Marieke J. van der Werf

Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa

Health policy making in developing countries requires estimates of the (global) burden of disease. At present, most of the available data on schistosomiasis is limited to numbers of individuals harbouring the infection. We explored the relationship between the presence of schistosome infection and clinical morbidity, in order to estimate numbers of individuals with disease-specific morbidity for Schistosoma haematobium and Schistosoma mansoni infection in sub-Saharan Africa. We searched the literature for cross-sectional data from field studies reporting both schistosome infection and morbidity. This was used to derive a functional relationship between morbidity and infection. After standardisation for diagnostic method, the number of individuals with specific types of clinical morbidity or pathology was predicted. As only aggregated prevalences of infection were available for countries or areas, we adjusted for heterogeneity in infection levels within communities in those countries. In total, 70 million individuals out of 682 million (2000 estimate) in sub-Saharan Africa were estimated to experience haematuria in the last 2 weeks associated with S. haematobium infection, and 32 million dysuria. Ultrasound detected serious consequences of S. haematobium, major bladder wall pathology and major hydronephrosis, were predicted at 18 and 10 million, respectively. Infection with S. mansoni was estimated to cause diarrhoea in 0.78 million individuals, blood in stool in 4.4 million and hepatomegaly in 8.5 million. As the associations between prevalence of S. mansoni infection and prevalence of diarrhoea and blood in stool were not very clear, the resulting estimates may be underestimations. Using the very limited data available, we estimated the mortality rates due to non-functioning kidney (from S. haematobium) and haematemesis (from S. mansoni) at 150000 and 130000 per year. Given the overall high number of cases with schistosomiasis-related disease and associated death, we conclude that schistosomiasis remains an important public health problem in sub-Saharan Africa.

Towards tuberculosis elimination: an action framework for low-incidence countries

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards “pre-elimination” (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions. Action framework for countries with low tuberculosis incidence: a coherent approach for eliminating tuberculosis http://ow.ly/H03ZZ

Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review

Background The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. Methodology and Principal Findings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory.

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone. Guidelines on LTBI for low TB incidence countries – essential element of the @WHO #EndTB strategy and TB elimination http://ow.ly/RW8xn

Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) substantially challenges TB control, especially in the European Region of the World Health Organization, where the highest prevalence of MDR/XDR cases is reported. The current management of patients with MDR/XDR-TB is extremely complex for medical, social and public health systems. The treatment with currently available anti-TB therapies to achieve relapse-free cure is long and undermined by a high frequency of adverse drug events, suboptimal treatment adherence, high costs and low treatment success rates. Availability of optimal management for patients with MDR/XDR-TB is limited even in the European Region. In the absence of a preventive vaccine, more effective diagnostic tools and novel therapeutic interventions the control of MDR/XDR-TB will be extremely difficult. Despite recent scientific advances in MDR/XDR-TB care, decisions for the management of patients with MDR/XDR-TB and their contacts often rely on expert opinions, rather than on clinical evidence. This document summarises the current knowledge on the prevention, diagnosis and treatment of adults and children with MDR/XDR-TB and their contacts, and provides expert consensus recommendations on questions where scientific evidence is still lacking. TBNET consensus statement on the management of patients with MDR/XDR-TB has been released in the Eur Respir J http://ow.ly/uizRD

Old ideas to innovate tuberculosis control: preventive treatment to achieve elimination

The introduction of new rapid diagnostic tools for tuberculosis (TB) and the promising TB drugs pipeline together with the development of a new World Health Organization Strategy post 2015 allows new discussions on how to direct TB control. The European Respiratory Society’s European Forum for TB Innovation was created to stimulate discussion on how to best take advantage of old and new opportunities, and advances, to improve TB control and eventually progress towards the elimination of TB. While TB control is aimed at reducing the incidence of TB by early diagnosis and treatment of infectious cases of TB, TB elimination requires focus on sterilising the pool of latently infected individuals, from which future TB cases would be generated. This manuscript describes the three core components that are necessary to implement the elimination strategy fully. 1) Improve diagnosis of latent TB infected individuals. 2) Improve regimens to treat latent TB infection. 3) ensure public health commitment to make both 1) and 2) possible. Old and new evidence is critically described, focusing on the European commitment to reach elimination and on the innovative experiences and best practices available. Diagnosis and treatment of latent TB infection is the core intervention to reach elimination http://ow.ly/mjW0R

Tuberculosis elimination: theory and practice in Europe

Although Europe identified the pathway to tuberculosis (TB) elimination in 1990, no information on programmes for country preparedness is available. A questionnaire investigating TB elimination activities was submitted to 38 national TB programme representatives of low TB incidence (<20 cases per 100 000 population) European countries/territories of the World Health Organization European region. Out of 31 providing a complete answer, 17 (54.8%) reported to have a dedicated national TB programme, 20 (64.5%) a national plan including TB elimination (13 (41.9%) including targets), 22 (71%) guidelines, 14 (45.2%) a specific budget for TB activities, and 23 (74.2%) TB reference centres. All countries reported having case-based electronic TB surveillance, 19 (61.3%) perform regular supervision, 12 (38.7%) have a monitoring and evaluation plan and five (16.1%) perform modelling. In three countries (9.7%), TB health services are free for insured individuals only. In 22 countries/territories (71%) not all TB drugs were available, while in 12 (38.7%) drug stock-outs have been described. Although high-risk group screening for latent TB infection is performed by the majority of countries, only 6 (19.4%) provided figures on preventive treatment completion rates. Not all elements identified as essential for country preparedness to achieve TB elimination are available in the countries surveyed. As TB elimination interventions are sub-optimally applied, more training, awareness and political commitment are necessary http://ow.ly/ru6PV

Vaccine-induced immunity circumvented by typical Mycobacterium tuberculosis Beijing strains.

The frequency of typical and atypical Beijing strains of Mycobacterium tuberculosis was determined in the Netherlands; Vietnam; and Hong Kong Special Administrative Region, People’s Republic of China. The strains’ associations with drug resistance, M. bovis BCG vaccination, and patient characteristics were assessed. BCG vaccination may have positively selected the prevalent typical Beijing strains.

Extrapulmonary tuberculosis by nationality, The Netherlands, 1993-2001

The growth of the number of inhabitants with a non-Western ethnic background most likely explains the growth of extrapulmonary TB in the Netherlands.

Multidrug resistance after inappropriate tuberculosis treatment: A meta-analysis

We conducted a systematic review and meta-analysis to assess the evidence for the postulation that inappropriate tuberculosis (TB) regimens are a risk for development of multidrug-resistant (MDR)-TB. MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Cohort studies including TB patients who received treatment were selected and data on treatment regimen, drug susceptibility testing results and genotyping results before treatment and at failure or relapse were abstracted from the articles. Four studies were included in the systematic review and two were included in the meta-analysis. In these two studies the risk of developing MDR-TB in patients who failed treatment and used an inappropriate treatment regimen was increased 27-fold (RR 26.7, 95% CI 5.0–141.7) when compared with individuals who received an appropriate treatment regimen. This review provides evidence that supports the general opinion that the development of MDR-TB can be caused by inadequate treatment, given the drug susceptibility pattern of the Mycobacterium tuberculosis bacilli. It should be noted that only two studies provided data for the meta-analysis. The information can be used to advocate for adequate treatment for patients based on drug resistance profiles.