RESUMEN
The SARS-CoV-2 epidemic in southern Africa has been characterized by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, while the second and third waves were driven by the Beta (B.1.351) and Delta (B.1.617.2) variants, respectively1-3. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron, B.1.1.529) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, which are predicted to influence antibody neutralization and spike function4. Here we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.
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COVID-19/epidemiología , COVID-19/virología , Evasión Inmune , SARS-CoV-2/aislamiento & purificación , Anticuerpos Neutralizantes/inmunología , Botswana/epidemiología , COVID-19/inmunología , COVID-19/transmisión , Humanos , Modelos Moleculares , Mutación , Filogenia , Recombinación Genética , SARS-CoV-2/clasificación , SARS-CoV-2/inmunología , Sudáfrica/epidemiología , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
Continued uncontrolled transmission of SARS-CoV-2 in many parts of the world is creating conditions for substantial evolutionary changes to the virus1,2. Here we describe a newly arisen lineage of SARS-CoV-2 (designated 501Y.V2; also known as B.1.351 or 20H) that is defined by eight mutations in the spike protein, including three substitutions (K417N, E484K and N501Y) at residues in its receptor-binding domain that may have functional importance3-5. This lineage was identified in South Africa after the first wave of the epidemic in a severely affected metropolitan area (Nelson Mandela Bay) that is located on the coast of the Eastern Cape province. This lineage spread rapidly, and became dominant in Eastern Cape, Western Cape and KwaZulu-Natal provinces within weeks. Although the full import of the mutations is yet to be determined, the genomic data-which show rapid expansion and displacement of other lineages in several regions-suggest that this lineage is associated with a selection advantage that most plausibly results from increased transmissibility or immune escape6-8.
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COVID-19/virología , Mutación , Filogenia , Filogeografía , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/transmisión , Análisis Mutacional de ADN , Evolución Molecular , Aptitud Genética , Humanos , Evasión Inmune , Modelos Moleculares , SARS-CoV-2/inmunología , SARS-CoV-2/patogenicidad , Selección Genética , Sudáfrica/epidemiología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Factores de TiempoRESUMEN
Infections are an underappreciated cause of stroke, particularly in young and immunocompromised individuals. Varicella-zoster virus (VZV) reactivation, particularly ophthalmic zoster, has been linked to increased risk of stroke but diagnosing VZV-associated cerebral vasculopathy is challenging as neither a recent zoster rash, nor detectable levels of VZV DNA are universally present at stroke presentation. Detection of VZV IgG in cerebrospinal fluid (CSF-VZVG) presents a promising alternative, but requires evaluation of individual blood-CSF dynamics, particularly in the setting of chronic inflammatory states such as HIV infection. Consequently, its use has not been broadly adopted as simple diagnostic algorithms are not available. In this study looking at young adults presenting with acute stroke, we used an algorithm that includes testing for both VZV nucleic acids and CSF-VZVG which was corrected for blood-CSF barrier dynamics and poly-specific immune activation. We found that 13 of 35 (37%), including 7 with a positive CSF VZV PCR, young HIV-infected adults presenting with stroke, 3 of 34 (9%) young HIV-uninfected adults presenting with stroke, and 1 of 18 (6%) HIV-infected nonstroke controls demonstrated evidence of central nervous system reactivation of VZV.
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Infecciones por VIH , Herpes Zóster , Accidente Cerebrovascular , Infecciones por VIH/complicaciones , Herpes Zóster/complicaciones , Herpes Zóster/diagnóstico , Herpesvirus Humano 3/genética , Humanos , Reacción en Cadena de la Polimerasa , Accidente Cerebrovascular/diagnóstico , Adulto JovenRESUMEN
HIV-1 viral load (VL) testing is a crucial element in providing an antiretroviral treatment monitoring program. The success of these programs depends on the availability and quality of the VL testing services. There are several pre-analytic factors which can affect the quality of VL testing. Many of the challenges faced by resource-limited countries result in a compromise of specimen integrity, thus limiting widespread access to VL monitoring. The various logistic and financial challenges that exist are not insurmountable and several innovative solutions currently exist to overcome these barriers to providing widespread VL testing. This review summarizes the VL testing challenges in resource-limited settings and provides an overview of potential solutions including testing dried blood spots, dried plasma spots, plasma separation cards and the use of point of care tests.
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Infecciones por VIH/diagnóstico , VIH-1/genética , Manejo de Especímenes/normas , Carga Viral/métodos , Carga Viral/normas , Infecciones por VIH/virología , Humanos , Garantía de la Calidad de Atención de SaludRESUMEN
During a measles virus (MeV) epidemic in 2009 in South Africa, measles inclusion body encephalitis (MIBE) was identified in several HIV-infected patients. Years later, children are presenting with subacute sclerosing panencephalitis (SSPE). To investigate the features of established MeV neuronal infections, viral sequences were analyzed from brain tissue samples of a single SSPE case and compared with MIBE sequences previously obtained from patients infected during the same epidemic. Both the SSPE and the MIBE viruses had amino acid substitutions in the ectodomain of the F protein that confer enhanced fusion properties. Functional analysis of the fusion complexes confirmed that both MIBE and SSPE F protein mutations promoted fusion with less dependence on interaction by the viral receptor-binding protein with known MeV receptors. While the SSPE F required the presence of a homotypic attachment protein, MeV H, in order to fuse, MIBE F did not. Both F proteins had decreased thermal stability compared to that of the corresponding wild-type F protein. Finally, recombinant viruses expressing MIBE or SSPE fusion complexes spread in the absence of known MeV receptors, with MIBE F-bearing viruses causing large syncytia in these cells. Our results suggest that alterations to the MeV fusion complex that promote fusion and cell-to-cell spread in the absence of known MeV receptors is a key property for infection of the brain.IMPORTANCE Measles virus can invade the central nervous system (CNS) and cause severe neurological complications, such as MIBE and SSPE. However, mechanisms by which MeV enters the CNS and triggers the disease remain unclear. We analyzed viruses from brain tissue of individuals with MIBE or SSPE, infected during the same epidemic, after the onset of neurological disease. Our findings indicate that the emergence of hyperfusogenic MeV F proteins is associated with infection of the brain. We also demonstrate that hyperfusogenic F proteins permit MeV to enter cells and spread without the need to engage nectin-4 or CD150, known receptors for MeV that are not present on neural cells.
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Virus del Sarampión/genética , Panencefalitis Esclerosante Subaguda/genética , Proteínas Virales de Fusión/genética , Sustitución de Aminoácidos , Animales , Encéfalo/virología , Moléculas de Adhesión Celular/metabolismo , Chlorocebus aethiops , Epidemias , Femenino , Genotipo , Células Gigantes/virología , Células HEK293 , Humanos , Masculino , Sarampión/epidemiología , Sarampión/metabolismo , Sarampión/virología , Mutación , Neuronas/virología , Sudáfrica , Panencefalitis Esclerosante Subaguda/virología , Células Vero , Proteínas Virales de Fusión/metabolismoRESUMEN
A clinical isolate of measles virus (MeV) bearing a single amino acid alteration in the viral fusion protein (F; L454W) was previously identified in two patients with lethal sequelae of MeV central nervous system (CNS) infection. The mutation dysregulated the viral fusion machinery so that the mutated F protein mediated cell fusion in the absence of known MeV cellular receptors. While this virus could feasibly have arisen via intrahost evolution of the wild-type (wt) virus, it was recently shown that the same mutation emerged under the selective pressure of small-molecule antiviral treatment. Under these conditions, a potentially neuropathogenic variant emerged outside the CNS. While CNS adaptation of MeV was thought to generate viruses that are less fit for interhost spread, we show that two animal models can be readily infected with CNS-adapted MeV via the respiratory route. Despite bearing a fusion protein that is less stable at 37°C than the wt MeV F, this virus infects and replicates in cotton rat lung tissue more efficiently than the wt virus and is lethal in a suckling mouse model of MeV encephalitis even with a lower inoculum. Thus, either during lethal MeV CNS infection or during antiviral treatment in vitro, neuropathogenic MeV can emerge, can infect new hosts via the respiratory route, and is more pathogenic (at least in these animal models) than wt MeV.IMPORTANCE Measles virus (MeV) infection can be severe in immunocompromised individuals and lead to complications, including measles inclusion body encephalitis (MIBE). In some cases, MeV persistence and subacute sclerosing panencephalitis (SSPE) occur even in the face of an intact immune response. While they are relatively rare complications of MeV infection, MIBE and SSPE are lethal. This work addresses the hypothesis that despite a dysregulated viral fusion complex, central nervous system (CNS)-adapted measles virus can spread outside the CNS within an infected host.
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Sistema Nervioso Central/virología , Encefalitis Viral , Cuerpos de Inclusión Viral , Pulmón/virología , Virus del Sarampión/fisiología , Sarampión , Mutación Missense , Proteínas Virales de Fusión , Replicación Viral , Sustitución de Aminoácidos , Animales , Sistema Nervioso Central/metabolismo , Chlorocebus aethiops , Modelos Animales de Enfermedad , Encefalitis Viral/genética , Encefalitis Viral/metabolismo , Encefalitis Viral/transmisión , Humanos , Cuerpos de Inclusión Viral/genética , Cuerpos de Inclusión Viral/metabolismo , Pulmón/metabolismo , Sarampión/metabolismo , Sarampión/transmisión , Ratones , Ratones Transgénicos , Sigmodontinae , Células Vero , Proteínas Virales de Fusión/genética , Proteínas Virales de Fusión/metabolismoRESUMEN
BACKGROUND: Congenital rubella syndrome (CRS) includes disorders associated with intrauterine rubella infection. Incidence of CRS is higher in countries with no rubella-containing vaccines (RCV) in their immunization schedules. In the World Health Organization African region, RCVs are being introduced as part of the 2012-2020 global measles and rubella strategic plan. This study aimed to describe the epidemiology of confirmed CRS in South Africa prior to introduction of RCVs in the immunization schedule. METHODS: This was a descriptive study with 28 sentinel sites reporting laboratory-confirmed CRS cases in all 9 provinces of South Africa. In the retrospective phase (2010 to 2014), CRS cases were retrieved from medical records, and in the prospective phase (2015 to 2017) clinicians at study sites reported CRS cases monthly. RESULTS: There were 42 confirmed CRS cases in the retrospective phase and 53 confirmed CRS cases in the prospective phase. Most frequently reported birth defects were congenital heart disease and cataracts. The median age of mothers of CRS cases was 21 years in the retrospective phase (range: 11 to 38 years) and 22 years in the prospective phase (range: 15 to 38 years). CONCLUSION: Baseline data on laboratory-confirmed CRS will enable planning and monitoring of RCV implementation in the South African Expanded Programme on Immunization program. Ninety-eight percent of mothers of infants with CRS were young women 14-30 years old, indicating a potential immunity gap in this age group for consideration during introduction of RCV.
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Anticuerpos Antivirales/sangre , Complicaciones Infecciosas del Embarazo/prevención & control , Síndrome de Rubéola Congénita/epidemiología , Síndrome de Rubéola Congénita/prevención & control , Vigilancia de Guardia , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Registros Médicos , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/virología , Estudios Prospectivos , Investigación Cualitativa , Estudios Retrospectivos , Virus de la Rubéola , Sudáfrica , Adulto JovenRESUMEN
Subacute sclerosing panencephalitis (SSPE) is a preventable condition reported in 6.5 to 11 per 100 000 cases of measles, and highest in children who contracted measles infection when they were less than 5 years of age. Children residing in areas with poor vaccination coverage and high prevalence of human immunodeficiency virus are at increased risk of developing SSPE. SSPE is life-threatening in most affected children. This report documents current data relating to the clinical phenotype, epidemiology, and understanding of SSPE, inclusive of preventive interventions. While improvements in disease progression with immunomodulation may occur, overall there is no cure. Most therapies focus on supportive needs. Seizures and abnormal movements may respond to carbamazepine. Many countries advocate policies to enhance vaccination coverage. Effective preventive health care programmes, assurance of parental perceptions, and crisis support for unprecedented events obstructing effective primary health care are needed. Until measles is eradicated worldwide, children in all regions remain at risk. WHAT THIS PAPER ADDS: Measles contracted under 5 years of age has highest risk of developing subacute sclerosing panencephalitis (SSPE). Children with, or exposed to, human immunodeficiency virus infection, who contract measles may be at increased risk of SSPE.
PANENCEFALITIS ESCLEROSANTE SUBAGUDA: FENOTIPO CLÍNICO, EPIDEMIOLOGÍA E INTERVENCIONES PREVENTIVAS: La panencefalitis esclerosante subaguda (SSPE, por sus siglas en inglés) es una afección prevenible notificada en 6,5 a 11 por cada 100 000 casos de sarampión, y es más alta en los niños que contrajeron una infección de sarampión cuando tenían menos de 5 años de edad. Los niños que residen en áreas con una cobertura de vacunación deficiente y una alta prevalencia del virus de inmunodeficiencia humana tienen un mayor riesgo de desarrollar SSPE. La SSPE es potencialmente mortal en la mayoría de los niños afectados. Este informe documenta los datos actuales relacionados con el fenotipo clínico, la epidemiología y la comprensión del SSPE, incluidas las intervenciones preventivas. Si bien pueden producirse mejoras en la progresión de la enfermedad con la inmunomodulación, en general no hay cura. La mayoría de las terapias se centran en las necesidades de apoyo. Las convulsiones y los movimientos anormales pueden responder a la carbamazepina. Muchos países abogan por políticas para mejorar la cobertura de vacunación. Se necesitan programas de atención médica preventiva eficaces, seguridad de las percepciones de los padres y apoyo a la crisis para eventos sin precedentes que obstruyan la atención primaria de salud efectiva. Hasta que se erradique el sarampión en todo el mundo, los niños en todas las regiones siguen en riesgo.
PANENCEFALITE ESCLEROSANTE SUB-AGUDA: FENÓTIPO CLÍNICO, EPIDEMIOLOGIA, E INTERVENÇÕES PREVENTIVAS: A panencefalite esclerosante sub-aguda (PEES) é uma condição prevenível reportada em 6,5 to 11 por 100.000 casos de sarampo, e é mais alta em crianças que contraíram infecção por sarampo com menos de 5 anos de idade. Crianças que residem em áreas com pobre cobertura vacinal e alta prevalência de vírus da imunodeficiência humana apresentam maior risco de desenvolver PEES. A PEES representa risco de vida para as crianças mais afetadas. Este relato documenta dados atuais relacionados a fenótipo clínico, epidemiologia, e compreensão da PEES, incluindo intervenções preventivas. Enquanto melhoras na progressão da doença com a imunomodulação podem ocorrer, em geral não há cura. A maior parte das terapias foca em necessidades de suporte. Convulsões e movimentos anormais podem responder a carbamazepina. Muitos países defendem políticas para melhorar a cobertura vacinal. Programas efetivos de cuidado preventivo em saúde, reforço das percepções parentais, e suporte de crise para eventos sem precedentes obstruindo o cuidado primário efetivo são necessários. Até que o sarampo esteja erradicado em todo o mundo, crianças de todas as regiões permanecem em risco.
Asunto(s)
Panencefalitis Esclerosante Subaguda , Humanos , Fenotipo , Factores de Riesgo , Panencefalitis Esclerosante Subaguda/diagnóstico , Panencefalitis Esclerosante Subaguda/epidemiología , Panencefalitis Esclerosante Subaguda/prevención & control , Resultado del Tratamiento , Vacunación/estadística & datos numéricosRESUMEN
BACKGROUND: Human enteroviruses (HEVs) are common causal agents of aseptic meningitis in young children. Laboratory and syndromic surveillance during December 2015 and January 2016 noted an unusually high number of paediatric aseptic meningitis cases at a hospital in Mossel Bay, Western Cape Province, South Africa. HEV was detected in clinical samples, prompting an outbreak investigation. METHODS: Epidemiological investigations were conducted to ascertain possible linkage between cases. Amplification, sequencing and phylogenetic analysis of the 5'UTR and VP1 regions was undertaken to determine the HEV serotype associated with the outbreak as well as other cases of aseptic meningitis in the area in the preceding 6 weeks. RESULTS: Over the 2-month period, 63 CSF samples were available for testing. A total of 43 outbreak cases (68.3%) were observed, and the 26 (60.5%) that could be typed were coxsackie virus A9 (CVA9). Children attending three crèche facilities were epidemiologically linked, accounting for 60.5% (26/43) of the CVA9 cases. The majority of patients were under 10 years of age (55/63, 87.3%) and there was a male predominance (66%). Nucleotide sequence analysis of the 5'UTR and VP1 regions identified 2 lineages of CVA9 co-circulating during the outbreak, although the VP1 capsid protein sequence was identical as all nucleotide differences were synonymous. There was a unique isoleucine at position 64 and all outbreak viruses had a valine to threonine change in the hypervariable BC loop of VP1. Other HEV types circulating in the preceding period were echovirus 30 (n = 4), echovirus 5 (n = 3) and 1 each of echovirus 6, echovirus 9 and echovirus 15. CONCLUSION: CVA9 was identified as the pathogen responsible for the large outbreak of aseptic meningitis, with 2 distinct co-circulating lineages.
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Brotes de Enfermedades , Infecciones por Enterovirus/epidemiología , Enterovirus/genética , Enterovirus/aislamiento & purificación , Meningitis Viral/epidemiología , Adolescente , Adulto , Niño , Preescolar , Enterovirus/clasificación , Enterovirus Humano B/genética , Infecciones por Enterovirus/complicaciones , Infecciones por Enterovirus/virología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Meningitis Viral/virología , Tipificación Molecular , Filogenia , ARN Viral/análisis , Vigilancia de Guardia , Sudáfrica/epidemiología , Adulto JovenRESUMEN
Background: Understanding factors that impact HIV viral load (VL) accuracy in resource-limited settings is key to quality improvement. Objective: We evaluated whether testing delay and specimen storage between 25 °C and 30 °C before testing affected results. Methods: Between November 2019 and June 2023, 249 individuals on antiretroviral therapy, or with newly diagnosed HIV, were recruited from clinics in Cape Town and Gqeberha, South Africa, and three plasma preparation tubes were collected. One tube was tested within 24 h, while the others were stored uncentrifuged at ambient temperatures before testing. Centrifugation and testing of matched samples were performed on Day 4 and Day 7 after collection. Results: Time delay and ambient storage had minimal impact in specimens with a Day 1 VL of > 100 copies/mL. When grouped by Day 1 VL range, 96% - 100% of specimens at Day 4 and 93% - 100% at Day 7 had VLs within 0.5 log copies/mL of the first result. The greatest variability at Days 4 and 7 was observed when the Day 1 VL was < 100 copies/mL. However, there was no trend of increasing difference over time. Of Day 1 specimens with undetectable VL, or VL < 50 copies/mL, 80% had concordant results at Day 4 and 78% at Day 7. Conclusion: These results show that VL is stable in plasma preparation tubes for 7 days when stored at room temperature. There is significant variability in specimens with low VL, but variability is not affected by testing delay. What this study adds: Ideal HIV VL testing conditions are frequently unachievable in resource-limited settings. Data are needed on whether this impacts on the validity of test results. Our results provide reassurance that storage at ambient temperature for up to 7 days before testing does not substantially affect the VL result.
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In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can help describe and characterise the extent of the pandemic, as well as elucidate protection conferred by prior exposure. We conducted repeated cross-sectional serosurveys (July 2020 -November 2021) using residual samples from patients from Cape Town, South Africa, sent for routine laboratory studies for non-COVID-19 conditions. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses. Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.19% (95% confidence interval [CI] 37.23-41.19) in July 2020 to 67.8% (95%CI 66.31-69.25) in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Using COVID-19 hospital admission and death data at the Provincial Health Data Centre, antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35). The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19 disease. In low-income communities, where diagnostic testing capacity is often limited, surveillance systems dependent on them will underestimate the true extent of an outbreak. Rapidly conducted seroprevalence studies can play an important role in addressing this.
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BACKGROUND: During 2009/10 a major measles epidemic caused by genotype B3 occurred in South Africa. Measles inclusion body encephalitis (MIBE) was diagnosed in a number of highly immuno-compromised HIV patients. The diagnosis was based on typical clinical and MRI findings and positive measles virus PCR in brain or CSF.To characterize the brain virus, nucleoprotein, matrix, fusion and haemagglutinin genes from 4 cases was compared with virus from acutely infected patients. METHODS: cDNA was synthesized using random primers and viral genes were amplified by nested RT-PCR. PCR products were sequenced in the forward and reverse direction and a contig of each gene was created. Sequences were aligned with reference sequences from GenBank and other local sequences. RESULTS: Brain virus was very similar to the South African epidemic virus. Features characteristic of persistent measles virus in the brain were absent. Mutation frequency in brain virus was similar to epidemic virus and had the same substitution preference (U to C and C to U). The virus of 2 patients had the same L454W mutation in the fusion protein. CONCLUSION: The brain virus was very similar to the epidemic strain. The relatively few mutations probably reflect the short time from infection to brain disease in these highly immuno-compromised patients.
Asunto(s)
Encéfalo/virología , Virus del Sarampión/genética , Virus del Sarampión/aislamiento & purificación , ARN Viral/genética , Panencefalitis Esclerosante Subaguda/virología , Adolescente , Adulto , Análisis por Conglomerados , Femenino , Humanos , Masculino , Datos de Secuencia Molecular , Tasa de Mutación , Filogenia , Mutación Puntual , Reacción en Cadena de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Análisis de Secuencia de ADN , Sudáfrica , Proteínas Virales/genética , Adulto JovenRESUMEN
Clinical metagenomics is the diagnostic approach with the broadest capacity to detect both known and novel pathogens. Clinical metagenomics is costly to run and requires infrastructure, but the use of next-generation sequencing for SARS-CoV-2 molecular epidemiology in low-income and middle-income countries (LMICs) offers an opportunity to direct this infrastructure to the establishment of clinical metagenomics programmes. Local implementation of clinical metagenomics is important to create relevant systems and evaluate cost-effective methodologies for its use, as well as to ensure that reference databases and result interpretation tools are appropriate to local epidemiology. Rational implementation, based on the needs of LMICs and the available resources, could ultimately improve individual patient care in instances in which available diagnostics are inadequate and supplement emerging infectious disease surveillance systems to ensure the next pandemic pathogen is quickly identified.
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COVID-19 , SARS-CoV-2 , Humanos , Países en Desarrollo , Metagenómica , Inversiones en SaludRESUMEN
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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HIV viral load (VL) testing plays a key role in the clinical management of HIV as a marker of adherence and antiretroviral efficacy. To date, national and international antiretroviral treatment recommendations have evolved to endorse routine VL testing. South Africa (SA) has recommended routine VL testing since 2004. Progressively, the centralised HIV VL program managed by its National Health Laboratory Service (NHLS) has undergone expansive growth. Retrospective de-identified VL data from 2013 to 2022 were evaluated to review program performance. Test volumes increased from 1,961,720 performed in 2013 to 45,334,864 in 2022. The median total in-laboratory turnaround time (TAT) ranged from 94 h (2015) to 51 h (2022). Implementation of two new assays improved median TATs in all laboratories. Samples of VL greater than 1000 copies/mL declined steadily. Despite initial increases, samples of fewer than 50 copies/mL stagnated at about 70% from 2019 and declined to 68% in 2022. Some variations between assays were observed. Overall, the SA VL program is successful. The scale of the VL program, the largest of its kind in the world by some margin, provides lessons for future public health programs dependent on laboratories for patient outcome and program performance monitoring.
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OBJECTIVES: To describe the prevalence and outcome of patients admitted to a pediatric intensive care unit with viral respiratory tract infections. DESIGN: Retrospective descriptive study. SETTING: Pediatric intensive care unit in a tertiary pediatric hospital situated in Cape Town, South Africa. PATIENTS: All children (n = 195; 20% pediatric intensive care unit admissions) with positive respiratory viral isolates between April 1 and December 31, 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, laboratory, and outcome data were recorded from medical folders. Complete data were available for 175 patients (median age [interquartile range] 4.7 months [2.3-12.9 months]; 49% male). One hundred four (59.4%) patients had comorbid conditions; 30 (17%) were HIV-infected. Rhinovirus (n = 76 [39%]), respiratory syncytial virus (n = 54 [27.7%]), adenovirus (n = 30 [15.4%]), influenza A (n = 26 [13.3%]), parainfluenza (n = 23 [11.8%]), and human metapneumovirus (n = 12 [6.2%]) were most commonly isolated. Ninety-five infections (51.4%) were isolated >48 hrs after admission. Seasonal patterns were identified for respiratory syncytial virus, human metapneumovirus, and influenza A, whereas others occurred throughout the year. Twenty-five patients (14.3%) had more than one viral isolate. Presumed bacterial coinfection, which occurred in 68 (39%) patients (18 [26.5%] HIV-infected), was associated with significantly longer pediatric intensive care unit and hospital stays but not with mortality. Twenty patients died (11%, standardized mortality ratio 0.64). High Pediatric Index of Mortality scores, HIV exposure and infection, nosocomial infection, and influenza A infection were associated with mortality. CONCLUSIONS: Viral respiratory tract infection is common in this pediatric intensive care unit associated with significant morbidity and mortality, which may relate to the high burden of comorbidity and HIV.
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Coinfección/epidemiología , Infección Hospitalaria/mortalidad , Infecciones por VIH/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Infecciones por Adenovirus Humanos/epidemiología , Infecciones Bacterianas/epidemiología , Coinfección/mortalidad , Intervalos de Confianza , Femenino , Infecciones por VIH/mortalidad , Humanos , Lactante , Virus de la Influenza A , Gripe Humana/mortalidad , Gripe Humana/virología , Unidades de Cuidado Intensivo Pediátrico , Tiempo de Internación , Modelos Logísticos , Masculino , Metapneumovirus , Oportunidad Relativa , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/virología , Infecciones por Picornaviridae/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/mortalidad , Estudios Retrospectivos , Estaciones del Año , Sudáfrica/epidemiologíaRESUMEN
BACKGROUND: The Omicron variant of concern is characterised by more than 50 distinct mutations, most in the spike protein. The implications of these for disease transmission, tissue tropism and diagnostic testing needs study. OBJECTIVES: We evaluated the performance of RT-PCR on saliva (SA) swabs and antigen testing on mid-turbinate MT samples relative to RT-PCR on MT swabs. Patients (n = 453) presenting for outpatient testing at the Groote Schuur Hospital COVID-19 testing centre in Cape Town South Africa were recruited. Participants were recruited during the Delta (n = 304) and Omicron (n = 149) waves. RESULTS: In 30 confirmed Delta infections, positive percent agreement (PPA) of RT-PCR on saliva was only 73% compared to a composite standard of either MT or SA RT-PCR positivity, with rapid decay by day 3 after symptom onset. In contrast, in the 70 Omicron infections, SA performed as well as, or better than, MT samples up to day 5, with an overall PPA of SA swabs of 96% and MT of 93%. A change in antigen test performance was noted, with PPA of 93% in Delta, but only 68% for Omicron. CONCLUSIONS: Altered shedding kinetics appear to be present in Omicron-infected patients with more viral RNA detectable in saliva. Saliva swabs are a promising alternative to nasal samples, especially early in infection when sampling of both sites could improve detection. Lower sensitivity of antigen tests in Omicron is a concern and requires further study.
Asunto(s)
Prueba de COVID-19 , COVID-19 , Humanos , SARS-CoV-2 , Sensibilidad y Especificidad , Sudáfrica , TropismoRESUMEN
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.
RESUMEN
Background: In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can characterise the scale and determinants of the pandemic, as well as elucidate protection conferred by prior exposure. Methods: We conducted repeated cross-sectional serosurveys (July 2020 - November 2021) using residual plasma from routine convenient blood samples from patients with non-COVID-19 conditions from Cape Town, South Africa. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses, to estimate variant disease severity. Findings: Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.2% in July 2020 to 67.8% in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35). Interpretation: The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19. Funding: Wellcome Trust, National Health Laboratory Service, the Division of Intramural Research, NIAID, NIH (ADR) and Western Cape Government Health.