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BACKGROUND: Each year more than 200,000 pregnant people become sick with TB, but little is known about how to optimize their diagnosis and therapy. Although there is a need for further research in this population, it is important to recognize that much can be done to improve the services they currently receive.METHODS: Following a systematic review of the literature and the input of a global team of health professionals, a series of best practices for the diagnosis, prevention and treatment of TB during pregnancy were developed.RESULTS: Best practices were developed for each of the following areas: 1) screening and diagnosis; 2) reproductive health services and family planning; 3) treatment of drug-susceptible TB; 4) treatment of rifampicin-resistant/multidrug-resistant TB; 5) compassionate infection control practices; 6) feeding considerations; 7) counseling and support; 8) treatment of TB infection/TB preventive therapy; and 9) research considerations.CONCLUSION: Effective strategies for the care of pregnant people across the TB spectrum are readily achievable and will greatly improve the lives and health of this under-served population.
Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Gravidez , Feminino , Humanos , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/prevenção & controle , Rifampina , Aconselhamento , Atenção à SaúdeRESUMO
OBJECTIVE: To describe the medical, socio-economic and geographical profiles of patients with rifampicin-resistant TB (RR-TB) and the implications for the provision of patient-centred care. SETTING: Thirteen districts across three South African provinces. DESIGN: This descriptive study examined laboratory and healthcare facility records of 194 patients diagnosed with RR-TB in the third quarter of 2016. RESULTS: The median age was 35 years; 120/194 (62%) of patients were male. Previous TB treatment was documented in 122/194 (63%) patients and 56/194 (29%) had a record of fluoroquinolone and/or second-line injectable resistance. Of 134 (69%) HIV-positive patients, viral loads were available for 68/134 (51%) (36/68 [53%] had viral loads of >1000 copies/ml) and CD4 counts were available for 92/134 (69%) (20/92 [22%] had CD4 <50 cells/mm3). Patients presented with varying other comorbidities, including hypertension (13/194, 7%) and mental health conditions (11/194, 6%). Of 194 patients, 44 (23%) were reported to be employed. Other socio-economic challenges included substance abuse (17/194, 9%) and ill family members (17/194, 9%). Respectively 13% and 42% of patients were estimated to travel more than 20 km to reach their diagnosing and treatment-initiating healthcare facility. CONCLUSIONS: RR-TB patients had diverse medical and social challenges highlighting the need for integrated, differentiated and patient-centred healthcare to better address specific needs and underlying vulnerabilities of individual patients.
OBJECTIF: Décrire les profils médicaux, socioéconomiques et géographiques des patients atteints de TB résistante à la rifampicine (RR-TB) et les implications en matière de soins centrés sur le patient. CONTEXTE: Treize districts de trois provinces d'Afrique du Sud. MÉTHODE: Cette étude descriptive a analysé les dossiers médicaux et de laboratoire de 194 patients ayant reçu un diagnostic de RR-TB au troisième trimestre de 2016. RÉSULTATS: L'âge médian était de 35 ans ; 120/194 (62%) patients étaient des hommes. Un traitement antituberculeux antérieur était documenté chez 122/194 (63%) patients, et 56/194 (29%) avaient une résistance à la fluoroquinolone et/ou à un agent injectable de deuxième ligne documentée. Sur 134 (69%) patients infectés par le VIH, les charges virales étaient disponibles pour 68/134 (51%) patients (36/68 [53%] avaient des charges virales >1 000 copies/ml) et les taux de CD4 étaient disponibles pour 92/134 (69%) patients (20/92 [22%] avaient un taux de CD4 <50 cellules/mm3). Les patients présentaient diverses autres comorbidités, dont hypertension (13/194, 7%) et troubles psychiques (11/194, 6%). Sur les 194 patients, 44 (23%) avaient un emploi. Les autres problèmes socioéconomiques comprenaient la toxicomanie (17/194, 9%) et le fait d'avoir un membre de sa famille malade (17/194, 9%). Respectivement 13% et 42% des patients parcouraient plus de 20 km pour se rendre à leur centre de diagnostic et au centre de soins responsable de l'instauration du traitement. CONCLUSIONS: Les patients atteints de RR-TB avaient divers problèmes médicaux et sociaux. Ces résultats soulignent le besoin de soins intégrés, différenciés et centrés sur le patient afin de mieux répondre aux besoins spécifiques et aux vulnérabilités sous-jacentes de chaque patient.
RESUMO
Breast milk provides optimal nutrition, and is recommended for neonates and infants. In women with TB, there has been uncertainty about optimal feeding practices due to the risk of transmission to the neonate and the possibility of drug exposure via breast milk. For women who have drug-susceptible TB (DS-TB) who are no longer infectious, it is safe to breastfeed as breast milk does not contain Mycobacterium tuberculosis bacilli and only minor, non-toxic quantities of the drugs pass into breast milk. Most guidelines therefore encourage breastfeeding in women with DS-TB. However, there is uncertainty and guidelines vary regarding women with DS-TB who are still infectious and in women with rifampicin-resistant TB (RR-TB). Although the transmission dynamics of DS- and RR-TB are similar, additional infection control precautions for RR-TB may be necessary until the mother is responding to treatment, as second-line therapy may be less efficacious and preventive therapy is not widely offered to infants. In addition, there are no published data describing the extent to which second-line drugs are secreted into breast milk or subsequent exposure in breastfed infants. The implications of limited information on policy and consequent dilemmas regarding patient care are illustrated in a patient scenario. Areas for future research are suggested.
Assuntos
Aleitamento Materno , Tuberculose , Feminino , Humanos , Lactente , Recém-Nascido , Controle de Infecções , Leite Humano , Tuberculose/tratamento farmacológico , Tuberculose/prevenção & controleRESUMO
Tuberculosis (TB) is a curable disease, but continues to contribute to large numbers of deaths globally and remains among the leading causes of death in South Africa (SA). Evaluating trends in TB deaths and progress towards the End TB strategy target of zero deaths is particularly important to guide policy and practice in SA. TB deaths are complicated by its relationship with HIV, and SA's initial slow response to HIV compounded this. In considering the reported deaths in SA that identify TB as the underlying cause of death, it is important to be aware of potential limitations and sources of bias. We have examined the relationship between TB and HIV and the recording of underlying and contributing causes of death, and clarified the World Health Organization's methodology for estimating TB deaths.
Assuntos
Tuberculose/mortalidade , Causas de Morte , Atestado de Óbito , Documentação , Infecções por HIV/mortalidade , Humanos , África do Sul/epidemiologia , Estatísticas Vitais , Organização Mundial da SaúdeRESUMO
The COVID-19 pandemic and phased nationwide lockdown have impacted negatively on individuals with tuberculosis (TB) and routine TB services. Through a literature review and the perspective of members of a national TB Think Tank task team, we describe the impact of the pandemic and lockdown on TB patients and services as well as the potential long-term setback to TB control in South Africa (SA). Strategies to mitigate risk and impact are explored, together with opportunities to leverage synergies from both diseases to the benefit of the National TB Programme (NTP). With the emergence of COVID-19, activities to address this new pandemic have been prioritised across all sectors. Within the health system, the health workforce and resources have been redirected away from routine services towards the new disease priority. The social determinants of health have deteriorated during the lockdown, potentially increasing progression to TB disease and impacting negatively on people with TB and their households, resulting in additional barriers to accessing TB care, with early reports of a decline in TB testing rates. Fewer TB diagnoses, less attention to adherence and support during TB treatment, poorer treatment outcomes and consequent increased transmission will increase the TB burden and TB-related mortality. People with TB or a history of TB are likely to be vulnerable to COVID-19. Modifications to current treatment practices are suggested to reduce visits to health facilities and minimise the risks of COVID-19 exposure. The COVID-19 pandemic has the potential to negatively impact on TB control in TB-endemic settings such as SA. However, there are COVID-19-related health systems-strengthening developments that may help the NTP mitigate the impact of the pandemic on TB control. By integrating TB case finding into the advanced screening, testing, tracing and monitoring systems established for COVID-19, TB case finding and linkage to care could increase, with many more TB patients starting treatment. Similarly, integrating knowledge and awareness of TB into the increased healthcare worker and community education on infectious respiratory diseases, behavioural practices around infection prevention and control, and cough etiquette, including destigmatisation of mask use, may contribute to reducing TB transmission. However, these potential gains could be overwhelmed by the impact of increasing poverty and other social determinants of health on the burden of TB.
Assuntos
COVID-19/prevenção & controle , Controle de Infecções/métodos , Telemedicina/métodos , Tuberculose Pulmonar/prevenção & controle , Antituberculosos/uso terapêutico , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/organização & administração , Busca de Comunicante , Acessibilidade aos Serviços de Saúde , Humanos , Controle de Infecções/organização & administração , Máscaras , Programas de Rastreamento , Retenção nos Cuidados , SARS-CoV-2 , Determinantes Sociais da Saúde , Estigma Social , África do Sul , Telemedicina/organização & administração , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/prevenção & controle , Tuberculose/transmissão , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/transmissãoRESUMO
SETTING: Thirteen districts in Eastern Cape (EC), KwaZulu-Natal (KZN) and Western Cape (WC) Provinces, South Africa.OBJECTIVE: To pilot a methodology for describing and visualising healthcare journeys among drug-resistant tuberculosis (DR-TB) patients using routine laboratory records.DESIGN: Laboratory records were obtained for 195 patients with laboratory-detected rifampicin-resistant TB (RR-TB) during July-September 2016. Health facility visits identified from these data were plotted to visualise patient healthcare journeys. Data were verified by facility visits.RESULTS: In the 9 months after the index RR-TB sample was collected, patients visited a mean of 2.3 health facilities (95% CI 2.1-2.6), with 9% visiting ≥4 facilities. The median distance travelled by patients from rural areas (116 km, interquartile range [IQR] 50-290) was greater than for urban patients (51 km, IQR 9-140). A median of 21% of patient's time was spent under the care of primary healthcare facilities: this was respectively 6%, 37% and 39% in KZN, EC and WC. Journey patterns were generally similar within districts. Some reflected a semi-centralised model of care where patients were referred to regional hospitals; other journeys showed greater involvement of primary care.CONCLUSION: Routine laboratory data can be used to explore DR-TB patient healthcare journeys and show how the use of healthcare services for DR-TB varies in different settings.
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Laboratórios , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Assistência ao Paciente , Projetos Piloto , África do Sul/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologiaRESUMO
Rapid diagnostics, newer drugs, repurposed medications, and shorter regimens have radically altered the landscape for treating rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB). There are multiple ongoing clinical trials aiming to build a robust evidence base to guide RR/MDR-TB treatment, and both observational studies and programmatic data have contributed to advancing the treatment field. In December 2019, the WHO issued their second 'Rapid Communication´ related to RR-TB management. This reiterated their prior recommendation that a majority of people with RR/MDR-TB receive all-oral treatment regimens, and now allow for specific shorter duration regimens to be used programmatically as well. Many TB programs need clinical advice as they seek to roll out such regimens in their specific setting. In this Perspective, we highlight our early experiences and lessons learned from working with National TB Programs, adult and pediatric clinicians and civil society, in optimizing treatment of RR/MDR-TB, using shorter, highly-effective, oral regimens for the majority of people with RR/MDR-TB.
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Rifampina , Tuberculose Resistente a Múltiplos Medicamentos , Adulto , Antituberculosos/uso terapêutico , Criança , Protocolos Clínicos , Humanos , Rifampina/uso terapêutico , Fatores de Tempo , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
South Africa (SA) is committed to reducing tuberculosis (TB) mortality rates in line with the World Health Organization's End TB Strategy and the Sustainable Development Goal (SDG) targets. From mortality reports released by Statistics South Africa, this study analysed reported TB mortality in SA from 2006 to 2016 to inform our understanding of TB mortality and the development of strategies needed to attain the SDG targets. TB mortality includes all deaths reported to the Department of Home Affairs with TB reported as the underlying cause of death based on the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) definition. Although TB remains the leading cause of death, TB mortality rates in SA have fallen substantially in the past decade. From 2006 to 2016, the number of deaths due to TB plummeted from 76 881 to 29 399 and the proportion of all-cause mortality due to TB more than halved from 13% to <6%. Furthermore, the profile of people dying from TB has changed, with a decrease in the proportion of children aged <15 years, adults of reproductive age (15 - 49) and women, and an increase in the proportion aged ≥50. This change has largely mirrored the overall pattern of deaths in SA, with large decreases in deaths in adults aged 15 - 49, especially women, thought to be because of the scale-up of the antiretroviral treatment programme for HIV. The End TB Strategy target of a 95% reduction in TB mortality by 2035 is achievable in SA. However, sustained effort in high-risk groups together with improved vital registration data are needed to ensure attainment of the target.
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Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/epidemiologia , Tuberculose/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Causas de Morte , Criança , Pré-Escolar , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição por Sexo , África do Sul/epidemiologia , Tuberculose/mortalidade , Adulto JovemRESUMO
Health policy and systems research (HPSR) guides health system reforms and is essential for South Africa (SA)'s progress towards universal coverage of high-quality healthcare. For HPSR evidence to inform and strengthen health systems, it needs to flow efficiently between evidence producers, evidence synthesisers, evidence processers and disseminators and evidence implementors in an evidence ecosystem. A substantial body of evidence for health systems strengthening is generated in SA, and this informs national and international health system guidelines and guidance. In this manuscript, in celebration of the 50th anniversary of the SA Medical Research Council, we apply an evidence ecosystem lens to the SA health system, and discuss its current functioning in support of the achievement of a high-quality health system that is able to achieve universal health coverage. We use three case studies to describe successes, challenges and gaps in the functioning of the evidence ecosystem. The first case study focuses on using evidence to strengthen health-system governance and support for community health worker programmes. The second case focuses on managing the growing epidemic of drug-resistant tuberculosis, while the third case focuses on social protection, the child support grant and its impact on health. SA scientists are part of global initiatives to strengthen the health-systems evidence ecosystem, specifically through pioneering methods to synthesise evidence and produce evidence-informed guidelines to facilitate evidence use in health-system decision-making. SA institutes of health policy analysis facilitate involvement of evidence producers and synthesisers in the national health system policy-making process. A future priority is to further strengthen national initiatives to translate evidence into policy and practice and to sustain capacity for continuous technical support to health-systems policy development and implementation.
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Atenção à Saúde/organização & administração , Prática Clínica Baseada em Evidências , Política de Saúde , Cobertura Universal do Seguro de Saúde , Criança , Agentes Comunitários de Saúde , Epidemias , Financiamento Governamental , Reforma dos Serviços de Saúde , Humanos , Estudos de Casos Organizacionais , Política Pública , África do Sul , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/terapiaRESUMO
Although the neonatal mortality rate in South Africa (SA) has remained stagnant at 12 deaths per 1 000 live births, the infant and under-5 mortality rates have significantly declined since peaking in 2003. Policy changes that have influenced this decline include policies to prevent vertical HIV transmission, earlier treatment of children living with HIV, expanded immunisation policies, strengthening breastfeeding practices, and health policies to contain tobacco and sugar use. The Sustainable Development Goals (2016 - 2030) have shifted the focus from keeping children alive, as expressed in the Millennium Development Goals (1990 - 2015), to achieving optimal health through the 'Survive, thrive and transform' global agenda. This paper focuses on important remaining causes of childhood mortality and morbidity in SA, specifically respiratory illness, environmental pollution, tuberculosis, malnutrition and vaccine-preventable conditions. The monitoring of maternal and child health (MCH) outcomes is crucial, and has improved in SA through both the District Health Information and Civil Registration and Vital Statistics systems, although gaps remain. Intermittent surveys and research augment the routinely collected data. However, availability and use of local data to inform quality and effectiveness of care is critical, and this requires ownership at the collection point to facilitate local redress. Potential game changers to improve MCH outcomes include mobile health and community-based interventions. In SA, improved MCH remains a crucial factor for human capital development. There is a pressing need to focus beyond childhood mortality and to ensure that each child thrives.
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Saúde da Criança , Política de Saúde , Saúde do Lactente , Fármacos Anti-HIV/uso terapêutico , Aleitamento Materno , Mortalidade da Criança , Transtornos da Nutrição Infantil/epidemiologia , Transtornos da Nutrição Infantil/mortalidade , Transtornos da Nutrição Infantil/prevenção & controle , Pré-Escolar , Poluição Ambiental/prevenção & controle , Poluição Ambiental/estatística & dados numéricos , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Humanos , Lactente , Fórmulas Infantis , Mortalidade Infantil , Transtornos da Nutrição do Lactente/epidemiologia , Transtornos da Nutrição do Lactente/mortalidade , Transtornos da Nutrição do Lactente/prevenção & controle , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Saúde Materna , Morbidade , Gravidez , Doenças Respiratórias/epidemiologia , Doenças Respiratórias/mortalidade , África do Sul/epidemiologia , Desenvolvimento Sustentável , Tuberculose/epidemiologia , Tuberculose/mortalidade , Doenças Preveníveis por Vacina/epidemiologia , Doenças Preveníveis por Vacina/mortalidade , Vacinas/uso terapêuticoRESUMO
SETTING: High mortality and high transmission rates of extensively drug-resistant tuberculosis (XDR-TB) in KwaZulu-Natal Province of South Africa have highlighted the role of hospitals in the spread of TB and drug-resistant TB. OBJECTIVES: To determine the operational effectiveness of the National TB Programme (NTP) at a regional/district hospital and its referral clinics. DESIGN: In this multi-faceted retrospective case study, a framework was developed to evaluate the different components of the TB services, their performance in relation to each other and the system as a whole. Different methods used included structured and semi-structured interviews, retrospective medical record reviews and retrospective register reviews. RESULTS: Only 18% of those diagnosed with smear-positive pulmonary TB (PTB) in the hospital laboratory completed their treatment and 11% were cured. Clinicians did not adhere to the diagnostic guidelines of the NTP. In the TB register, 85% of PTB cases were diagnosed in the absence of sputum microscopy. Chest X-rays alone were used to diagnose PTB in 45% of the records reviewed. In addition, clinicians failed to document a clinical history suggestive of TB. Only 66 (29%) of the hospital's 225 smear-positive PTB patients reached the clinics for completion of their treatment. CONCLUSION: System failures, together with inadequate knowledge and understanding of clinicians, undermined the effectiveness of the NTP. A reduction in TB and drug-resistant forms of TB is dependent on effective diagnosis, treatment and improved communication systems between the hospital, laboratory and its down-referral clinics.
Assuntos
Atenção à Saúde/organização & administração , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Programas Nacionais de Saúde/organização & administração , Encaminhamento e Consulta/organização & administração , Antituberculosos/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos/diagnóstico , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Prontuários Médicos , Pesquisa Operacional , Pacientes Desistentes do Tratamento , Encaminhamento e Consulta/estatística & dados numéricos , Sistema de Registros , Estudos Retrospectivos , África do Sul , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
SETTING: Referral hospital for drug-resistant tuberculosis (TB) in KwaZulu-Natal, South Africa. OBJECTIVES: We conducted interviews with primary care givers of children admitted with multidrug-resistant TB (MDR-TB) during a 3-month period in 2015 to identify broader household challenges. RESULTS: We interviewed 26 care givers, most of whom were women (85%). Most households had been decimated by TB/MDR-TB and human immunodeficiency virus (HIV) infection, and were dependent upon government grants. In 54% of cases, parents were absent due to illness or death, or their whereabouts were not known. The median age of the children treated for MDR-TB was 8 years (range 2-14); 72% were HIV-co-infected. Four themes emerged in the interviews: 1) the psychosocial impact of hospitalisation and separation on the child and the household, 2) the psychosocial impact of MDR-TB on children and 3) on care givers, and 4) the economic hardship of affected households. Children had to contend with multiple diseases and medications, and personal family losses; they faced behavioural, emotional and cognitive difficulties. Care givers were often anxious and concerned about the child's longer-term prospects, while the cost of hospital visits exacerbated the pre-existing economic vulnerability of affected households. CONCLUSION: The socio-economic impact of childhood MDR-TB reverberates beyond diseased children to their affected households. Enhanced social protection, psychosocial support and treatment literacy would create the foundations for family-centred care.
Assuntos
Cuidadores/estatística & dados numéricos , Infecções por HIV/epidemiologia , Apoio Social , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adolescente , Cuidadores/psicologia , Criança , Pré-Escolar , Coinfecção , Saúde da Família/estatística & dados numéricos , Feminino , Custos Hospitalares , Hospitalização/estatística & dados numéricos , Humanos , Entrevistas como Assunto , Masculino , Pais/psicologia , Fatores Socioeconômicos , África do Sul/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/economia , Tuberculose Resistente a Múltiplos Medicamentos/psicologiaRESUMO
SETTING: Referral hospital for drug-resistant tuberculosis (DR-TB) in KwaZulu-Natal Province, South Africa. OBJECTIVE: To review the clinical outcomes of patients (age î¶ 14 years) with a laboratory-confirmed diagnosis of DR-TB who had minimal symptoms and/or did not have chest radiographic evidence of active disease at referral. These patients were not started on treatment, but were enrolled in an observation programme with follow-up at 2, 6 and 12 months. RESULTS: Of 3345 referred patients diagnosed with DR-TB, 192 (6%) were enrolled in the observation programme. The median duration from initial sputum collection in primary care to examination at our hospital was 92 days (IQR 64-124). After 12 months, 120 (62%) patients were well, 36 (19%) were lost to follow-up, 30 (16%) had deteriorated and were started on second-line anti-tuberculosis treatment and 6 (3%) had died. Bilateral disease (OR 4.25, 95%CI 1.14-15.77, P = 0.030) and previous TB (OR 2.14, 95%CI 1.10-4.19, P = 0.026) were independent predictors of an unfavourable end result in a multivariate model. CONCLUSION: In our high-burden setting, most patients diagnosed with DR-TB who had minimal symptoms at referral remained well without treatment. Longitudinal observation, coupled with symptom checking and chest radiograph, is a viable strategy.
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Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/terapia , Conduta Expectante/métodos , Adulto , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Perda de Seguimento , Masculino , Análise Multivariada , Atenção Primária à Saúde , Encaminhamento e Consulta , África do Sul , Fatores de TempoAssuntos
Assistência Centrada no Paciente , Autocuidado , Tuberculose , Humanos , Tuberculose/terapiaRESUMO
SETTING: KwaZulu-Natal, South Africa, a predominantly rural province with a high burden of tuberculosis (TB), multidrug-resistant TB (MDR-TB) and human immunodeficiency virus (HIV) infection. OBJECTIVE: To determine the most effective care model by comparing MDR-TB treatment outcomes at community-based sites with traditional care at a central, specialised hospital. DESIGN: A non-randomised observational prospective cohort study comparing community-based and centralised care. Patients at community-based sites were closer to home and had easier access to care, and home-based care was available from treatment initiation. RESULTS: Four community-based sites treated 736 patients, while 813 were treated at the centralised hospital (total = 1549 patients). Overall, 75% were HIV co-infected (community: 76% vs. hospitalised: 73%, P = 0.45) and 86% received antiretroviral therapy (community: 91% vs. hospitalised: 82%, P = 0.22). On multivariate analysis, MDR-TB patients were more likely to have a successful treatment outcome if they were treated at a community-based site (adjusted OR 1.43, P = 0.01). However, outcomes at the four community-based sites were heterogeneous, with Site 1 demonstrating that home-based care was associated with an increased treatment success of 72% compared with success rates of 52-60% at the other three sites. CONCLUSION: Community-based care for MDR-TB patients was more effective than care in a central, specialised hospital. Home-based care further increased treatment success.
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Antituberculosos/uso terapêutico , Serviços de Saúde Comunitária/organização & administração , Hospitalização , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Acessibilidade aos Serviços de Saúde , Serviços de Assistência Domiciliar/organização & administração , Humanos , Masculino , Modelos Teóricos , Estudos Prospectivos , África do Sul , Resultado do TratamentoRESUMO
1. Citrated platelet-rich plasma from human donors was used to examine turbidometrically the platelet aggregation response to collagen (2.5 micrograms ml-1) and ADP (1.6 microgram ml-1). 2. With collagen as an aggregating agent, the limited (35% maximal inhibition) inhibitory effects of glyceryl trinitrate (GTN, 0.78-50 micrograms ml-1) were markedly potentiated by threshold (3.3-10 ng ml-1) concentrations of RS93427, an orally active prostacyclin-mimetic. Almost complete inhibition of aggregation could then be produced. 3. A threshold concentration of RS93427 (3.3 ng ml-1) similarly potentiated the ability of sodium nitroprusside (NaNp, 0.78-10 micrograms ml-1) to inhibit collagen-induced platelet aggregation. There was an 8 fold reduction in the IC25 concentration of NaNp. 4. Threshold concentrations of the nitrodilators were also able to potentiate the anti-aggregatory effects of RS93427 (0.03-30 ng ml-1) on collagen-induced platelet aggregation. With threshold concentrations of either GTN (6.3-25 micrograms ml-1) or NaNp (0.3-1.3 microgram ml-1), the mean IC50 concentration of RS93427 was reduced 4 or 6 fold, respectively, while the IC25 concentration was reduced 6 or 10 fold, respectively. 5. No similar synergistic interactions were seen between RS93427 and the nitrodilators when ADP was used as an aggregating agent. 6. In spontaneously hypertensive rats, the dose-response for the hypotensive response to bolus doses of RS93427 was not altered by concomitant steady state infusion of a threshold dose (1 micrograms kg-1 min-1) of GTN. 7. Possible therapeutic implications of these findings are discussed.
Assuntos
Hidrocarbonetos Aromáticos com Pontes/farmacologia , Epoprostenol/farmacologia , Ferricianetos/farmacologia , Nitroglicerina/farmacologia , Nitroprussiato/farmacologia , Inibidores da Agregação Plaquetária , Difosfato de Adenosina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Humanos , Técnicas In Vitro , Masculino , Ratos , Ratos Endogâmicos SHRRESUMO
The common marmoset (Callithrix jacchus) is increasingly being utilised as a nonhuman primate model for human disease, ranging from autoimmune to infectious disease. In order to fully exploit these models, meaningful comparison to the human host response is necessary. Commercially available reagents, primarily targeted to human cells, were utilised to assess the phenotype and activation status of key immune cell types and cytokines in naive and infected animals. Single cell suspensions of blood, spleen, and lung were examined. Generally, the phenotype of cells was comparable between humans and marmosets, with approximately 63% of all lymphocytes in the blood of marmosets being T cells, 25% B-cells, and 12% NK cells. The percentage of neutrophils in marmoset blood were more similar to human values than mouse values. Comparison of the activation status of cells following experimental systemic or inhalational infection exhibited different trends in different tissues, most obvious in cell types active in the innate immune response. This work significantly enhances the ability to understand the immune response in these animals and fortifies their use as models of infectious disease.
Assuntos
Doenças Transmissíveis/imunologia , Imunidade Inata , Animais , Antígenos de Superfície/metabolismo , Callithrix , Doenças Transmissíveis/metabolismo , Doenças Transmissíveis/microbiologia , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Imunofenotipagem , Contagem de Leucócitos , Leucócitos/imunologia , Leucócitos/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/microbiologia , Masculino , Camundongos , Baço/imunologia , Baço/metabolismo , Baço/microbiologiaRESUMO
To improve the treatment of patients co-infected with multidrug-resistant tuberculosis (MDR-TB) and the human immunodeficiency virus, we measured the relationship between treatment outcomes and hospital performance at four decentralised MDR-TB sites in South Africa. We describe hospital performance from the patient's perspective by the use of a graphic that visually represents a patient's treatment journey. The graphic was used to report study findings to study sites and as a catalyst for a quality improvement process.