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1.
BMC Public Health ; 22(1): 1772, 2022 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123653

RESUMO

BACKGROUND: Ventilation rates are a key determinant of the transmission rate of Mycobacterium tuberculosis and other airborne infections. Targeting infection prevention and control (IPC) interventions at locations where ventilation rates are low and occupancy high could be a highly effective intervention strategy. Despite this, few data are available on ventilation rates and occupancy in congregate locations in high tuberculosis burden settings. METHODS: We collected carbon dioxide concentration and occupancy data in congregate locations and public transport on 88 occasions, in Cape Town, South Africa. For each location, we estimated ventilation rates and the relative rate of infection, accounting for ventilation rates and occupancy. RESULTS: We show that the estimated potential transmission rate in congregate settings and public transport varies greatly between different settings. Overall, in the community we studied, estimated infection risk was higher in minibus taxis and trains than in salons, bars, and shops. Despite good levels of ventilation, infection risk could be high in the clinic due to high occupancy levels. CONCLUSION: Public transport in particular may be promising targets for infection prevention and control interventions in this setting, both to reduce Mtb transmission, but also to reduce the transmission of other airborne pathogens such as measles and SARS-CoV-2.


Assuntos
COVID-19 , Mycobacterium tuberculosis , Tuberculose dos Linfonodos , COVID-19/epidemiologia , Dióxido de Carbono/análise , Humanos , SARS-CoV-2 , África do Sul/epidemiologia
2.
J Intern Med ; 288(6): 661-681, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33128834

RESUMO

Tuberculosis remains a major source of morbidity and mortality worldwide, with 10 million cases and 1.5 million deaths in 2018. Achieving 'End TB' prevention and care goals by 2035 will likely require a new tuberculosis vaccine. The tuberculosis vaccine development pipeline has seen encouraging progress; however, questions around their population impact and implementation remain. Mathematical modelling investigates these questions to inform vaccine development and deployment strategies. We provide an update on the current vaccine development pipeline, and a systematic literature review of mathematical modelling of the epidemiological impact of new tuberculosis vaccines. Fourteen prophylactic tuberculosis vaccine candidates are currently in clinical trials. Two candidates have shown promise in phase II proof-of-concept efficacy trials: M72/AS01E demonstrated 49.7% (95% CI; 2.1, 74.2) protection against tuberculosis disease, and BCG revaccination demonstrated 45.4% (95% CI; 6.4, 68.1) protection against sustained Mycobacterium tuberculosis infection. Since the last modelling review, new studies have investigated the epidemiological impact of differential vaccine characteristics, age targeting and spatial/risk group targeting. Critical research priorities for M72/AS01E include completing the currently in-design trial, powered to improve the precision of efficacy estimates, include uninfected populations and further assess safety and immunogenicity in HIV-infected people. For BCG revaccination, the priority is completing the ongoing confirmation of efficacy trial. Critical modelling gaps remain on the full value proposition of vaccines, comparisons with other interventions and more realistic implementation strategies. Using carefully designed trials and modelling, we must prepare for success, to ensure that new vaccines will be promptly received by those most in need.


Assuntos
Desenvolvimento de Medicamentos , Vacinas contra a Tuberculose , Tuberculose/prevenção & controle , Vacina BCG , Ensaios Clínicos como Assunto , Humanos , Imunização Secundária , Modelos Teóricos , Revisões Sistemáticas como Assunto , Vacinas contra a Tuberculose/classificação , Vacinas contra a Tuberculose/imunologia
3.
BMC Med ; 14: 56, 2016 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-27012808

RESUMO

Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, predominantly affecting low- and middle-income countries (LMICs), where resources are limited. As such, countries need to be able to choose the most efficient interventions for their respective setting. Mathematical models can be valuable tools to inform rational policy decisions and improve resource allocation, but are often unavailable or inaccessible for LMICs, particularly in TB. We developed TIME Impact, a user-friendly TB model that enables local capacity building and strengthens country-specific policy discussions to inform support funding applications at the (sub-)national level (e.g. Ministry of Finance) or to international donors (e.g. the Global Fund to Fight AIDS, Tuberculosis and Malaria).TIME Impact is an epidemiological transmission model nested in TIME, a set of TB modelling tools available for free download within the widely-used Spectrum software. The TIME Impact model reflects key aspects of the natural history of TB, with additional structure for HIV/ART, drug resistance, treatment history and age. TIME Impact enables national TB programmes (NTPs) and other TB policymakers to better understand their own TB epidemic, plan their response, apply for funding and evaluate the implementation of the response.The explicit aim of TIME Impact's user-friendly interface is to enable training of local and international TB experts towards independent use. During application of TIME Impact, close involvement of the NTPs and other local partners also builds critical understanding of the modelling methods, assumptions and limitations inherent to modelling. This is essential to generate broad country-level ownership of the modelling data inputs and results. In turn, it stimulates discussions and a review of the current evidence and assumptions, strengthening the decision-making process in general.TIME Impact has been effectively applied in a variety of settings. In South Africa, it informed the first South African HIV and TB Investment Cases and successfully leveraged additional resources from the National Treasury at a time of austerity. In Ghana, a long-term TIME model-centred interaction with the NTP provided new insights into the local epidemiology and guided resource allocation decisions to improve impact.


Assuntos
Política de Saúde , Modelos Teóricos , Formulação de Políticas , Tuberculose/epidemiologia , Recursos em Saúde , Humanos , África do Sul/epidemiologia
4.
BMC Infect Dis ; 16(1): 726, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27905897

RESUMO

BACKGROUND: Despite improvements in treatment success rates for tuberculosis (TB), current six-month regimen duration remains a challenge for many National TB Programmes, health systems, and patients. There is increasing investment in the development of shortened regimens with a number of candidates in phase 3 trials. METHODS: We developed an individual-based decision analytic model to assess the cost-effectiveness of a hypothetical four-month regimen for first-line treatment of TB, assuming non-inferiority to current regimens of six-month duration. The model was populated using extensive, empirically-collected data to estimate the economic impact on both health systems and patients of regimen shortening for first-line TB treatment in South Africa, Brazil, Bangladesh, and Tanzania. We explicitly considered 'real world' constraints such as sub-optimal guideline adherence. RESULTS: From a societal perspective, a shortened regimen, priced at USD1 per day, could be a cost-saving option in South Africa, Brazil, and Tanzania, but would not be cost-effective in Bangladesh when compared to one gross domestic product (GDP) per capita. Incorporating 'real world' constraints reduces cost-effectiveness. Patient-incurred costs could be reduced in all settings. From a health service perspective, increased drug costs need to be balanced against decreased delivery costs. The new regimen would remain a cost-effective option, when compared to each countries' GDP per capita, even if new drugs cost up to USD7.5 and USD53.8 per day in South Africa and Brazil; this threshold was above USD1 in Tanzania and under USD1 in Bangladesh. CONCLUSION: Reducing the duration of first-line TB treatment has the potential for substantial economic gains from a patient perspective. The potential economic gains for health services may also be important, but will be context-specific and dependent on the appropriate pricing of any new regimen.


Assuntos
Antituberculosos/economia , Tuberculose/tratamento farmacológico , Tuberculose/economia , Bangladesh , Brasil , Análise Custo-Benefício , Atenção à Saúde/economia , Custos de Medicamentos , Custos de Cuidados de Saúde , Gastos em Saúde , Serviços de Saúde/economia , Humanos , Modelos Teóricos , África do Sul , Tanzânia , Resultado do Tratamento
5.
Ann Bot ; 110(8): 1559-72, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22989463

RESUMO

BACKGROUND AND AIMS: Legumes overcome nitrogen limitations by entering into a mutualistic symbiosis with N(2)-fixing bacteria (rhizobia). Fully compatible associations (effective) between Trifolium spp. and Rhizobium leguminosarum bv. trifolii result from successful recognition of symbiotic partners in the rhizosphere, root hair infection and the formation of nodules where N(2)-fixing bacteroids reside. Poorly compatible associations can result in root nodule formation with minimal (sub-optimal) or no (ineffective) N(2)-fixation. Despite the abundance and persistence of strains in agricultural soils which are poorly compatible with the commercially grown clover species, little is known of how and why they fail symbiotically. The aims of this research were to determine the morphological aberrations occurring in sub-optimal and ineffective clover nodules and to determine whether reduced bacteroid numbers or reduced N(2)-fixing activity is the main cause for the Sub-optimal phenotype. METHODS: Symbiotic effectiveness of four Trifolium hosts with each of four R. leguminosarum bv. trifolii strains was assessed by analysis of plant yields and nitrogen content; nodule yields, abundance, morphology and internal structure; and bacteroid cytology, quantity and activity. KEY RESULTS: Effective nodules (Nodule Function 83-100 %) contained four developmental zones and N(2)-fixing bacteroids. In contrast, Sub-optimal nodules of the same age (Nodule Function 24-57 %) carried prematurely senescing bacteroids and a small bacteroid pool resulting in reduced shoot N. Ineffective-differentiated nodules carried bacteroids aborted at stage 2 or 3 in differentiation. In contrast, bacteroids were not observed in Ineffective-vegetative nodules despite the presence of bacteria within infection threads. CONCLUSIONS: Three major responses to N(2)-fixation incompatibility between Trifolium spp. and R. l. trifolii strains were found: failed bacterial endocytosis from infection threads into plant cortical cells, bacteroid differentiation aborted prematurely, and a reduced pool of functional bacteroids which underwent premature senescence. We discuss possible underlying genetic causes of these developmental abnormalities and consider impacts on N(2)-fixation of clovers.


Assuntos
Rhizobium leguminosarum/fisiologia , Nódulos Radiculares de Plantas/crescimento & desenvolvimento , Simbiose , Trifolium/fisiologia , Genótipo , Fixação de Nitrogênio , Fenótipo , Filogenia , Rhizobium leguminosarum/citologia , Rhizobium leguminosarum/genética , Rhizobium leguminosarum/crescimento & desenvolvimento , Nódulos Radiculares de Plantas/citologia , Nódulos Radiculares de Plantas/fisiologia , Trifolium/citologia , Trifolium/crescimento & desenvolvimento , Trifolium/microbiologia
6.
Epidemiol Psychiatr Sci ; 31: e39, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35674122

RESUMO

AIMS: As refugees and asylum seekers are at high risk of developing mental disorders, we assessed the effectiveness of Self-Help Plus (SH + ), a psychological intervention developed by the World Health Organization, in reducing the risk of developing any mental disorders at 12-month follow-up in refugees and asylum seekers resettled in Western Europe. METHODS: Refugees and asylum seekers with psychological distress (General Health Questionnaire-12 ⩾ 3) but without a mental disorder according to the Mini International Neuropsychiatric Interview (M.I.N.I.) were randomised to either SH + or enhanced treatment as usual (ETAU). The frequency of mental disorders at 12 months was measured with the M.I.N.I., while secondary outcomes included self-identified problems, psychological symptoms and other outcomes. RESULTS: Of 459 participants randomly assigned to SH + or ETAU, 246 accepted to be interviewed at 12 months. No difference in the frequency of any mental disorders was found (relative risk [RR] = 0.841; 95% confidence interval [CI] 0.389-1.819; p-value = 0.659). In the per protocol (PP) population, that is in participants attending at least three group-based sessions, SH + almost halved the frequency of mental disorders at 12 months compared to ETAU, however so few participants and events contributed to this analysis that it yielded a non-significant result (RR = 0.528; 95% CI 0.180-1.544; p-value = 0.230). SH + was associated with improvements at 12 months in psychological distress (p-value = 0.004), depressive symptoms (p-value = 0.011) and wellbeing (p-value = 0.001). CONCLUSIONS: The present study failed to show any long-term preventative effect of SH + in refugees and asylum seekers resettled in Western European countries. Analysis of the PP population and of secondary outcomes provided signals of a potential effect of SH + in the long-term, which would suggest the value of exploring the effects of booster sessions and strategies to increase SH + adherence.


Assuntos
Transtornos Mentais , Angústia Psicológica , Refugiados , Transtornos de Estresse Pós-Traumáticos , Europa (Continente) , Comportamentos Relacionados com a Saúde , Humanos , Transtornos Mentais/epidemiologia , Refugiados/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia
7.
Epidemics ; 41: 100648, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36343495

RESUMO

OBJECTIVES: Disease transmission models are used in impact assessment and economic evaluations of infectious disease prevention and treatment strategies, prominently so in the COVID-19 response. These models rarely consider dimensions of equity relating to the differential health burden between individuals and groups. We describe concepts and approaches which are useful when considering equity in the priority setting process, and outline the technical choices concerning model structure, outputs, and data requirements needed to use transmission models in analyses of health equity. METHODS: We reviewed the literature on equity concepts and approaches to their application in economic evaluation and undertook a technical consultation on how equity can be incorporated in priority setting for infectious disease control. The technical consultation brought together health economists with an interest in equity-informative economic evaluation, ethicists specialising in public health, mathematical modellers from various disease backgrounds, and representatives of global health funding and technical assistance organisations, to formulate key areas of consensus and recommendations. RESULTS: We provide a series of recommendations for applying the Reference Case for Economic Evaluation in Global Health to infectious disease interventions, comprising guidance on 1) the specification of equity concepts; 2) choice of evaluation framework; 3) model structure; and 4) data needs. We present available conceptual and analytical choices, for example how correlation between different equity- and disease-relevant strata should be considered dependent on available data, and outline how assumptions and data limitations can be reported transparently by noting key factors for consideration. CONCLUSIONS: Current developments in economic evaluations in global health provide a wide range of methodologies to incorporate equity into economic evaluations. Those employing infectious disease models need to use these frameworks more in priority setting to accurately represent health inequities. We provide guidance on the technical approaches to support this goal and ultimately, to achieve more equitable health policies.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Política de Saúde , Saúde Pública , Análise Custo-Benefício
8.
Int J Tuberc Lung Dis ; 25(6): 436-446, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34049605

RESUMO

Early in the COVID-19 pandemic, models predicted hundreds of thousands of additional TB deaths as a result of health service disruption. To date, empirical evidence on the effects of COVID-19 on TB outcomes has been limited. Here we summarise the evidence available at a country level, identifying broad mechanisms by which COVID-19 may modify TB burden and mitigation efforts. From the data, it is clear that there have been substantial disruptions to TB health services and an increase in vulnerability to TB. Evidence for changes in Mycobacterium tuberculosis transmission is limited, and it remains unclear how the resources required and available for the TB response have changed. To advocate for additional funding to mitigate the impact of COVID-19 on the global TB burden, and to efficiently allocate resources for the TB response, requires a significant improvement in the TB data available.


Assuntos
COVID-19 , Tuberculose , Humanos , Mycobacterium tuberculosis , Pandemias , SARS-CoV-2 , Tuberculose/epidemiologia
9.
Int J Tuberc Lung Dis ; 25(12): 1001-1005, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34886930

RESUMO

BACKGROUND: Tests that identify individuals at greatest risk of TB will allow more efficient targeting of preventive therapy. The WHO target product profile for such tests defines optimal sensitivity of 90% and minimum sensitivity of 75% for predicting incident TB. The CORTIS (Correlate of Risk Targeted Intervention Study) evaluated a blood transcriptomic signature (RISK11) for predicting incident TB in a high transmission setting. RISK11 is able to predict TB disease progression but optimal prognostic performance was limited to a 6-month horizon.METHODS: Using a mathematical model, we estimated how subsequent Mycobacterium tuberculosis (MTB) infection may have contributed to the decline in sensitivity of RISK11. We calculated the effect at different RISK11 thresholds (60% and 26%) and for different assumptions about the risk of MTB infection.RESULTS: Modelled sensitivity over 15 months, excluding new infection, was 28.7% (95% CI 12.3-74.1) compared to 25.0% (95% CI 12.7-45.9) observed in the trial. Modelled sensitivity exceeded the minimum criteria (>75%) over a 9-month horizon at the 60% threshold and over 12 months at the 26% threshold.CONCLUSIONS: The effect of new infection on prognostic signature performance is likely to be small. Signatures such as RISK11 may be most useful in individuals, such as household contacts, where probable time of infection is known.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Progressão da Doença , Humanos , Mycobacterium tuberculosis/genética , Prognóstico , Transcriptoma , Tuberculose/diagnóstico , Tuberculose/epidemiologia
10.
Int J Tuberc Lung Dis ; 25(8): 614-619, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34330345

RESUMO

Mathematical modelling is increasingly used to inform budgeting and strategic decision-making by national TB programmes. Despite the importance of these decisions, there is currently no mechanism to review and confirm the appropriateness of modelling analyses. We have developed a benchmarking, reporting, and review (BRR) approach and accompanying tools to allow constructive review of country-level TB modelling applications. This approach has been piloted in five modelling applications and the results of this study have been used to revise and finalise the approach. The BRR approach consists of 1) quantitative benchmarks against which model assumptions and results can be compared, 2) standardised reporting templates and review criteria, and 3) a multi-stage review process providing feedback to modellers during the application, as well as a summary evaluation after completion. During the pilot, use of the tools prompted important changes in the approaches taken to modelling. The pilot also identified issues beyond the scope of a review mechanism, such as a lack of empirical evidence and capacity constraints. This approach provides independent evaluation of the appropriateness of modelling decisions during the course of an application, allowing meaningful changes to be made before results are used to inform decision-making. The use of these tools can improve the quality and transparency of country-level TB modelling applications.


Assuntos
Benchmarking , Modelos Teóricos , Tuberculose , Humanos , Tuberculose/epidemiologia
11.
Trop Med Int Health ; 15(5): 554-66, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20345559

RESUMO

OBJECTIVE: To compare adolescent risk factors for HIV infection in two countries with high adolescent HIV prevalence and two lower prevalence countries with the aim of identifying risk factors that may help explain differences in adolescent HIV prevalence. METHODS: Data were available from two nationally representative surveys (South Africa, Zimbabwe), two behavioural intervention trials (Tanzania, Zimbabwe) and one population-based cohort (Uganda). Data on variables known or postulated to be risk factors for HIV infection were compared. RESULTS: Few risk behaviours were markedly more common in the high HIV prevalence populations. Risk factors more common in high HIV prevalence settings were genital ulcers and discharge, and women were more likely to report older male partners. DISCUSSION: Age mixing may be an important determinate of HIV prevalence in adolescents. Potential reasons for the general lack of association between other adolescent risk factors and adolescent HIV prevalence include adult HIV prevalence, misreported behaviour, different survey methods and other unmeasured adolescent behaviours. If adult factors dominate adolescent HIV risk, it would help explain the failure of behavioural interventions targeted at adolescents and suggests future interventions should include adults.


Assuntos
Infecções por HIV/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Comportamento Sexual/psicologia , Adolescente , Adulto , África Subsaariana/epidemiologia , Fatores Etários , Países em Desenvolvimento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Comportamento Sexual/estatística & dados numéricos , Estatística como Assunto , Adulto Jovem
12.
Int J Tuberc Lung Dis ; 24(4): 403-408, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32317064

RESUMO

BACKGROUND: In South Africa, it is generally estimated that only 0.5-0.6% of people's contacts occur in clinics. Both people with infectious tuberculosis and people with increased susceptibility to disease progression may spend more time in clinics, however, increasing the importance of clinic-based transmission to overall disease incidence.METHODS: We developed an illustrative mathematical model of Mycobacterium tuberculosis transmission in clinics and other settings. We assumed that 1% of contact time occurs in clinics. We varied the ratio of clinic contact time of human immunodeficiency virus (HIV) positive people compared to HIV-negative people, and of people with infectious TB compared to people without TB, while keeping the overall proportion of contact time occurring in clinics, and each person's total contact time, constant.RESULTS: With clinic contact rates respectively 10 and 5 times higher in HIV-positive people and people with TB, 10.7% (plausible range 8.5-13.4%) of TB resulted from transmission in clinics. With contact rates in HIV-positive people and people with TB respectively 5 and 2 times higher, 5.3% (plausible range 4.3-6.3%) of all TB was due to transmission in clinics.CONCLUSION: The small amount of contact time that generally occurs in clinics may greatly underestimate their contribution to TB disease in high TB-HIV burden settings.


Assuntos
Infecções por HIV , Soropositividade para HIV , Mycobacterium tuberculosis , Tuberculose , Infecções por HIV/epidemiologia , Humanos , África do Sul/epidemiologia , Tuberculose/diagnóstico , Tuberculose/epidemiologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-31143467

RESUMO

BACKGROUND: Psychiatric diagnostic manuals recognise the importance of local expressions of distress in culturally diverse settings [i.e. idioms/cultural concepts of distress (CCDs)], yet there is a lack of consensus on how these should be incorporated into mental health related research. AIMS: To perform a narrative synthesis and critical review of research exploring how idioms/CCDs have been integrated into assessment measures and interventions. METHOD: A systematic review was conducted in accordance with PRISMA guidelines. An adapted version of the COSMIN checklist was used to assess the quality of the linguistic translation of the idioms/CCDs. RESULTS: Twenty-nine papers were included in the final review. Primary qualitative research was the most common method of gathering information about idioms/CCDs. The majority of studies described integrating idioms/CCDs into assessment measures as opposed to interventions. Some studies used information relating to idioms/CCDs to develop novel assessment measures, while others adapted pre-existing assessment measures. The measures generated moderate to high levels of validity. Information relating to the linguistic translation conducted in the completion of the studies tended to be inadequately reported. CONCLUSIONS: Integrating information about idioms/CCDs into assessment measures can enhance the validity of these assessments. Allocating greater research attention to idioms/CCDs can also promote more equitable exchanges of knowledge about mental health and wellbeing between the Global North and the Global South.

14.
Int J Tuberc Lung Dis ; 23(4): 387-395, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31053179

RESUMO

Mathematical modelling is commonly used to evaluate policy options for tuberculosis (TB) control in high-burden countries. Although major policy and funding decisions are made based on these analyses, there is concern about the variability of results produced using modelled policy analyses. We discuss new guidance for country-level TB policy modelling. The guidance was developed by the TB Modelling and Analysis Consortium in collaboration with the World Health Organization Global TB Programme, with input from a range of TB stakeholders (funders, modelling groups, country TB programme staff and subject matter experts). The guidance describes principles for country-level TB modelling, as well as good practices for operationalising the principles. The principles cover technical concerns such as model design, parameterisation and validation, as well as approaches for incorporating modelling into country-led policy making and budgeting. For modellers, this guidance suggests approaches to improve the quality and relevance of modelling undertaken to support country-level planning. For non-modellers, this guidance describes considerations for engaging modelling technical assistance, contributing to a modelling exercise and reviewing the results of modelled analyses. If routinely adopted, this guidance should improve the reliability, transparency and usefulness of modelling for country-level TB policy making. However, this guidance will not address all challenges facing modelling, and ongoing work is needed to improve the empirical evidence base for TB policy evaluation and develop stronger mechanisms for validating models. Increasing country ownership of the modelling process remains a challenge, requiring sustained engagement and capacity building.


Assuntos
Política de Saúde , Modelos Teóricos , Tuberculose/prevenção & controle , Fortalecimento Institucional , Tomada de Decisões , Humanos , Formulação de Políticas , Reprodutibilidade dos Testes , Tuberculose/epidemiologia
15.
J Exp Bot ; 59(11): 2945-54, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18617505

RESUMO

The structure and transport properties of pit membranes at the interface between the metaxylem and xylem parenchyma cells and the possible role of these pit membranes in solute transfer to the phloem were investigated. Electron microscopy revealed a fibrillar, almost tubular matrix within the pit membrane structure between the xylem vessels and xylem parenchyma of leaf blade bundles in rice (Oryza sativa). These pits are involved primarily with regulating water flux to the surrounding xylem parenchyma cells. Vascular parenchyma cells contain large mitochondrial populations, numerous dictyosomes, endomembrane complexes, and vesicles in close proximity to the pit membrane. Taken collectively, this suggests that endocytosis may occur at this interface. A weak solution of 5,6-carboxyfluorescein diacetate (5,6-CFDA) was applied to cut ends of leaves and, after a minimum of 30 min, the distribution of the fluorescent cleavage product, 5,6-carboxyfluorescein (5,6-CF), was observed using confocal microscopy. Cleavage of 5,6-CFDA occurred within the xylem parenchyma cells, and the non-polar 5,6-CF was then symplasmically transported to other parenchyma elements and ultimately, via numerous pore plasmodesmata, to adjacent thick-walled sieve tubes. Application of Lucifer Yellow, and, separately, Texas Red-labelled dextran (10 kDa) to the transpiration stream, confirmed that these membrane-impermeant probes could only have been offloaded from the xylem via the xylem vessel-xylem parenchyma pit membranes, suggesting endocytotic transmembrane transfer of these membrane-impermeant fluorophores. Accumulation within the thick-walled sieve tubes, but not in thin-walled sieve tubes, confirms the presence of a symplasmic phloem loading pathway, via pore plasmodesmata between xylem parenchyma and thick-walled sieve tubes, but not thin-walled sieve tubes.


Assuntos
Endocitose , Floema/fisiologia , Folhas de Planta/fisiologia , Poaceae/fisiologia , Xilema/fisiologia , Fluoresceínas/metabolismo , Microscopia Eletrônica de Transmissão , Floema/ultraestrutura , Folhas de Planta/ultraestrutura , Poaceae/ultraestrutura , Xilema/ultraestrutura
16.
Sex Transm Infect ; 84(7): 528-34, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18708485

RESUMO

OBJECTIVES: Syndromic sexually transmitted infection (STI) treatment remains a cost-saving HIV prevention intervention in many countries in Africa. We estimate the effectiveness of syndromic treatment for curable STIs in rural KwaZulu-Natal, South Africa, and the trend in STI prevalences before and after the introduction of syndromic treatment in 1995. METHODS: Data were available from various clinical studies, surveys of public and private health providers, the general population and women attending antenatal, family planning and child immunisation clinics in rural northern KwaZulu-Natal between 1987 and 2004. Overall effectiveness was defined as the estimated proportion of the annual number of symptomatic curable STI episodes cured by syndromic treatment based on separate estimates for six curable STI aetiologies by gender. RESULTS: Median overall effectiveness was 13.1% (95% CI 8.9 to 17.8%) of symptomatic curable STI episodes cured. Effectiveness increased to 25.0% (95% CI 17.3 to 33.8%), 47.6% (95% CI 44.5 to 50.8%) or 14.3% (95% CI 9.9 to 19.4%) if 100% treatment seeking, 100% correct treatment provision or 100% cure were assumed, respectively. Time-trends were difficult to assess formally but there was little evidence of decreasing STI prevalences. Including incurable but treatable herpes simplex virus (HSV)-2 ulcers in the effectiveness calculation would halve the proportion of ulcers cured or correctly treated, but this reduction could be entirely countered by including episodic antiviral treatment in the national guidelines. CONCLUSION: Overall effectiveness of syndromic treatment for curable STIs in rural KwaZulu-Natal remains low and there is little evidence of reduced curable STI prevalences. As syndromic treatment is likely to be a cost-saving HIV prevention intervention in South Africa, innovative strategies are urgently needed to increase rates of treatment seeking and correct treatment provision.


Assuntos
Antibacterianos/uso terapêutico , Infecções Sexualmente Transmissíveis/tratamento farmacológico , Adolescente , Adulto , Assistência Ambulatorial , Medicina de Família e Comunidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Saúde da População Rural , África do Sul , Resultado do Tratamento , Adulto Jovem
17.
Sex Transm Infect ; 84 Suppl 2: ii12-8, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18799486

RESUMO

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection increases acquisition and transmission of HIV, but the results of trials measuring the impact of HSV-2 therapy on HIV genital shedding and HIV acquisition are mixed, and the potential impact of HSV-2 therapy on the incidence of HIV at the population level is unknown. METHODS: The effects of episodic and suppressive HSV-2 therapy were simulated using the individual-level model STDSIM fitted to data from Cotonou, Benin (relatively low HIV prevalence) and Kisumu, Kenya (high HIV prevalence). Clinician- and patient-initiated episodic therapy, started when symptomatic, were assumed to reduce ulcer duration. Suppressive therapy, given regardless of symptoms, was also assumed to reduce ulcer frequency and HSV-2 infectiousness. RESULTS: Clinician-initiated episodic therapy in the general population had almost no effect on the incidence of HIV. The impact of patient-initiated therapy was higher because of earlier treatment initiation, but still low (<5%) unless symptom recognition and treatment-seeking behaviour were very high. Suppressive therapy given to female sex workers (FSW) in Kisumu had little effect on population HIV incidence. In Cotonou, suppressive therapy in FSW with high coverage and long duration reduced population HIV incidence by >20% in the long term. Impact was increased in both cities by also treating a proportion of their clients. Long-term suppressive therapy with high coverage in the general population could reduce HIV incidence by more than 30%. CONCLUSIONS: These results show that HSV-2 therapy could potentially have a population-level impact on the incidence of HIV, especially in more concentrated epidemics. However, a substantial impact requires high coverage and long duration therapy, or very high symptom recognition and treatment-seeking behaviour.


Assuntos
Infecções por HIV/epidemiologia , HIV-1 , Herpes Genital/tratamento farmacológico , Herpes Genital/epidemiologia , Herpesvirus Humano 2 , Adolescente , Adulto , África Subsaariana/epidemiologia , Distribuição por Idade , Feminino , Infecções por HIV/complicações , Infecções por HIV/prevenção & controle , Herpes Genital/complicações , Humanos , Incidência , Masculino , Prevalência
18.
Int J Tuberc Lung Dis ; 22(7): 723-730, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29914597

RESUMO

BACKGROUND: Global tuberculosis (TB) targets were set as part of the World Health Organization's End TB Strategy (2016-2035) and the Sustainable Development Goals (2016-2030). OBJECTIVE: To define and explain the rationale for these targets. DESIGN: Scenarios for plausible reductions in TB deaths and cases were developed using empirical evidence from best-performing countries and modelling of the scale-up of under-used interventions and hypothetical TB vaccines. Results were discussed at consultations in 2012 and 2013. A final proposal was presented to the World Health Assembly in 2014 and unanimously endorsed by all Member States. RESULTS: The 2030 targets are a 90% reduction in TB deaths and 80% reduction in TB incidence compared with 2015 levels. The 2035 targets are for reductions of 95% and 90%, respectively. A third target-that no TB-affected households experience catastrophic costs due to the disease by 2020-was also agreed. CONCLUSION: The global TB targets and milestones set for the period 2016-2035 are ambitious. Achieving them requires concerted action on several fronts, but two things are fundamental: 1) progress towards universal health coverage to ensure that everyone with TB can access high-quality treatment; and 2) substantial investment in research and development for new tools to prevent TB disease among the approximately 1.7 billion people infected.


Assuntos
Saúde Global , Desenvolvimento Sustentável , Tuberculose/prevenção & controle , Humanos , Tuberculose/epidemiologia , Tuberculose/mortalidade , Vacinas contra a Tuberculose/administração & dosagem , Cobertura Universal do Seguro de Saúde , Organização Mundial da Saúde
19.
Artigo em Inglês | MEDLINE | ID: mdl-30128161

RESUMO

BACKGROUND: In this period of unprecedented levels of displacement, scalable interventions are needed to address mental health concerns of forced migrants in low-resource settings. This paper describes the adaptation and piloting of a guided, multi-media, self-help intervention, Self-Help Plus (SH+), which was developed to reduce psychological distress in large groups of people affected by adversity. METHODS: Using a phased approach that included community consultations, cognitive interviewing, facilitator training, pilot implementation, and a qualitative process evaluation, we adapted SH+ for use among South Sudanese refugees in a refugee settlement in northern Uganda. RESULTS: The SH+ materials, including audio-recorded sessions and an accompanying illustrated manual, were translated into Juba Arabic. Cognitive interviewing primarily resulted in adaptations to language with some minor adaptations to content. Facilitator training and supervision led to further suggested changes to delivery methods. An uncontrolled pilot study (n = 65) identified changes in the expected direction on measures of psychological distress, functional impairment, depression, wellbeing, and psychological flexibility. The process evaluation resulted in further adaptations to intervention materials and the decision to focus future effectiveness evaluations of the intervention in its current form on South Sudanese female refugees. CONCLUSIONS: We found that this potentially scalable, guided self-help intervention could be adapted for and feasibly implemented among female South Sudanese refugees in northern Uganda. These findings lay the groundwork for a future rigorous evaluation of SH+ in this context.

20.
Int J Tuberc Lung Dis ; 22(6): 606-613, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29862943

RESUMO

BACKGROUND: National Tuberculosis Programmes (NTPs) require specialist input to support the development of policy and practice informed by evidence, typically against tight deadlines. OBJECTIVE: To describe lessons learned from establishing a dedicated tuberculosis (TB) think tank to advise the South African NTP on TB policy. INTERVENTION AND EVALUATION METHODS: A national TB think tank was established to advise the NTP in support of evidence-informed policy. Support was provided for activities, including meetings, modelling and regular telephone calls, with a wider network of unpaid expert advisers under an executive committee and working groups. Intervention evaluation used desktop analysis of documentary evidence, interviews and direct observation. RESULTS: The TB Think Tank evolved over time to acquire three key roles: an 'institution', a 'policy dialogue forum' and an 'interface'. Although enthusiasm was high, motivating participation among the NTP and external experts proved challenging. Motivation of working groups was most successful when aligned to a specific need for NTP decision making. Despite challenges, the TB Think Tank contributed to South Africa's first ever TB and human immunodeficiency virus (HIV) investment case, and the decision to create South Africa's first ever ring-fenced grant for TB. The TB Think Tank also assisted the NTP in formulating strategy to accelerate progress towards reaching World Health Organization targets. DISCUSSION: With partners, the TB Think Tank achieved major successes in supporting evidence-informed decision making, and garnered increased funding for TB in South Africa. Identifying ways to increase the involvement of NTP staff and other experts, and keeping the scope of the Think Tank well defined, could facilitate greater impact. Think tank initiatives could be replicated in other settings to support evidence-informed policy making.


Assuntos
Política de Saúde , Programas Nacionais de Saúde/organização & administração , Formulação de Políticas , Tuberculose/prevenção & controle , Tomada de Decisões , Medicina Baseada em Evidências , Infecções por HIV/epidemiologia , Humanos , África do Sul , Organização Mundial da Saúde
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