Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 55
Filtrar
1.
Int J Mol Sci ; 25(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38928045

RESUMO

Mutations have driven the evolution and development of new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with potential implications for increased transmissibility, disease severity and vaccine escape among others. Genome sequencing is a technique that allows scientists to read the genetic code of an organism and has become a powerful tool for studying emerging infectious diseases. Here, we conducted a cross-sectional study in selected districts of the Eastern Province of Zambia, from November 2021 to February 2022. We analyzed SARS-CoV-2 samples (n = 76) using high-throughput sequencing. A total of 4097 mutations were identified in 69 SARS-CoV-2 genomes with 47% (1925/4097) of the mutations occurring in the spike protein. We identified 83 unique amino acid mutations in the spike protein of the seven Omicron sublineages (BA.1, BA.1.1, BA.1.14, BA.1.18, BA.1.21, BA.2, BA.2.23 and XT). Of these, 43.4% (36/83) were present in the receptor binding domain, while 14.5% (12/83) were in the receptor binding motif. While we identified a potential recombinant XT strain, the highly transmissible BA.2 sublineage was more predominant (40.8%). We observed the substitution of other variants with the Omicron strain in the Eastern Province. This work shows the importance of pandemic preparedness and the need to monitor disease in the general population.


Assuntos
COVID-19 , Genoma Viral , Mutação , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Zâmbia/epidemiologia , Humanos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , COVID-19/virologia , COVID-19/epidemiologia , Glicoproteína da Espícula de Coronavírus/genética , Estudos Transversais , Estudos Retrospectivos , Filogenia , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos
2.
Clin Infect Dis ; 75(1): e224-e233, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34549260

RESUMO

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.


Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Efeitos Psicossociais da Doença , Humanos , Pandemias/prevenção & controle , Preparações Farmacêuticas
3.
Clin Infect Dis ; 73(6): e1321-e1328, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-33784382

RESUMO

BACKGROUND: Healthcare workers (HCWs) in Zambia have become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). However, SARS-CoV-2 prevalence among HCWs is not known in Zambia. METHODS: We conducted a cross-sectional SARS-CoV-2 prevalence survey among Zambian HCWs in 20 health facilities in 6 districts in July 2020. Participants were tested for SARS-CoV-2 infection using polymerase chain reaction (PCR) and for SARS-CoV-2 antibodies using enzyme-linked immunosorbent assay (ELISA). Prevalence estimates and 95% confidence intervals (CIs), adjusted for health facility clustering, were calculated for each test separately, and a combined measure for those who had PCR and ELISA was performed. RESULTS: In total, 660 HCWs participated in the study, with 450 (68.2%) providing a nasopharyngeal swab for PCR and 575 (87.1%) providing a blood specimen for ELISA. Sixty-six percent of participants were females, and median age was 31.5 years (interquartile range, 26.2-39.8). The overall prevalence of the combined measure was 9.3% (95% CI, 3.8%-14.7%). PCR-positive prevalence of SARS-CoV-2 was 6.6% (95% CI, 2.0%-11.1%), and ELISA-positive prevalence was 2.2% (95% CI, .5%-3.9%). CONCLUSIONS: SARS-CoV-2 prevalence among HCWs was similar to a population-based estimate (10.6%) during a period of community transmission in Zambia. Public health measures such as establishing COVID-19 treatment centers before the first cases, screening for COVID-19 symptoms among patients who access health facilities, infection prevention and control trainings, and targeted distribution of personal protective equipment based on exposure risk might have prevented increased SARS-CoV-2 transmission among Zambian HCWs.


Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Adulto , Estudos Transversais , Feminino , Pessoal de Saúde , Humanos , Prevalência , Zâmbia
4.
N Engl J Med ; 378(11): 1004-1017, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29539274

RESUMO

BACKGROUND: Cryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)-related deaths per year. We tested two treatment strategies that could be more sustainable in Africa than the standard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy. METHODS: We randomly assigned HIV-infected adults with cryptococcal meningitis to receive an oral regimen (fluconazole [1200 mg per day] plus flucytosine [100 mg per kilogram of body weight per day] for 2 weeks), 1 week of amphotericin B (1 mg per kilogram per day), or 2 weeks of amphotericin B (1 mg per kilogram per day). Each patient assigned to receive amphotericin B was also randomly assigned to receive fluconazole or flucytosine as a partner drug. After induction treatment, all the patients received fluconazole consolidation therapy and were followed to 10 weeks. RESULTS: A total of 721 patients underwent randomization. Mortality in the oral-regimen, 1-week amphotericin B, and 2-week amphotericin B groups was 18.2% (41 of 225), 21.9% (49 of 224), and 21.4% (49 of 229), respectively, at 2 weeks and was 35.1% (79 of 225), 36.2% (81 of 224), and 39.7% (91 of 229), respectively, at 10 weeks. The upper limit of the one-sided 97.5% confidence interval for the difference in 2-week mortality was 4.2 percentage points for the oral-regimen group versus the 2-week amphotericin B groups and 8.1 percentage points for the 1-week amphotericin B groups versus the 2-week amphotericin B groups, both of which were below the predefined 10-percentage-point noninferiority margin. As a partner drug with amphotericin B, flucytosine was superior to fluconazole (71 deaths [31.1%] vs. 101 deaths [45.0%]; hazard ratio for death at 10 weeks, 0.62; 95% confidence interval [CI], 0.45 to 0.84; P=0.002). One week of amphotericin B plus flucytosine was associated with the lowest 10-week mortality (24.2%; 95% CI, 16.2 to 32.1). Side effects, such as severe anemia, were more frequent with 2 weeks than with 1 week of amphotericin B or with the oral regimen. CONCLUSIONS: One week of amphotericin B plus flucytosine and 2 weeks of fluconazole plus flucytosine were effective as induction therapy for cryptococcal meningitis in resource-limited settings. (ACTA Current Controlled Trials number, ISRCTN45035509 .).


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Anfotericina B/administração & dosagem , Antifúngicos/uso terapêutico , Fluconazol/administração & dosagem , Flucitosina/administração & dosagem , Meningite Criptocócica/tratamento farmacológico , Administração Oral , Adulto , África/epidemiologia , Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Fluconazol/efeitos adversos , Flucitosina/efeitos adversos , Soropositividade para HIV/complicações , Humanos , Estimativa de Kaplan-Meier , Masculino , Meningite Criptocócica/mortalidade , Modelos de Riscos Proporcionais
5.
MMWR Morb Mortal Wkly Rep ; 70(22): 807-810, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34081684

RESUMO

The effect of HIV infection on COVID-19 outcomes is unclear. Studies in South Africa (1) and the United Kingdom (2) found an independent association between HIV infection and COVID-19 mortality; however, other studies have not found an association between poor COVID-19 outcomes and either HIV status among hospitalized patients (3-5) or HIV-associated factors such as CD4 count, viral load, or type of antiretroviral therapy (ART) (6). The effect of HIV infection on COVID-19 outcomes remains an urgent question in sub-Saharan Africa, where many countries are experiencing dual HIV and COVID-19 epidemics, and capacity to treat severe COVID-19 is limited. Using data from patients with probable or confirmed COVID-19 admitted to specialized treatment centers during March-December 2020 in Zambia, the Zambian Ministry of Health and CDC assessed the relationship between HIV infection and severe COVID-19 and COVID-19-associated death. Among 443 patients included in the study, 122 (28%) were HIV-positive, and of these, 91 (89%) were receiving ART at the time of hospitalization. HIV status alone was not significantly associated with severe COVID-19 at admission or during hospitalization or with COVID-19-associated death. However, among HIV-positive persons, those with severe HIV disease were more likely to develop severe COVID-19 and were at increased risk for COVID-19-associated death. Ensuring that persons maintain HIV disease control, including maintaining ART continuity and adherence, achieving viral suppression, and addressing and managing underlying medical conditions, could help reduce COVID-19-associated morbidity and mortality in sub-Saharan Africa.


Assuntos
COVID-19/mortalidade , COVID-19/terapia , Infecções por HIV/epidemiologia , Índice de Gravidade de Doença , Adolescente , Adulto , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem , Zâmbia/epidemiologia
6.
Clin Infect Dis ; 70(8): 1652-1657, 2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-31149704

RESUMO

BACKGROUND: A randomized trial demonstrated that among people living with late-stage human immunodeficiency virus (HIV) infection initiating antiretroviral therapy, screening serum for cryptococcal antigen (CrAg) combined with adherence support reduced all-cause mortality by 28%, compared with standard clinic-based care. Here, we present the cost-effectiveness. METHODS: HIV-infected adults with CD4 count <200 cells/µL were randomized to either CrAg screening plus 4 weekly home visits to provide adherence support or to standard clinic-based care in Dar es Salaam and Lusaka. The primary economic outcome was health service care cost per life-year saved as the incremental cost-effectiveness ratio (ICER), based on 2017 US dollars. We used nonparametric bootstrapping to assess uncertainties and univariate deterministic sensitivity analysis to examine the impact of individual parameters on the ICER. RESULTS: Among the intervention and standard arms, 1001 and 998 participants, respectively, were enrolled. The annual mean cost per participant in the intervention arm was US$339 (95% confidence interval [CI], $331-$347), resulting in an incremental cost of the intervention of US$77 (95% CI, $66-$88). The incremental cost was similar when analysis was restricted to persons with CD4 count <100 cells/µL. The ICER for the intervention vs standard care, per life-year saved, was US$70 (95% CI, $43-$211) for all participants with CD4 count up to 200 cells/µL and US$91 (95% CI, $49-$443) among those with CD4 counts <100 cells /µL. Cost-effectveness was most sensitive to mortality estimates. CONCLUSIONS: Screening for cryptococcal antigen combined with a short period of adherence support, is cost-effective in resource-limited settings.


Assuntos
Infecções por HIV , Meningite Criptocócica , Adulto , Antígenos de Fungos , Contagem de Linfócito CD4 , Análise Custo-Benefício , Infecções por HIV/tratamento farmacológico , Humanos , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/tratamento farmacológico , Tanzânia , Zâmbia
7.
Clin Infect Dis ; 70(1): 26-29, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30816418

RESUMO

BACKGROUND: Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain. METHODS: The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER. RESULTS: The mean costs per patient were US $847 (95% confidence interval [CI] $776-927) for FLU+5FC, and US $628 (95% CI $557-709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9-41.7%) with FLU+5FC and 53.8% (95% CI 43.1-64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28-208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved. CONCLUSIONS: The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus-infected persons in Africa.


Assuntos
Flucitosina , Meningite Criptocócica , África , Antifúngicos/uso terapêutico , Análise Custo-Benefício , Fluconazol/uso terapêutico , Flucitosina/uso terapêutico , Humanos , Meningite Criptocócica/tratamento farmacológico
8.
MMWR Morb Mortal Wkly Rep ; 69(42): 1547-1548, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33090982

RESUMO

Zambia is a landlocked, lower-middle income country in southern Africa, with a population of 17 million (1). The first known cases of coronavirus disease 2019 (COVID-19) in Zambia occurred in a married couple who had traveled to France and were subject to port-of-entry surveillance and subsequent remote monitoring of travelers with a history of international travel for 14 days after arrival. They were identified as having suspected cases on March 18, 2020, and tested for COVID-19 after developing respiratory symptoms during the 14-day monitoring period. In March 2020, the Zambia National Public Health Institute (ZNPHI) defined a suspected case of COVID-19 as 1) an acute respiratory illness in a person with a history of international travel during the 14 days preceding symptom onset; or 2) acute respiratory illness in a person with a history of contact with a person with laboratory-confirmed COVID-19 in the 14 days preceding symptom onset; or 3) severe acute respiratory illness requiring hospitalization; or 4) being a household or close contact of a patient with laboratory-confirmed COVID-19. This definition was adapted from World Health Organization (WHO) interim guidance issued March 20, 2020, on global surveillance for COVID-19 (2) to also include asymptomatic contacts of persons with confirmed COVID-19. Persons with suspected COVID-19 were identified through various mechanisms, including port-of-entry surveillance, contact tracing, health care worker (HCW) testing, facility-based inpatient screening, community-based screening, and calls from the public into a national hotline administered by the Disaster Management and Mitigation Unit and ZNPHI. Port-of-entry surveillance included an arrival screen consisting of a temperature scan, report of symptoms during the preceding 14 days, and collection of a history of travel and contact with persons with confirmed COVID-19 in the 14 days before arrival in Zambia, followed by daily remote telephone monitoring for 14 days. Travelers were tested for SARS-CoV-2, the virus that causes COVID-19, if they were symptomatic upon arrival or developed symptoms during the 14-day monitoring period. Persons with suspected COVID-19 were tested as soon as possible after evaluation for respiratory symptoms or within 7 days of last known exposure (i.e., travel or contact with a confirmed case). All COVID-19 diagnoses were confirmed using real-time reverse transcription-polymerase chain reaction (RT-PCR) testing (SARS-CoV-2 Nucleic Acid Detection Kit, Maccura) of nasopharyngeal specimens; all patients with confirmed COVID-19 were admitted into institutional isolation at the time of laboratory confirmation, which was generally within 36 hours. COVID-19 patients were deemed recovered and released from isolation after two consecutive PCR-negative test results ≥24 hours apart. A Ministry of Health memorandum was released on April 13, 2020, mandating testing in public facilities of 1) all persons admitted to medical and pediatric wards regardless of symptoms; 2) all patients being admitted to surgical and obstetric wards, regardless of symptoms; 3) any outpatient with fever, cough, or shortness of breath; and 4) any facility or community death in a person with respiratory symptoms, and 5) biweekly screening of all HCWs in isolation centers and health facilities where persons with COVID-19 had been evaluated. This report describes the first 100 COVID-19 cases reported in Zambia, during March 18-April 28, 2020.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Vigilância em Saúde Pública , Adulto , COVID-19 , Teste para COVID-19 , Vacinas contra COVID-19 , Técnicas de Laboratório Clínico , Busca de Comunicante , Feminino , Humanos , Masculino , Pandemias , Doença Relacionada a Viagens , Zâmbia/epidemiologia
9.
Clin Infect Dis ; 69(4): 588-595, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30863852

RESUMO

BACKGROUND: Mortality from cryptoccocal meningitis remains high. The ACTA trial demonstrated that, compared with 2 weeks of amphotericin B (AmB) plus flucystosine (5FC), 1 week of AmB and 5FC was associated with lower mortality and 2 weeks of oral flucanozole (FLU) plus 5FC was non-inferior. Here, we assess the cost-effectiveness of these different treatment courses. METHODS: Participants were randomized in a ratio of 2:1:1:1:1 to 2 weeks of oral 5FC and FLU, 1 week of AmB and FLU, 1 week of AmB and 5FC, 2 weeks of AmB and FLU, or 2 weeks of AmB and 5FC in Malawi, Zambia, Cameroon, and Tanzania. Data on individual resource use and health outcomes were collected. Cost-effectiveness was measured as incremental costs per life-year saved, and non-parametric bootstrapping was done. RESULTS: Total costs per patient were US $1442 for 2 weeks of oral FLU and 5FC, $1763 for 1 week of AmB and FLU, $1861 for 1 week of AmB and 5FC, $2125 for 2 weeks of AmB and FLU, and $2285 for 2 weeks of AmB and 5FC. Compared to 2 weeks of AmB and 5FC, 1 week of AmB and 5FC was less costly and more effective and 2 weeks of oral FLU and 5FC was less costly and as effective. The incremental cost-effectiveness ratio for 1 week of AmB and 5FC versus oral FLU and 5FC was US $208 (95% confidence interval $91-1210) per life-year saved. CLINICAL TRIALS REGISTRATION: ISRCTN45035509. CONCLUSIONS: Both 1 week of AmB and 5FC and 2 weeks of Oral FLU and 5FC are cost-effective treatments.


Assuntos
Antifúngicos , Meningite Criptocócica , África Subsaariana , Antifúngicos/economia , Antifúngicos/uso terapêutico , Flucitosina/economia , Flucitosina/uso terapêutico , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/economia , Meningite Criptocócica/epidemiologia , Meningite Criptocócica/terapia
10.
Lancet ; 387(10024): 1187-97, 2016 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-26970721

RESUMO

BACKGROUND: HIV-associated tuberculosis is difficult to diagnose and results in high mortality. Frequent extra-pulmonary presentation, inability to obtain sputum, and paucibacillary samples limits the usefulness of nucleic-acid amplification tests and smear microscopy. We therefore assessed a urine-based, lateral flow, point-of-care, lipoarabinomannan assay (LAM) and the effect of a LAM-guided anti-tuberculosis treatment initiation strategy on mortality. METHODS: We did a pragmatic, randomised, parallel-group, multicentre trial in ten hospitals in Africa--four in South Africa, two in Tanzania, two in Zambia, and two in Zimbabwe. Eligible patients were HIV-positive adults aged at least 18 years with at least one of the following symptoms of tuberculosis (fever, cough, night sweats, or self-reported weightloss) and illness severity necessitating admission to hospital. Exclusion criteria included receipt of any anti-tuberculosis medicine in the 60 days before enrolment. We randomly assigned patients (1:1) to either LAM plus routine diagnostic tests for tuberculosis (smear microscopy, Xpert-MTB/RIF, and culture; LAM group) or routine diagnostic tests alone (no LAM group) using computer-generated allocation lists in blocks of ten. All patients were asked to provide a urine sample of at least 30 mL at enrolment, and trained research nurses did the LAM test in patients allocated to this group using the Alere Determine tuberculosis LAM Ag lateral flow strip test (Alere, USA) at the bedside on enrolment. On the basis of a positive test result, the nurses made a recommendation for initiating anti-tuberculosis treatment. The attending physician made an independent decision about whether to start treatment or not. Neither patients nor health-care workers were masked to group allocation and test results. The primary endpoint was 8-week all-cause mortality assessed in the modified intention-to-treat population (those who received their allocated intervention). This trial is registered with ClinicalTrials.gov, number NCT01770730. FINDINGS: Between Jan 1, 2013, and Oct 2, 2014, we screened 8728 patients and randomly assigned 2659 to treatment (1336 to LAM, 1323 to no LAM). 108 patients did not receive their allocated treatment, mainly because they did not meet the inclusion criteria, and 23 were excluded from analysis, leaving 2528 in the final modified intention-to-treat analysis (1257 in the LAM group, 1271 in the no LAM group). Overall all-cause 8-week mortality occurred in 578 (23%) patients, 261 (21%) in LAM and 317 (25%) in no LAM, an absolute reduction of 4% (95% CI 1-7). The risk ratio adjusted for country was 0·83 (95% CI 0·73-0·96), p=0·012, with a relative risk reduction of 17% (95% CI 4-28). With the time-to-event analysis, there were 159 deaths per 100 person-years in LAM and 196 per 100 person-years in no LAM (hazard ratio adjusted for country 0·82 [95% CI 0·70-0·96], p=0·015). No adverse events were associated with LAM testing. INTERPRETATION: Bedside LAM-guided initiation of anti-tuberculosis treatment in HIV-positive hospital inpatients with suspected tuberculosis was associated with reduced 8-week mortality. The implementation of LAM testing is likely to offer the greatest benefit in hospitals where diagnostic resources are most scarce and where patients present with severe illness, advanced immunosuppression, and an inability to self-expectorate sputum. FUNDING: European Developing Clinical Trials Partnership, the South African Medical Research Council, and the South African National Research Foundation.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Lipopolissacarídeos/urina , Sistemas Automatizados de Assistência Junto ao Leito , Tuberculose/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Adulto , África/epidemiologia , Antituberculosos/uso terapêutico , Biomarcadores/urina , Contagem de Linfócito CD4 , Testes Diagnósticos de Rotina , Feminino , Hospitalização , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Sensibilidade e Especificidade , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose/imunologia , Tuberculose/mortalidade
11.
Mol Ecol ; 26(7): 1991-2005, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27862555

RESUMO

Emerging infections caused by fungi have become a widely recognized global phenomenon and are causing an increasing burden of disease. Genomic techniques are providing new insights into the structure of fungal populations, revealing hitherto undescribed fine-scale adaptations to environments and hosts that govern their emergence as infections. Cryptococcal meningitis is a neglected tropical disease that is responsible for a large proportion of AIDS-related deaths across Africa; however, the ecological determinants that underlie a patient's risk of infection remain largely unexplored. Here, we use genome sequencing and ecological genomics to decipher the evolutionary ecology of the aetiological agents of cryptococcal meningitis, Cryptococcus neoformans and Cryptococcus gattii, across the central African country of Zambia. We show that the occurrence of these two pathogens is differentially associated with biotic (macroecological) and abiotic (physical) factors across two key African ecoregions, Central Miombo woodlands and Zambezi Mopane woodlands. We show that speciation of Cryptococcus has resulted in adaptation to occupy different ecological niches, with C. neoformans found to occupy Zambezi Mopane woodlands and C. gattii primarily recovered from Central Miombo woodlands. Genome sequencing shows that C. neoformans causes 95% of human infections in this region, of which over three-quarters belonged to the globalized lineage VNI. We show that VNI infections are largely associated with urbanized populations in Zambia. Conversely, the majority of C. neoformans isolates recovered in the environment belong to the genetically diverse African-endemic lineage VNB, and we show hitherto unmapped levels of genomic diversity within this lineage. Our results reveal the complex evolutionary ecology that underpins the reservoirs of infection for this, and likely other, deadly pathogenic fungi.


Assuntos
Adaptação Fisiológica/genética , Cryptococcus gattii/genética , Cryptococcus neoformans/genética , Florestas , Meningite Criptocócica/microbiologia , Código de Barras de DNA Taxonômico , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Genética Populacional , Genoma Fúngico , Genômica , Humanos , Meningite Criptocócica/epidemiologia , Modelos Biológicos , Filogenia , Casca de Planta/microbiologia , Polimorfismo de Nucleotídeo Único , Microbiologia do Solo , Árvores/microbiologia , Zâmbia
12.
Clin Infect Dis ; 62(8): 995-1001, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26908793

RESUMO

BACKGROUND: Patients with previous tuberculosis may have residual DNA in sputum that confounds nucleic acid amplification tests such as Xpert MTB/RIF. Little is known about the frequency of Xpert-positive, culture-negative ("false positive") results in retreatment patients, whether these are distinguishable from true positives, and whether Xpert's automated filter-based wash step reduces false positivity by removing residual DNA associated with nonintact cells. METHODS: Pretreatment patients (n = 2889) with symptoms of tuberculosis from Cape Town, South Africa, underwent a sputum-based liquid culture and Xpert. We also compared Xpert results from dilutions of intact or heat-lysed and mechanically lysed bacilli. RESULTS: Retreatment cases were more likely to be Xpert false-positive (45/321 Xpert-positive retreatment cases were false-positive) than new cases (40/461) (14% [95% confidence interval {CI}, 10%-18%] vs 8% [95% CI, 6%-12%];P= .018). Fewer years since treatment completion (adjusted odds ratio [aOR], 0.85 [95% CI, .73-.99]), less mycobacterial DNA (aOR, 1.14 [95% CI, 1.03-1.27] per cycle threshold [CT]), and a chest radiograph not suggestive of active tuberculosis (aOR, 0.22 [95% CI, .06-.82]) were associated with false positivity. CThad suboptimal accuracy for false positivity: 46% of Xpert-positives with CT> 30 would be false positive, although 70% of false positives would be missed. CT's predictive ability (area under the curve, 0.83 [95% CI, .76-.90]) was not improved by additional variables. Xpert detected nonviable, nonintact bacilli without a change in CTvs controls. CONCLUSIONS: One in 7 Xpert-positive retreatment patients were culture negative and potentially false positive. False positivity was associated with recent previous tuberculosis, high CT, and a chest radiograph not suggestive of active tuberculosis. Clinicians may consider awaiting confirmatory testing in retreatment patients with CT> 30; however, most false positives fall below this cut-point. Xpert can detect DNA from nonviable, nonintact bacilli.


Assuntos
Técnicas de Amplificação de Ácido Nucleico , Tuberculose/diagnóstico , Adulto , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Curva ROC , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , África do Sul/epidemiologia , Escarro/microbiologia , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia
13.
Lancet ; 385(9983): 2173-82, 2015 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-25765698

RESUMO

BACKGROUND: Mortality in people in Africa with HIV infection starting antiretroviral therapy (ART) is high, particularly in those with advanced disease. We assessed the effect of a short period of community support to supplement clinic-based services combined with serum cryptococcal antigen screening. METHODS: We did an open-label, randomised controlled trial in six urban clinics in Dar es Salaam, Tanzania, and Lusaka, Zambia. From February, 2012, we enrolled eligible individuals with HIV infection (age ≥18 years, CD4 count of <200 cells per µL, ART naive) and randomly assigned them to either the standard clinic-based care supplemented with community support or standard clinic-based care alone, stratified by country and clinic, in permuted block sizes of ten. Clinic plus community support consisted of screening for serum cryptococcal antigen combined with antifungal therapy for patients testing antigen positive, weekly home visits for the first 4 weeks on ART by lay workers to provide support, and in Tanzania alone, re-screening for tuberculosis at 6-8 weeks after ART initiation. The primary endpoint was all-cause mortality at 12 months, analysed by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number registry, number ISCRTN 20410413. FINDINGS: Between Feb 9, 2012, and Sept 30, 2013, 1001 patients were randomly assigned to clinic plus community support and 998 to standard care. 89 (9%) of 1001 participants in the clinic plus community support group did not receive their assigned intervention, and 11 (1%) of 998 participants in the standard care group received a home visit or a cryptococcal antigen screen rather than only standard care. At 12 months, 25 (2%) of 1001 participants in the clinic plus community support group and 24 (2%) of 998 participants in the standard care group had been lost to follow-up, and were censored at their last visit for the primary analysis. At 12 months, 134 (13%) of 1001 participants in the clinic plus community support group had died compared with 180 (18%) of 998 in the standard care group. Mortality was 28% (95% CI 10-43) lower in the clinic plus community support group than in standard care group (p=0·004). INTERPRETATION: Screening and pre-emptive treatment for cryptococcal infection combined with a short initial period of adherence support after initiation of ART could substantially reduce mortality in HIV programmes in Africa. FUNDING: European and Developing Countries Clinical Trials Partnership.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Serviços de Saúde Comunitária/métodos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/mortalidade , Adulto , Antifúngicos/uso terapêutico , Feminino , Humanos , Masculino , Meningite Criptocócica/tratamento farmacológico , Pessoa de Meia-Idade , Cooperação do Paciente , Tanzânia/epidemiologia , Resultado do Tratamento , Zâmbia/epidemiologia
14.
Lancet ; 383(9915): 424-35, 2014 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-24176144

RESUMO

BACKGROUND: The Xpert MTB/RIF test for tuberculosis is being rolled out in many countries, but evidence is lacking regarding its implementation outside laboratories, ability to inform same-day treatment decisions at the point of care, and clinical effect on tuberculosis-related morbidity. We aimed to assess the feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing at primary-care health-care facilities in southern Africa. METHODS: In this pragmatic, randomised, parallel-group, multicentre trial, we recruited adults with symptoms suggestive of active tuberculosis from five primary-care health-care facilities in South Africa, Zimbabwe, Zambia, and Tanzania. Eligible patients were randomly assigned using pregenerated tables to nurse-performed Xpert MTB/RIF at the clinic or sputum smear microscopy. Participants with a negative test result were empirically managed according to local WHO-compliant guidelines. Our primary outcome was tuberculosis-related morbidity (measured with the TBscore and Karnofsky performance score [KPS]) in culture-positive patients who had begun anti-tuberculosis treatment, measured at 2 months and 6 months after randomisation, analysed by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT01554384. FINDINGS: Between April 12, 2011, and March 30, 2012, we randomly assigned 758 patients to smear microscopy (182 culture positive) and 744 to Xpert MTB/RIF (185 culture positive). Median TBscore in culture-positive patients did not differ between groups at 2 months (2 [IQR 0-3] in the smear microscopy group vs 2 [0·25-3] in the MTB/RIF group; p=0·85) or 6 months (1 [0-3] vs 1 [0-3]; p=0·35), nor did median KPS at 2 months (80 [70-90] vs 90 [80-90]; p=0·23) or 6 months (100 [90-100] vs 100 [90-100]; p=0·85). Point-of-care MTB/RIF had higher sensitivity than microscopy (154 [83%] of 185 vs 91 [50%] of 182; p=0·0001) but similar specificity (517 [95%] 544 vs 540 [96%] of 560; p=0·25), and had similar sensitivity to laboratory-based MTB/RIF (292 [83%] of 351; p=0·99) but higher specificity (952 [92%] of 1037; p=0·0173). 34 (5%) of 744 tests with point-of-care MTB/RIF and 82 (6%) of 1411 with laboratory-based MTB/RIF failed (p=0·22). Compared with the microscopy group, more patients in the MTB/RIF group had a same-day diagnosis (178 [24%] of 744 vs 99 [13%] of 758; p<0·0001) and same-day treatment initiation (168 [23%] of 744 vs 115 [15%] of 758; p=0·0002). Although, by end of the study, more culture-positive patients in the MTB/RIF group were on treatment due to reduced dropout (15 [8%] of 185 in the MTB/RIF group did not receive treatment vs 28 [15%] of 182 in the microscopy group; p=0·0302), the proportions of all patients on treatment in each group by day 56 were similar (320 [43%] of 744 in the MTB/RIF group vs 317 [42%] of 758 in the microscopy group; p=0·6408). INTERPRETATION: Xpert MTB/RIF can be accurately administered by a nurse in primary-care clinics, resulting in more patients starting same-day treatment, more culture-positive patients starting therapy, and a shorter time to treatment. However, the benefits did not translate into lower tuberculosis-related morbidity, partly because of high levels of empirical-evidence-based treatment in smear-negative patients. FUNDING: European and Developing Countries Clinical Trials Partnership, National Research Foundation, and Claude Leon Foundation.


Assuntos
Sistemas Automatizados de Assistência Junto ao Leito/normas , Tuberculose Pulmonar/diagnóstico , Adulto , África , Técnicas Bacteriológicas/normas , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/enfermagem , Tuberculose Pulmonar/enfermagem
15.
BMC Infect Dis ; 15: 262, 2015 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-26156025

RESUMO

BACKGROUND: The commercially available urine LAM strip test, a point-of-care tuberculosis (TB) assay, requires evaluation in a primary care setting where it is most needed. There is currently inadequate data to guide implementation in TB and HIV-endemic settings. METHODS: Adult HIV-infected outpatients with suspected pulmonary TB able to self-expectorate sputum from four primary clinics in South Africa, Zambia and Tanzania underwent diagnostic evaluation [sputum smear microscopy, Xpert-MTB/RIF, and culture (reference standard)] as part of a prospective parent study. Urine LAM testing (grade-2 cut-point) was performed on archived samples. Performance characteristics of LAM alone or in combination with sputum-based diagnostics were evaluated. Potential impact on 2 and 6-month morbidity (TBscore), patient dropout rates, and prognosis (death/ loss to follow-up) were evaluated. RESULTS: Among 583 participants with suspected TB that were HIV-infected or refused testing, the overall LAM sensitivity (95 % CI; n/N) and in the CD4 ≤ 100 cells/mm(3) sub-group was 22.7 % (16.6-28.7; 41/181) and 30.4 % (17.1-43.7; 14/46), respectively. Overall specificity was 93.0 % (90.5-95.6; 361/388). Amongst culture-positive TB cases, adjunctive LAM testing did not improve the sensitivity of either sputum Xpert-MTB/RIF [78.2 % (69.8-86.7; 72/92) versus 76.1 % (67.4-84.8; 70/92), p = 0.7] or smear-microscopy [56.2 % (45.9-66.5; 50/89) versus 43.8 % (33.5-54.1; 39/89), p = 0.1). Clinic-based LAM, as an adjunct to either smear microscopy or Xpert MTB/RIF same-day testing, would neither have decreased patient dropout, nor increased same-day treatment initiation in this clinical setting where same-day chest radiography was available. LAM positivity was associated with 6-month lost-to-follow-up/death (AOR 4.4; p = 0.002) but not TBscore (at baseline or change in TBscore 2-months post-treatment) (p = 0.17). CONCLUSIONS: In African HIV-TB co-infected outpatients able to self-expectorate sputum LAM had limited sensitivity even at low CD4 counts, and offered no significant incremental diagnostic yield over Xpert-MTB/RIF or smear microscopy. In primary care clinics with chest radiography and where empiric TB treatment is common, LAM seems unlikely to improve rates of same-day treatment initiation and patient dropout, however, the ability of LAM to identify patients at high risk of death or lost-to-follow-up may offer important prognostic value.


Assuntos
Infecções por HIV/imunologia , Lipopolissacarídeos/urina , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Adulto , Idoso , Instituições de Assistência Ambulatorial , Bioensaio , Contagem de Linfócito CD4 , Coinfecção , Estudos Transversais , Testes Diagnósticos de Rotina , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Sistemas Automatizados de Assistência Junto ao Leito , Estudos Prospectivos , Sensibilidade e Especificidade , África do Sul , Tanzânia , Tuberculose/diagnóstico , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/imunologia , Urinálise , Adulto Jovem , Zâmbia
16.
BMC Infect Dis ; 15: 253, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-26126655

RESUMO

BACKGROUND: The successful cure of tuberculosis (TB) is dependent on adherence to treatment. Various factors influence adherence, however, few are easily modifiable. There are limited data regarding correlates of psychological distress and their association with non-adherence to anti-TB treatment. METHODS: In a trial of a new TB test, we measured psychological distress (K-10 score), TB-related health literacy, and morbidity (TBscore), prior to diagnosis in 1502 patients with symptoms of pulmonary TB recruited from clinics in Cape Town (n = 419), Harare (n = 400), Lusaka (n = 400), Durban (n = 200), and Mbeya (n = 83). Socioeconomic, demographic, and alcohol usage-related data were captured. Patients initiated on treatment had their DOTS cards reviewed at two-and six-months. RESULTS: 22 %(95 % CI: 20 %, 25 %) of patients had severe psychological distress (K-10 ≥ 30). In a multivariable linear regression model, increased K-10 score was independently associated with previous TB [estimate (95 % CI) 0.98(0.09-1.87); p = 0.0304], increased TBscore [1(0.80, 1.20); p <0.0001], and heavy alcohol use [3.08(1.26, 4.91); p = 0.0010], whereas male gender was protective [-1.47(-2.28, -0.62); p = 0.0007]. 26 % (95 % CI: 21 %, 32 %) of 261 patients with culture-confirmed TB were non-adherent. In a multivariable logistic regression model for non-adherence, reduced TBscore [OR (95 % CI) 0.639 (0.497, 0.797); p = 0.0001], health literacy score [0.798(0.696, 0.906); p = 0.0008], and increased K-10 [1.082(1.033, 1.137); p = 0.0012], and heavy alcohol usage [14.83(2.083, 122.9); p = 0.0002], were independently associated. Culture-positive patients with a K-10 score ≥ 30 were more-likely to be non-adherent (OR = 2.290(1.033-5.126); p = 0.0416]. CONCLUSION: Severe psychological distress is frequent amongst TB patients in Southern Africa. Targeted interventions to alleviate psychological distress, alcohol use, and improve health literacy in newly-diagnosed TB patients could reduce non-adherence to treatment.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Antituberculosos/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Estresse Psicológico/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Consumo de Bebidas Alcoólicas/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Depressão/epidemiologia , Depressão/psicologia , Feminino , Humanos , Modelos Logísticos , Masculino , Adesão à Medicação/psicologia , Pessoa de Meia-Idade , Análise Multivariada , Fatores Sexuais , África do Sul/epidemiologia , Estresse Psicológico/psicologia , Tanzânia/epidemiologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/psicologia , Zâmbia/epidemiologia , Zimbábue/epidemiologia
17.
JAC Antimicrob Resist ; 6(2): dlae061, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38680604

RESUMO

Background: The overuse and misuse of antimicrobials has worsened the problem of antimicrobial resistance (AMR) globally. This study investigated the AMR profiles of Escherichia coli isolated from clinical and environmental samples in Lusaka, Zambia. Methods: This was a cross-sectional study conducted from February 2023 to June 2023 using 450 samples. VITEK® 2 Compact was used to identify E. coli and perform antimicrobial susceptibility testing. Data analysis was done using WHONET 2022 and SPSS version 25.0. Results: Of the 450 samples, 66.7% (n = 300) were clinical samples, whereas 33.3% (n = 150) were environmental samples. Overall, 47.8% (n = 215) (37.8% clinical and 10% environmental) tested positive for E. coli. Of the 215 E. coli isolates, 66.5% were MDR and 42.8% were ESBL-producers. Most isolates were resistant to ampicillin (81.4%), sulfamethoxazole/trimethoprim (70.7%), ciprofloxacin (67.9%), levofloxacin (64.6%), ceftriaxone (62.3%) and cefuroxime (62%). Intriguingly, E. coli isolates were highly susceptible to amikacin (100%), imipenem (99.5%), nitrofurantoin (89.3%), ceftolozane/tazobactam (82%) and gentamicin (72.1%). Conclusions: This study found a high resistance of E. coli to some antibiotics that are commonly used in humans. The isolation of MDR and ESBL-producing E. coli is a public health concern and requires urgent action. Therefore, there is a need to instigate and strengthen interventional strategies including antimicrobial stewardship programmes to combat AMR in Zambia.

18.
Antibiotics (Basel) ; 13(10)2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39452217

RESUMO

BACKGROUND: Extended-spectrum ß-lactamases (ESBL) in Escherichia coli are a serious concern due to their role in developing multidrug resistance (MDR) and difficult-to-treat infections. OBJECTIVE: This study aimed to identify ESBL-carrying E. coli strains from both clinical and environmental sources in Lusaka District, Zambia. METHODS: This cross-sectional study included 58 ESBL-producing E. coli strains from hospital inpatients, outpatients, and non-hospital environments. Antimicrobial susceptibility was assessed using the Kirby-Bauer disk diffusion method and the VITEK® 2 Compact System, while genotypic analyses utilised the Illumina NextSeq 2000 sequencing platform. RESULTS: Among the strains isolated strains, phylogroup B2 was the most common, with resistant MLST sequence types including ST131, ST167, ST156, and ST69. ESBL genes such as blaTEM-1B, blaCTX-M,blaOXA-1, blaNDM-5, and blaCMY were identified, with ST131 and ST410 being the most common. ST131 exhibited a high prevalence of blaCTX-M-15 and resistance to fluoroquinolones. Clinical and environmental isolates carried blaNDM-5 (3.4%), with clinical isolates showing a higher risk of carbapenemase resistance genes and the frequent occurrence of blaCTX-M and blaTEM variants, especially blaCTX-M-15 in ST131. CONCLUSIONS: This study underscores the public health risks of blaCTX-M-15- and blaNDM-5-carrying E. coli. The strengthening antimicrobial stewardship programmes and the continuous surveillance of AMR in clinical and environmental settings are recommended to mitigate the spread of resistant pathogens.

19.
PLoS One ; 19(7): e0306131, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38954717

RESUMO

INTRODUCTION: A number of seroprevalence studies in Zambia document the extent of spread of acute SARS-CoV-2 infection, yet knowledge gaps still exist on symptoms and conditions that continue or develop after acute COVID-19 (long COVID). This is an important gap given the estimated prevalence of long COVID in other African countries. We assessed factors associated with long COVID at the initial visit to a post-acute COVID-19 (PAC-19) clinic and longitudinally among a cohort of patients with ≥2 review visits. METHODS: We implemented a cross-sectional and longitudinal analysis of PAC-19 clinic patients from Aug-2020 to Jan-2023. The study outcome was long COVID; defined as the presence of new, relapsing, or persistent COVID-19 symptoms that interfere with the ability to function at home or work. Explanatory variables were demographic and clinical characteristics of patients which included sex, age group, presence of new onset medical conditions, presence of pre-existing comorbidities, vaccination status and acute COVID-19 episode details. We fitted logistic and mixed effects regression models to assess for associated factors and considered statistical significance at p<0.05. RESULTS: Out of a total 1,359 PAC-19 clinic patients in the cross-sectional analysis, 548 (40.3%) patients with ≥2 PAC-19 clinic visits were in the longitudinal analysis. Patients' median age was 53 (interquartile range [IQR]: 41-63) years, 919 (67.6%) were hospitalized for acute COVID-19, and of whom 686 (74.6%) had severe acute COVID-19. Overall, 377 (27.7%) PAC-19 clinic patients had long COVID. Patients with hospital length of stay ≥15 days (adjusted odds ratio [aOR]: 5.37; 95% confidence interval [95% CI]: 2.99-10.0), severe acute COVID-19 (aOR: 3.22; 95% CI: 1.68-6.73), and comorbidities (aOR:1.50; 95% CI: 1.02-2.21) had significantly higher chance of long COVID. Longitudinally, long COVID prevalence significantly (p<0.001) declined from 75.4% at the initial PAC-19 visit to 26.0% by the final visit. The median follow-up time was 7 (IQR: 4-12) weeks. CONCLUSION: Factors associated with long COVID in Zambia were consistent both cross-sectionally at the initial visit to PAC-19 clinics and longitudinally across subsequent review visits. This highlights the importance of ongoing monitoring and tailored interventions for patients with comorbidities and severe COVID-19 to mitigate the long-term impacts of COVID-19.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Zâmbia/epidemiologia , COVID-19/epidemiologia , Masculino , Feminino , Estudos Transversais , Estudos Longitudinais , Adulto , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Síndrome de COVID-19 Pós-Aguda , Idoso , Adulto Jovem , Adolescente , Comorbidade , Fatores de Risco , Prevalência
20.
Int J Infect Dis ; 148: 107248, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39341421

RESUMO

OBJECTIVES: The diagnostic gaps for childhood tuberculosis (TB) remain considerable in settings with high TB incidence and resource constraints. We established and evaluated the performance of a scoring system based on a combination of serological tests and T-cell cytokine release assays, chosen for their ability to detect immune responses indicative of TB, in a context of high prevalence of pediatric HIV infection. METHODS: We enrolled 628 consecutive children aged ≤15 years, admitted for TB suspicion. Multiple cytokine levels in QuantiFERON Gold In-Tube supernatants and antigen 85B (Ag85B) antibodies were assessed in children who tested positive with either Xpert TB or mycobacterial culture. The results were compared with those of control children. RESULTS: Among the biomarkers most strongly associated with TB, random forest classification analysis selected Ag85B antibodies, interleukin-2/interferon-γ ratio, and monokine induced by interferon-γ for the scoring system. The receiver operating characteristic curve derived from our scoring system showed an area under the curve of 0.95 (0.91-0.99), yielding 91% sensitivity and 88% specificity. The internal bootstrap validation gave the following 95% confidence intervals for the score performance: sensitivity 71%-97% and specificity 79%-99%. CONCLUSIONS: This study suggests that supplementing the QuantiFERON assay with a combination of serological and T-cell markers could enhance childhood TB screening regardless of HIV status and age. Further validation among the target population is necessary to confirm the performance of this scoring system.


Assuntos
Citocinas , Tuberculose , Humanos , Criança , Masculino , Pré-Escolar , Feminino , Citocinas/sangue , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/sangue , Tuberculose/imunologia , Lactente , Zâmbia/epidemiologia , Adolescente , Sensibilidade e Especificidade , Biomarcadores/sangue , Mycobacterium tuberculosis/imunologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Testes de Liberação de Interferon-gama/métodos , Curva ROC , Antígenos de Bactérias/imunologia , Testes Sorológicos/métodos , Anticorpos Antibacterianos/sangue , Interferon gama/sangue
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa