanism to overcome herd immunity. This is illustrated by the appearance of the BA genotype with a 60 nucleotide duplication dominating the subtype B genotypes in epidemics worldwide. To investigate the evolution of subtype A and B in South Africa (SA) since 2002 the genetic variability in the G protein was analysed in all recent strains isolated over four years (2006-2009) in SA hospitals. Bayesian analysis revealed a replacement of all subtype B genotypes previously identified in SA with the BA genotype since 2006, while subtype A genotypes identified in previous years are still circulating. The evolutionary rate of the SA BA genotype was shown to be 2.305 x 10-3 nucleotide substitutions/site/year while subtype A was shown to have 3.382 x 10-3 substitutions/site/year and drift was evident. The most recent common ancestor (MRCA) of the SA BA viruses was determined to date back to 1997. All SA BA isolates clustered with the BA-IV sub-genotype and the appearance of new sub-genotypes within this branch may occur if drift continues. Sequencing of the complete G protein of selected BA SA strains revealed an additional 6 nucleotide deletion. When comparing G protein variability with disease severity, the dominating subtype/genotype in each season was also the subtype/genotype that was associated with increased hospitalizations. No direct association between G protein variability and disease severity was seen. Subtype/genotype switching was evident over the four years most probably because of herd immunity. G protein variability may play a role in RSV‟s ability to re-establish annual epidemics by allowing immune evasion. Certain substitutions or alterations may enhance the fitness of viruses as is evident with the BA strains that replaced all other B genotypes previously identified in SA. The G protein‟s ability to accommodate such substantial changes and facilitate immune evasion may complicate vaccine development. It remains to be seen if this BA genotype will remain dominant or if the dominance will eventually fade because of herd immunity. Subtyping of RSV strains over the four years identified G protein PCR amplicons significantly reduced in size in 2 out of 209 clinical specimens. Sequence analysis revealed subtype B strains lacking nearly the entire G protein ectodomain in one HIV positive and one HIV exposed child hospitalized with pneumonia. G protein deletion mutants replicate effectively in vitro but have not been detected in nature. This study suggests that RSV clinical strains that lack most of the G protein gene may occur in immunocompromised patients with lower respiratory tract infection (LRTI). The molecular mechanism whereby this occurs is not clear, however reduced immune pressure in these patients may allow these strains to utilise the F protein for binding and replication. Further characterization of such strains may elucidate the replication and pathogenic potential, however low viral load and long term storage of specimens complicated the isolation of such strains. Acquisition of the 60 nucleotide duplication appeared to have improved the fitness of the BA viruses and more recent subtype B strains may need to be included in experimental vaccines to evaluate their efficacy in the current setting of evolved circulating strains. In addition, the association of clinical strains lacking most of the G protein with LRTI may have implications for the utilisation of certain attenuated strains in immunocompromised children. RSV is unique among paramyxoviruses in having two non-structural (NS) proteins that play a major role in inhibiting the host‟s immune response. Sequence and quantification analysis of these proteins were performed to determine its role in disease severity. We were unable to attribute specific protein polymorphisms with differences in disease severity but identified genome heterogeneity (quasispecies) within patients which may have an influence on the NS protein function, and also have an influence on the innate immune response and thus an effect on disease severity. When comparing patients with mild and severe disease, higher expression levels of NS1 were seen in the hospitalized group compared to the out-patient group, supporting our hypothesis that increased levels of NS may lead to enhanced suppression of the interferon pathway and in effect result in more severe disease. However, the opposite was found for NS2 with higher expression levels in the mild group. Genetic variability within the gene-end and gene-start sequences were not seen thus could not explain the differences in expression levels observed, although variability within the promoter area may need to be investigated.Dissertation (MSc)--University of Pretoria, 2012.Medical VirologyMScUnrestricte

Factors associated with resilience in families after a house robbery incident

Thesis (MA)--Stellenbosch University, 2018.ENGLISH SUMMARY: The primary aim of this study was to identify the characteristics and resources that families possess that enable them to adapt successfully, and as such be resilient, despite having experienced a house robbery. The study was rooted within the contextual framework of the Resiliency Model of Adjustment and Adaptation of McCubbin, Thompson and McCubbin (1996). Self-report questionnaires were completed by 32 families who had experienced a house robbery between January 2010 and December 2014. The self-report questionnaires were based on the Resiliency Model of Adjustment and Adaptation. In addition, families were required to complete a biographical questionnaire and seven open-ended questions relating to their experience of factors relating to adaptation. The results point towards the importance of resilience factors in adaptation. The most significant resilience factors identified in this study are: family hardiness and commitment; the ability to redefine the stressor; support from family, relatives and friends; the importance of having family time and routines (specifically mealtimes together, regular communication between children and parents, and quality time spent together); and the security measures that were installed/upgraded following the event. The clinical utility of the study in facilitating adaptation lies in its ability to provide families with confirmation of the value of their efforts to provide support and encouragement to each other and to promote their unity and togetherness through routines and family time together. Family resilience theory provides a relevant framework within which the process of adapting to a house robbery can be considered. By applying these theories to their specific crisis situation, families can work towards identifying, as well as implementing, those factors that will lead to better adaptation, and thus increased resilience.AFRIKAANSE OPSOMMING: Die hoofdoelstelling van hierdie ondersoek was om die eienskappe en hulpbronne van gesinne te identifiseer wat dit moontlik maak dat hulle suksesvol aanpas, en dus veerkragtigheid te vertoon, ten spyte van die ervaring van huisroof. Die ondersoek is gebaseer op die kontekstuele raamwerk van McCubbin, Thompson en McCubbin (1996) se Veerkragtigheidsmodel (Resiliency Model of Adjustment and Adaptation). Selfbeskrywingsvraelyste is voltooi deur 32 gesinne wat ’n huisroof tussen Januarie 2010 en Desember 2014 ervaar het. Die selfbeskrywingsvraelyste is gebaseer op die Veerkragtigheidsmodel. Daar is ook van die gesinne verwag om ’n biografiese vraelys sowel as sewe oopeinde-vrae te voltooi oor hul ondervinding van faktore wat verband hou met hulle aanpassing. Die resultate beklemtoon die belangrikheid van veerkragtigheidsfaktore in gesinsaanpassing. Die belangrikste veerkragtigheidsfaktore wat in hierdie studie geïdentifiseer is, is: gesinsgehardheid en -verbintenis; die vermoë om die stressor te herdefinieer, ondersteuning van die gesin, familie en vriende; die belangrikheid van familie tyd en roetines (spesifiek maaltye saam, gereelde kommunikasie tussen kinders en ouers, en kwaliteit tyd wat hulle saam spandeer); en die sekuriteitstelsels wat ná die gebeurtenis geïnstalleer/opgegradeer is. Die kliniese bruikbaarheid van hierdie studie is gekoppel aan die vermoë om gesinne te voorsien van bevestiging van die waarde van hulle pogings om ondersteuning en aanmoediging aan mekaar te bied en om hulle eenheid en samesyn deur middel van roetines en gesinstyd saam te bevorder. Gesinsveerkragtigheidsteorie bied ’n relevante raamwerk waarbinne die proses van aanpassing ná ’n huisroof oorweeg kan word. Deur hierdie teorieë toe te pas op hulle spesifieke krisissituasie kan gesinne daaraan werk om die faktore te identifiseer en te implementeer wat sal lei tot beter aanpassing en dus verhoogde veerkragtigheid