Evaluation of influenza vaccine effectiveness and description of circulating strains in outpatient settings in South Africa, 2014

The effectiveness of the trivalent seasonal influenza vaccine during the 2014 season in South Africa was assessed using a test-negative case–control study design including 472 cases and 362 controls. Influenza A(H3N2) was the dominant strain circulating. The overall vaccine effectiveness estimate, adjusted for age and underlying conditions, was43.1% (95% CI: 26.8-74.5). 2014 H3N2 viruses from South Africa were mainly in sublineage 3C.3 with accumulation of amino acid changes that differentiate them from the vaccine strain in 3C.1

Conserved positive selection signals in gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infection

<p>Abstract</p> <p>Background</p> <p>The high diversity of HIV variants driving the global AIDS epidemic has caused many to doubt whether an effective vaccine against the virus is possible. However, by identifying the selective forces that are driving the ongoing diversification of HIV and characterising their genetic consequences, it may be possible to design vaccines that pre-empt some of the virus' more common evasion tactics. One component of such vaccines might be the envelope protein, gp41. Besides being targeted by both the humoral and cellular arms of the immune system this protein mediates fusion between viral and target cell membranes and is likely to be a primary determinant of HIV transmissibility.</p> <p>Results</p> <p>Using recombination aware analysis tools we compared site specific signals of selection in gp41 sequences from different HIV-1 M subtypes and circulating recombinant forms and identified twelve sites evolving under positive selection across multiple major HIV-1 lineages. To identify evidence of selection operating during transmission our analysis included two matched datasets sampled from patients with acute or chronic subtype C infections. We identified six gp41 sites apparently evolving under different selection pressures during acute and chronic HIV-1 infections. These sites mostly fell within functional gp41 domains, with one site located within the epitope recognised by the broadly neutralizing antibody, 4E10.</p> <p>Conclusion</p> <p>Whereas these six sites are potentially determinants of fitness and are therefore good candidate targets for subtype-C specific vaccines, the twelve sites evolving under diversifying selection across multiple subtypes might make good candidate targets for broadly protective vaccines.</p

Evaluation of influenza vaccine effectiveness and description of circulating strains in outpatient settings in South Africa, 2014

The effectiveness of the trivalent seasonal influenza vaccine during the 2014 season in South Africa was assessed using a test-negative case–control study design including 472 cases and 362 controls. Influenza A(H3N2) was the dominant strain circulating. The overall vaccine effectiveness estimate, adjusted for age and underlying conditions, was43.1% (95% CI: 26.8-74.5). 2014 H3N2 viruses from South Africa were mainly in sublineage 3C.3 with accumulation of amino acid changes that differentiate them from the vaccine strain in 3C.1

TNFAIP3-interacting protein 1 polymorphisms and their association with symptomatic human respiratory syncytial virus infection and bronchiolitis in infants younger than one year from South Africa: A case-control study

Objectives: This study analyzed the association of TNFAIP3-interacting protein 1 (TNIP1) polymorphisms with the symptomatic human respiratory syncytial virus (HRSV) infection and bronchiolitis in infants. Methods: A case-control study was conducted involving 129 hospitalized infants with symptomatic HRSV infection (case group) and 161 healthy infants (control group) in South Africa (2016-2018). Six TNIP1 polymorphisms (rs869976, rs4958881, rs73272842, rs3792783, rs17728338, and rs999011) were genotyped. Genetic associations were evaluated using logistic regression adjusted by age and gender. Results: Both rs73272842 G and rs999011 C alleles were associated with reduced odds for symptomatic HRSV infection (adjusted odd ratio [aOR] = 0.68 [95% confidence interval {CI} = 0.48-0.96] and aOR = 0.36 [95% CI = 0.19-0.68], respectively] and bronchiolitis (aOR = 0.71 [95% CI = 0.50-1.00] and aOR = 0.38 [95% CI = 0.22-0.66], respectively). The significance of these associations was validated using the BCa Bootstrap method (P <0.05). The haplotype GC (composed of rs73272842 and rs999011) was associated with reduced odds of symptomatic HRSV infection (aOR = 0.53 [95% CI = 0.37-0.77]) and bronchiolitis (aOR = 0.62 [95% CI = 0.46-0.84]), which were validated by the BCa Bootstrap method (P = 0.002 for both). Conclusion: TNIP1 rs73272842 G allele and rs999011 C allele were associated with reduced odds of symptomatic HRSV infection and the development of bronchiolitis in infants, suggesting that TNIP1 polymorphisms could impact susceptibility to HRSV illness.The study was funded by Poliomyelitis Research Foundation (grant # 19/27 to FKT), South Africa. The study was also funded by the CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU (grant #CB21/13/00044 to SR).S

Adaptive changes in HIV-1 subtype C proteins during early infection are driven by changes in HLA-associated immune pressure

It is unresolved whether recently transmitted human immunodeficiency viruses (HIV) have genetic features that specifically favour their transmissibility. To identify potential "transmission signatures", we compared 20 full-length HIV-1 subtype C genomes from primary infections, with 66 sampled from ethnically and geographically matched individuals with chronic infections. Controlling for recombination and phylogenetic relatedness, we identified 39 sites at which amino acid frequency spectra differed significantly between groups. These sites were predominantly located within Env, Pol and Gag (14/39, 9/39 and 6/39 respectively) and were significantly clustered (33/39) within known immunoreactive peptides. Within 6 months of infection, we detected reversion-to-consensus mutations at 14 sites and potential CTL escape mutations at seven. Here we provide evidence that frequent reversion mutations probably allows the virus to recover replicative fitness which, together with immune escape driven by the HLA alleles of the new hosts, differentiate sequences from chronic infections from those sampled shortly after transmission

Enterovirus D68 and other enterovirus serotypes identified in South African patients with severe acute respiratory illness, 2009-2011

BACKGROUND : Human enteroviruses (EV) have been associated with severe acute respiratory illness (SARI) in South Africa. OBJECTIVES : We aimed to describe the molecular epidemiology of EV serotypes among patients hospitalized with SARI during 2009-2011. PATIENTS/METHODS : Study samples from patients were tested for the presence of enterovirus using a polymerase chain reaction assay. RESULTS : 8.2% (842/10 260) of SARI cases tested positive for enterovirus; 16% (7/45) were species EV-A, 44% (20/45) EV-B, 18% (8/45) EV-C and 22% (10/45) EV-D. Seventeen different EV serotypes were identified within EV-A to EV-D, of which EV-D68 (22%; 10/45) and Echovirus 3 (11%; 5/45) were the most prevalent. CONCLUSIONS : EV-D68 should be monitored in South Africa to assess the emergence of highly pathogenic strains.The United States Centers for Disease Control and Prevention, Atlanta, Georgia, USA (co-operative agreement number: 5U51IP000155).http://www.wileyonlinelibrary.com/journal/irvhttp://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1750-2659am2018Medical Virolog

Decreased incidence of dual infections in South African subtype C-infected women compared to a cohort ten years earlier.

Previously, we determined the incidence of dual infections in a South African cohort and its association with higher viral setpoint. Ten years later, we compare the incidence and impact of dual infections at transmission on viral setpoint in a geographically similar cohort (n=46) making use of both the heteroduplex mobility assay (HMA) and the more recent single genome amplification (SGA) approach. HIV incidence was lower in this cohort (7% compared to 18%), and we find a similar reduction in the number of dual infections (9% compared to 19%). Unlike the previous study, there was no association between either dual infection (n=4) or multivariant transmission (n=7) and disease progression. This study emphasized the importance of monitoring changes in the HIV epidemic as it may have important ramifications on our understanding of the natural history of disease

The role of influenza, RSV and other common respiratory viruses in severe acute respiratory infections and influenza-like illness in a population with a high HIV sero-prevalence, South Africa, 2012-2015

BACKGROUND : Viruses detected in patients with acute respiratory infections may be the cause of illness or colonizers. METHODS : We compared the prevalence of 10 common respiratory viruses (influenza A and B viruses, parainfluenza virus 1, 2, and 3; respiratory syncytial virus (RSV); adenovirus, rhinovirus, human metapneumovirus (hMPV) and enterovirus) in patients hospitalized with severe acute respiratory illness (SARI), outpatients with influenza-like illness (ILI), and control subjects who did not report any febrile, respiratory or gastrointestinal illness during 2012-2015 in South Africa. We estimated the attributable fraction (AF) and the detection rate attributable to illness for each of the different respiratory viruses. RESULTS : We enrolled 1959 SARI, 3784 ILI and 1793 controls. Influenza virus (AF: 86.3%; 95%CI: 77.7%-91.6%), hMPV (AF: 85.6%%; 95%CI: 72.0%-92.6%), and RSV (AF: 83.7%; 95%CI: 77.5%-88.2%) infections were highly associated with severe disease, while rhinovirus (AF: 46.9%; 95%CI: 37.6%-56.5%) and adenovirus (AF: 36.4%; 95%CI: 20.6%-49.0%) were only moderately associated. The estimated detection rate associated with severe disease was: 20.2% for rhinovirus, 16.7% for RSV, 7.0% for adenovirus, 4.9% for influenza virus and 3.8% for hMPV. Similar patterns were observed for patients with ILI. CONCLUSIONS : Influenza, RSV and hMPV can be considered likely pathogens if detected in patients with ILI and SARI while rhinovirus and adenovirus were commonly identified also among controls suggesting that they may cause only a proportion of clinical disease observed in positive patients. Nonetheless, given their high estimated detection rate attributable to illness, they may be important contributors to disease.Co-operative agreement 5U51/IP000155 with the Centers for Disease Control and Prevention, Atlanta, Georgia, USA.http://www.elsevier.com/locate/jcv2017-02-28hb2016Medical Virolog

Development of a respiratory severity score for hospitalized adults in a high HIV-prevalence setting—South Africa, 2010-2011

BACKGROUND : Acute lower respiratory tract infections (LRTI) are a frequent cause of hospitalization and mortality in South Africa; however, existing respiratory severity scores may underestimate mortality risk in HIV-infected adults in resource limited settings. A simple predictive clinical score for low-resource settings could aid healthcare providers in the management of patients hospitalized with LRTI. METHODS : We analyzed 1,356 LRTI hospitalizations in adults aged ≥18 years enrolled in Severe Acute Respiratory Illness (SARI) surveillance in three South African hospitals from January 2010 to December 2011. Using demographic and clinical data at admission, we evaluated potential risk factors for in-hospital mortality. We evaluated three existing respiratory severity scores, CURB-65, CRB-65, and Classification Tree Analysis (CTA) Score assessing for discrimination and calibration. We then developed a new respiratory severity score using a multivariable logistic regression model for in-hospital mortality and assigned points to risk factors based on the coefficients in the multivariable model. Finally we evaluated the model statistically using bootstrap resampling techniques. RESULTS : Of the 1,356 patients hospitalized with LRTI, 101 (7.4%) died while hospitalized. The CURB-65, CRB-65, and CTA scores had poor calibration and demonstrated low discrimination with c-statistics of 0.594, 0.548, and 0.569 respectively. Significant risk factors for in-hospital mortality included age ≥ 45 years (A), confusion on admission (C), HIV-infection (H), and serum blood urea nitrogen >7 mmol/L (U), which were used to create the seven-point ACHU clinical predictor score. In-hospital mortality, stratified by ACHU score was: score ≤1, 2.4%, score 2, 6.4%, score 3, 11. 9%, and score ≥ 4, 29.3%. Final models showed good discrimination (c-statistic 0.789) and calibration (chi-square 1.6, Hosmer-Lemeshow goodness-of-fit p-value = 0.904) and discriminated well in the bootstrap sample (average optimism of 0.003). CONCLUSIONS : Existing clinical predictive scores underestimated mortality in a low resource setting with a high HIV burden. The ACHU score incorporates a simple set a risk factors that can accurately stratify patients ≥18 years of age with LRTI by in-hospital mortality risk. This score can quantify in-hospital mortality risk in an HIV-endemic, resource-limited setting with limited clinical information and if used to facilitate timely treatment may improve clinical outcomes.Additional file 1: BMC Pulmonary_Severity Score Data.xlsx. Severity Score Dataset. Dataset generated and used for analysis and creation of the ACHU score. Two tabs are included 1) includes the data used for the analysis 2) includes important notes related to the analytical methods and definitions for several composite variables.Additional file 2: Table S1. CURB-65, CRB-65, Classification Tree Analysis (CTA) severity scores. Table S2. Predicted and observed risk of mortality based on CURB-65, CRB-65, Classification Tree Analysis (CTA), and CURB-45 severity scores among hospitalized adults with lower respiratory tract infections, South Africa, 2010–2011. Table S3. Predicted and observed risk of mortality based by ACHU (Age, confusion, HIV, urea) respiratory severity score among hospitalized adults with lower respiratory tract infections, South Africa, 2010–2011.The Centers for Disease Control and Preventionhttp://www.biomedcentral.com/bmccom/plementalternmedam2017Medical Virolog