RESUMEN
Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme in conversion of tryptophan to kynurenines, feeding de novo nicotinamide synthesis. IDO orchestrates materno-foetal tolerance, increasing human reproductive fitness. IDO mediates immune suppression through depletion of tryptophan required by T lymphocytes and other mechanisms. IDO is expressed by alternatively activated macrophages, suspected to play a key role in tuberculosis (TB) pathogenesis. Unlike its human host, Mycobacterium tuberculosis can synthesize tryptophan, suggesting possible benefit to the host from infection with the microbe. Intriguingly, nicotinamide analogues are used to treat TB. In reviewing this field, it is postulated that flux through the nicotinamide synthesis pathway reflects switching between aerobic glycolysis and oxidative phosphorylation in M. tuberculosis-infected macrophages. The evolutionary cause of such shifts may be ancient mitochondrial behavior related to reproductive fitness. Evolutionary perspectives on the IDO pathway may elucidate why, after centuries of co-existence with the Tubercle bacillus, humans still remain susceptible to TB disease.
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Indolamina-Pirrol 2,3,-Dioxigenasa , Tuberculosis , Catálisis , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Macrófagos , Niacinamida , Tuberculosis/genéticaRESUMEN
BACKGROUND: Hepatitis B virus (HBV), a global public health threat, is targeted for elimination by 2030. As national HBV prevalence and incidence is lacking for South Africa, our study aimed to provide such data in the public health sector. METHODS: We analysed laboratory-confirmed HBV data from 2015 to 2019 to determine annual prevalence and incidence rates of HBV infection per 100,000 population, HBsAg and anti-HBc IgM test positivity rates, and HBsAg and anti-HBc IgM testing rates per 100,000 population. Time trend and statistical analyses were performed on HBsAg and anti-HBc IgM test positivity rates. RESULTS: The national prevalence rate of HBV infection per 100,000 population increased from 56.14 in 2015 to 67.76 in 2019. Over the five years, the prevalence rate was higher in males than females, highest amongst individuals 25 to 49 years old and highest in Gauteng province. The HBsAg test positivity rate dropped from 9.77% in 2015 to 8.09% in 2019. Over the five years, the HBsAg test positivity rate was higher in males than females, amongst individuals 25 to 49 years old and amongst individuals of Limpopo province. Amongst HBsAg positive children under 5 years old, the majority (65.7%) were less than a year old. HBsAg testing rates per 100,000 population were higher in females under 45 years of age and in males 45 years and above. The national incidence rate of acute HBV infection per 100,000 population dropped from 3.17 in 2015 to 1.69 in 2019. Over the five-year period, incidence rates were similar between males and females, highest amongst individuals 20 to 39 years old and highest in Mpumalanga province. Amongst individuals 20 to 24 years old, there was a substantial decline in the incidence and anti-HBc IgM test positivity rates over time. Anti-HBc IgM testing rates per 100,000 population were higher in females under 40 years of age and in males 40 years and above. CONCLUSION: Critical to hepatitis B elimination is strengthened infant vaccination coverage and interruption of vertical transmission. Transmission of HBV infection in adults may be reduced through heightened awareness of transmission routes and prevention measures.
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Antígenos de Superficie de la Hepatitis B , Hepatitis B , Adulto , Niño , Preescolar , Femenino , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Anticuerpos contra la Hepatitis B , Virus de la Hepatitis B , Humanos , Inmunoglobulina M , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Prevalencia , Sudáfrica/epidemiología , Adulto JovenRESUMEN
In 2012 the World Health Organization (WHO) aimed to eliminate measles in five regions by 2020. This retrospective descriptive study reviewed measles surveillance data in South Africa for the period 2015-2020 to document the epidemiology of measles and the progress made towards meeting the 2020 measles elimination goal.A total of 22,578 specimens were tested over the period 2015-2020 yielding 401 (1.8%) confirmed measles cases, 321 (1.4%) compatible and 21,856 (96.8%) discarded cases. The most affected age group was 0-4 year olds. At the provincial level, South Africa achieved adequate surveillance, defined as more than two cases of febrile rash notified annually per 100 000 popoulation, except for KwaZulu-Natal and Limpopo in 2020, probably due to COVID-19 lockdown restrictions. Of confirmed cases, only 26% were vaccinated, 3% were too young to receive vaccines, 5% were not vaccinated, and 65% had unknown vaccination status. Measles vaccine effectiveness amongst 1-4 year olds was 80%. Using the standard case definition, South Africa achieved the measles elimination target of less than one case per one million nationally in years 2015, 2016 and 2020. The years 2017 to 2019 had incidence rates exceeding one per million nationally. Using a narrow case definition, that excluded positive rubella cases, improved the indicators with only the year 2017 having an incidence rate of more than one per million.South Africa displays intermittent measles outbreaks approximately six-yearly interspersed by inter-epidemic periods in which the country meets measles elimination targets. Intense effort is needed to increase the vaccine coverage to avoid periodic outbreaks. Enhanced molecular testing of each case will be required as measles incidence declines regionally.
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COVID-19 , Sarampión , Preescolar , Control de Enfermedades Transmisibles , Erradicación de la Enfermedad , Brotes de Enfermedades , Humanos , Programas de Inmunización , Incidencia , Lactante , Sarampión/epidemiología , Sarampión/prevención & control , Vacuna Antisarampión/uso terapéutico , Estudios Retrospectivos , Sudáfrica/epidemiología , VacunaciónRESUMEN
BACKGROUND: For pregnant women living with human immunodeficiency virus (HIV), concurrent active tuberculosis (TB) disease increases the risk of maternal mortality and poor pregnancy outcomes. Plasma indoleamine 2,3-dioxygenase (IDO) activity measured by kynurenine-to-tryptophan (K/T) ratio has been proposed as a blood-based TB biomarker. We investigated whether plasma K/T ratio could be used to diagnose active TB among pregnant women with HIV. METHODS: Using an enzyme-linked immunosorbent assay (ELISA), we measured K/T ratio in 72 pregnant women with and active TB and compared them to 117 pregnant women with HIB but without TB, matched by age and gestational age. RESULTS: Plasma K/T ratio was significantly elevated during pregnancy compared to sampling done after pregnancy (Pâ <â .0001). Pregnant women who had received isoniazid preventive therapy (IPT) before enrollment had decreased plasma K/T ratio compared to those who had not received IPT (Pâ =â .0174). Plasma K/T ratio was elevated in women with active TB at time of diagnosis compared to those without TB (Pâ <â .0001). Using a cutoff of 0.100, plasma K/T ratio gave a diagnostic sensitivity of 94% (95% confidence interval [CI]: 82-95), specificity of 90% (95% CI: 80-91), positive predictive value (PPV) 85% and negative predictive value (NPV) 98%. A receiver operating characteristic curve (ROC) gave an area under the curve of 0.95 (95% CI: .92-.97, Pâ <â .0001).In conclusion, plasma K/T ratio is a sensitive blood-based diagnostic test for active TB disease in pregnant women living with HIV. Plasma K/T ratio should be further evaluated as an initial TB diagnostic test to determine its impact on patient care.
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Infecciones por VIH , Tuberculosis , Pruebas Diagnósticas de Rutina , Femenino , VIH , Infecciones por VIH/complicaciones , Humanos , Quinurenina , Embarazo , Mujeres Embarazadas , Triptófano , Tuberculosis/diagnósticoRESUMEN
Enteroviruses (EVs) are RNA viruses that can cause many clinical syndromes including acute flaccid paralysis (AFP). Within the global polio laboratory network, EVs are categorized either as polioviruses or non-polio enteroviruses (NPEVs). Specific NPEVs have been described in polio-like residual paralytic events in AFP patients. Retrospective analysis of 112 NPEV isolates from AFP patients was performed and thirty one NPEV types were identified of which 91% were Enterovirus B and 9% were Enterovirus A species. The NPEVs were distributed across the country with most patients in the eastern region (41/89; 46.1%). The highest proportion of patients were children less than 5 years (77/89; 86.5%) and male patients were more common (54/89; 60.7%). Echovirus 11 (11/89; 12.4%) was frequently observed and phylogenetic analysis of these sequences revealed high diversity. Coxsackievirus B5 (CV-B5), CV-B6, E21, and EV-B69 were only seen in patients with residual paralysis. Analyses of the EV-A71 sequence indicated a unique genogroup.
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Enfermedades Virales del Sistema Nervioso Central/virología , Infecciones por Enterovirus/virología , Enterovirus/genética , Enterovirus/aislamiento & purificación , Genotipo , Mielitis/virología , Enfermedades Neuromusculares/virología , Filogenia , Adolescente , Enfermedades Virales del Sistema Nervioso Central/epidemiología , Niño , Preescolar , Estudios Transversales , Enterovirus/clasificación , Infecciones por Enterovirus/epidemiología , Monitoreo Epidemiológico , Heces/virología , Femenino , Variación Genética , Humanos , Masculino , Mielitis/epidemiología , Enfermedades Neuromusculares/epidemiología , Poliomielitis/virología , Estudios Retrospectivos , Análisis de Secuencia de ADN , Factores Sexuales , Uganda/epidemiologíaRESUMEN
Primary B-cell immunodeficiencies are risk factors for the generation of vaccine-derived polioviruses. We report immunodeficiency-associated vaccine-derived poliovirus serotype 3 in an 11-week-old boy with X-linked agammaglobulinemia. Unique characteristics of this case include early age of presentation, high viral evolutionary rate, and the child's perinatal exposure to human immunodeficiency virus.
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Agammaglobulinemia , Poliomielitis , Poliovirus , Niño , Enfermedades Genéticas Ligadas al Cromosoma X , VIH/genética , Humanos , Masculino , Poliovirus/genética , Vacuna Antipolio Oral/efectos adversos , SerogrupoRESUMEN
Human immunodeficiency virus (HIV)-exposed, uninfected infants have higher risks of respiratory syncytial virus-associated hospitalization than HIV-unexposed infants. Despite similar neutralizing antibody titers between HIV-infected and -uninfected women, maternal HIV infection and hypergammaglobulinemia were independently associated with lower titers in newborns. Maternal hypergammaglobulinemia was associated with lower cord-to-maternal antibody ratio.
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Anticuerpos Neutralizantes/fisiología , Anticuerpos Antivirales/fisiología , Infecciones por VIH/complicaciones , Inmunidad Materno-Adquirida , Virus Sincitial Respiratorio Humano/inmunología , Femenino , Humanos , Hipergammaglobulinemia , Recién Nacido , EmbarazoRESUMEN
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
BACKGROUND: Measles continues to circulate in the Democratic Republic of Congo, and the country suffered from several important outbreaks over the last 5 years. Despite a large outbreak starting in the former province of Katanga in 2010 and the resulting immunization activities, another outbreak occurred in 2015 in this same region. We conducted measles seroprevalence surveys in four health zones (HZ) in the former Katanga Province in order to assess the immunity against measles in children 6 months to 14 years after the 2015 outbreak. METHODS: We conducted multi-stage cluster surveys stratified by age group in four HZs, Kayamba, Malemba-Nkulu, Fungurume, and Manono. The age groups were 6-11 months, 12-59 months, and 5-14 years in Kayamba and Malemba-Nkulu, 6-59 months and 5-14 years in Manono and Fungurume. The serological status was measured on dried capillary blood spots collected systematically along with vaccination status (including routine Extended Program of Immunization (EPI), and supplementary immunization activities (SIAs)) and previous self-reported history of suspected measles. RESULTS: Overall seroprevalence against measles was 82.7% in Kayamba, 97.6% in Malemba-Nkulu, 83.2% in Manono, and 74.4% in Fungurume, and it increased with age in all HZs. It was 70.7 and 93.8% in children 12-59 months in Kayamba and Malemba-Nkulu, and 49.8 and 64.7% in children 6-59 months in Fungurume and Manono. The EPI coverage was low but varied across HZ. The accumulation of any type of vaccination against measles resulted in an overall vaccine coverage (VC) of at least 85% in children 12-59 months in Kayamba and Malemba-Nkulu, 86.1 and 74.8% in children 6-59 months in Fungurume and Manono. Previous measles infection in 2015-early 2016 was more frequently reported in children aged 12-59 months or 6-59 months (depending on the HZ). CONCLUSION: The measured seroprevalence was consistent with the events that occurred in these HZs over the past few years. Measles seroprevalence might prove a valuable source of information to help adjust the timing of future SIAs and prioritizing support to the EPI in this region as long as the VC does not reach a level high enough to efficiently prevent epidemic flare-ups.
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Brotes de Enfermedades/prevención & control , Programas de Inmunización , Vacuna Antisarampión/administración & dosificación , Sarampión/epidemiología , Adolescente , Niño , Preescolar , República Democrática del Congo/epidemiología , Femenino , Humanos , Lactante , Masculino , Sarampión/prevención & control , Estudios SeroepidemiológicosRESUMEN
BACKGROUND: There is no biomarker for diagnosing active tuberculosis in patients with human immunodeficiency virus (HIV) infection. Indoleamine 2, 3-dioxygenase (IDO) is an immunoregulatory enzyme that breaks down tryptophan (Trp) to metabolites known as kynurenines (Kyns). We investigated whether IDO activity, as measured by the ratio of Kyn to Trp, could be used to diagnose or predict active tuberculosis disease in HIV-infected adults. METHODS: Kyn and Trp concentrations were measured using ultraperformance liquid chromatography mass spectrometry in plasma samples from 32 HIV-infected patients in whom active tuberculosis developed and who were followed up prospectively. We compared to 70 HIV-infected control subjects from the same cohort in whom tuberculosis did not develop, matched by age, sex, and CD4 cell count, and 37 unmatched HIV-infected patients with a diagnosis of pneumonia. Clinical parameters, including body mass index, CD4 cell count, HIV load, and C-reactive protein levels were analyzed. RESULTS: At the time of tuberculosis diagnosis, IDO activity was significantly higher in patients with tuberculosis than in controls (P < .001). Six months before tuberculosis diagnosis, IDO activity was significantly higher in all patients who later developed tuberculosis (P < .001) than controls. After 6 months of tuberculosis treatment, IDO activity in patients with tuberculosis declined to levels similar to those in controls. IDO activity was 4-fold higher in patients with tuberculosis than in those with pneumonia, and could be used to distinguish them. With a receiver operating characteristic curve, IDO activity had a sensitivity of 97%, a specificity of 99%, and positive and negative predictive values of 89% and 100% for detecting active tuberculosis disease. CONCLUSION: Plasma IDO activity is suitable as a biomarker of active tuberculosis in HIV-positive patients.
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Biomarcadores/sangre , Infecciones por VIH/complicaciones , Indolamina-Pirrol 2,3,-Dioxigenasa/sangre , Tuberculosis/sangre , Tuberculosis/complicaciones , Adulto , Femenino , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tuberculosis/epidemiologíaRESUMEN
Introduction: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy of B-cells frequently encountered among people living with HIV. Immunological abnormalities are common in immunocompetent individuals with DLBCL, and are often associated with poorer outcomes. Currently, data on derangements of immunological proteins, such as cytokines and acute phase reactants, and their impact on outcomes in HIV-associated DLBCL (HIV-DLBCL) is lacking. This study assessed the levels and prognostic relevance of interleukin (IL)-6, IL-10 and Transforming Growth Factor Beta (TGFß), the acute phase proteins C-reactive protein (CRP) and ferritin; serum free light chains (SFLC) (elevation of which reflects a prolonged pro-inflammatory state); and the activity of the immunosuppressive enzyme Indoleamine 2,3-dioxygenase (IDO)in South African patients with DLBCL. Methods: Seventy-six patients with incident DLBCL were enrolled, and peripheral blood IL-6, IL-10, TGFß, SFLC and IDO-activity measured in selected patients. Additional clinical and laboratory findings (including ferritin and CRP) were recorded from the hospital records. Results: Sixty-one (80.3%) of the included patients were people living with HIV (median CD4-count = 148 cells/ul), and survival rates were poor (12-month survival rate 30.0%). The majority of the immunological proteins, except for TGFß and ferritin, were significantly higher among the people living with HIV. Elevation of IL-6, SFLC and IDO-activity were not associated with survival in HIV-DLBCL, while raised IL-10, CRP, ferritin and TGFß were. On multivariate analysis, immunological proteins associated with survival independently from the International Prognostic Index (IPI) included TGFß, ferritin and IL-10. Conclusion: Derangements of immunological proteins are common in HIV-DLBCL, and have a differential association with survival compared to that reported elsewhere. Elevation of TGFß, IL-10 and ferritin were associated with survival independently from the IPI. In view of the poor survival rates in this cohort, investigation of the directed targeting of these cytokines would be of interest in our setting.
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Infecciones por VIH , Linfoma de Células B Grandes Difuso , Humanos , Interleucina-10 , Pronóstico , Interleucina-6 , Proteína C-Reactiva , Citocinas , Linfoma de Células B Grandes Difuso/patología , Ferritinas , Factor de Crecimiento Transformador beta , Estudios RetrospectivosRESUMEN
Patients with severe primary immunodeficiency are at risk for complications from live-attenuated vaccines. Here, we report a case of a vaccine-associated paralytic polio and Bacille Calmette-Guérin disease in a 6-month-old girl with severe combined immunodeficiency resulting from homozygous recombinant activating gene 1 deficiency. The patient was successfully treated with intravenous immunoglobulins and oral pocapavir for poliovirus, and antimycobacterial therapy for regional Bacille Calmette-Guérin disease, allowing stem cell transplant. Following transplantation, poliovirus type 3 with 13 mutations was detected from cerebrospinal fluid but not from stool, indicating ongoing viral evolution in the central nervous system despite pocapavir treatment. Clinical improvement and immune reconstitution allowed the patient to be successfully discharged with no further detection of poliovirus.
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As global SARS-CoV-2 burden and testing frequency have decreased, wastewater surveillance has emerged as a key tool to support clinical surveillance efforts. The aims of this study were to identify and characterize SARS-CoV-2 variants in wastewater samples collected from urban centers across South Africa. Here we show that wastewater sequencing analyses are temporally concordant with clinical genomic surveillance and reveal the presence of multiple lineages not detected by clinical surveillance. We show that wastewater genomics can support SARS-CoV-2 epidemiological investigations by reliably recovering the prevalence of local circulating variants, even when clinical samples are not available. Further, we find that analysis of mutations observed in wastewater can provide a signal of upcoming lineage transitions. Our study demonstrates the utility of wastewater genomics to monitor evolution and spread of endemic viruses.
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COVID-19 , Aguas Residuales , Humanos , SARS-CoV-2/genética , COVID-19/epidemiología , Monitoreo Epidemiológico Basado en Aguas Residuales , GenómicaRESUMEN
The uptake of wastewater-based epidemiology (WBE) for SARS-CoV-2 as a complementary tool for monitoring population-level epidemiological features of the COVID-19 pandemic in low-and-middle-income countries (LMICs) is low. We report on the findings from the South African SARS-CoV-2 WBE surveillance network and make recommendations regarding the implementation of WBE in LMICs. Eight laboratories quantified influent wastewater collected from 87 wastewater treatment plants in all nine South African provinces from 01 June 2021 to 31 May 2022 inclusive, during the 3rd and 4th waves of COVID-19. Correlation and regression analyses between wastewater levels of SARS-CoV-2 and district laboratory-confirmed caseloads were conducted. The sensitivity and specificity of novel 'rules' based on WBE data to predict an epidemic wave were determined. Amongst 2158 wastewater samples, 543/648 (85 %) samples taken during a wave tested positive for SARS-CoV-2 compared with 842 positive tests from 1512 (55 %) samples taken during the interwave period. Overall, the regression-co-efficient was 0,66 (95 % confidence interval = 0,6-0,72, R2 = 0.59), ranging from 0.14 to 0.87 by testing laboratory. Early warning of the 4th wave of SARS-CoV-2 in Gauteng Province in November-December 2021 was demonstrated. A 50 % increase in log copies of SARS-CoV-2 compared with a rolling mean over the previous five weeks was the most sensitive predictive rule (58 %) to predict a new wave. Our findings support investment in WBE for SARS-CoV-2 surveillance in LMICs as an early warning tool. Standardising test methodology is necessary due to varying correlation strengths across laboratories and redundancy across testing plants. A sentinel site model can be used for surveillance networks without affecting WBE finding for decision-making. Further research is needed to identify optimal test frequency and the need for normalisation to population size to identify predictive and interpretive rules to support early warning and public health action.
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Divergent pathways of macrophage metabolism occur during infection, notably switching between oxidative phosphorylation and aerobic glycolysis (Warburg-like metabolism). Concurrently, macrophages shift between alternate and classical activation. A key enzyme upregulated in alternatively activated macrophages is indoleamine 2,3-dioxygenase, which converts tryptophan to kynurenine for de novo synthesis of nicotinamide. Nicotinamide can be used to replenish cellular NAD+ supplies. We hypothesize that an insufficient cellular NAD+ supply is the root cause of metabolic shifts in macrophages. We assert that manipulation of nicotinamide pathways may correct deleterious immune responses. We propose evaluation of nicotinamide (Vitamin B3) and analogues, including isoniazid, nicotinamide mononucleotide and nicotinamide riboside, as potential therapy for infectious causes of sepsis, including COVID-19.
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COVID-19/complicaciones , Metabolismo Energético , Macrófagos/metabolismo , Niacinamida/metabolismo , Sepsis/metabolismo , Animales , Evolución Biológica , Humanos , Macrófagos/inmunología , Sepsis/etiologíaRESUMEN
BACKGROUND: Preeclampsia is a considerable cause of maternal and infant morbidity and mortality. Although its etiology is unknown, preeclampsia has been described as a state of exaggerated maternal inflammatory response. Therefore, it has been hypothesized that preeclampsia would occur less commonly in states of immune deficiency. OBJECTIVE: This study aimed to compare the prevalence of treated and untreated HIV infections among preeclamptic cases and controls, determine infant outcomes, and evaluate the association between HIV and preeclampsia after adjusting for known predictor variables, including maternal age, gravidity, body mass index, and smoking. STUDY DESIGN: This case-control study investigated the association between preeclampsia and HIV infection using secondary data from an unrelated study. We defined preeclamptic cases as pregnant women who were normotensive until 20 weeks of gestation and thereafter had at least 1 high blood pressure measurement either before or at delivery and proteinuria, defined as protein excretion of ≥300 mg within 24 hours or >2 protein on dipstick urinalysis. The prevalence of HIV infection was compared between cases and controls. Multivariate logistic regression analysis was used to assess the association between preeclampsia and potential confounding variables and reported using odds ratios and 95% confidence intervals. RESULTS: There were 571 cases with preeclampsia and 596 normotensive controls included in this study. The median age was 27 years for cases and 26 years for controls (P=.008). Most participants (69%) had ≥2 previous pregnancies with no difference between the cases and controls (P=.176). Overall, 43% of the participants were obese, with a mean body mass index of 29 (interquartile range, 24.5-34.2), with higher proportions of women who were overweight and obese in the group with preeclampsia (P=.031). The prevalence of HIV was significantly lower in cases than in controls (24% vs 30%, respectively; P=.014). Compared with 16% of infants born preterm to normotensive controls, 48% of infants were born preterm born to women with preeclampsia (P<.001). Compared with 14% of infants born with low birthweight to normotensive controls, 53% of infants were born with low birthweight to women with preeclampsia (P<.0001). Untreated HIV infection was negatively associated with preeclampsia (unadjusted odds ratio, 0.330; 95% confidence interval, 0.197-0.552; P<.0001), whereas factors associated with preeclampsia were advanced maternal age (odds ratio, 1.673; 95% confidence interval, 1.209-2.316; P=.002) and obesity (odds ratio, 1.611; 95% confidence interval, 1.023-2.537; P=.040). After adjusting for maternal age, gravidity, smoking, and body mass index in the multivariate regression, only obesity remained significantly associated with preeclampsia (adjusted odds ratio, 1.624; 95% confidence interval, 1.024-2.575; P=.039). CONCLUSION: Before the large-scale rollout of antiretroviral therapy in a setting with a high burden of HIV and preeclampsia, untreated HIV infection was found to have a protective effect against preeclampsia. The protective effect against preeclampsia was not apparent for HIV infection treated with antiretroviral therapy.
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South Africa has yet to introduce a rubella-containing vaccine (RCV) into its Expanded Programme on Immunisation (EPI). Here we evaluated the incidence of laboratory-confirmed rubella and congenital rubella syndrome (CRS) cases over the years 2015 to 2019, to document the epidemiology of rubella and CRS within South Africa prior to a RCV introduction. This retrospective study evaluated the number of laboratory-confirmed rubella cases reported through the national febrile rash surveillance system. A positive test for rubella immunoglobulin M (IgM) antibodies was considered a confirmed rubella case. For CRS cases, we reported laboratory-confirmed CRS cases collected from 28 sentinel-sites from all nine provinces of South Africa. From 2015-2019, 19 773 serum samples were tested for rubella IgM antibodies, 6 643 (33.6%) were confirmed rubella cases. Rubella was seasonal, with peaks in spring (September to November). Case numbers were similar between males (n = 3 239; 50.1%) and females (n = 3 232; 49.9%). The highest burden of cases occurred in 2017 (n = 2 526; 38%). The median age was 5 years (IQR: 3-7 years). Importantly, of females with rubella, 5.0% (161 of 3 232) of the cases were among women of reproductive age (15-44 years). A total of 62 CRS cases were reported, the mortality rate was 12.9% (n = 8), and the most common birth defect was congenital heart disease. In conclusion, rubella is endemic in South Africa. Children below the age of 10 years were the most affected, however, rubella was also reported among women of reproductive age. The baseline data represented here provides insight into the burden of rubella and CRS in South Africa prior to the introduction of a RCV, and can enable planning of RCV introduction into the South African EPI.
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Síndrome de Rubéola Congénita , Rubéola (Sarampión Alemán) , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina M , Incidencia , Lactante , Masculino , Estudios Retrospectivos , Rubéola (Sarampión Alemán)/epidemiología , Rubéola (Sarampión Alemán)/prevención & control , Síndrome de Rubéola Congénita/epidemiología , Síndrome de Rubéola Congénita/prevención & control , Vacuna contra la Rubéola , Virus de la Rubéola , Sudáfrica/epidemiología , Adulto JovenRESUMEN
Enveloped viruses, including the Human Immunodeficiency Virus-1 (HIV), incorporate host proteins such as human leucocyte antigens (HLA) into their envelope. Pre-existing antibodies against HLA, termed HLA antibodies, may bind to these surface proteins and reduce viral infectivity. Related evidence includes macaque studies which suggest that xenoimmunization with HLA antigens may protect against simian immunodeficiency virus infection. Since HIV gp120 shows homology with class 2 HLA, including shared affinity for binding to CD4, class 2 HLA antibodies may influence HIV acquisition via binding to gp120 on the viral envelope. We conducted a nested case-control study on HIV serodiscordant couples, comparing the frequency of HLA antibodies among highly exposed persistently seronegative controls with those who went on to acquire HIV (HIV-seroconverters). We first performed low resolution HLA typing on 143 individuals who were HIV-infected at enrollment (index partners) and their corresponding sexual partners (115 highly exposed persistently seronegative individuals and 28 HIV-seroconverters). We then measured HLA class 1 and 2 antibodies in the highly exposed persistently seronegative individuals and HIV-seroconverters at early and late timepoints. We analyzed whether such antibodies were directed at HLA specificities of their HIV-infected index partners, and whether autoantibodies or complement-fixing class 2 HLA antibodies were present. Seventy-nine percent of highly exposed persistently seronegative individuals had HLA antibodies; 56% against class 1 and 50% against class 2 alleles. Half of the group of highly exposed persistently seronegative individuals, prior to seroconversion, expressed class 2 HLA antibodies, compared with only 29% of controls (p=0.05). HIV infection was a sensitizing event leading to de novo development of antibodies against HLA-A and HLA-B loci, but not against class 2 loci. HLA autoantibodies were present in 27% of highly exposed persistently seronegative individuals. Complement-fixing class 2 HLA antibodies did not differ significantly between highly exposed persistently seronegative individuals and seroconverters. In multivariable regression, presence of class 2 HLA antibodies at early timepoints was associated with reduced odds of HIV acquisition (odds ratio 0.330, confidence interval 0.112-0.976, p=0.045). These epidemiological data suggest that pre-existing class 2 HLA antibodies were associated with reduced odds of HIV acquisition.
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Infecciones por VIH , VIH-1 , Autoanticuerpos , Estudios de Casos y Controles , Antígenos HLA , HumanosRESUMEN
As South Africa transitions from endemic to intermediate endemicity, hepatitis A surveillance needs strengthening to monitor trends in disease incidence and to identify outbreaks. We used passive laboratory-based surveillance data from the National Health Laboratory Services to calculate national hepatitis A incidence and to establish thresholds for outbreaks. Incidence was calculated by age and geographic location. The static threshold used two or three standard deviations (SDs) above the mean hepatitis A incidence in 2017-2019, and a cumulative summation (CuSum2) threshold used three SDs above the mean of the preceding seven months. These thresholds were applied to hepatitis A data for 2020. From 2017 to 2020, the mean incidence of hepatitis A IgM was 4.06/100,000 and ranged from 4.23 to 4.85/100,000 per year. Hepatitis A incidence was highest in the Western Cape province (WCP) (7.00-10.92/100,000 per year). The highest incidence was in the 1-9-year-olds. The incidence of hepatitis A in 2020 exceeded the static threshold in two districts of the WCP: Cape Winelands in January and Overberg district in August. The provincial incidence did not exceed the static and CuSum2 thresholds. District-level analysis using either threshold was sensitive enough to monitor trends and to alert district health authorities, allowing early outbreak responses.
Asunto(s)
Brotes de Enfermedades , Monitoreo Epidemiológico , Hepatitis A/epidemiología , Adolescente , Adulto , Distribución por Edad , Anticuerpos Antivirales/sangre , Niño , Preescolar , Femenino , Virus de la Hepatitis A Humana/inmunología , Humanos , Inmunoglobulina M/sangre , Incidencia , Masculino , Persona de Mediana Edad , Sudáfrica/epidemiología , Adulto JovenRESUMEN
Introduction. Global poliovirus eradication is a public health emergency of international concern. The acute flaccid paralysis (AFP) surveillance programme in South Africa has been instrumental in eliminating polioviruses and keeping the country poliovirus free.Gap statement. The sensitivity of surveillance for polioviruses by every African country is of global interest in the effort to ensure global health security from poliovirus re-emergence.Aim. To describe the epidemiology of polioviruses from AFP cases and environmental samples in South Africa and to report the performance of the AFP surveillance system for the years 2016-2019 against targets established by the World Health Organization (WHO).Methods. Stool specimens from AFP or suspected AFP cases were received and tested as per WHO guidelines. Environmental samples were gathered from sites across the Gauteng province using the grab collection method. Concentration was effected by the two-phase polyethylene glycol method approved by the WHO. Suspected polioviruses were isolated in RD and/or L20B cell cultures through identification of typical cytopathic effects. The presence of polioviruses was confirmed by intratypic differentiation PCR. All polioviruses were sequenced using the Sanger method, and their VP1 gene analysed for mutations.Results. Data from 4597 samples (2385 cases) were analysed from the years 2016-2019. Two cases of immunodeficiency-associated vaccine-derived poliovirus (iVDPV) type 3 were detected in 2017 and 2018. A further 24 Sabin type 1 or type 3 polioviruses were detected for the 4 years. The national surveillance programme detected an average of 3.1 cases of AFP/100â000 individuals under 15 years old (2.8/100â000-3.5/100â000). The stool adequacy of the samples received was 53.0â% (47.0-55.0%), well below the WHO target of 80â% adequacy. More than 90â% of results were released from the laboratory within the turnaround time (96.6â%) and non-polio enteroviruses were detected in 11.6â% of all samples. Environmental surveillance detected non-polio enterovirus in 87.5â% of sewage samples and Sabin polioviruses in 12.5â% of samples.Conclusion. The AFP surveillance programme in South Africa is sensitive to detect polioviruses in South Africa and provided no evidence of wild poliovirus or VDPV circulation in the country.