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BACKGROUND: We estimated the household secondary infection risk (SIR) and serial interval (SI) for influenza transmission from HIV-infected and HIV-uninfected index cases. METHODS: Index cases were the first symptomatic person in a household with influenza-like illness, testing influenza positive on real-time reverse transcription polymerase chain reaction (rRT-PCR). Nasopharyngeal swabs collected from household contacts every 4 days were tested by rRT-PCR. Factors associated with SIR were evaluated using logistic regression. RESULTS: We enrolled 28 HIV-infected and 57 HIV-uninfected index cases. On multivariable analysis, HIV-infected index cases were less likely to transmit influenza to household contacts (odds ratio [OR] 0.2; 95% confidence interval [CI], 0.1-0.6; SIR 16%, 18/113 vs 27%, 59/220). Factors associated with increased SIR included index age group 1-4 years (OR 3.6; 95% CI, 1.2-11.3) and 25-44 years (OR 8.0; 95% CI, 1.8-36.7), and contact age group 1-4 years (OR 3.5; 95% CI, 1.2-10.3) compared to 5-14 years, and sleeping with index case (OR 2.7; 95% CI, 1.3-5.5). HIV infection of index case was not associated with SI. CONCLUSIONS: HIV-infection was not associated with SI. Increased infectiousness of HIV-infected individuals is likely not an important driver of community influenza transmission.
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Infecciones por VIH/complicaciones , Gripe Humana/epidemiología , Gripe Humana/transmisión , Adolescente , Adulto , Anciano , Niño , Preescolar , Composición Familiar , Femenino , Infecciones por VIH/epidemiología , Humanos , Lactante , Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/aislamiento & purificación , Masculino , Persona de Mediana Edad , Factores de Riesgo , Sudáfrica/epidemiología , Adulto JovenRESUMEN
Background: Prolonged shedding of influenza viruses may be associated with increased transmissibility and resistance mutation acquisition due to therapy. We compared duration and magnitude of influenza shedding between human immunodeficiency virus (HIV)-infected and -uninfected individuals. Methods: A prospective cohort study during 3 influenza seasons enrolled patients with influenza-like illness and a positive influenza rapid test. Influenza viruses were detected by real-time reverse transcription polymerase chain reaction. Weibull accelerated failure time regression models were used to describe influenza virus shedding. Mann-Whitney U tests explored initial influenza viral loads (VL). Results: Influenza virus shedding duration was similar in 65 HIV-infected (6 days; interquartile range [IQR] 3-10) and 176 HIV-uninfected individuals (7 days; IQR 4-11; P = .97), as was initial influenza VL (HIV-uninfected 5.28 ± 1.33 log10 copies/mL, HIV-infected 4.73 ± 1.68 log10 copies/mL; P = .08). Adjusted for age, HIV-infected individuals with low CD4 counts shed influenza virus for longer than those with higher counts (adjusted hazard ratio 3.55; 95% confidence interval, 1.05-12.08). Discussion: A longer duration of influenza virus shedding in HIV-infected individuals with low CD4 counts may suggest a possible increased risk for transmission or viral evolution in severely immunocompromised individuals. HIV-infected individuals should be prioritized for annual influenza immunization.
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Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Gripe Humana/complicaciones , Gripe Humana/virología , Orthomyxoviridae/fisiología , Esparcimiento de Virus , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Gripe Humana/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Sudáfrica/epidemiología , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children in both the community and hospital setting. METHODS: The clinical presentation, patient and phylogenetic characteristicsof laboratory-confirmed cases of RSV, as well as risk factors for nosocomial infectionat Red Cross War Memorial Children's Hospital in Cape Town were analysed. A multiplex PCR assay that detects 7 respiratory viruses was used to identify RSV nucleic acid on respiratory specimens. RESULTS: A total of 226 children were studied, ages ranging between 1 week and 92.5 months (median: 2.8 months, IQR: 1.3-6.3 months) and 51.8 % were males. The median duration of symptoms prior to diagnosis was 2 days (IQR: 1-4 days). Nosocomial infections wereidentified in 22 (9.7 %) children. There were pre-existing medical conditions in 113 (50.0 %) excluding HIV, most commonly prematurity (n = 58, 50.0 %) and congenital heart disease (n = 34, 29.3 %). The commonest presenting symptoms were cough (196, 86.7 %), difficulty in breathing (115, 50.9 %) and fever (91, 41.6 %).A case fatality rate of 0.9 % was recorded. RSV group A predominated (n = 181, 80.1 %) while group B accounted for only 45 (19.9 %) of the infections. The prevalent genotypes were NA1 (n = 127,70.1 %), ON1 (n = 45,24.9 %) and NA2 (n = 9,5.0 %) for group A while the only circulating RSV B genotype was BA4. There was no significant difference in the genotype distribution between the nosocomial and community-acquired RSV infections. Age ≥ 6 months was independently associated with nosocomial infection. CONCLUSIONS: A large percentage of children with RSV infection had pre-existing conditions. Approximately one tenth of the infections were nosocomial with age 6 months or older being a risk factor. Though both RSV groups co-circulated during the season, group A was predominant and included the novel ON1 genotype. Continued surveillance is necessary to identify prevalent and newly emerging genotypes ahead of vaccine development and efficacy studies.
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Niño Hospitalizado , Infecciones por Virus Sincitial Respiratorio/epidemiología , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Niño , Niño Hospitalizado/estadística & datos numéricos , Preescolar , Infección Hospitalaria/epidemiología , Infección Hospitalaria/virología , Femenino , Genotipo , Hospitales Pediátricos , Humanos , Lactante , Recién Nacido , Masculino , Filogenia , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/clasificación , Sudáfrica/epidemiologíaRESUMEN
Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of developing various solid cancers, but mostly colorectal cancer (CRC). Despite having the same germline pathogenic variant (PV) in one of the mis-match repair genes or the EPCAM gene, Lynch syndrome variant heterozygotes (LSVH) exhibit a remarkable phenotypic variability in the risk of developing cancer. The role of human leukocyte antigen (HLA) in modifying cancer development risk prompted our hypothesis into whether HLA variations act as potential genetic modifiers influencing the age at cancer diagnosis in LSVH. To investigate this, we studied a unique cohort of 426 LSVH carrying the same germline PV in the hMLH1 gene (MLH1:c.1528C > T) in South Africa. We intuitively selected 100 LSVH with the greatest diversity in age at cancer diagnosis (N = 80) and the oldest cancer unaffected LSVH (N = 20) for a high-throughput HLA genotyping of 11 HLA class I and class II loci using the shotgun next-generation sequencing (NGS) technique on the Illumina MiSeq platform. Statistical analyses employed Kaplan-Meier survival analyses with log-rank tests, and Cox proportional hazards using binned HLA data to minimize type I error. Significant associations were observed between young age at cancer diagnosis and HLA-DPB1*04:02 (mean age: 37 y (25-50); hazard ratio (HR) = 3.37; corrected p-value (q) = 0.043) as well as HLA-DPB1 binned alleles (including HLA-DPB1*09:01, HLA-DPB1*10:01, HLA-DPB1*106:01, HLA-DPB1*18:01, HLA-DPB1*20:01, HLA-DPB1*26:01, HLA-DPB1*28:01, HLA-DPB1*296:01, and HLA-DPB1*55:01) (mean age: 37 y (17-63); HR = 2.30, q = 0.045). The involvement of HLA-DPB1 alleles in the age at cancer diagnosis may highlight the potential role of HLA class II in the immune response against cancer development in LSVH. When validated in a larger cohort, these high-risk HLA-DPB1 alleles could be factored into cancer risk prediction models for personalized cancer screening in LSVH.
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Alterations of the genital mucosal barrier may influence the number of viruses transmitted from a human immunodeficiency virus-infected source host to the newly infected individual. We used heteroduplex tracking assay and single-genome sequencing to investigate the effect of a tenofovir-based microbicide gel on the transmission bottleneck in women who seroconverted during the CAPRISA 004 microbicide trial. Seventy-seven percent (17 of 22; 95% confidence interval [CI], 56%-90%) of women in the tenofovir gel arm were infected with a single virus compared with 92% (13 of 14; 95% CI, 67%->99%) in the placebo arm (P = .37). Tenofovir gel had no discernable impact on the transmission bottleneck.
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Adenina/análogos & derivados , Fármacos Anti-VIH/administración & dosificación , Antiinfecciosos Locales/administración & dosificación , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , VIH-1/efectos de los fármacos , Organofosfonatos/administración & dosificación , Adenina/administración & dosificación , Cuello del Útero/virología , Estudios de Cohortes , Femenino , Geles/administración & dosificación , Humanos , Membrana Mucosa/virología , TenofovirRESUMEN
The epidemiology of human parainfluenza viruses (HPIV), particularly its role as a cause of acute respiratory infection (ARI) in infants, has not been formally studied in South Africa. We evaluated HPIV prevalence in diagnostic samples from hospitalized children from public sector hospitals in the Western Cape between 2014 and 2022. HPIV infection was detected in 2-10% of patients, with the majority of infections detected in children less than 1 year of age. Prior to 2020, HPIV 4 (40%) and HPIV 3 (34%) were the most prevalent types, with seasonal peaks in late winter/spring for HPIV 3 and autumn/winter for HPIV 4. HPIV 4A and 4B co-circulated during the seasonal activity between 2014 and 2017. Pandemic restrictions in 2020 had a profound effect on HPIV circulation and the rebound was dominated by waves of HPIV 3, accounting for 66% of detections and a sustained decline in the circulation of HPIV 1, 2 and 4. An immunity gap could account for the surge in HPIV 3 infections, but the decline in prior HPIV 4 dominance is unexplained and requires further study.
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BACKGROUND: We aimed to describe the prevalence of human respiratory syncytial virus (HRSV) and evaluate associations between HRSV subgroups and/or genotypes and epidemiologic characteristics and clinical outcomes in patients hospitalized with severe respiratory illness (SRI). METHODS: Between January 2012 and December 2015, we enrolled patients of all ages admitted to two South African hospitals with SRI in prospective hospital-based syndromic surveillance. We collected respiratory specimens and clinical and epidemiological data. Unconditional random effect multivariable logistic regression was used to assess factors associated with HRSV infection. RESULTS: HRSV was detected in 11.2% (772/6908) of enrolled patients of which 47.0% (363/772) were under the age of 6 months. There were no differences in clinical outcomes of HRSV subgroup A-infected patients compared with HRSV subgroup B-infected patients but among patients aged <5 years, children with HRSV subgroup A were more likely be coinfected with Streptococcus pneumoniae (23/208, 11.0% vs. 2/90, 2.0%; adjusted odds ratio 5.7). No significant associations of HRSV A genotypes NA1 and ON1 with specific clinical outcomes were observed. CONCLUSIONS: While HRSV subgroup and genotype dominance shifted between seasons, we showed similar genotype diversity as noted worldwide. We found no association between clinical outcomes and HRSV subgroups or genotypes.
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Niño , Genotipo , Humanos , Lactante , Filogenia , Estudios Prospectivos , Infecciones por Virus Sincitial Respiratorio/epidemiología , Virus Sincitial Respiratorio Humano/genética , Sudáfrica/epidemiologíaRESUMEN
Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced RT-PCR amplification efficiency of the RdRp-gene target of the Seegene, Allplex 2019-nCoV diagnostic assay from June 2021 when detecting the Delta variant. We investigated whether the reduced amplification efficiency denoted by an increased RT-PCR cycle threshold value (RΔE) can be used as an indirect measure of SARS-CoV-2 Delta variant prevalence. We found a significant increase in the median RΔE for patient samples tested from June 2021, which coincided with the emergence of the SARS-CoV-2 Delta variant within our sample set. Whole genome sequencing on a subset of patient samples identified a highly conserved G15451A, non-synonymous mutation exclusively within the RdRp gene of Delta variants, which may cause reduced RT-PCR amplification efficiency. While whole genome sequencing plays an important in identifying novel SARS-CoV-2 variants, monitoring RΔE value can serve as a useful surrogate for rapid tracking of Delta variant prevalence.
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Prueba de Ácido Nucleico para COVID-19 , COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , COVID-19/virología , Pruebas Diagnósticas de Rutina , Humanos , ARN , ARN Polimerasa Dependiente del ARN , SARS-CoV-2/genéticaRESUMEN
Background: The SARS-CoV-2 Delta variant (B.1.617.2) has been associated with more severe disease, particularly when compared to the Alpha variant. Most of this data, however, is from high income countries and less is understood about the variant's disease severity in other settings, particularly in an African context, and when compared to the Beta variant. Methods: A novel proxy marker, RNA-dependent RNA polymerase (RdRp) target delay in the Seegene Allplex TM 2019-nCoV (polymerase chain reaction) PCR assay, was used to identify suspected Delta variant infection in routine laboratory data. All cases diagnosed on this assay in the public sector in the Western Cape, South Africa, from 1 April to 31 July 2021, were included in the dataset provided by the Western Cape Provincial Health Data Centre (PHDC). The PHDC collates information on all COVID-19 related laboratory tests, hospital admissions and deaths for the province. Odds ratios for the association between the proxy marker and death were calculated, adjusted for prior diagnosed infection and vaccination status. Results: A total of 11,355 cases with 700 deaths were included in this study. RdRp target delay (suspected Delta variant) was associated with higher mortality (adjusted odds ratio [aOR] 1.45; 95% confidence interval [CI]: 1.13-1.86), compared to presumptive Beta infection. Prior diagnosed infection during the previous COVID-19 wave, which was driven by the Beta variant, was protective (aOR 0.32; 95%CI: 0.11-0.92) as was vaccination (aOR [95%CI] 0.15 [0.03-0.62] for complete vaccination [≥28 days post a single dose of Ad26.COV2.S or ≥14 days post second BNT162b2 dose]). Conclusion: RdRp target delay, a proxy for infection with the Delta variant, is associated with an increased risk of mortality amongst those who were tested for COVID-19 in our setting.
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BACKGROUND: At present, it is unclear whether the extent of reduced risk of severe disease seen with SARS-Cov-2 Omicron variant infection is caused by a decrease in variant virulence or by higher levels of population immunity. METHODS: RdRp target delay (RTD) in the Seegene AllplexTM 2019-nCoV PCR assay is a proxy marker for the Delta variant. The absence of this proxy marker in the transition period was used to identify suspected Omicron infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene AllplexTM assay from November 1 to December 14, 2021 in the Western Cape Province, South Africa, in the public sector. Adjustments were made for vaccination status and prior diagnosis of infection. RESULTS: A total of 150 cases with RTD and 1486 cases without RTD were included. Cases without RTD had a lower hazard of admission (adjusted hazard ratio [aHR], 0.56; 95% confidence interval [CI], 0.34-0.91). Complete vaccination was protective against admission, with an aHR of 0.45 (95% CI, 0.26-0.77). CONCLUSION: Omicron has resulted in a lower risk of hospital admission compared with contemporaneous Delta infection, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant remains a challenge to accurately assessing variant virulence.
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COVID-19 , Hepatitis D , COVID-19/diagnóstico , Humanos , Reacción en Cadena de la Polimerasa , ARN Polimerasa Dependiente del ARN , SARS-CoV-2/genética , Sudáfrica/epidemiología , Análisis de SupervivenciaRESUMEN
SARS-CoV-2 variants that escape neutralization and potentially affect vaccine efficacy have emerged. T cell responses play a role in protection from reinfection and severe disease, but the potential for spike mutations to affect T cell immunity is incompletely understood. We assessed neutralizing antibody and T cell responses in 44 South African COVID-19 patients either infected with the Beta variant (dominant from November 2020 to May 2021) or infected before its emergence (first wave, Wuhan strain) to provide an overall measure of immune evasion. We show that robust spike-specific CD4 and CD8 T cell responses were detectable in Beta-infected patients, similar to first-wave patients. Using peptides spanning the Beta-mutated regions, we identified CD4 T cell responses targeting the wild-type peptides in 12 of 22 first-wave patients, all of whom failed to recognize corresponding Beta-mutated peptides. However, responses to mutated regions formed only a small proportion (15.7%) of the overall CD4 response, and few patients (3 of 44) mounted CD8 responses that targeted the mutated regions. Among the spike epitopes tested, we identified three epitopes containing the D215, L18, or D80 residues that were specifically recognized by CD4 T cells, and their mutated versions were associated with a loss of response. This study shows that despite loss of recognition of immunogenic CD4 epitopes, CD4 and CD8 T cell responses to Beta are preserved overall. These observations may explain why several vaccines have retained the ability to protect against severe COVID-19 even with substantial loss of neutralizing antibody activity against Beta.
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COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Epítopos , Humanos , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
BACKGROUND: HIV-1 Gag virus like particles (VLPs) used as candidate vaccines are regarded as inert particles as they contain no replicative nucleic acid, although they do encapsidate cellular RNAs. During HIV-1 Gag VLP production in baculovirus-based expression systems, VLPs incorporate the baculovirus Gp64 envelope glycoprotein, which facilitates their entry into mammalian cells. This suggests that HIV-1 Gag VLPs produced using this system facilitate uptake and subsequent expression of encapsidated RNA in mammalian cells - an unfavourable characteristic for a vaccine. METHODS: HIV-1 Gag VLPs encapsidating reporter chloramphenicol acetyl transferase (CAT) RNA, were made in insect cells using the baculovirus expression system. The presence of Gp64 on the VLPs was verified by western blotting and RT-PCR used to detect and quantitate encapsidated CAT RNA. VLP samples were heated to inactivate CAT RNA. Unheated and heated VLPs incubated with selected mammalian cell lines and cell lysates tested for the presence of CAT protein by ELISA. Mice were inoculated with heated and unheated VLPs using a DNA prime VLP boost regimen. RESULTS: HIV-1 Gag VLPs produced had significantly high levels of Gp64 (~1650 Gp64 molecules/VLP) on their surfaces. The amount of encapsidated CAT RNA/µg Gag VLPs ranged between 0.1 to 7 ng. CAT protein was detected in 3 of the 4 mammalian cell lines incubated with VLPs. Incubation with heated VLPs resulted in BHK-21 and HeLa cell lysates showing reduced CAT protein levels compared with unheated VLPs and HEK-293 cells. Mice inoculated with a DNA prime VLP boost regimen developed Gag CD8 and CD4 T cell responses to GagCAT VLPs which also boosted a primary DNA response. Heating VLPs did not abrogate these immune responses but enhanced the Gag CD4 T cell responses by two-fold. CONCLUSIONS: Baculovirus-produced HIV-1 Gag VLPs encapsidating CAT RNA were taken up by selected mammalian cell lines. The presence of CAT protein indicates that encapsidated RNA was expressed in the mammalian cells. Heat-treatment of the VLPs altered the ability of protein to be expressed in some cell lines tested but did not affect the ability of the VLPs to stimulate an immune response when inoculated into mice.
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Vacunas contra el SIDA/genética , Baculoviridae/genética , Productos del Gen gag/genética , Infecciones por VIH/prevención & control , VIH-1/genética , Inmunización , Vacunas de ADN/genética , Vacunas de Partículas Similares a Virus/genética , Vacunas contra el SIDA/administración & dosificación , Vacunas contra el SIDA/química , Animales , Baculoviridae/inmunología , Baculoviridae/metabolismo , Linfocitos T CD4-Positivos/inmunología , Cloranfenicol O-Acetiltransferasa/análisis , Ensayo de Inmunoadsorción Enzimática , Femenino , Productos del Gen gag/química , Productos del Gen gag/inmunología , Genes Reporteros , Células HEK293 , Infecciones por VIH/virología , VIH-1/química , VIH-1/inmunología , Células HeLa , Calor , Humanos , Ratones , Ratones Endogámicos BALB C , ARN/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Vacunas de ADN/administración & dosificación , Vacunas de ADN/química , Vacunas de Partículas Similares a Virus/administración & dosificación , Vacunas de Partículas Similares a Virus/química , Virión/genética , Virión/inmunologíaRESUMEN
HLA-DQB1*05:272 has a single transversion compared to the most similar variant, HLA-DQB1*05:01:01 in IPD-IMGT/HLA database.
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Cadenas beta de HLA-DQ , Alelos , Cadenas beta de HLA-DQ/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , SudáfricaRESUMEN
The SARS-CoV-2 pandemic has resulted in shortages of both critical reagents for nucleic acid purification and highly trained staff as supply chains are strained by high demand, public health measures and frequent quarantining and isolation of staff. This created the need for alternate workflows with limited reliance on specialised reagents, equipment and staff. We present here the validation and implementation of such a workflow for preparing samples for downstream SARS-CoV-2 RT-PCR using liquid handling robots. The rapid sample preparation technique evaluated, which included sample centrifugation and heating prior to RT-PCR, showed a 97.37% (95% CI: 92.55-99.28%) positive percent agreement and 97.30% (95% CI: 90.67-99.52%) negative percent agreement compared to nucleic acid purification-based testing. This method was subsequently adopted as the primary sample preparation method in the Groote Schuur Hospital Virology Diagnostic Laboratory in Cape Town, South Africa.
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Betacoronavirus/genética , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Laboratorios de Hospital , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Robótica/métodos , COVID-19 , Prueba de COVID-19 , Infecciones por Coronavirus/virología , Humanos , Pandemias , Neumonía Viral/virología , ARN Viral/genética , Reproducibilidad de los Resultados , SARS-CoV-2 , Sensibilidad y Especificidad , Sudáfrica/epidemiología , Manejo de EspecímenesRESUMEN
BACKGROUND: In June 2017, an outbreak of the highly pathogenic avian influenza A(H5N8) was detected in commercial poultry farms in South Africa, which rapidly spread to all nine South African provinces. OBJECTIVES: We conducted active surveillance for the transmission of influenza A(H5N8) to humans working with infected birds during the South African outbreak. METHODS: Influenza A(H5N8)-positive veterinary specimens were used to evaluate the ability of real-time PCR-based assays to detect contemporary avian influenza A(H5N8) strains. Whole genome sequences were generated from these specimens by next-generation sequencing for phylogenetic characterization and screening for mammalian-adaptive mutations. RESULTS: Human respiratory samples from 74 individuals meeting our case definition, all tested negative for avian influenza A(H5) by real-time PCR, but 2 (3%) were positive for human influenza A(H3N2). 54% (40/74) reported wearing personal protective equipment including overalls, boots, gloves, masks, and goggles. 94% (59/63) of veterinary specimens positive for H5N8 were detected on an influenza A(H5) assay for human diagnostics. A commercial H5N8 assay detected H5 in only 6% (3/48) and N8 in 92% (44/48). Thirteen (13/25; 52%) A(H5N8) genomes generated from veterinary specimens clustered in a single monophyletic clade. These sequences contained the NS (P42S) and PB2 (L89V) mutations noted as markers of mammalian adaptation. CONCLUSIONS: Diagnostic assays were able to detect and characterize influenza A(H5N8) viruses, but poor performance is reported for a commercial assay. Absence of influenza A(H5N8) in humans with occupational exposure and no clear impression of molecular adaptation for mammalian infection suggest that this avian pathogen continues to be low-risk human pathogen.
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Subtipo H5N8 del Virus de la Influenza A/genética , Gripe Aviar/virología , Gripe Humana/virología , Enfermedades de las Aves de Corral/virología , Adolescente , Adulto , Animales , Animales Salvajes/virología , Pollos/virología , Brotes de Enfermedades , Patos/virología , Monitoreo Epidemiológico , Femenino , Gansos/virología , Humanos , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Subtipo H5N8 del Virus de la Influenza A/clasificación , Subtipo H5N8 del Virus de la Influenza A/aislamiento & purificación , Gripe Aviar/epidemiología , Gripe Humana/epidemiología , Masculino , Persona de Mediana Edad , Filogenia , Enfermedades de las Aves de Corral/epidemiología , Sudáfrica/epidemiología , Struthioniformes/virología , Adulto JovenAsunto(s)
Infecciones por Virus Sincitial Respiratorio/epidemiología , Virus Sincitial Respiratorio Humano/genética , Proteínas del Envoltorio Viral/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Niño , Humanos , Datos de Secuencia Molecular , Prevalencia , Infecciones por Virus Sincitial Respiratorio/transmisión , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/clasificación , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Alineación de Secuencia , Sudáfrica/epidemiología , Proteínas del Envoltorio Viral/clasificaciónRESUMEN
Limited information is available on influenza virus sequence drift between transmission events. In countries with high HIV burdens, like South Africa, the direct and indirect effect of HIV on influenza sequence drift between transmission events may be of public health concern. To this end, we measured hemagglutinin sequence diversity between influenza transmission events using data and specimens from a study investigating household transmission dynamics of seasonal influenza viruses in 2 peri-urban communities in South Africa during the 2013 influenza season. Thirty index cases and 107 of 110 eligible household contacts were enrolled into the study, 47% (14/30) demonstrating intra-household laboratory-confirmed influenza transmission. In this study 35 partial hemagglutinin gene sequences were obtained by Sanger sequencing from 11 index cases (sampled at enrolment only) and 16 secondary cases (8 cases sampled at 1 and 8 cases sampled at 2 time-points). Viral sequence identities confirmed matched influenza transmission pairs within the 11 households with corresponding sequenced index and secondary cases. Phylogenetic analysis revealed 10 different influenza viral lineages in the 14 households. Influenza A(H1N1)pdm09 strains were shown to be genetically distinct between the 2 communities (from distinct geographic regions), which was not observed for the influenza A(H3N2) strains. Intra-host/intra-household influenza A(H3N2) sequence drift was identified in 2 households. The first was a synonymous mutation between the index case and a household contact, and the second a non-synonymous mutation between 2 serial samples taken at days 0 and 4 post enrolment from an HIV-infected secondary case. Limited inter-household sequence diversity was observed as highlighted by sharing of the same influenza strain between different households within each community. The limited intra-household sequence drift is in line with previous studies also using Sanger sequencing, corroborating the presence of strict selective bottlenecks that limit sequence variance. We were not able to directly ascertain the effect of HIV on influenza sequence drift between transmission events.
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Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Virus de la Influenza A/clasificación , Gripe Humana/transmisión , Gripe Humana/virología , Composición Familiar , Variación Genética , Humanos , Virus de la Influenza A/genética , Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Filogenia , ARN Viral/genética , Factores de Riesgo , Análisis de Secuencia de ADN , Sudáfrica/epidemiologíaRESUMEN
Trivalent seasonal influenza vaccine effectiveness during the 2015 season in South Africa was assessed using a test-negative case control study design. Influenza A(H1N1)pdm09 was the dominant circulating strain. Overall influenza vaccine coverage was 3.2% (29/899). The vaccine effectiveness estimate, against any influenza virus infection, adjusted for age, underlying conditions and timing within season was 46.2% (95% CI: -23.5 to 76.5), and 53.6% (95% CI: -62.6 to 80.3) against influenza A(H1N1)pdm09.
Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Pacientes Ambulatorios/estadística & datos numéricos , Potencia de la Vacuna , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/inmunología , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/epidemiología , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Estaciones del Año , Vigilancia de Guardia , Sudáfrica , Vacunación , Adulto JovenRESUMEN
Traditional modes of investigating influenza nosocomial transmission have entailed a combination of confirmatory molecular diagnostic testing and epidemiological investigation. Common hospital-acquired infections like influenza require a discerning ability to distinguish between viral isolates to accurately identify patient transmission chains. We assessed whether influenza hemagglutinin sequence phylogenies can be used to enrich epidemiological data when investigating the extent of nosocomial transmission over a four-month period within a paediatric Hospital in Cape Town South Africa. Possible transmission chains/channels were initially determined through basic patient admission data combined with Maximum likelihood and time-scaled Bayesian phylogenetic analyses. These analyses suggested that most instances of potential hospital-acquired infections resulted from multiple introductions of Influenza A into the hospital, which included instances where virus hemagglutinin sequences were identical between different patients. Furthermore, a general inability to establish epidemiological transmission linkage of patients/viral isolates implied that identified isolates could have originated from asymptomatic hospital patients, visitors or hospital staff. In contrast, a traditional epidemiological investigation that used no viral phylogenetic analyses, based on patient co-admission into specific wards during a particular time-frame, suggested that multiple hospital acquired infection instances may have stemmed from a limited number of identifiable index viral isolates/patients. This traditional epidemiological analysis by itself could incorrectly suggest linkage between unrelated cases, underestimate the number of unique infections and may overlook the possible diffuse nature of hospital transmission, which was suggested by sequencing data to be caused by multiple unique introductions of influenza A isolates into individual hospital wards. We have demonstrated a functional role for viral sequence data in nosocomial transmission investigation through its ability to enrich traditional, non-molecular observational epidemiological investigation by teasing out possible transmission pathways and working toward more accurately enumerating the number of possible transmission events.