Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 84
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-34739648

RESUMO

PURPOSE: Despite evidence of myocardial infarct size reduction in animal studies, remote ischaemic conditioning (RIC) failed to improve clinical outcomes in the large CONDI-2/ERIC-PPCI trial. Potential reasons include that the predominantly low-risk study participants all received timely optimal reperfusion therapy by primary percutaneous coronary intervention (PPCI). Whether RIC can improve clinical outcomes in higher-risk STEMI patients in environments with poor access to early reperfusion or PPCI will be investigated in the RIC-AFRICA trial. METHODS: The RIC-AFRICA study is a sub-Saharan African multi-centre, randomized, double-blind, sham-controlled clinical trial designed to test the impact of RIC on the composite endpoint of 30-day mortality and heart failure in 1200 adult STEMI patients without access to PPCI. Randomized participants will be stratified by whether or not they receive thrombolytic therapy within 12 h or arrive outside the thrombolytic window (12-24 h). Participants will receive either RIC (four 5-min cycles of inflation [20 mmHg above systolic blood pressure] and deflation of an automated blood pressure cuff placed on the upper arm) or sham control (similar protocol but with low-pressure inflation of 20 mmHg and deflation) within 1 h of thrombolysis and applied daily for the next 2 days. STEMI patients arriving greater than 24 h after chest pain but within 72 h will be recruited to participate in a concurrently running independent observational arm. CONCLUSION: The RIC-AFRICA trial will determine whether RIC can reduce rates of death and heart failure in higher-risk sub-optimally reperfused STEMI patients, thereby providing a low-cost, non-invasive therapy for improving health outcomes.

2.
Lancet Infect Dis ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34780706

RESUMO

BACKGROUND: Bedaquiline improves outcomes of patients with rifampicin-resistant and multidrug-resistant (MDR) tuberculosis; however, emerging resistance threatens this success. We did a cross-sectional and longitudinal analysis evaluating the epidemiology, genetic basis, and treatment outcomes associated with bedaquiline resistance, using data from South Africa (2015-19). METHODS: Patients with drug-resistant tuberculosis starting bedaquiline-based treatment had surveillance samples submitted at baseline, month 2, and month 6, along with demographic information. Culture-positive baseline and post-baseline isolates had phenotypic resistance determined. Eligible patients were aged 12 years or older with a positive culture sample at baseline or, if the sample was invalid or negative, a sample within 30 days of the baseline sample submitted for bedaquiline drug susceptibility testing. For the longitudinal study, the first surveillance sample had to be phenotypically susceptible to bedaquiline for inclusion. Whole-genome sequencing was done on bedaquiline-resistant isolates and a subset of bedaquiline-susceptible isolates. The National Institute for Communicable Diseases tuberculosis reference laboratory, and national tuberculosis surveillance databases were matched to the Electronic Drug-Resistant Tuberculosis Register. We assessed baseline resistance prevalence, mutations, transmission, cumulative resistance incidence, and odds ratios (ORs) associating risk factors for resistance with patient outcomes. FINDINGS: Between Jan 1, 2015, and July 31, 2019, 8041 patients had surveillance samples submitted, of whom 2023 were included in the cross-sectional analysis and 695 in the longitudinal analysis. Baseline bedaquiline resistance prevalence was 3·8% (76 of 2023 patients; 95% CI 2·9-4·6), and it was associated with previous exposure to bedaquiline or clofazimine (OR 7·1, 95% CI 2·3-21·9) and with rifampicin-resistant or MDR tuberculosis with additional resistance to either fluoroquinolones or injectable drugs (pre-extensively-drug resistant [XDR] tuberculosis: 4·2, 1·7-10·5) or to both (XDR tuberculosis: 4·8, 2·0-11·7). Rv0678 mutations were the sole genetic basis of phenotypic resistance. Baseline resistance could be attributed to previous bedaquiline or clofazimine exposure in four (5·3%) of 76 patients and to primary transmission in six (7·9%). Odds of successful treatment outcomes were lower in patients with baseline bedaquiline resistance (0·5, 0·3-1). Resistance during treatment developed in 16 (2·3%) of 695 patients, at a median of 90 days (IQR 62-195), with 12 of these 16 having pre-XDR or XDR. INTERPRETATION: Bedaquiline resistance was associated with poorer treatment outcomes. Rapid assessment of bedaquiline resistance, especially when patients were previously exposed to bedaquiline or clofazimine, should be prioritised at baseline or if patients remain culture-positive after 2 months of treatment. Preventing resistance by use of novel combination therapies, current treatment optimisation, and patient support is essential. FUNDING: National Institute for Communicable Diseases of South Africa.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34528769

RESUMO

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.

4.
Lancet Infect Dis ; 21(12): e364-e374, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34364529

RESUMO

The global burden of the endemic mycoses (blastomycosis, coccidioidomycosis, emergomycosis, histoplasmosis, paracoccidioidomycosis, sporotrichosis, and talaromycosis) continues to rise yearly and these infectious diseases remain a leading cause of patient morbidity and mortality worldwide. Management of the associated pathogens requires a thorough understanding of the epidemiology, risk factors, diagnostic methods and performance characteristics in different patient populations, and treatment options unique to each infection. Guidance on the management of these infections has the potential to improve prognosis. The recommendations outlined in this Review are part of the "One World, One Guideline" initiative of the European Confederation of Medical Mycology. Experts from 23 countries contributed to the development of these guidelines. The aim of this Review is to provide an up-to-date consensus and practical guidance in clinical decision making, by engaging physicians and scientists involved in various aspects of clinical management.

5.
Euro Surveill ; 26(29)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34296675

RESUMO

BackgroundIn South Africa, COVID-19 control measures to prevent SARS-CoV-2 spread were initiated on 16 March 2020. Such measures may also impact the spread of other pathogens, including influenza virus and respiratory syncytial virus (RSV) with implications for future annual epidemics and expectations for the subsequent northern hemisphere winter.MethodsWe assessed the detection of influenza and RSV through facility-based syndromic surveillance of adults and children with mild or severe respiratory illness in South Africa from January to October 2020, and compared this with surveillance data from 2013 to 2019.ResultsFacility-based surveillance revealed a decline in influenza virus detection during the regular season compared with previous years. This was observed throughout the implementation of COVID-19 control measures. RSV detection decreased soon after the most stringent COVID-19 control measures commenced; however, an increase in RSV detection was observed after the typical season, following the re-opening of schools and the easing of measures.ConclusionCOVID-19 non-pharmaceutical interventions led to reduced circulation of influenza and RSV in South Africa. This has limited the country's ability to provide influenza virus strains for the selection of the annual influenza vaccine. Delayed increases in RSV case numbers may reflect the easing of COVID-19 control measures. An increase in influenza virus detection was not observed, suggesting that the measures may have impacted the two pathogens differently. The impact that lowered and/or delayed influenza and RSV circulation in 2020 will have on the intensity and severity of subsequent annual epidemics is unknown and warrants close monitoring.


Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Adulto , Criança , Humanos , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , SARS-CoV-2 , África do Sul/epidemiologia
6.
Front Immunol ; 12: 623941, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777003

RESUMO

Host-directed therapies (HDTs) enhance the host response to tuberculosis (TB) infection to reduce disease severity. For instance, the manipulation of lipid mediator production diminishes the hyperactive immune response which is a known pathological feature of TB that generates lung tissue damage. Non-steroidal anti-inflammatory drugs (NSAIDs) and omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) are examples of such HDTs. In this mini-review, we recapitulate the literature available on the effects of NSAIDs and n-3 LCPUFA in TB as well as the immunological pathways underpinning these effects. Many NSAIDs have a great deal of data describing their effects and safety and in many jurisdictions are inexpensive, and sold over the counter in neighborhood convenience stores and supermarkets. The potential benefits of NSAIDs in TB are well-documented in pre-clinical studies. The reduction of pro-inflammatory lipid mediator production by inhibiting cyclooxygenase (COX) pathways with NSAIDs has been found to improve lung histopathology, bacterial control, and survival. Additionally, n-3 LCPUFA and its novel bioactive metabolites produced by COX and lipoxygenase (LOX) have been identified as safe and effective pro-resolving and antibacterial pharmaconutrients. Nevertheless, heterogeneous results have been reported in pre-clinical TB studies. Recently, the importance of the correct timing of NSAIDs and n-3 LCPUFA administration in TB has also been highlighted. This mini-review will provide a better understanding of the potential contribution of these therapies toward reducing inflammatory lung damage and improving bactericidal activity, especially during later stages of TB infection. It further highlights that clinical trials are required to confirm benefit and safety in TB patients.


Assuntos
Antituberculosos/uso terapêutico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Pulmonar/tratamento farmacológico , Animais , Interações Hospedeiro-Patógeno , Humanos , Inibidores de Lipoxigenase/uso terapêutico , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/microbiologia , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/patogenicidade , Resultado do Tratamento , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/metabolismo , Tuberculose Pulmonar/microbiologia
7.
Clin Infect Dis ; 73(3): e745-e753, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-33530100

RESUMO

BACKGROUND: Policy recommendations on pertussis vaccination need to be guided by data, which are limited from low- and middle-income countries. We aimed to describe the epidemiology of pertussis in South Africa, a country with high human immunodeficiency virus (HIV) prevalence and routine pertussis vaccination for 6 decades including the acellular vaccine since 2009. METHODS: Hospitalized patients of all ages were enrolled at 5 sentinel sites as part of a pneumonia surveillance program from January 2013 through December 2018. Nasopharyngeal specimens and induced sputum were tested by polymerase chain reaction (PCR) for Bordetella pertussis. In addition, demographic and clinical information were collected. Incidence rates were calculated for 2013-2016, and multivariable logistic regression performed to identify factors associated with pertussis. RESULTS: Over the 6-year period 19 429 individuals were enrolled, of which 239 (1.2%) tested positive for B. pertussis. Detection rate was highest in infants aged <6 months (2.8%, 155/5524). Mean annual incidence was 17 cases per 100 000 population, with the highest incidence in children <1 year of age (228 per 100 000). Age-adjusted incidence was 65.9 per 100 000 in HIV-infected individuals compared to 8.5 per 100 000 in HIV-uninfected individuals (risk ratio 30.4, 95% confidence interval: 23.0-40.2). Ten individuals (4.2%) with pertussis died; of which 7 were infants aged <6 months and 3 were immunocompromised adults. CONCLUSIONS: Pertussis continues to be a significant cause of illness and hospitalization in South Africa, despite routine vaccination. The highest burden of disease and death occurred in infants; however, HIV-infected adults were also identified as an important group at risk of B. pertussis infection.


Assuntos
Coqueluche , Adulto , Bordetella pertussis , Criança , Humanos , Incidência , Lactente , Vacina contra Coqueluche , África do Sul/epidemiologia , Coqueluche/epidemiologia
8.
BMC Nurs ; 20(1): 29, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557831

RESUMO

BACKGROUND: Tuberculosis is a top-10 cause of under-5 mortality, despite policies promoting tuberculosis preventive therapy (TPT). We previously conducted a cluster randomized trial to evaluate the effectiveness of symptom-based versus tuberculin skin-based screening on child TPT uptake. Symptom-based screening did not improve TPT uptake and nearly two-thirds of child contacts were not identified or not linked to care. Here we qualitatively explored healthcare provider perceptions of factors that impacted TPT uptake among child contacts. METHODS: Sixteen in-depth interviews were conducted with key informants including healthcare providers and administrators who participated in the trial in Matlosana, South Africa. The participants' experience with symptom-based screening, study implementation strategies, and ongoing challenges with child contact identification and linkage to care were explored. Interviews were systematically coded and thematic content analysis was conducted. RESULTS: Participants' had mixed opinions about symptom-based screening and high acceptability of the study implementation strategies. A key barrier to optimizing child contact screening and evaluation was the supervision and training of community health workers. CONCLUSIONS: Symptom screening is a simple and effective strategy to evaluate child contacts, but additional pediatric training is needed to provide comfort with decision making. New clinic-based child contact files were highly valued by providers who continued to use them after trial completion. Future interventions to improve child contact management will need to address how to best utilize community health workers in identifying and linking child contacts to care. TRIAL REGISTRATION: The results presented here were from research related to NCT03074799 , retrospectively registered on 9 March 2017.

9.
BMC Infect Dis ; 21(1): 5, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33446115

RESUMO

BACKGROUND: Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children < 14 kg while dosing was in development. METHODS: ODYSSEY (Once-daily DTG based ART in Young people vS. Standard thErapY) is an open-label, randomised, non-inferiority, basket trial comparing the efficacy and safety of DTG + 2 nucleos(t) ides (NRTIs) versus standard-of-care (SOC) in HIV-infected children < 18 years starting first-line ART (ODYSSEY A) or switching to second-line ART (ODYSSEY B). The primary endpoint is clinical or virological failure by 96 weeks. RESULTS: Between September 2016 and June 2018, 707 children weighing ≥14 kg were enrolled; including 311 ART-naïve children and 396 children starting second-line. 47% of children were enrolled in Uganda, 21% Zimbabwe, 20% South Africa, 9% Thailand, 4% Europe. 362 (51%) participants were male; median age [range] at enrolment was 12.2 years [2.9-18.0]. 82 (12%) children weighed 14 to < 20 kg, 135 (19%) 20 to < 25 kg, 206 (29%) 25 to < 35 kg, 284 (40%) ≥35 kg. 128 (18%) had WHO stage 3 and 60 (8%) WHO stage 4 disease. Challenges encountered include: (i) running the trial across high- to low-income countries with differing frequencies of standard-of-care viral load monitoring; (ii) evaluating pragmatic DTG dosing in PK sub-studies alongside FDA- and EMA-approved dosing and subsequently transitioning participants to new recommended doses; (iii) delays in dosing information for children weighing 3 to < 14 kg and rapid recruitment of ART-naïve older/heavier children, which led to capping recruitment of participants weighing ≥35 kg in ODYSSEY A and extending recruitment (above 700) to allow for ≥60 additional children weighing between 3 to < 14 kg with associated PK; (iv) a safety alert associated with DTG use during pregnancy, which required a review of the safety plan for adolescent girls. CONCLUSIONS: By employing a basket design, to include ART-naïve and -experienced children, and nested PK sub-studies, the ODYSSEY trial efficiently evaluates multiple scientific questions regarding dosing and effectiveness of DTG-based ART in children. TRIAL REGISTRATION: NCT, NCT02259127 , registered 7th October 2014; EUDRACT, 2014-002632-14, registered 18th June 2014 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002632-14/ES ); ISRCTN, ISRCTN91737921 , registered 4th October 2014.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/administração & dosagem , Inibidores de Integrase de HIV/efeitos adversos , HIV-1/genética , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Oxazinas/administração & dosagem , Oxazinas/efeitos adversos , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Adolescente , Peso Corporal , Criança , Pré-Escolar , Estudos de Coortes , Cálculos da Dosagem de Medicamento , Europa (Continente)/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , RNA Viral/genética , África do Sul/epidemiologia , Tailândia/epidemiologia , Resultado do Tratamento , Uganda/epidemiologia , Carga Viral/efeitos dos fármacos , Organização Mundial da Saúde , Zimbábue/epidemiologia
10.
Vaccine ; 38(45): 7007-7014, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-32980198

RESUMO

BACKGROUND: Data on influenza economic burden in risk groups for severe influenza are important to guide targeted influenza immunization, especially in resource-limited settings. However, this information is limited in low- and middle-income countries. METHODS: We estimated the cost (from a health system and societal perspective) and years of life lost (YLL) for influenza-associated illness in South Africa during 2013-2015 among (i) children aged 6-59 months, (ii) individuals aged 5-64 years with HIV, pulmonary tuberculosis (PTB) and selected underlying medical conditions (UMC), separately, (iii) pregnant women and (iv) individuals aged ≥65 years, using publicly available data and data collected through laboratory-confirmed influenza surveillance and costing studies. All costs were expressed in 2015 prices using the South Africa all-items Consumer Price Index. RESULTS: During 2013-2015, the mean annual cost of influenza-associated illness among the selected risk groups accounted for 52.1% ($140.9/$270.5 million) of the total influenza-associated illness cost (for the entire population of South Africa), 45.2% ($52.2/$115.5 million) of non-medically attended illness costs, 43.3% ($46.7/$107.9 million) of medically-attended mild illness costs and 89.3% ($42.0/$47.1 million) of medically-attended severe illness costs. The YLL among the selected risk groups accounted for 86.0% (262,069 /304,867 years) of the total YLL due to influenza-associated death. CONCLUSION: In South Africa, individuals in risk groups for severe influenza accounted for approximately half of the total influenza-associated illness cost but most of the cost of influenza-associated medically attended severe illness and YLL. This study provides the foundation for future studies on the cost-effectiveness of influenza immunization among risk groups.


Assuntos
Efeitos Psicossociais da Doença , Influenza Humana , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Análise Custo-Benefício , Feminino , Humanos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pessoa de Meia-Idade , Gravidez , África do Sul/epidemiologia , Vacinação , Adulto Jovem
11.
Vaccine ; 38(27): 4288-4297, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32389494

RESUMO

BACKGROUND: Data on influenza burden in risk groups for severe influenza are important to guide targeted influenza immunization, especially in resource limited settings. However, this information is limited overall and in particular in low- and middle-income countries. We sought to assess the mean annual national burden of medically and non-medically attended influenza-associated mild, severe-non-fatal and fatal illness among potential target groups for influenza immunization in South Africa during 2013-2015. METHODS: We used published mean national annual estimates of mild, severe-non-fatal, and fatal influenza-associated illness in South Africa during 2013-2015 and estimated the number of such illnesses occurring among the following risk groups: (i) children aged 6-59 months; (ii) individuals aged 5-64 years with HIV, and/or pulmonary tuberculosis (PTB), and/or selected underlying medical conditions (UMC); (iii) pregnant women; and (iv) individuals aged ≥65 years. We also estimated the number of individuals among the same risk groups in the population. RESULTS: During 2013-2015, individuals in the selected risk groups accounted for 45.3% (24,569,328/54,086,144) of the population and 43.5% (4,614,763/10,598,138), 86.8% (111,245/128,173) and 94.5% (10,903/11,536) of the mean annual estimated number of influenza-associated mild, severe-non-fatal and fatal illness episodes, respectively. The rates of influenza-associated illness were highest in children aged 6-59 months (23,983 per 100,000 population) for mild illness, in pregnant women (930 per 100,000 population) for severe-non-fatal illness and in individuals aged ≥65 years (138 per 100,000 population) for fatal illness. CONCLUSION: Influenza immunization of the selected risk groups has the potential to prevent a substantial number of influenza-associated severe illness. Nonetheless, because of the high number of individuals at risk, South Africa, due to financial resources constrains, may need to further prioritize interventions among risk populations. Cost-burden and cost-effectiveness estimates may assist with further prioritization.


Assuntos
Influenza Humana , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Feminino , Humanos , Lactente , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pessoa de Meia-Idade , Gravidez , África do Sul/epidemiologia , Vacinação , Adulto Jovem
12.
AIDS Behav ; 24(12): 3511-3521, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32415616

RESUMO

South Africa processes 5.1 million HIV CD4, viral load (VL), and tuberculosis (TB) tests annually. This pilot non-randomized trial in South Africa explored an intervention ("MatlaMobile") to deliver laboratory results via mobile phone. Adults completing CD4, VL, and/or TB laboratory tests were enrolled-either receiving results by returning to clinic (control, n = 174) or mobile phone (intervention, n = 226). Study staff instructed control participants to return within 6 days (standard-of-care). MatlaMobile instructed intervention participants with clinically actionable results requiring intervention or treatment change (i.e., < 200 CD4 cells per milliliter, ≥ 400 viral copies per milliliter, or TB positive) to return immediately. A greater proportion of intervention participants than controls saw their results within 7 days of enrollment (73% vs. 8.6%, p < 0.001). Among participants instructed to return, more intervention participants (20%, n = 14/70) returned than controls (8.6%, n = 15/174, p = 0.02). MatlaMobile demonstrated that patients can quickly receive and respond appropriately to digital delivery of health information.


Assuntos
Telefone Celular , Infecções por HIV , Tuberculose , Humanos , África do Sul , Carga Viral
13.
PLoS One ; 15(3): e0230376, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32182274

RESUMO

INTRODUCTION: Household contacts of patients with active pulmonary tuberculosis (TB) often have latent TB infection, and are at risk of progression to disease. We set out to investigate whether index TB case HIV status was linked to a higher probability of latent TB infection among household contacts. MATERIALS AND METHODS: Data were collected prospectively from participants in the intervention arm of a household cluster-randomised trial in two South Africa provinces (Mangaung, Free State, and Capricorn, Limpopo). In intervention group households, TB contacts underwent HIV testing and tuberculin skin testing (TST). TST induration was estimated at two cut-offs (≥5mm, ≥10mm). Multilevel Bayesian regression models estimated posterior distributions of the percentage of household contacts with TST induration ≥5mm and ≥10mm by age group, and compared the odds of latent TB infection by key risk factors including HIV status index case age and study province. RESULTS: A total of 2,985 household contacts of 924 index cases were assessed, with most 2,725 (91.3%) undergoing TST. HIV prevalence in household contacts was 14% and 10% in Mangaung and Capricorn respectively. Overall, 16.8% (458/2,725) had TST induration of ≥5mm and 13.1% (359/2,725) ≥10mm. In Mangaung, children aged 0-4 years had a high TST positivity prevalence compared to their peers in Capricorn (22.0% vs. 7.6%, and 20.5% vs. 2.3%, using TST thresholds of ≥5mm and ≥10mm respectively). Compared to contacts from Capricorn, household contacts living in Mangaung were more likely to have TST induration ≥5mm (odds ratio [OR]: 3.08, 95% credibility interval [CI]: 2.13-4.58) and ≥10mm (OR: 4.52, 95% CI: 3.03-6.97). There was a 90% and 92% posterior probability that the odds of TST induration ≥5mm (OR: 0.79, 95% CI: 0.56-1.14) and ≥10mm (OR: 0.77, 95% CI: 0.53-1.10) respectively were lower in household contacts of HIV-positive compared to HIV-negative index cases. CONCLUSIONS: High TST induration positivity, especially among young children and people living in Mangaung indicates considerable TB transmission despite high antiretroviral therapy coverage. Household contact of HIV-positive index TB cases were less likely to have evidence of latent TB infection than contacts of HIV-negative index cases.


Assuntos
Busca de Comunicante/estatística & dados numéricos , Infecções por HIV/epidemiologia , Tuberculose Latente/epidemiologia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/transmissão , Adulto , Características da Família , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/imunologia , Tuberculose Latente/microbiologia , Masculino , Mycobacterium tuberculosis/imunologia , Prevalência , Fatores de Risco , África do Sul/epidemiologia , Teste Tuberculínico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia
15.
J Glob Antimicrob Resist ; 21: 434-438, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31733411

RESUMO

OBJECTIVE: Rifampicin-resistant (RR) tuberculosis (TB) on X-pert Mycobacterium tuberculosis/rifampicin (MTB/Rif) is assumed to be a surrogate for multi-drug resistant (MDR) TB. Following an RR result, a second specimen was taken for confirmatory culture and drug-susceptibility testing (DST). This study compared the initial diagnostic X-pert MTB/RIF result with the confirmatory DST in a high human immunodeficiency virus (HIV) seroprevalence setting. DESIGN: Records analysing demographics, HIV serostatus, prior TB treatments, and DST results were retrospectively reviewed. RESULTS: Of 604 patients with X-pert MTB/RIF RR, 374 (61.9%) had DST and were included. The mean age was 36.9 years and 82% were HIV infected. Following DST, MDR was confirmed in 49% and Rif mono-resistant (RMR) TB in 36%. Amongst RMR TB, 84% were HIV-infected, and amongst those with CD4 < 50 versus those 50-350 cells/mm3 RMR TB was noted in 51% versus 33%, respectively (P = 0.012). Primary DR was diagnosed in 43% (61% MDR and 33% RMR). CONCLUSION: Rifampicin resistance detected on a diagnostic X-pert MTB/Rif assay did not always predict MDR. Rifampicin mono-resistance is emerging amongst those with HIV co-infection and low CD4 counts (<50 cells/mm3). Research is needed to reduce the number of drugs and treatment durations for RMR TB.


Assuntos
Mycobacterium tuberculosis , Preparações Farmacêuticas , Adulto , Humanos , Estudos Retrospectivos , Rifampina/farmacologia , Estudos Soroepidemiológicos , Escarro
16.
AIDS Res Hum Retroviruses ; 36(3): 186-192, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31631667

RESUMO

Understanding of the burden of HIV infection and comorbid conditions in older adults is limited, especially in low- and middle-income countries. Antiretroviral therapy (ART) has increased longevity of HIV-positive individuals, making age-related comorbidities more likely. This study aimed to compare the demographic and disease profiles, including chronic comorbid conditions of inpatients, at least 50 years of age, by HIV status, admitted to a regional hospital in South Africa. Adults, 50 years of age and older, admitted to internal medicine wards from November 2015 to February 2016 were approached to participate. Sociodemographic data, laboratory results, anthropometric data, discharge diagnoses, and HIV status were collected and compared by HIV serostatus. Overall, 151 participants were enrolled. Their median age was 61 years (IQR: 56-68 years); 89 (58.9%) were women. Overall, 47 (31.1%) were HIV positive, of whom 10 (6.6%) were first diagnosed during the admission. HIV-positive inpatients were younger than HIV-negative patients. The leading discharge diagnoses of all participants were acute gastroenteritis (11.5%) and community-acquired pneumonia (11.5%). Hypertension and type 2 diabetes mellitus (T2DM) were the leading comorbidities in both HIV-negative and HIV-positive participants. Prevalence of hypertension was 75.0% in seronegative, 59.5% in those with a prior diagnosis of HIV, and 40.0% in newly diagnosed; similarly, prevalence of T2DM was 22.1% in HIV-negative and 24.3% in known HIV-positive participants. Similar proportions died during admission; 11.3% of HIV-negative and 12.7% of HIV-positive admitted inpatients died. Almost one third of patients admitted were HIV positive. In HIV-positive older admitted to hospital, the leading cause for hospitalization was coinfections. In the ART era, irrespective of HIV status, older patients have similar age-related chronic illnesses and similar mortality rates, despite younger age at admission.


Assuntos
Infecções por HIV/epidemiologia , Morbidade , Fatores Etários , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Infecções por HIV/mortalidade , Hospitalização/estatística & dados numéricos , Humanos , Hipertensão/epidemiologia , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , África do Sul/epidemiologia
17.
Clin Infect Dis ; 70(8): 1725-1732, 2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-31127284

RESUMO

BACKGROUND: Tuberculosis preventive therapy (TPT) is highly effective at preventing tuberculosis disease in household child contacts (<5 years), but is poorly implemented worldwide. In 2006, the World Health Organization recommended symptom-based screening as a replacement for tuberculin skin testing (TST) to simplify contact evaluation and improve implementation. We aimed to determine the effectiveness of this recommendation. METHODS: We conducted a pragmatic, cluster-randomized trial to determine whether contact evaluation using symptom screening improved the proportion of identified child contacts who initiated TPT, compared to TST-based screening, in Matlosana, South Africa. We randomized 16 clinics to either symptom-based or TST-based contact evaluations. Outcome data were abstracted from customized child contact management files. RESULTS: Contact tracing identified 550 and 467 child contacts in the symptom and TST arms, respectively (0.39 vs 0.32 per case, respectively; P = .27). There was no significant difference by arm in the adjusted proportion of identified child contacts who were screened (52% in symptom arm vs 60% in TST arm; P = .39). The adjusted proportion of identified child contacts who initiated TPT or tuberculosis treatment was 51.5% in the symptom clinics and 57.1% in the TST clinics (difference -5.6%, 95% confidence interval -23.7 to 12.6; P = .52). Based on the district's historic average of 0.7 child contacts per index case, 14% and 15% of child contacts completed 6 months of TPT in the symptom and TST arms, respectively (P = .89). CONCLUSIONS: Symptom-based screening did not improve the proportion of identified child contacts evaluated or initiated on TPT, compared to TST-based screening. Further research is needed to identify bottlenecks and evaluate interventions to ensure all child contacts receive TPT. CLINICAL TRIALS REGISTRATION: NCT03074799.


Assuntos
Teste Tuberculínico , Tuberculose , Criança , Pré-Escolar , Busca de Comunicante , Características da Família , Humanos , África do Sul , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle
18.
Afr J Infect Dis ; 14(2): 1-9, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33884344

RESUMO

Background: In acute sepsis, reduced lipid and lipoprotein levels occur in HIV negative patients, in particular, low high-density lipoprotein cholesterol (HDL-c) levels are inversely correlated with sepsis severity and increased mortality. However, due to the limited data describing lipid and lipoprotein levels in septic HIV-infected individuals we aimed to investigate the changes in this subgroup. Materials and Methods: A prospective cross-sectional observational study of HIV-infected patients comparing admitted HIV - infected patients with sepsis to healthy controls from the antiretroviral therapy (ART) clinic. Non fasting - lipograms, ART use, diagnosis of tuberculosis (TB), markers of infection, renal function and mortality outcome to 3 months post discharge were reviewed. Results: Total cholesterol (TC), low-density lipoprotein (LDL-c) and HDL-c were all significantly lower in the sepsis group (p < 0.001). HDL-c was significantly associated with a higher white cell count (p = 0.018), higher C- reactive protein (p = 0.036) and low serum albumin (p < 0.001). In those with active TB (55%) HDL-c was reduced even further (0.55 vs. 0.72mmol/L, p = 0.013). Acute kidney injury (p = 0.560) and mortality at discharge (p = 0.097) or 3 months follow up (p = 0.953) was not associated with reduced HDL-c. Conclusion: Septic HIV-infected patients had significantly reduced lipid and lipoprotein levels at admission. Of note however, a low HDL-c was associated with markers of infection and reductions in HDL-c was more marked in those with active TB.

19.
Lancet Respir Med ; 7(12): 1048-1058, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31732485

RESUMO

BACKGROUND: New anti-tuberculosis regimens that are shorter, simpler, and less toxic than those that are currently available are needed as part of the global effort to address the tuberculosis epidemic. We aimed to investigate the bactericidal activity and safety profile of combinations of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide in the first 8 weeks of treatment of pulmonary tuberculosis. METHODS: In this multicentre, open-label, partially randomised, phase 2b trial, we prospectively recruited patients with drug-susceptible or rifampicin-resistant pulmonary tuberculosis from seven sites in South Africa, two in Tanzania, and one in Uganda. Patients aged 18 years or older with sputum smear grade 1+ or higher were eligible for enrolment, and a molecular assay (GeneXpert or MTBDRplus) was used to confirm the diagnosis of tuberculosis and to distinguish between drug-susceptible and rifampicin-resistant tuberculosis. Patients who were HIV positive with a baseline CD4 cell count of less than 100 cells per uL were excluded. Patients with drug-susceptible tuberculosis were randomly assigned (1:1:1) using numbered treatment packs with sequential allocation by the pharmacist to receive 56 days of treatment with standard tuberculosis therapy (oral isoniazid, rifampicin, pyrazinamide, and ethambutol; HRZE), or pretomanid (oral 200 mg daily) and pyrazinamide (oral 1500 mg daily) with either oral bedaquiline 400 mg daily on days 1-14 then 200 mg three times per week (BloadPaZ) or oral bedaquiline 200 mg daily (B200PaZ). Patients with rifampicin-resistant tuberculosis received 56 days of the B200PaZ regimen plus moxifloxacin 400 mg daily (BPaMZ). All treatment groups were open label, and randomisation was not stratified. Patients, trial investigators and staff, pharmacists or dispensers, laboratory staff (with the exception of the mycobacteriology laboratory staff), sponsor staff, and applicable contract research organisations were not masked. The primary efficacy outcome was daily percentage change in time to sputum culture positivity (TTP) in liquid medium over days 0-56 in the drug-susceptible tuberculosis population, based on non-linear mixed-effects regression modelling of log10 (TTP) over time. The efficacy analysis population contained patients who received at least one dose of medication and who had efficacy data available and had no major protocol violations. The safety population contained patients who received at least one dose of medication. This study is registered with ClinicalTrials.gov, NCT02193776, and all patients have completed follow-up. FINDINGS: Between Oct 24, 2014, and Dec 15, 2015, we enrolled 180 patients with drug-susceptible tuberculosis (59 were randomly assigned to BloadPaZ, 60 to B200PaZ, and 61 to HRZE) and 60 patients with rifampicin-resistant tuberculosis. 57 patients in the BloadPaZ group, 56 in the B200PaZ group, and 59 in the HRZE group were included in the primary analysis. B200PaZ produced the highest daily percentage change in TTP (5·17% [95% Bayesian credibility interval 4·61-5·77]), followed by BloadPaZ (4·87% [4·31-5·47]) and HRZE group (4·04% [3·67-4·42]). The bactericidal activity in B200PaZ and BloadPaZ groups versus that in the HRZE group was significantly different. Higher proportions of patients in the BloadPaZ (six [10%] of 59) and B200PaZ (five [8%] of 60) groups discontinued the study drug than in the HRZE group (two [3%] of 61) because of adverse events. Liver enzyme elevations were the most common grade 3 or 4 adverse events and resulted in the withdrawal of ten patients (five [8%] in the BloadPaZ group, three [5%] in the B200PaZ group, and two [3%] in the HRZE group). Serious treatment-related adverse events affected two (3%) patients in the BloadPaZ group and one (2%) patient in the HRZE group. Seven (4%) patients with drug-susceptible tuberculosis died and four (7%) patients with rifampicin-resistant tuberculosis died. None of the deaths were considered to be related to treatment. INTERPRETATION: B200PaZ is a promising regimen to treat patients with drug-susceptible tuberculosis. The bactericidal activity of both these regimens suggests that they have the potential to shorten treatment, and the simplified dosing schedule of B200PaZ could improve treatment adherence in the field. However, these findings must be investigated further in a phase 3 trial assessing treatment outcomes. FUNDING: TB Alliance, UK Department for International Development, Bill & Melinda Gates Foundation, US Agency for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and the Federal Ministry for Education and Research of Germany.


Assuntos
Antituberculosos/administração & dosagem , Diarilquinolinas/administração & dosagem , Moxifloxacina/administração & dosagem , Nitroimidazóis/administração & dosagem , Pirazinamida/administração & dosagem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Esquema de Medicação , Quimioterapia Combinada , Humanos , Rifampina/administração & dosagem , África do Sul , Escarro/microbiologia , Tanzânia , Resultado do Tratamento , Uganda
20.
BMC Infect Dis ; 19(1): 839, 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606032

RESUMO

BACKGROUND: Household contact tracing of index TB cases has been advocated as a key part of TB control for many years, but has not been widely implemented in many low-resource setting because of the current dearth of high quality evidence for effectiveness. Innovative strategies for earlier, more effective treatment are particularly important in contexts with hyper-endemic levels of HIV, where levels of TB infection remain extremely high. METHODS: We present the design of a household cluster-randomised controlled trial of interventions aimed at improving TB-free survival and reducing childhood prevalence of Mycobacterium tuberculosis infection among household contacts of index TB cases diagnosed in two provinces of South Africa. Households of index TB cases will be randomly allocated in a 1:1 ratio to receive either an intensified home screening and linkage for TB and HIV intervention, or enhanced standard of care. The primary outcome will compare between groups the TB-free survival of household contacts over 15 months. All participants, or their next-of-kin, will provide written informed consent to participate. DISCUSSION: Evidence from randomised trials is required to identify cost-effective approaches to TB case-finding that can be applied at scale in sub-Saharan Africa. TRIAL REGISTRATION: ISRCTN16006202 (01/02/2017: retrospectively registered) and NHREC4399 (11/04/2016: prospectively registered). Protocol version: 4.0 (date: 18th January 2018).


Assuntos
Busca de Comunicante/métodos , Tuberculose/prevenção & controle , Adulto , Criança , Análise Custo-Benefício , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Estudos Retrospectivos , Risco , África do Sul/epidemiologia , Padrão de Cuidado , Resultado do Tratamento , Teste Tuberculínico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Carga Viral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...