Search

Background: The surveillance of drug resistance among tuberculosis (TB) patients is central to combatting the global TB epidemic and preventing the spread of antimicrobial resistance. Isoniazid and rifampicin are two of the most powerful first-line anti-TB medicines, and resistance to either of them increases the risk of treatment failure, relapse, or acquisition of resistance to other drugs. The global prevalence of rifampicin resistance is well documented, occurring in 3.4% (95% CI 2.5%-4.4%) of new TB patients and 18% (95% CI 7.6%-31%) of previously treated TB patients in 2018, whereas the prevalence of isoniazid resistance at global and regional levels is less understood. In 2018, the World Health Organization (WHO) recommended a modified 6-month treatment regimen for people with isoniazid-resistant, rifampicin-susceptible TB (Hr-TB), which includes rifampicin, pyrazinamide, ethambutol, and levofloxacin. We estimated the global prevalence of Hr-TB among TB patients and investigated associated phenotypic and genotypic drug resistance patterns.Methods and Findings: Aggregated drug resistance data reported to WHO from either routine continuous surveillance or nationally representative periodic surveys of TB patients for the period 2003-2017 were reviewed. Isoniazid data were available from 156 countries or territories for 211,753 patients. Among these, the global prevalence of Hr-TB was 7.4% (95% CI 6.5%-8.4%) among new TB patients and 11.4% (95% CI 9.4%-13.4%) among previously treated TB patients. Additional data on pyrazinamide and levofloxacin resistance were available from 6 countries (Azerbaijan, Bangladesh, Belarus, Pakistan, the Philippines, and South Africa). There were no cases of resistance to both pyrazinamide and levofloxacin among Hr-TB patients, except for the Philippines (1.8%, 95% CI 0.2-6.4) and Belarus (5.3%, 95% CI 0.1-26.0). Sequencing data for all genomic regions involved in isoniazid resistance were available for 4,563 patients. Among the 1,174 isolates that were resistant by either phenotypic testing or sequencing, 78.6% (95% CI 76.1%-80.9%) had resistance-conferring mutations in the katG gene and 14.6% (95% CI 12.7%-16.8%) in both katG and the inhA promoter region. For 6.8% (95% CI 5.4%-8.4%) of patients, mutations occurred in the inhA promoter alone, for whom an increased dose of isoniazid may be considered. The main limitations of this study are that most analyses were performed at the national rather than individual patient level and that the quality of laboratory testing may vary between countries.Conclusions: In this study, the prevalence of Hr-TB among TB patients was higher than the prevalence of rifampicin resistance globally. Many patients with Hr-TB would be missed by current diagnostic algorithms driven by rifampicin testing, highlighting the need for new rapid molecular technologies to ensure access to appropriate treatment and care. The low prevalence of resistance to pyrazinamide and fluoroquinolones among patients with Hr-TB provides further justification for the recommended modified treatment regimen. [ABSTRACT FROM AUTHOR]

The article discusses the study on the surveillance of antituberculosis-drug resistance for 20 years since 1994 according to the Global Tuberculosis Program of the World Health Organization (WHO) with the support of International Union against Tuberculosis and Lung Disease. The first documented report was the development of drug resistance in Mycobacterium tuberculosis and then the introduction of antibiotic treatment.

Background: Transboundary animal movements facilitate the spread of pathogens across large distances. Cross-border cattle trade is of economic and cultural importance in West Africa. This study explores the potential disease risk resulting from large-scale, cross-border cattle trade between Togo, Burkina Faso, Ghana, Benin, and Nigeria for the first time. Methods and Principal Findings: A questionnaire-based survey of livestock movements of 226 cattle traders was conducted in the 9 biggest cattle markets of northern Togo in February-March 2012. More than half of the traders (53.5%) operated in at least one other country. Animal flows were stochastically simulated based on reported movements and the risk of regional disease spread assessed. More than three quarters (79.2%, range: 78.1–80.0%) of cattle flowing into the market system originated from other countries. Through the cattle market system of northern Togo, non-neighbouring countries were connected via potential routes for disease spread. Even for diseases with low transmissibility and low prevalence in a given country, there was a high risk of disease introduction into other countries. Conclusions: By stochastically simulating data collected by interviewing cattle traders in northern Togo, this study identifies potential risks for regional disease spread in West Africa through cross-border cattle trade. The findings highlight that surveillance for emerging infectious diseases as well as control activities targeting endemic diseases in West Africa are likely to be ineffective if only conducted at a national level. A regional approach to disease surveillance, prevention and control is essential. [ABSTRACT FROM AUTHOR]

Background: Although brucellosis (Brucella spp.) and Q Fever (Coxiella burnetii) are zoonoses of global importance, very little high quality data are available from West Africa. Methods/Principal Findings: A serosurvey was conducted in Togo’s main livestock-raising zone in 2011 in 25 randomly selected villages, including 683 people, 596 cattle, 465 sheep and 221 goats. Additionally, 464 transhumant cattle from Burkina Faso were sampled in 2012. The serological analyses performed were the Rose Bengal Test and ELISA for brucellosis and ELISA and the immunofluorescence assay (IFA) for Q Fever Brucellosis did not appear to pose a major human health problem in the study zone, with only 7 seropositive participants. B. abortus was isolated from 3 bovine hygroma samples, and is likely to be the predominant circulating strain. This may explain the observed seropositivity amongst village cattle (9.2%, 95%CI:4.3–18.6%) and transhumant cattle (7.3%, 95%CI:3.5–14.7%), with an absence of seropositive small ruminants. Exposure of livestock and people to C. burnetii was common, potentially influenced by cultural factors. People of Fulani ethnicity had greater livestock contact and a significantly higher seroprevalence than other ethnic groups (Fulani: 45.5%, 95%CI:37.7–53.6%; non-Fulani: 27.1%, 95%CI:20.6–34.7%). Appropriate diagnostic test cut-off values in endemic settings requires further investigation. Both brucellosis and Q Fever appeared to impact on livestock production. Seropositive cows were more likely to have aborted a foetus during the previous year than seronegative cows, when adjusted for age. This odds was 3.8 times higher (95%CI: 1.2–12.1) for brucellosis and 6.7 times higher (95%CI: 1.3–34.8) for Q Fever. Conclusions: This is the first epidemiological study of zoonoses in Togo in linked human and animal populations, providing much needed data for West Africa. Exposure to Brucella and C. burnetii is common but further research is needed into the clinical and economic impact. [ABSTRACT FROM AUTHOR]

Background: The objectives of this systematic review, commissioned by WHO, were to assess the frequency and severity of clinical manifestations of human brucellosis, in view of specifying a disability weight for a DALY calculation. Methods/Principal Findings: Thirty three databases were searched, with 2,385 articles published between January 1990–June 2010 identified as relating to human brucellosis. Fifty-seven studies were of sufficient quality for data extraction. Pooled proportions of cases with specific clinical manifestations were stratified by age category and sex and analysed using generalized linear mixed models. Data relating to duration of illness and risk factors were also extracted. Severe complications of brucellosis infection were not rare, with 1 case of endocarditis and 4 neurological cases per 100 patients. One in 10 men suffered from epididymo-orchitis. Debilitating conditions such as arthralgia, myalgia and back pain affected around half of the patients (65%, 47% and 45%, respectively). Given that 78% patients had fever, brucellosis poses a diagnostic challenge in malaria-endemic areas. Significant delays in appropriate diagnosis and treatment were the result of health service inadequacies and socioeconomic factors. Based on disability weights from the 2004 Global Burden of Disease Study, a disability weight of 0.150 is proposed as the first informed estimate for chronic, localised brucellosis and 0.190 for acute brucellosis. Conclusions: This systematic review adds to the understanding of the global burden of brucellosis, one of the most common zoonoses worldwide. The severe, debilitating, and chronic impact of brucellosis is highlighted. Well designed epidemiological studies from regions lacking in data would allow a more complete understanding of the clinical manifestations of disease and exposure risks, and provide further evidence for policy-makers. As this is the first informed estimate of a disability weight for brucellosis, there is a need for further debate amongst brucellosis experts and a consensus to be reached. Author Summary: Brucellosis is a bacterial disease transmitted to humans by consumption of infected, unpasteurised animal milk or through direct contact with infected animals, particularly aborted foetuses. The livestock production losses resulting from these abortions have a major economic impact on individuals and communities. Infected people often suffer from a chronic, debilitating illness. This systematic review on the symptoms of human brucellosis is the first ever conducted. Using strict exclusion criteria, 57 scientific articles published between January 1990–June 2010 which included high quality data were identified. Severe complications of brucellosis infection were not rare, with 1 case of endocarditis and 4 neurological cases per 100 patients. One in 10 men suffered from testicular infection, which can case sterility. Debilitating conditions such as joint, muscle, and back pain affected around half of the patients. Given that most patients had fever, brucellosis poses a diagnostic challenge in malaria-endemic areas where fever is often assumed to be malaria. More high quality data is needed for a more complete understanding of the clinical manifestations of disease and exposure risks, and to provide further evidence for policy-makers. [ABSTRACT FROM AUTHOR]

Background: This report presents a systematic review of scientific literature published between 1990–2010 relating to the frequency of human brucellosis, commissioned by WHO. The objectives were to identify high quality disease incidence data to complement existing knowledge of the global disease burden and, ultimately, to contribute towards the calculation of a Disability-Adjusted Life Years (DALY) estimate for brucellosis. Methods/Principal Findings: Thirty three databases were searched, identifying 2,385 articles relating to human brucellosis. Based on strict screening criteria, 60 studies were selected for quality assessment, of which only 29 were of sufficient quality for data analysis. Data were only available from 15 countries in the regions of Northern Africa and Middle East, Western Europe, Central and South America, Sub-Saharan Africa, and Central Asia. Half of the studies presented incidence data, six of which were longitudinal prospective studies, and half presented seroprevalence data which were converted to incidence rates. Brucellosis incidence varied widely between, and within, countries. Although study biases cannot be ruled out, demographic, occupational, and socioeconomic factors likely play a role. Aggregated data at national or regional levels do not capture these complexities of disease dynamics and, consequently, at-risk populations or areas may be overlooked. In many brucellosis-endemic countries, health systems are weak and passively-acquired official data underestimate the true disease burden. Conclusions: High quality research is essential for an accurate assessment of disease burden, particularly in Eastern Europe, the Asia-Pacific, Central and South America and Africa where data are lacking. Providing formal epidemiological and statistical training to researchers is essential for improving study quality. An integrated approach to disease surveillance involving both human health and veterinary services would allow a better understanding of disease dynamics at the animal-human interface, as well as a more cost-effective utilisation of resources. Author Summary: Brucellosis is a bacterial disease transmitted to humans by consumption of infected, unpasteurised animal milk or through direct contact with infected animals, particularly aborted foetuses. The livestock production losses resulting from these abortions have a major economic impact on individuals and communities. Infected people often suffer from a chronic, debilitating illness. This systematic review of the incidence of human brucellosis is the first ever conducted. Using strict exclusion criteria, 28 scientific articles published between January 1990–June 2010 which included high quality data were identified. Half of these studies presented incidence data and half presented seroprevalence data which were converted to incidence rates. Data were only available from 15 countries in the regions of Northern Africa and Middle East, Western Europe, Central and South America, Sub-Saharan Africa and Central Asia. Brucellosis incidence varied widely between and within countries. Demographic, occupational and socioeconomic factors may play a role in these differences. In many brucellosis-endemic countries, health systems are weak, and official data are likely to underestimate the true disease burden. High quality research is needed, particularly from Eastern Europe, the Asia-Pacific, Central and South America and Africa. An integrated approach to disease surveillance involving both human health and veterinary services would allow a better understanding of the disease, as well as a more cost-effective utilisation of resources. [ABSTRACT FROM AUTHOR]

Background: Influenza is an important cause of morbidity and mortality for frail older people. Whilst the antiviral drug oseltamivir (a neuraminidase inhibitor) is approved for treatment and prophylaxis of influenza during outbreaks, there have been no trials comparing treatment only (T) versus treatment and prophylaxis (T&P) in Aged Care Facilities (ACFs). Our objective was to compare a policy of T versus T&P for influenza outbreaks in ACFs. Methods and Findings: We performed a cluster randomised controlled trial in 16 ACFs, that followed a policy of either "T" -- oseltamivir treatment (75 mg twice a day for 5 days)--or "T&P" -- treatment and prophylaxis (75 mg once a day for 10 days) for influenza outbreaks over three years, in addition to enhanced surveillance. The primary outcome measure was the attack rate of influenza. Secondary outcomes measures were deaths, hospitalisation, pneumonia and adverse events. Laboratory testing was performed to identify the viral cause of influenza-like illness (ILI) outbreaks. The study period 30 June 2006 to 23 December 2008 included three southern hemisphere winters. During that time, influenza was confirmed as the cause of nine of the 23 ILI outbreaks that occurred amongst the 16 ACFs. The policy of T&P resulted in a significant reduction in the influenza attack rate amongst residents: 93/255 (36%) in residents in T facilities versus 91/397 (23%) in T&P facilities (p = 0.002). We observed a non-significant reduction in staff: 46/216 (21%) in T facilities versus 47/350 (13%) in T&P facilities (p = 0.5). There was a significant reduction in mean duration of outbreaks (T = 24 days, T&P = 11 days, p = 0.04). Deaths, hospitalisations and pneumonia were non-significantly reduced in the T&P allocated facilities. Drug adverse events were common but tolerated. Conclusion: Our trial lacked power but these results provide some support for a policy of "treatment and prophylaxis" with oseltamivir in controlling influenza outbreaks in ACFs. Trail Registration: Australian Clinical Trials Registry ACTRN12606000278538 [ABSTRACT FROM AUTHOR]

Abstract: A cluster-randomised controlled trial of antiviral treatment to control influenza outbreaks in aged-care facilities (ACFs) provided an opportunity to assess VE in the frail, institutionalised elderly. Data were pooled from five influenza outbreaks in 2007. Rapid testing methods for influenza were used to confirm outbreaks and/or identify further cases. Vaccination coverage among ACF residents ranged from 59% to 100%, whereas it was consistently low in staff (11–33%). The attack rates for laboratory-confirmed influenza in residents ranged from 9% to 24%, with the predominate strain determined to be influenza A. Sequencing of the hemagglutinin gene from a sub-sample demonstrated an incomplete match with the 2007 southern hemisphere influenza vaccine. Influenza VE was estimated to be 61% (95%CI 6%, 84%) against laboratory-confirmed influenza, 51% (95%CI −16%, 79%) against influenza-like illness, 82% (95%CI 27%, 96%) against pneumonia-related and influenza-related hospitalisations and 71% (95%CI −28%, 95%) against death from all causes. This supports the continued policy of targeted vaccination of the institutionalised, frail elderly. There is also reassurance that influenza vaccine can be effective against disease and severe outcomes, despite an incomplete vaccine match. This benefit is additional to protection from antivirals. [Copyright &y& Elsevier]

Previous analyses suggest that children with tuberculosis (TB) are no more or no less likely to have multidrug (MDR)- or rifampicin-resistant (RR)-TB than adults. However, the availability of new data, particularly for high MDR/RR-TB burden countries, suggest updates of country-specific estimates are warranted.We used data from population-representative surveys and surveillance collected between 2000 and 2018 to compare the odds ratio of MDR/RR-TB among children (aged <15 years) with TB, compared to the odds of MDR/RR-TB among adults (aged ≥15 years) with TB.In most settings (45 out of 55 countries), and globally as a whole, there is no evidence that age is associated with odds of MDR/RR-TB. However, in some settings, such as former Soviet Union countries in general, and Georgia, Kazakhstan, Lithuania, Tajikistan and Uzbekistan in particular, as well as Peru, MDR/RR-TB is positively associated with age ≥15 years. Meanwhile, in Western Europe in general, and the United Kingdom, Poland, Finland and Luxembourg in particular, MDR/RR-TB is positively associated with age <15 years. 16 countries had sufficient data to compare over time between 2000-2011 and 2012-2018, with evidence for decreases in the odds ratio in children compared to adults in Germany, Kazakhstan and the United States of America.Our results support findings that in most settings a child with TB is as likely as an adult with TB to have MDR/RR-TB. However, setting-specific heterogeneity requires further investigation. Furthermore, the odds ratio for MDR/RR-TB in children compared to adults is generally either stable or decreasing. There are important gaps in detection, recording and reporting of drug resistance among paediatric TB cases, limiting our understanding of transmission risks and measures needed to combat the global TB epidemic., Competing Interests: Conflict of interest: C.F. McQuaid has nothing to disclose. Conflict of interest: T. Cohen has nothing to disclose. Conflict of interest: A.S. Dean has nothing to disclose. Conflict of interest: R.M.G.J. Houben has nothing to disclose. Conflict of interest: G.M. Knight has nothing to disclose. Conflict of interest: M. Zignol has nothing to disclose. Conflict of interest: R.G. White has nothing to disclose., (Copyright ©ERS 2021.)

Males are at an increased risk of tuberculosis (TB) disease compared to females. Additionally, several risk factors for multidrug-resistant (MDR) or rifampicin-resistant (RR) TB disease are more common in males, hence male TB patients may have a higher relative risk of MDR/RR-TB than female TB patients.We used sex-disaggregated data of TB patients reported to the World Health Organization for 106 countries to calculate male-to-female (M:F) risk ratios of having MDR/RR-TB.There was no evidence of either sex being more at risk of MDR/RR-TB in 81% (86 out of 106) of countries, with an overall random-effects weighted M:F risk ratio of 1.04 (95% CI 0.97-1.11). In 12% (13 out of 106) of countries there was evidence that males were more at risk, while in 7% (seven out of 106), females were more at risk. The risk of having TB that was MDR/RR increased for males compared to females as MDR/RR-TB incidence increased, and was higher for males than females in the former Soviet Union, where the risk ratio was 1.16 (1.06-1.28). Conversely, the risk increased for females compared to males as gross domestic product purchase power parity increased, and was higher for females than males in countries where the majority of TB burden was found in the foreign-born population, where the risk ratio was 0.84 (0.75-0.94).In general, the risk of MDR/RR-TB, among those with TB, is the same for males as for females. However, males in higher MDR/RR-TB burden countries, particularly the former Soviet Union, face an increased risk that their infection is MDR/RR-TB, highlighting the need for a sex-differentiated approach to TB case-finding and care., Competing Interests: Conflict of interest: C.F. McQuaid has nothing to disclose. Conflict of interest: K.C. Horton has nothing to disclose. Conflict of interest: A.S. Dean has nothing to disclose. Conflict of interest: G.M. Knight has nothing to disclose. Conflict of interest: R.G. White has nothing to disclose., (The content of this work is copyright of the authors or their employers. Design and branding are copyright ©ERS 2020.)

As we move into the era of the Sustainable Development Goals (SDGs), the World Health Organization (WHO) has developed the End TB strategy 2016-2035 with a goal to end the global epidemic of tuberculosis (TB) by 2035. Achieving the targets laid out in the Strategy will require strengthening of the whole TB diagnosis and treatment cascade, including improved case detection, the establishment of universal drug susceptibility testing and rapid treatment initiation. An estimated 3.9% of new TB cases and 21% of previously treated cases had rifampicin-resistant (RR) or multidrug-resistant (MDR) TB in 2015. These levels have remained stable over time, although limited data are available from major high burden settings. In addition to the emergence of drug resistance due to inadequate treatment, there is growing evidence that direct transmission is a large contributor to the RR/MDR-TB epidemic. Only 340,000 of the estimated 580,000 incident cases of RR/MDR-TB were notified to WHO in 2015. Among these, only 125,000 were initiated on second-line treatment. RR/MDR-TB epidemics are likely to be driven by direct transmission. The most important risk factor for MDR-TB is a history of previous treatment. Other risk factors vary according to setting but can include hospitalisation, incarceration and HIV infection. Children have the same risk of MDR-TB as adults and represent a diagnostic and treatment challenge. Rapid molecular technologies have revolutionized the diagnosis of drug-resistant TB. Until capacity can be established to test every TB patient for rifampicin resistance, countries should focus on gradually expanding their coverage of testing. DNA sequencing technologies are being increasingly incorporated into patient management and drug resistance surveillance. They offer additional benefits over conventional culture-based phenotypic testing, including a faster turn-around time for results, assessment of resistance patterns to a range of drugs, and investigation of strain clustering and transmission.