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SummaryThis study investigated the trends in tuberculosis mortality through time in Switzerland. Information on the decline in mortality before chemotherapies were introduced may be useful in developing countries where drug-resistant tuberculosis is now becoming a major problem. Swiss data were collected from historical records and comparative data were obtained from the literature for England and Wales, New York, Japan, Brazil and Sierra Leone. Logistic curves were fitted to examine the rate of decline before introduction of pharmacotherapies and these show that the decline would have continued without the introduction of chemical therapies, including antibiotics. In Switzerland, England and Wales and New York, the decline had occurred long before the introduction of specific anti-tuberculosis agents. In Brazil and Japan, chemical therapy was co-incident with the decline in tuberculosis mortality rates. Overall, it is suggested that the effective control of tuberculosis can be achieved through a combination of chemical interventions, conservative therapy (rest, good nutrition, ventilation, etc.) as well as public health interventions addressing hygiene, nutrition, reducing exposure to infections and educating the population about tuberculosis.

Molecular epidemiology of circulating clinical isolates is crucial to improve prevention strategies. The Spanish Working Group on multidrug resistant tuberculosis (MDR-TB) is a network that monitors the MDR-TB isolates in Spain since 1998. The aim of this study was to present the study of the MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) patterns in Spain using the different recommended genotyping methods over time by a national coordinated system. Based on the proposed genotyping methods in the European Union until 2018, the preservation of one method, MIRU-VNTR, applied to selected clustered strains permitted to maintain our study open for 20 years. The distribution of demographic, clinical and epidemiological characteristics of clustered and non-clustered cases of MDR/XDR tuberculosis with proportion differences as assessed by Pearson's chi-squared or Fisher's exact test was compared. The differences in the quantitative variables using the Student's-t test and the Mann-Whitney U test were evaluated. The results obtained showed a total of 48.4% of the cases grouped in 77 clusters. Younger age groups, having a known TB case contact (10.2% vs 4.7%) and XDR-TB (16.5% vs 1.8%) were significantly associated with clustering. The largest cluster corresponded to a Mycobacterium bovis strain mainly spread during the nineties. A total of 68.4% of the clusters detected were distributed among the different Spanish regions and six clusters involving 104 cases were grouped in 17 and 18 years. Comparison of the genotypes obtained with those European genotypes included in The European Surveillance System (TESSy) showed that 87 cases had become part of 20 European clusters. The continuity of MDR strain genotyping in time has offered a widespread picture of the situation that allows better management of this public health problem. It also shows the advantage of maintaining one genotyping method over time, which allowed the comparison between ancient, present and future samples. ; The molecular methods applied in ...

Yuou Zhang,1 Xuan Liu,1 Linghe Yang,1 Guifang Zhang,2 Zhaoru Gu,3 Zhongdan Chen,4 Jing Sun1 1School of Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; 2Institute of Geriatrics, Beijing Hospital, Beijing, People's Republic of China; 3Institute of Cancer, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, People's Republic of China; 4Hepatitis/TB/HIV/STI, World Health Organization, Office of the WHO Representative in China, Beijing, People's Republic of ChinaCorrespondence: Jing Sun Email sunjing@sph.pumc.edu.cnAbstract: This study analyzed the barriers of patient access to affordable MDR-TB medication in China and the reasons behind, and proposed strategies towards removing the barriers based on literature review and key informant interviews. Reasons behind the high financial burden of MDR-TB patients in China are the lack of a coordinated and multi-sourced financing model to secure patients' access to the expensive novel medicines, and the absence of the safety-net for the patients with low ability to pay the costs. Appropriate health insurance benefit packages and provider payment mechanisms, supportive legal framework, coordinated policies as well as incentives for off-label use of evidence-based repurposed medicines are missing. The observations identified key intervention areas including continued efforts to make the novel effective medicines affordable and to strengthen the legislative protection for off-label use of evidence-based medicines; increase incentives for pharmaceutical companies to expand indications of established medicines based on the evidence; implement public initiatives to support the use of repurposed medicines for diseases with major public health significance, and scale up good practices from local pilots to create a coordinated multi-sourced financing model. A comprehensive approach to address the barriers in the full treatment course of MDR-TB and a safety-net for low-ability-to-pay patients are also critical to secure universal access to affordable MDR-TB medication.Keywords: MDR-TB, medication, affordable, financing, safety-net, off-label use, repurposed medicines

This study analyzed the barriers of patient access to affordable MDR-TB medication in China and the reasons behind, and proposed strategies towards removing the barriers based on literature review and key informant interviews. Reasons behind the high financial burden of MDR-TB patients in China are the lack of a coordinated and multi-sourced financing model to secure patients' access to the expensive novel medicines, and the absence of the safety-net for the patients with low ability to pay the costs. Appropriate health insurance benefit packages and provider payment mechanisms, supportive legal framework, coordinated policies as well as incentives for off-label use of evidence-based repurposed medicines are missing. The observations identified key intervention areas including continued efforts to make the novel effective medicines affordable and to strengthen the legislative protection for off-label use of evidence-based medicines; increase incentives for pharmaceutical companies to expand indications of established medicines based on the evidence; implement public initiatives to support the use of repurposed medicines for diseases with major public health significance, and scale up good practices from local pilots to create a coordinated multi-sourced financing model. A comprehensive approach to address the barriers in the full treatment course of MDR-TB and a safety-net for low-ability-to-pay patients are also critical to secure universal access to affordable MDR-TB medication.

We report a case of extensive pulmonary destruction due to delayed effective pulmonary tuberculosis (TB) treatment in an adult artisanal miner in eastern Democratic Republic of Congo. Xpert MTB/RIF was positive after his second rifampicin-susceptible TB treatment. Chest X-rays were suggestive of large cavity, fibrosis of remaining lung and air-fluid levels at the base of the destroyed lung. The patient passed away after delayed effective TB regimens. Clinicians should be aware that urgent surgical intervention is often required to prevent lethal acute respiratory failure and shock notwithstanding effective chemotherapy in such condition. Effort is needed to timely diagnose multidrug resistance TB and to implement thoracic surgery for TB in high burden countries.

Molecular epidemiology of circulating clinical isolates is crucial to improve prevention strategies. The Spanish Working Group on multidrug resistant tuberculosis (MDR-TB) is a network that monitors the MDR-TB isolates in Spain since 1998. The aim of this study was to present the study of the MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) patterns in Spain using the different recommended genotyping methods over time by a national coordinated system. Based on the proposed genotyping methods in the European Union until 2018, the preservation of one method, MIRU-VNTR, applied to selected clustered strains permitted to maintain our study open for 20 years. The distribution of demographic, clinical and epidemiological characteristics of clustered and non-clustered cases of MDR/XDR tuberculosis with proportion differences as assessed by Pearson's chi-squared or Fisher's exact test was compared. The differences in the quantitative variables using the Student's-t test and the Mann–Whitney U test were evaluated. The results obtained showed a total of 48.4% of the cases grouped in 77 clusters. Younger age groups, having a known TB case contact (10.2% vs 4.7%) and XDR-TB (16.5% vs 1.8%) were significantly associated with clustering. The largest cluster corresponded to a Mycobacterium bovis strain mainly spread during the nineties. A total of 68.4% of the clusters detected were distributed among the different Spanish regions and six clusters involving 104 cases were grouped in 17 and 18 years. Comparison of the genotypes obtained with those European genotypes included in The European Surveillance System (TESSy) showed that 87 cases had become part of 20 European clusters. The continuity of MDR strain genotyping in time has offered a widespread picture of the situation that allows better management of this public health problem. It also shows the advantage of maintaining one genotyping method over time, which allowed the comparison between ancient, present and future samples.

Multi-drug-resistant tuberculosis (MDR-TB) poses a major threat to public health worldwide, particularly in low-income countries. The current long (20 month) and arduous treatment regime uses powerful drugs with side-effects that include mental ill-health. It has a high loss-to-follow-up (25%) and higher case fatality and lower cure-rates than those with drug sensitive tuberculosis (TB). While some national TB programmes provide small financial allowances to patients, other aspects of psychosocial ill-health, including iatrogenic ones, are not routinely assessed or addressed. We aimed to develop an intervention to improve psycho-social well-being for MDR-TB patients in Nepal. To do this we conducted qualitative work with MDR-TB patients, health professionals and the National TB programme (NTP) in Nepal. We conducted semi-structured interviews (SSIs) with 15 patients (10 men and 5 women, aged 21 to 68), four family members and three frontline health workers. In addition, three focus groups were held with MDR-TB patients and three with their family members. We conducted a series of meetings and workshops with key stakeholders to design the intervention, working closely with the NTP to enable government ownership. Our findings highlight the negative impacts of MDR-TB treatment on mental health, with greater impacts felt among those with limited social and financial support, predominantly married women. Michie et al's (2011) framework for behaviour change proved helpful in identifying corresponding practice- and policy-level changes. The findings from this study emphasise the need for tailored psycho-social support. Recent work on simple psychological support packages for the general population can usefully be adapted for use with people with MDR-TB.

Background: Explaining policy change is one of the central tasks of contemporary policy analysis. In this article, we examine the changes in infection control policies for multi-drug resistant tuberculosis (MDR-TB) in South Africa from the time the country made the transition to democracy in 1994, until 2015. We focus on MDR-TB infection control and refer to decentralised management as a form of infection control. Using Kingdon's theoretical framework of policy streams, we explore the temporal ordering of policy framework changes. We also consider the role of research in motivating policy changes. Methods: Policy documents addressing MDR-TB in South Africa over the period 1994 to 2014 were extracted. Literature on MDR-TB infection control in South Africa was extracted from PubMed using key search terms. The documents were analysed to identify the changes that occurred and the factors driving them. Results: During the period under study, five different policy frameworks were implemented. The policies were meant to address the overwhelming challenge of MDR-TB in South Africa, contextualised by high prevalence of HIV infection, that threatened to undermine public health programmes and the success of antiretroviral therapy rollouts. Policy changes in MDR-TB infection control were supported by research evidence and driven by the high incidence and complexity of the disease, increasing levels of dissatisfaction among patients, challenges of physical, human and financial resources in public hospitals, and the ideologies of the political leadership. Activists and people living with HIV played an important role in highlighting the importance of MDR-TB as well as exerting pressure on policymakers, while the mass media drew public attention to infection control as both a cause of and a solution to MDR-TB. Conclusion: The critical factors for policy change for infection control of MDR-TB in South Africa were rooted in the socioeconomic and political environment, were supported by extensive research, and can be framed using Kingdon's policy streams approach as an interplay of the problem of the disease, political forces that prevailed and alternative proposals.

BACKGROUND: Explaining policy change is one of the central tasks of contemporary policy analysis. In this article, we examine the changes in infection control policies for multi-drug resistant tuberculosis (MDR-TB) in South Africa from the time the country made the transition to democracy in 1994, until 2015. We focus on MDR-TB infection control and refer to decentralised management as a form of infection control. Using Kingdon's theoretical framework of policy streams, we explore the temporal ordering of policy framework changes. We also consider the role of research in motivating policy changes. METHODS: Policy documents addressing MDR-TB in South Africa over the period 1994 to 2014 were extracted. Literature on MDR-TB infection control in South Africa was extracted from PubMed using key search terms. The documents were analysed to identify the changes that occurred and the factors driving them. RESULTS: During the period under study, five different policy frameworks were implemented. The policies were meant to address the overwhelming challenge of MDR-TB in South Africa, contextualised by high prevalence of HIV infection, that threatened to undermine public health programmes and the success of antiretroviral therapy rollouts. Policy changes in MDR-TB infection control were supported by research evidence and driven by the high incidence and complexity of the disease, increasing levels of dissatisfaction among patients, challenges of physical, human and financial resources in public hospitals, and the ideologies of the political leadership. Activists and people living with HIV played an important role in highlighting the importance of MDR-TB as well as exerting pressure on policymakers, while the mass media drew public attention to infection control as both a cause of and a solution to MDR-TB. CONCLUSION: The critical factors for policy change for infection control of MDR-TB in South Africa were rooted in the socioeconomic and political environment, were supported by extensive research, and can be framed using Kingdon's policy streams approach as an interplay of the problem of the disease, political forces that prevailed and alternative proposals.

BACKGROUND: Even though the WHO-endorsed, non-commercial MODS assay offers rapid, reliable TB liquid culture and phenotypic drug susceptibility testing (DST) at lower cost than any other diagnostic, uptake has been patchy. In part this reflects misperceptions about in-house assay quality assurance, but user convenience of one-stop procurement is also important. A commercial MODS kit was developed by Hardy Diagnostics (Santa Maria, CA, USA) with PATH (Seattle, WA, USA) to facilitate procurement, simplify procedures through readymade media, and enhance safety with a sealing silicone plate lid. Here we report the results from a large-scale field evaluation of the MODS kit in a government service laboratory. METHODS & FINDINGS: 2446 sputum samples were cultured in parallel in Lowenstein-Jensen (LJ), conventional MODS and in the MODS kit. MODS kit DST was compared with conventional MODS (direct) DST and proportion method (indirect) DST. 778 samples (31.8%) were Mycobacterium tuberculosis culture-positive. Compared to conventional MODS the sensitivity, specificity, positive, and negative predictive values (95% confidence intervals) of the MODS Kit were 99.3% (98.3-99.8%), 98.3% (97.5-98.8%), 95.8% (94.0-97.1%), and 99.7% (99.3-99.9%). Median (interquartile ranges) time to culture-positivity (and rifampicin and isoniazid DST) was 10 (9-13) days for conventional MODS and 8.5 (7-11) for MODS Kit (p<0.01). Direct rifampicin and isoniazid DST in MODS kit was almost universally concordant with conventional MODS (97.9% agreement, 665/679 evaluable samples) and reference indirect DST (97.9% agreement, 687/702 evaluable samples). CONCLUSIONS: MODS kit delivers performance indistinguishable from conventional MODS and offers a convenient, affordable alternative with enhanced safety from the sealing silicone lid. The availability in the marketplace of this platform, which conforms to European standards (CE-marked), readily repurposed for second-line DST in the near future, provides a fresh opportunity for improving equity of access to TB diagnosis and first and second-line DST in settings where the need is greatest.

Abstract Background Vietnam is ranked 14 th among 27 countries with high burden of multidrug-resistant tuberculosis (MDR-TB). In 2009, the Vietnamese government issued a policy on MDR-TB called Programmatic Management of Drug-resistant Tuberculosis (PMDT) to enhance and scale up diagnosis and treatment services for MDR-TB. Here we assess the PMDT performance in 2013 to determine the challenges to the successful identification and enrollment for treatment of MDR-TB in Vietnam. Methods In 35 provinces implementing PMDT, we quantified the number of MDR-TB presumptive patients tested for MDR-TB by Xpert MTB/RIF and the number of MDR-TB patients started on second-line treatment. In addition, existing reports and documents related to MDR-TB policies and guidelines in Vietnam were reviewed, supplemented with focus group discussions and in-depth interviews with MDR-TB key staff members. Results 5,668 (31.2 %) of estimated 18,165 MDR-TB presumptive cases were tested by Xpert MTB/RIF and second-line treatment was provided to 948 out of 5100 (18.7 %) of MDR-TB patients. Those tested for MDR-TB were 340/3224 (10.5 %) of TB-HIV co-infected patients and 290/2214 (13.1 %) of patients who remained sputum smear-positive after 2 and 3 months of category I TB regimen. Qualitative findings revealed the following challenges to detection and enrollment of MDR-TB in Vietnam: insufficient TB screening capacity at district hospitals where TB units were not available and poor communication and implementation of policy changes. Instructions for policy changes were not always received, and training was inconsistent between training courses. The private sector did not adequately report MDR-TB cases to the NTP. Conclusions The proportion of MDR-TB patients diagnosed and enrolled for second-line treatment is less than 20 % of the estimated total. The low enrollment is largely due to the fact that many patients at risk are missed for MDR-TB screening. In order to detect more MDR-TB cases, Vietnam should intensify case finding of MDR-TB by a comprehensive strategy to screen for MDR-TB among new cases rather than targeting previously treated cases, in particular those with HIV co-infection and contacts of MDR-TB patients, and should engage the private sector in PMDT.

Tuberculosis (TB) remains one of the health problems in Nigeria and worldwide. Adenosine Deaminase acts in proliferation and differentiation of lymphocyte, especially T lymphocyte. It also acts in maturation of monocytes transforming them to macrophage. Adenosine Deaminase is a significant indicator of active cellular immunity. Adenosine Deaminase has been proposed to be a useful surrogate marker for TB because it can be detected in body fluids such as pleural, pericardial and peritoneal fluid. This study aimed to determine the relationship between Adenosine Deaminase and drug Resistant Tuberculosis (DR-TB) among patients attending Tuberculosis Clinic in Government Chest Hospital, Jericho, Oyo State, Nigeria. Methodology: A prospective case-control study involving thirty (30) Multi-Drug Resistance Tuberculosis patients and thirty (30) apparently healthy participants in Tuberculosis Clinic in Government Chest Clinic Hospital, Jericho, Oyo State, Nigeria. Theparticipants socio-demographic data was obtained using questionnaire. Sputum samples were collected from each patient from the two groups of participants in leak proof screw capped specimen containers. About 5 mL of venous blood sample was collected from the antecubital fossa of the study participants into vacutainer plain tubes. Sputum samples collected were analysed for Mycobacterium tuberculosis using Gene Xpert. Blood sample collected was analyzed for Adenosine Deaminase using ELISA method. The prevalence of MDR-TB was 0.18%, majority of MDR-TB were within age of 15-30 years with mean age 36.30±13.40 years with female having 63.3% and male 36.7%. Among MDR-TB, the mean±SD Adenosine Deaminase activity was 37.67±15.25 IU/L and among Healthy controls, the mean±SD of Adenosine Deaminase was 12.26±5.11 IU/L. There was significance increased in ADA activity among MDR-TB participants when compared to Healthy controls at p-value<0.05 (p=0.001). ADA level of 18 IU/L cut off point has a sensitivity of 90.0%, specificity of 87.0% and diagnostic accuracy of ...