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Background Brucellosis, as a serious zoonotic infectious disease, has been recognized as a re-emerging disease in the developing countries worldwide. In china, the incidence of brucellosis is increasing each year, seriously threatening the health of humans as well as animal populations. Despite a quite number of diagnostic methods currently being used for brucellosis, innovative technologies are still needed for its rapid and accurate diagnosis, especially in area where traditional diagnostic is unavailable. Methodology/Principal findings In this study, a total of 22 B cell linear epitopes were predicted from five Brucella outer membrane proteins (OMPs) using an immunoinformatic approach. These epitopes were then chemically synthesized, and with the method of indirect ELISA (iELISA), each of them displayed a certain degree of capability in identifying human brucellosis positive sera. Subsequently, a fusion protein consisting of the 22 predicted epitopes was prokaryotically expressed and used as diagnostic antigen in a newly established brucellosis testing method, nano-ZnO modified paper-based ELISA (nano-p-ELISA). According to the verifying test using a collection of sera collected from brucellosis and non-brucellosis patients, the sensitivity and specificity of multiepitope based nano-p-ELISA were 92.38% and 98.35% respectively. The positive predictive value was 98.26% and the negative predictive value was 91.67%. The multiepitope based fusion protein also displayed significantly higher specificity than Brucella lipopolysaccharide (LPS) antigen. Conclusions B cell epitopes are important candidates for serologically testing brucellosis. Multiepitope fusion protein based nano-p-ELISA displayed significantly sensitivity and specificity compared to Brucella LPS antigen. The strategy applied in this study will be helpful to develop rapid and accurate diagnostic method for brucellosis in human as well as animal populations., Author summary Brucellosis is one of the most important zoonosis in the world and has caused tremendous economic losses in agriculture and animal husbandry in many countries. Developing rapid, sensitive and specific diagnostic methods is very important for early detection and treatment of brucellosis patients. In this study, a novel diagnostic technique, nano-ZnO modified paper ELISA, was established. The antigen used in this technique was a fusion protein containing multiple B cell epitopes, which were predicted from Brucella major outer membrane proteins such as Bp26, Omp31, Omp16, Omp2b and Omp25. Comparing to traditional LPS antigen, this multiepitope based antigen displayed considerably higher sensitivity and higher specificity in laboratory. With the strategy described in this paper, more efficient epitopes and protein antigen can be identified in the future. Currently, LPS antigen is only prepared from live Brucella, while protein antigen can be produced in large quantities in prokaryotic expression system. In addition to nano-p-ELISA, this protein antigen can also be used for development other methods such as fluorescent polarization assay (FPA) and immunochromatographic assay (ICA) to meet the varied demand for brucellosis testing.

Introduction Pure Neural Leprosy (PNL) is a rare clinical form of leprosy in which patients do not present with the classical skin lesions but have a high burden of the disability associated with the disease. Clinical characteristics and follow up of patients in PNL are still poorly described in the literature. Objective This paper aims to describe the clinical, electrophysiological and histopathological characteristics of PNL patients, as well as their evolution after multidrug therapy (MDT). Methods Fifty-two PNL patients were selected. Clinical, nerve conduction studies (NCS), histopathological and anti-PGL-1serology were evaluated. Patients were also assessed monthly during the MDT. At the end of the MDT, all of the patients had a new neurological examination and 44 were submitted to another NCS. Results Paresthesia was the complaint most frequently reported by patients, and in the neurological examination the most common pattern observed was impairment in sensory and motor examination and a mononeuropathy multiplex. Painful nerve enlargement, a classical symptom of leprosy neuropathy, was observed in a minority of patients and in the motor NCS axonal injuries, alone or in combination with demyelinating features, were the most commonly observed. 88% of the patients did not present any leprosy reaction during MDT. There was no statistically significant difference between the neurological examinations, nor the NCS pattern, performed before and after the MDT. Discussion The classical hallmarks of leprosy neuropathy are not always present in PNL making the diagnosis even more challenging. Nerve biopsy is an important tool for PNL diagnosis as it may guide therapeutic decisions. This paper highlights unique characteristics of PNL in the spectrum of leprosy in an attempt to facilitate the diagnosis and management of these patients., Author summary Neuropathy is responsible for most of the disability associated with leprosy disease. The pure neural leprosy (PNL), in spite of being a rare clinical presentation of that, has some singular characteristics that are still poorly studied. In this study, we selected 52 patients at the diagnosis to describe their clinical, neurophysiological and histopathological presentation patterns as well as their evolution during the multidrug therapy (MDT). We confirmed that sensitive symptoms were the most commonly described by PNL patients but neural pain is rare. Also confirmed that mononeuropathy mutiplex was the most common pattern observed at neurological examination and at the nerve conduction studies at the moment of the diagnosis. However we showed that painful nerve enlargement other cardinal signs of leprosy, besides the skin lesions, is not common in this group of patients, There was no statistically significant difference between the neurological examination and NCS performed before and after the MDT.During the MDT88.4% of the patients did not have any leprosy reaction. This may suggest that that MDT was effective in stopping disease progression. Our results highlight the difficulties in the diagnosis of PNL and the progression following MDT in an attempt to prevent further disability in PNL patients.

The microscopic agglutination test (MAT) is the standard serological reference test for the diagnosis of leptospirosis, despite being a technically demanding and laborious procedure. The use of a locally optimised MAT panel is considered essential for proper performance and interpretation of results. This paper describes the procedure of selecting such an optimised panel for Sri Lanka, a country hyper-endemic for leptospirosis. MAT was performed using 24 strains on 1132 serum samples collected from patients presenting with acute undifferentiated fever. Of 24 strains, 15 were selected as the optimised panel, while only 11% of serum samples showed positivity. A geographical variation in predominantly reactive serovars was observed, whereas reactivity was low with the saprophytic strain Patoc. Testing with paired sera yielded a higher sensitivity but provided only a retrospective diagnosis. Serological tests based on ELISA with complementary molecular diagnosis using PCR are a feasible and robust alternative approach to diagnose leptospirosis in countries having a higher burden of the disease., Author summary Microscopic agglutination test is the most commonly used serological test in the diagnosis of leptospirosis. The test uses a live panel of Leptospira representing main serogroups and for proper performance of the test, an optimised panel which react well with patient samples need to be selected. This paper describes the procedure of selecting such an optimised panel for Sri Lanka which is a country hyper-endemic for leptospirosis. The test was done on serum samples collected from patients presented with acute undifferentiated fever with 24 panel of serogroups and 15 were selected as the optimised panel. The test was found to have a low sensitivity in the acute stage and ELISA based serological tests with molecular diagnosis using PCR assays would be a better way for diagnosis of leptospirosis.

Replication is an important tool to promote high quality research and ensure policy makers can rely on studies in making guidelines or funding programs. By ensuring influential studies are replicable we provide assurance that the policies based on these studies are well-founded and the conclusions and recommendations are robust-to different estimation models or different choices. In this paper, we argue that replication is not only useful but necessary to ensure that an author's choice in how to analyse data is not the only factor that determines whether an intervention is effective or not. We also show that while most research is done well and provides robust results, small differences can lead to different interpretations and these differences need to be acknowledged. This special issue highlights 5 such replication studies, which are replications of influential studies on biomedical, social, behavioural and structural interventions for HIV prevention and treatment. We reflect on their findings. Four out of five studies, which conduct push button replication and pure replication, were able to reproduce the results of the original studies with minor differences, mainly due to minor typographical errors or rounding differences. The analysis of the measurement and estimation analyses conducted in these five studies reveals that the original results are not very robust to alternative analytical approaches, especially when these results rely on a small number of observations. In these cases, the original results are weakened. Furthermore, in contrast to the original papers, two of the five included replication studies conducted a theory of change analysis-to explore how or why the interventions work (or do not) not just whether the intervention works or not. These two analyses indicate that the estimated impacts of the interventions are drawn from few mediators. In addition, they demonstrate that, in some cases, a lack of effect may be related to lack of adequate exposure to the intervention rather than inefficacy of the intervention per se. However, overall, the included replication studies show that the results presented in the original papers are trustworthy and robust, especially when based on larger sample sizes. Replication studies can not only verify the results of a study, they can also provide additional insights on the published results, such as how and why an intervention was effective or less effective than expected. They can thus be a tool to inform the research community and/ or policymakers about whether and how interventions could be adopted, which need to be tested further, and which should be discontinued because of their ineffectiveness. Thus, publishing these replication studies in peer-reviewed journals makes the work public and publicized. The work advances knowledge, and publication should be encouraged, as it is for other types of research.

Background Although trachoma causes more cases of preventable blindness than any other infectious disease, a combination of strategies is reducing its global prevalence. As a district moves toward eliminating trachoma as a public health problem, national programs conduct trachoma impact surveys (TIS) to assess whether to stop preventative interventions and trachoma surveillance surveys (TSS) to determine whether the prevalence of active trachoma has rebounded after interventions have halted. In some contexts, programs also conduct trachomatous trichiasis (TT)-only surveys. A few costing studies of trachoma prevalence surveys exist, but none examine TIS, TSS, or TT-only surveys. Methodology/Principal findings We assessed the incremental financial cost to the national program of TIS, TSS, and TT-only surveys, which are standardized cluster-sampled prevalence surveys. We conducted a retrospective review of expenditures and grant disbursements for TIS and TSS in 322 evaluation units in 11 countries between 2011 and 2018. We also assessed the costs of three pilot and five standard TT-only surveys in four countries between 2017 and 2018. The median cost of TIS and TSS was $8,298 per evaluation unit [interquartile range (IQR): $6,532–$10,111, 2017 USD]. Based on a linear regression with bootstrapped confidence intervals, after controlling for country, costs per survey did not change significantly over time but did decline by $83 per survey implemented in a single round (95% CI: -$108 –-$63). Of total costs, 80% went to survey fieldwork; of that, 58% went towards per diems and 38% towards travel. TT-only surveys cost a median of $9,707 (IQR: $8,537–$11,635); within a given country, they cost slightly more (106% [IQR: 94%–136%]) than TIS and TSS. Conclusions/Significance The World Health Organization requires trachoma prevalence estimates for validating the elimination of trachoma as a public health problem. This study will help programs improve their planning as they assemble resources for that effort., Author summary The global health community is working to eliminate trachoma, a bacterial disease that causes blindness. The elimination strategy includes offering antibiotics to everyone living in communities with a high prevalence of active trachoma, also known as mass drug administration, and providing surgeries for people with advanced trachoma. The World Health Organization requires that countries conduct surveys to see whether a district has reached the prevalence benchmarks for stopping population-level prevention interventions against trachoma. After stopping these interventions, programs conduct more surveys to make sure that trachoma has remained at bay. Trachoma programs must include the costs of these surveys in their budgets. Although some estimates of the costs of baseline trachoma prevalence surveys already exist, none examine the costs of additional surveys required later in the program. In this paper, we analyze the costs of over 300 of these surveys. We find that they cost about $8,000-$10,000 per survey, varying widely by country. Variations are mostly driven by how much it costs to pay surveyors and transport them to survey sites. Costs did not appear to change over time. With the data that we present in this paper, national programs will be more prepared to plan for monitoring the elimination of trachoma.

Background Leprosy is a condition that has long been associated with stigma and discrimination, even when infected persons have been cured. This paper describes stigma and discrimination as viewed by caregivers who are associated with people affected by leprosy in Ghana. Methods A qualitative interview with semi-structured interviews were conducted for twenty caregivers. Results Findings indicated that caregivers were of the view that people affected by leprosy in Ghana are stigmatized and discriminated against by the larger society thus making their movements and interactions restricted to the Leprosarium. Besides, employments opportunities are unavailable to them thus making them exposed to financial challenges. The livelihood Empowerment Against poverty (LEAP) money given them is not sufficient for their daily upkeep. Conclusion People affected by leprosy in Ghana are stigmatized and therefore find it difficult to interact freely with the public. The associated physical deformities with the disease also tend to impede their ability to relate to the general public. The LEAP cash given to people affected by leprosy is helpful however, it could be enhanced to keep pace with prevailing economic conditions in the country., Author summary In Ghana, the social interpretation of leprosy regardless of the language, culture and tradition engenders stigmatization and discrimination that leads to social rejection and exclusion of persons who have been cured of the disease. Often, these persons are cared for by relatives who happen to live with them in a confined place. From the views of these caregivers, this paper identifies areas of stigmatizing and discriminatory tendencies against people affected by leprosy who reside in a Leprosarium in Accra, the capital city. It is expected that persons suffering from such neglected tropical disease would be empowered to enable them go about their daily routines without the fear of being rejected. Besides, the intensification of public education about curing tendencies of stigma becomes paramount.

TB is rated as one of the world's deadliest diseases and South Africa ranks 9th out of the 22 countries with hardest hit of TB. Although many pieces of research have been carried out on this subject, this paper steps further by inculcating past knowledge into the model, using Bayesian approach with informative prior. Bayesian statistics approach is getting popular in data analyses. But, most applications of Bayesian inference technique are limited to situations of non-informative prior, where there is no solid external information about the distribution of the parameter of interest. The main aim of this study is to profile people living with TB in South Africa. In this paper, identical regression models are fitted for classical and Bayesian approach both with non-informative and informative prior, using South Africa General Household Survey (GHS) data for the year 2014. For the Bayesian model with informative prior, South Africa General Household Survey dataset for the year 2011 to 2013 are used to set up priors for the model 2014.

Background One Health is particularly relevant to the Horn of Africa where many people’s livelihoods are highly dependent on livestock and their shared environment. In this context, zoonoses may have a dramatic impact on both human and animal health, but also on country economies. This scoping review aimed to characterise and evaluate the nature of zoonotic disease research in the Horn region. Specifically, it addressed the following questions: (i) what specific zoonotic diseases have been prioritised for research, (ii) what data have been reported (human, animal or environment), (iii) what methods have been applied, and (iv) who has been doing the research? Methodology/principal findings We used keyword combinations to search online databases for peer-reviewed papers and theses. Screening and data extraction (disease, country, domain and method) was performed using DistillerSR. A total of 2055 studies focusing on seven countries and over 60 zoonoses were included. Brucellosis attracted the highest attention in terms of research while anthrax, Q fever and leptospirosis have been comparatively under-studied. Research efforts did not always align with zoonoses priorities identified at national levels. Despite zoonoses being a clear target for ‘One Health’ research, a very limited proportion of studies report data on the three domains of human, animal and environment. Descriptive and observational epidemiological studies were dominant and only a low proportion of publications were multidisciplinary. Finally, we found that a minority of international collaborations were between Global South countries with a high proportion of authors having affiliations from outside the Horn of Africa. Conclusions/significance There is a growing interest in zoonoses research in the Horn of Africa. Recommendations arising from this scoping review include: (i) ensuring zoonoses research aligns with national and global research agendas; (ii) encouraging researchers to adopt a holistic, transdisciplinary One Health approach following high quality reporting standards (COHERE, PRISMA, etc.); and (iii) empowering local researchers supported by regional and international partnerships to engage in zoonoses research., Author summary Zoonoses are diseases that are transmissible between animals and humans. Some emerging or re-emerging zoonoses, like avian influenza, regularly make the headlines in international media. Others, like rabies or echinococcosis, which mainly affect poor communities, attract much less attention, and are considered neglected by the World Health Organisation (WHO). In the Horn of Africa, many people live in close proximity to livestock and depend on them for food and income. Their frequent interaction with animals increases the risk of contracting zoonoses. In our work, we have searched for existing research publications on zoonoses in the Horn of Africa to guide future research on most neglected areas. Based on 2055 publications, we have described which zoonoses have been studied where and using which method. Notably, we found that very limited research followed One Health approaches. That implies that separate focus was given to animals or humans and a single method or discipline was used, while the One Health approach advocates for multidisciplinary and multisectoral collaboration to address complex issues like zoonoses. Finally, we identified that a majority of authors were affiliated with countries from the Global North which hinders relevance, equity and sustainability of Global North-Global South research collaborations.

The World Health Organization (WHO) considers mycetoma, chromoblastomycosis, and paracoccidioidomycosis to be fungal neglected tropical diseases (FNTDs). Depending on climatic, cultural, and economic contexts, these diseases have a similar geographical distribution as many other diseases, particularly tuberculosis (TB) and malaria, but are often less targeted by the national and many international healthcare systems. Another subgroup of fungal infections, such as candidiasis, cryptococcosis, pneumocystosis, histoplasmosis, and to a lesser extent, aspergillosis, are known as AIDS-related mycoses. Although antiretroviral therapy (ART) has been able to decrease the mortality rate of these diseases, particularly cryptococcosis, the disproportionately low distribution of funds to their diagnosis and treatment remains an obstacle in saving and improving the lives of patients affected. A new wave of viral diseases dubbed the Coronavirus Disease 2019 (COVID-19) hit the world at the end of 2019. Due to progressive symptoms and high mortality rates of COVID-19 compared to fungal infections, particularly the FNTDs, funding is currently allocated predominantly for diagnostic and therapeutic research on COVID-19. As a result, advances in FNTDs and AIDS-related mycosis care are considerably reduced. This paper explores the association between COVID-19, FNTDs, and AIDS-related mycoses with a predictive perspective.

In several nations, caries in pre-school children remain a significant oral health issue. In an outbreak period such as the Coronavirus disease 2019 (COVID-19), remote contact and education aimed at the prevention of oral diseases and the preservation of children’s oral health are more relevant than ever. Currently, the amount of published applications is far higher than the published scientific studies while the problems of usability remains vulnerable. The goal of this paper was to comprehensively document the phase of development and usability testing of a mobile application for diet and oral health, namely Gigiku Sihat, which was primarily intended to be used by parents and guardians of pre-school children. The mobile application was developed using the System Development Life Cycle principle. Apart from searching for the available oral health application on Android platform, the initial requirement gathering process consisted of situational analysis, concept generation, content development, and features and functional requirement determination. The mobile application design and implementation evolved at each phase before being finalised. Gigiku Sihat was successfully developed in the Bahasa Malaysia. Finalised Gigiku Sihat was installed on mobile devices to determine the usability using translated and validated System Usability Scale questionnaire namely Skala Kebolehgunaan Aplikasi Mudah Alih (SKAMA). The mean score usability with score of 68 and above was deemed to have good usability. This study found that Gigiku Sihat mean (SD) usability score was 77.0 (14.18). The results were promising as they showed that Gigiku Sihat had a good usability. Thus, the development of this mobile application focusing on diet and oral health served as a new source of oral health education and provided a necessary foundation in developing future improved mobile application development for parents in the prevention of early childhood caries.

Introduction Tuberculosis screening of people living with human immunodeficiency virus is an intervention recommended by the WHO to control the dual epidemic of TB and HIV. The extent to which the intervention is adhered to by the HIV healthcare providers (fidelity) determines the intervention’s effectiveness as measured by patient outcomes, but literature on fidelity is scarce. This study assessed provider implementation fidelity to national guidelines on TB screening at HIV clinics in Ghana. Methods It was a cross-sectional study that used structured questionnaires to gather data, involving 226 of 243 HIV healthcare providers in 27 HIV clinics across Ghana. The overall fidelity score comprised sixteen items with a maximum score of 48 grouped into three components of the screening intervention (TB diagnosis, TB awareness and TB symptoms questionnaire). Simple summation of item scores was done to determine fidelity score per provider. In this paper, we define the level of fidelity as low if the scores were below the median score and were otherwise categorized as high. Background factors potentially associated with implementation fidelity level were assessed using cluster-based logistic regression. Odds ratio with 95% confidence interval (CI) was used as the measure of association. Results Of the 226 healthcare providers interviewed, 60% (135) were females with a mean age of 34.5 years (SD = 8.3). Most of them were clinicians [63% (142)] and had post-secondary non-tertiary education [62% (141)]. Overall, 53% (119) of the healthcare providers were categorized to have implemented the intervention with high fidelity. Also, 56% (126), 53% (120), and 59% (134) of the providers implemented the TB diagnosis, TB awareness and TB symptoms questionnaire components respectively with high fidelity. After adjusting for cluster effect, female providers (AOR = 2.36, 95%CI: 1.09–5.10, p = Conclusion The number of providers with fidelity scores above the median was marginally greater (6%) than the number with fidelity score below the median. Similarly, for each of the components, the number of providers with fidelity scores higher than the median was marginally higher. This could explain the existing fluctuations in the intervention outcomes in Ghana. We found gender, profession and education were associated with provider implementation fidelity. To improve fidelity level among HIV healthcare providers, and realize the aims of the TB screening intervention among PLHIV in Ghana, further training on implementing all components of the intervention is critical.

Background There are few data on the on post-treatment experiences of people who have been successfully treated for rifampicin-resistant (RR-)TB. Objective To describe the experiences and impact of RR-TB disease and therapy on post-treatment life of individuals who were successfully treated. Methods In this qualitative study in-depth interviews were conducted among a purposively selected sample from a population of individuals who were successfully treated for RR-TB between January 2008 and December 2018. Interview transcripts and notes were analysed using a thematic network analysis which included grounded theory and a framework for understanding pathophysiological mechanisms for post-TB morbidity and mortality. The analysis was iterative and the coding system developed focused on disease, treatment and post-treatment experiences of individuals. This paper follows the COREQ guidelines. Results For all 12 participants interviewed, the development of RR-TB disease, its diagnosis and the subsequent treatment were a major disruption to their lives as well as a transformative experience. On diagnosis of RR-TB disease, participants entered a liminal period in which their lives were marked with uncertainty and dominated by physical and mental suffering. Irrespective of how long ago they had completed their treatment, they all remembered with clarity the signs and symptoms of the disease and the arduous treatment journey. Post-treatment participants reported physical, social, psychological and economic changes as consequences of their RR-TB disease and treatment. Many participants reported a diminished ability to perform physical activities and, once discharged from the RR-TB hospital, inadequate physical rehabilitation. For some, these physical limitations impacted on their social life, and ultimately on their psychological health as well as on their ability to earn money and support their families. Conclusion The experiences and impact of RR-TB disease and therapy on post-treatment life of individuals successfully treated, highlights gaps in the current health care system that need to be addressed to improve the life of individuals post-treatment. A more holistic and long-term view of post-TB health, including the provision of comprehensive medical and social services for post-treatment care of physical ailments, social re-integration and the mitigation of the perceived fear and risk of getting TB again could be a central part of person-centred TB care.

Millions of people worldwide develop foodborne illnesses caused by Salmonella enterica (S. enterica) every year. The pathogenesis of S. enterica depends on flagella, which are appendages that the bacteria use to move through the environment. Interestingly, populations of genetically identical bacteria exhibit heterogeneity in the number of flagella. To understand this heterogeneity and the regulation of flagella quantity, we propose a mathematical model that connects the flagellar gene regulatory network to flagellar construction. A regulatory network involving more than 60 genes controls flagellar assembly. The most important member of the network is the master operon, flhDC, which encodes the FlhD4C2 protein. FlhD4C2 controls the construction of flagella by initiating the production of hook basal bodies (HBBs), protein structures that anchor the flagella to the bacterium. By connecting a model of FlhD4C2 regulation to a model of HBB construction, we investigate the roles of various feedback mechanisms. Analysis of our model suggests that a combination of regulatory mechanisms at the protein and transcriptional levels induce bistable FlhD4C2 levels and heterogeneous numbers of flagella. Also, the balance of regulatory mechanisms that become active following HBB construction is sufficient to provide a counting mechanism for controlling the total number of flagella produced., Author summary Salmonella causes foodborne illnesses in millions of people worldwide each year. Flagella, which are appendages that the bacteria use to move through the environment, are a key factor in the infection process. Populations of genetically identical bacteria have been observed to contain both motile cells, generally with 6–10 flagella, and nonmotile cells, with no flagella. In this paper, we use mathematical models of the gene network that regulates flagellar construction to explore how the bacteria controls the number of flagella produced. We suggest that a bacterium must accumulate a threshold amount of a master regulator protein to initiate flagella production and failure to reach the threshold results in no flagella. Downstream mechanisms that impact the amount of master regulator protein are sufficient to determine how many flagella are produced.

BackgroundDiagnosis of TB in pediatric population poses several challenges. A novel initiative was implemented in several major cities of India aimed at providing upfront access to free-of-cost Xpert MTB/RIF to presumptive pediatric TB cases. This paper aims to describe the experience of implementing this large initiative and assess feasibility of the intervention in high TB burden settings.MethodsData were drawn from the pediatric TB project implemented in 10 major cities of India between April 2014 and March 2018. In each city, providers, both public and private, were engaged and linked with a high throughput Xpert MTB/RIF lab (established in that city) through rapid specimen transportation and electronic reporting system. Rates and proportions were estimated to describe the characteristics of this cohort.ResultsOf the total 94,415 presumptive pediatric TB cases tested in the project, 6,270 were diagnosed positive for MTB (6.6%) on Xpert MTB/RIF (vs 2% on smear microscopy). Among MTB positives, 545 cases were rifampicin resistant (8.7%). The median duration between collection of specimens and reporting of results was 0 days (same day) and >89% cases were initiated on treatment. Approximately 50% of the specimens tested were non-sputum. The number of providers/facilities engaged under the project increased >10-fold (from 124 in Q2'14 to 1416 in Q1'18).ConclusionThis project, which was one of the largest initiatives globally among pediatric population, demonstrated the feasibility of sustaining rapid and upfront access to free-of-cost Xpert MTB/RIF testing. The project underscores the efficiency of this rapid diagnostic assay in tackling several challenges in pediatric TB diagnosis, identifies opportunities for further interventions as well as brings to light scope for effective engagement with healthcare providers. The findings have facilitated a policy decision by National TB Programme mandating the use of Xpert MTB/RIF as a primary diagnostic tool for TB diagnosis in children, which is being scaled-up.

BackgroundInfection, particularly in the first 5 years of life, is a major cause of childhood deaths globally, many deaths from infections such as pneumonia and meningococcal disease are avoidable, if treated in time. Some factors that contribute to morbidity and mortality can be modified. These include organisational and environmental factors as well as those related to the child, family or professional.ObjectiveExamine what organizational and environmental factors and individual child, family and professional factors affect timing of admission to hospital for children with a serious infectious illness.DesignSystematic review.Data sourcesKey search terms were identified and used to search CINAHL Plus, Medline, ASSIA, Web of Science, The Cochrane Library, Joanna Briggs Institute Database of Systematic Review.Study appraisal methodsPrimary research (e.g. quantitative, qualitative and mixed methods studies) and literature reviews (e.g., systematic, scoping and narrative) were included if participants included or were restricted to children under 5 years of age with serious infectious illnesses, included parents and/or first contact health care professionals in primary care, urgent and emergency care and where the research had been conducted in OECD high income countries. The Mixed Methods Appraisal Tool was used to review the methodological quality of the studies.Main findingsThirty-six papers were selected for full text review; 12 studies fitted the inclusion criteria. Factors influencing the timing of admission to hospital included the variability in children's illness trajectories and pathways to hospital, parental recognition of symptoms and clinicians non-recognition of illness severity, parental help-seeking behaviour and clinician responses, access to services, use and non-use of 'gut feeling' by clinicians, and sub-optimal management within primary, secondary and tertiary services.ConclusionsThe pathways taken by children with a serious infectious illness to hospital are complex and influenced by a variety of potentially modifiable individual, organisational, environmental and contextual factors. Supportive, accessible, respectful services that provide continuity, clear communication, advice and safety-netting are important as is improved training for clinicians and a mandate to attend to 'gut feeling'.ImplicationsRelatively simple interventions such as improved communication have the potential to improve the quality of care and reduce morbidity and mortality in children with a serious infectious illness.

Background Global roll out of Xpert MTB/RIF technology has resulted in dramatic changes in TB diagnosis. However, benefits in resource-limited, high-burden TB/HIV settings, remain to be verified. In this paper we describe the characteristics of a large cohort of TB patients in a rural hospital in Southern Mozambique before and after Xpert MTB/RIF introduction, together with some determinants of favorable treatment outcome. Methods We conducted a retrospective cohort study of TB infected patients ≥15 years of age, diagnosed and treated at Carmelo Hospital of Chokwe between January 1, 2006 and December 31, 2017. Patient demographic and clinical characteristics, and treatment outcomes were recorded and compared before and after Xpert MTB/RIF, which was introduced in the second semester of 2012. Results 9,655 patients were analyzed, with 44.1% females. HIV testing was conducted in 99.9% of patients, with 82.8% having TB/HIV co-infection. 73.2% of patients had a favorable treatment outcome. No increase was observed in the number of TB patients identified after introduction of Xpert MTB/RIF testing. Conclusion Upon introduction, Xpert testing seemed to have a punctual beneficial effect on TB treatment outcomes, however this effect apparently disappeared shortly afterwards. Challenges remain for integration of TB and HIV care, as worse outcomes are reported for those patients diagnosed with TB shortly after starting ART, and also for those never starting ART. The need of reasonably excluding TB disease before ART start should be highlighted to every health care provider engaged in HIV care.

Background Differentiated antiretroviral therapy (ART) delivery models, in which patients are provided with care relevant to their current status (e.g., newly initiating, stable on treatment, or unstable on treatment) has become an essential part of patient-centered health systems. In 2015, the South African government implemented Chronic Disease Adherence Guidelines (AGLs), which involved five interventions: Fast Track Initiation Counseling for newly initiating patients, Enhanced Adherence Counseling for patients with an unsuppressed viral load, Early Tracing of patients who miss visits, and Adherence Clubs (ACs) and Decentralized Medication Delivery (DMD) for stable patients. We evaluated two of these interventions in 24 South African facilities: ACs, in which patients meet in groups outside usual clinic procedures and receive medication; and DMD, in which patients pick up their medication outside usual pharmacy queues. Methods and findings We compared those participating in ACs or receiving DMD at intervention sites to those eligible for ACs or DMD at control sites. Outcomes were retention and sustained viral suppression (, Matthew Fox and colleagues report on outcomes of two tailored service delivery models for HIV therapy in South Africa., Author summary Why was this study done? Antiretroviral therapy (ART) has brought enormous benefits, enabling HIV patients to live longer and healthier lives. However, many patients struggle to adhere to this lifelong treatment, and their retention in care is suboptimal. To address this, South Africa’s National Department of Health has introduced National Adherence Guidelines for Chronic Diseases that recommend key interventions suitable for new patients, clinically stable patients, patients with advanced HIV disease or on a failing ART regimen, and lost-to-follow-up patients. The early implementation of these guidelines from 2015 was evaluated to understand the effectiveness of five interventions and learn about improvements for the guidelines’ rollout. This paper provides the results on adherence clubs and decentralized medication delivery, two interventions for efficient medication pick-up by clinically stable patients. What did the researchers do and find? We used a cluster-randomized evaluation design for adherence clubs and an observational study for decentralized medication delivery across 12 intervention and 12 control health facilities in 4 provinces. The 275 adherence club patients had improved retention in care at one year compared to the 294 controls, especially men, and comparable viral suppression within 18 months. The 232 patients receiving decentralized medication delivery had apparently lower retention in care than the 346 controls (possibly due to medication pick-up data not reaching clinics), and viral suppression was comparable overall, but men on decentralized medication delivery had apparently increased viral suppression. What do these findings mean? This programmatic evaluation with a comparison group provides the National Department of Health with many lessons for the national rollout of the guidelines and the effect one can expect from such alternative medication pick-up services. The control facilities were already offering some adherence and retention services, and the observed benefits of the guideline interventions are therefore additional. The comparable outcomes for decentralized medication delivery against standard of care, the retention benefit by adherence clubs, and the apparent increased effects among men suggest that these interventions can play an important role in South Africa’s ART program. Because the interventions also decentralize ART and reduce patients’ inconvenience, comparable outcomes are a potential success, and further work should investigate the cost–benefit relation and possible effects on decongesting clinics.

Biofilm-related infections of bones pose a significant therapeutic issue. In this article we present in vitro results of the efficacy of gentamicin released from a collagen sponge carrier against Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumoniae biofilms preformed on hydroxyapatite surface. The results indicate that high local concentrations of gentamicin released from a sponge eradicate the biofilm formed not only by gentamicin-sensitive strains but, to some extent, also by those that display a resistance pattern in routine diagnostics. The data presented in this paper is of high clinical translational value and may find application in the treatment of bone infections.

The survey described in this research paper aimed to investigate the economic and health impacts of birds on dairies. Birds are common pests on dairies, consuming and contaminating feed intended for cattle. As a result, dairy operators experience increased feed costs and increased pathogen and disease risk. We surveyed dairy operators attending the 2017 Washington Dairy Conference to examine the impact of birds on dairies in Washington State. Dairy operators reported feed losses valued at $55 per cow resulting in annual losses totaling $5.5 million in the Western region of the state and $9.2 million in the Eastern region of the state. Shooting was the most commonly used bird management method and European starlings (Sternus vulgaris) were the most frequently implicated species statewide. Bird abundance greater than 10,000 birds per day was associated with larger herd size and with self-reported presence of Johne's disease and Salmonella.

We refine and clinically parameterize a mathematical model of the humoral immune response against Shigella, a diarrheal bacteria that infects 80-165 million people and kills an estimated 600,000 people worldwide each year. Using Latin hypercube sampling and Monte Carlo simulations for parameter estimation, we fit our model to human immune data from two Shigella EcSf2a-2 vaccine trials and a rechallenge study in which antibody and B-cell responses against Shigella′s lipopolysaccharide (LPS) and O-membrane proteins (OMP) were recorded. The clinically grounded model is used to mathematically investigate which key immune mechanisms and bacterial targets confer immunity against Shigella and to predict which humoral immune components should be elicited to create a protective vaccine against Shigella. The model offers insight into why the EcSf2a-2 vaccine had low efficacy and demonstrates that at a group level a humoral immune response induced by EcSf2a-2 vaccine or wild-type challenge against Shigella′s LPS or OMP does not appear sufficient for protection. That is, the model predicts an uncontrolled infection of gut epithelial cells that is present across all best-fit model parameterizations when fit to EcSf2a-2 vaccine or wild-type challenge data. Using sensitivity analysis, we explore which model parameter values must be altered to prevent the destructive epithelial invasion by Shigella bacteria and identify four key parameter groups as potential vaccine targets or immune correlates: 1) the rate that Shigella migrates into the lamina propria or epithelium, 2) the rate that memory B cells (BM) differentiate into antibody-secreting cells (ASC), 3) the rate at which antibodies are produced by activated ASC, and 4) the Shigella-specific BM carrying capacity. This paper underscores the need for a multifaceted approach in ongoing efforts to design an effective Shigella vaccine.

BACKGROUND Homebased index case HIV testing (HHTC) has shown higher uptake and good yield than traditional HIV testing methods. World Health Organization has called for increased operational research to evaluate HIV care processes particularly linkage to care. In this paper, we present project results of the time taken to link newly identified PLHIV to care after HHTC in the Manicaland and Midlands provinces of Zimbabwe. METHODS We retrospectively reviewed community-facility referral data from the Zimbabwe HIV Care and Treatment project for newly diagnosed PLHIV for the period March-September 2016. A referral slip was given to a client after receiving a positive HIV results and was presented and filed upon reaching a health facility. In July 2016, the project started working with trained expert clients to assist with linkage to care. Data was entered in a spreadsheet and then imported for descriptive statistical analysis with EpiInfoTM Version 7.2.0.1. Odd ratios were used to identify factors associated with linkage to care within seven days. RESULTS Out of 1004 newly identified PLHIV between March and September 2016, 650 (64.7%) were linked to care. The median time taken to be linked to care was four days (Interquartile range 19 days). Overall, 63.1% (410) of PLHIV were linked to care within seven days of diagnosis and 85% within 30 days. PLHIV were more likely to be linked to care within seven days of diagnosis between July and September 2016 (OR = 4.1; p< 0.001), a period when ZHCT started working with expert clients to support linkage to care. CONCLUSION HHTC resulted in almost 63% of newly diagnosed PLHIV being linked into care within seven days, and 85% within 30 days. Linkage to care within seven days was significantly associated with the period of engaging expert clients in the project. We recommend community based HIV testing programs to work with expert clients to ensure timely linkages of new PLHIV.

Background Migrant labourers living in the slums of urban and industrial patches across India make up a key sub-population so far controlling Tuberculosis (TB) in the country is concerned. This is because many TB patients from these communities- remain under reached by the Revised National Tuberculosis Control Programme (RNTCP) of India. This marginalized community usually seeks early-stage healthcare from “friendly neighbourhood” non-formal health providers (NFHPs). Because, RNTCP has limited capacity to involve the NFHPs, an implementation research project was conceived, whereby an external partner would engage with the NFHPs to enable them to identify early TB symptomatics from this key sub-population who would be then tested using Xpert MTB/RIF technology. Diagnosed TB cases among them would be referred promptly to RNTCP for treatment. This paper aimed to describe the project and its impact. Methods Adopting a quasi-experimental before-after design, four RNTCP units from two major urban-industrial areas of Odisha were selected for intervention, which spanned five quarters and covered 151,400 people, of which 30% were slum-dwelling migrants. Two similar units comprised the control population. The hypothesis was, reaching the under reached in the intervention area through NFHPs would increase TB notification from these traditionally under-notifying units. RNTCP notification data during intervention was compared with pre-intervention era, adjusted for contemporaneous changes in control population Results The project detected 488 Xpert+ TB cases, of whom 466 were administered RNTCP treatment. This translated into notification of additional 198 new bacteriologically positive cases to RNTCP, a 30% notification surge, after adjustment for 2% decline in control. This meant an average quarterly increase in notification of 41.20(20.08, 62.31; p

In light of the increasing refusal of some parents to vaccinate children, public health strategies have focused on increasing knowledge and awareness based on a “knowledge-deficit” approach. However, decisions about vaccination are based on more than mere knowledge of risks, costs, and benefits. Individual decision making about vaccinating involves many other factors including those related to emotion, culture, religion, and socio-political context. In this paper, we use a nationally representative internet survey in the U.S. to investigate socio-political characteristics to assess attitudes about vaccination. In particular, we consider how political ideology and trust affect opinions about vaccinations for flu, pertussis, and measles. Our findings demonstrate that ideology has a direct effect on vaccine attitudes. In particular, conservative respondents are less likely to express pro-vaccination beliefs than other individuals. Furthermore, ideology also has an indirect effect on immunization propensity. The ideology variable predicts an indicator capturing trust in government medical experts, which in turn helps to explain individual-level variation with regards to attitudes about vaccine choice.

Background Yaws is an infectious, debilitating and disfiguring disease of poverty that mainly affects children in rural communities in tropical areas. In Cameroon, mass-treatment campaigns carried out in the 1950s reduced yaws to such low levels that it was presumed the disease was eradicated. In 2010, an epidemiological study in Bankim Health District detected 29 cases of yaws. Five different means of detecting yaws in clinical and community settings were initiated in Bankim over the following five years. Methodology This observational study reviews data on the number of cases of yaws identified by each of the five yaws detection approaches: 1) passive yaws detection at local clinics after staff attended Neglected Tropical Disease awareness workshops, 2) community-based case detection carried out in remote communities by hospital staff who relied on community health workers to identify cases, 3) yaws screening following mass Buruli Ulcer outreach programs being piloted in the district, 4) school-based screening programs conducted as stand-alone and follow-up activities to mass outreach events, and 5) house to house active surveillance activities conducted in thirty-eight communities. Implementation of each of the four community-based approaches was observed by a team of health social scientists tasked with assessing the strengths and limitations of each detection method. Findings Eight hundred and fifteen cases of yaws were detected between 2012 and 2015. Only 7% were detected at local clinics. Small outreach programs and household surveys detected yaws in a broad spectrum of communities. The most successful means of yaws detection, accounting for over 70% of cases identified, were mass outreach programs and school based screenings in communities where yaws was detected. Conclusion The five interventions for detecting yaws had a synergistic effect and proved to be valuable components of a yaws eradication program. Well planned, culturally sensitive mass outreach educational programs accompanied by school-based programs proved to be particularly effective in Bankim. Including yaws detection in a Buruli Ulcer outreach program constituted a win-win situation, as the demonstration effect of yaws treatment (rapid cure) increased confidence in early Buruli ulcer treatment. Mass outreach programs functioned as magnets for both diseases as well as other kinds of chronic wounds that future outreach programs need to address., Author summary Yaws is an infectious and disfiguring disease of poverty primarily affecting children in rural communities in tropical areas. Yaws is easily treated by a single dose of antibiotics and is on the World Health Organization’s eradication list. Yaws was thought eradicated in the Cameroon in the 1950s following aggressive mass-treatment campaigns. In 2010, epidemiological research revealed a resurgence of the disease. This paper discusses the relative success of five different means of detecting yaws in rural areas of Bankim District between 2012 and 2015. While few cases of yaws were detected at local clinics during this time, many cases were detected in the community. The most successful means of detecting yaws were mass outreach programs designed to educate the public about neglected tropical diseases found in the region, and follow up school-based screening programs. These programs were supported by local chiefs and traditional healers and found to be the best way of increasing community awareness about yaws, motivating community health workers to participate in outreach, and fostering trust in the free medical treatment being provided.

This is the first study to evaluate the serologic and molecular prevalence of Coxiella burnetii in cattle at national breeding stock farms in South Korea. These government farms have well-organized biosecurity and management systems to prevent livestock diseases. Of the 736 cattle in this study, 77 tested positive for antibodies against C. burnetii antigens (10.5%, 95% CI: 8.3–12.7) and 11 were positive for a C. burnetti infection on PCR analysis (1.5%, 95% CI: 0.6–2.4). Since the 16S rRNA sequences of C. burnetii from all 11 PCR-positive samples were identical, three representative samples (C-CN-3 from the southern region, C-JJ-9 from Jeju Island, and C-CB-37 from the central region) are described in this paper. These three sequences had 99.3–100% identity to those of C. burnetii deposited in GenBank. These sequences clustered with those from USA, Japan, and Greenland, underscoring the sequence similarity among C. burnetii isolates in these countries. Because C. burnetii was detected in cattle at well-managed national breeding stock farms, cattle at non-government operated farms may be more likely to be exposed to C. burnetii in South Korea. Thus, continuous surveillance and control strategies in animals and humans are required to prevent the transmission of C. burnetii to humans.

Background Studies have been conducted in developing countries using SMS to communicate with patients to reduce the number of missed appointments and improve retention in treatment, however; very few have been scaled up. One possible reason for this could be that patients or staff are dissatisfied with the method in some way. This paper reports a study of patients’ and healthcare workers’ (HCW) views on an mHealth intervention aiming to support retention in antiretroviral therapy (ART) and tuberculosis (TB) treatment in Mozambique. Methods The study was conducted at five healthcare centres in Mozambique. Automated SMS health promotions and reminders were sent to patients in a RCT. A total of 141 patients and 40 HCWs were interviewed. Respondents rated usefulness, perceived benefits, ease of use, satisfaction, and risks of the SMS system using a Likert scale questionnaire. A semi-structured interview guide was followed. Interviews were transcribed and thematic analysis was conducted. Results Both patients and HCW found the SMS system useful and reliable. Most highly rated positive effects were reducing the number of failures to collect medication and avoiding missing appointments. Patients’ confidence in the system was high. Most perceived the system to improve communication between health-care provider and patient and assist in education and motivation. The automatic recognition of questions from patients and the provision of appropriate answers (a unique feature of this system) was especially appreciated. A majority would recommend the system to other patients or healthcare centres. Risks also were mentioned, mostly by HCW, of unintentional disclosure of health status in cases where patients use shared phones. Conclusions The results suggest that SMS technology for HIV and TB should be used to transmit reminders for appointments, medications, motivational texts, and health education to increase retention in care. Measures must be taken to reduce risks of privacy intrusion, but these are not a main obstacle for scaling up systems of this kind.

Background Reducing social distance between hospital staff and patients and establishing clear lines of communication is a major challenge when providing in-patient care for people afflicted by Buruli ulcer (BU) and chronic ulcers. Research on hospitals as therapeutic communities is virtually non-existent in Africa and is currently being called for by medical anthropologists working in the field of health service and policy planning. This paper describes a pioneering attempt to establish a therapeutic community for patients suffering from BU and other chronic ulcers requiring long term hospital care in Benin. Methods A six-month pilot project was undertaken with the objectives of establishing a therapeutic community and evaluating its impact on practitioner and patient relations. The project was designed and implemented by a team of social scientists working in concert with the current and previous director of a hospital serving patients suffering from advanced stage BU and other chronic ulcers. Qualitative research initially investigated patients’ understanding of their illness and its treatment, identified questions patients had about their hospitalization, and ascertained their level of social support. Newly designed question–answer health education sessions were developed. Following these hospital wide education sessions, open forums were held each week to provide an opportunity for patients and hospital staff to express concerns and render sources of discontent transparent. Patient group representatives then met with hospital staff to problem solve issues in a non-confrontational manner. Psychosocial support for individual patients was provided in a second intervention which took the form of drop-in counseling sessions with social scientists trained to serve as therapy facilitators and culture brokers. Results Interviews with patients revealed that most patients had very little information about the identity of their illness and the duration of their treatment. This knowledge gap surprised clinic staff members, who assumed someone had provided this information. Individual counseling and weekly education sessions corrected this information gap and reduced patient concerns about their treatment and the status of their healing process. This led to positive changes in staff–patient interactions. There was widespread consensus among both patients and staff that the quality of communication had increased significantly. Open forums providing an opportunity for patients and staff to air grievances were likewise popular and patient representative meetings resulted in productive problem solving supported by the hospital administration. Some systemic problems, however, remained persistent challenges. Patients with ulcers unrelated to BU questioned why BU patients were receiving preferential treatment, given special medicines, and charged less for their care. The idea of subsidized treatment for one disease and not another was hard to justify, especially given that BU is not contagious. Conclusion This pilot project illustrates the basic principles necessary for transforming long term residential hospitals into therapeutic communities. Although the focus of this case study was patients suffering from chronic ulcers, the model presented is relevant for other types of patients with cultural adaptation., Author Summary Little is known about communication patterns and social relations between health staff and long -term patients in African hospitals. An ethnography of a reference hospital treating patients afflicted with Buruli Ulcer (BU) and other chronic ulcers in Benin was conducted. Sources of psychosocial distress and communication patterns compromising quality of care were documented. Based on this research, an intervention was mounted to transform the hospital into a higher functioning therapeutic community. Question: answer education sessions were introduced to provide patients the opportunity to inquire about their illness, it’s treatment and trajectory; weekly open- forums were established to give patients and hospital staff a chance to air grievances; patient representatives met with hospital staff to resolve problems in a non-confrontational manner, and psychosocial support for individual patients was provided through drop-in counseling sessions with social scientists in residence. Patients reported positive changes in the quality of their care and interactions with care providers, care providers reported that the problem solving process instituted was productive, and hospital administrators actively supported efforts to improve social relations and lines of communication. Systemic problems related to perceptions of preferential treatment for BU patients provided subsidized treatment supported by a national program remained contentious.

In a previous article, we outlined the efforts of the Neglected Tropical Diseases (NTD) lobby to overcome the diseases' snub in the 2000 Millennium Development Goals (MDGs) and to campaign for inclusion in the post-2015 development agenda [1]. In doing so, we noted the extraordinary achievements made by the lobby despite its view from outside of the MDG juggernaut, which singled out just three diseases for special consideration (HIV/AIDS, Malaria, and, latterly, Tuberculosis), leaving a group of previously disparate diseases to be formulated within a plan for inclusion. The plan resulted in a three-pronged attack forged on advocacy, policy, and science. The NTD lobby has grown significantly since the original 2003 WHO/Deutsche Gesellschaft fur Technische Zusammenarbeit (GTZ) meetings were convened to float the idea that the NTDs should be reconceptualised and tackled as a group moving forward. The original core group—Peter J. Hotez, David Molyneux, and Alan Fenwick (along with WHO’s Lorenzo Savioli and others)—has since been joined by representation from academia (e.g., PLOS Neglected Tropical Diseases), the third sector (e.g., the Global Network, the Neglected Tropical Disease Non-Governmental Development Organization Network), the pharmaceutical industry, donor agencies, and the philanthropic sector (cf. Uniting to Combat NTDs). The lobby is also formally supported by the World Health Organisation (through the WHO Roadmap [2] and WHA Resolution 66.12 [3]) and by the disease endemic country governments that have signed the Addis Ababa NTD Commitment. Yet, despite boasting swelling ranks and a number of sizeable achievements in the intervening period—for instance the landmark London Declaration—the NTD lobby has remained interested in the more mainstream development agenda. The advocacy goal has always been the formal inclusion of NTDs in the successor framework to the Millennium Development Goals: the post-2015 Sustainable Development Agenda. On 1 January 2016, the Sustainable Development Goals (SDGs or Global Goals) came into force. The particulars of the goals were finalised at the United Nations summit in September 2015, and, as hoped, NTDs gained a special mention in goal 3.3: "By 2030, end the epidemics of AIDS, tuberculosis, malaria, and neglected tropical diseases and combat hepatitis, waterborne diseases, and other communicable diseases" (p 16) [4]. But what is this mention worth and what are its implications? The SDGs are similar to the MDGs in that they represent time-bound targets and retain a focus on ending world poverty, but they break with the original eight MDGs in terms of their colossal scope. Composed of 17 goals and 169 targets, the SDGs are the result of an extensive three-year consultation involving multiple perspectives from government, civil society, expert groups, the private sector, and individuals. The MDGs were regularly critiqued as restricted in focus and top-down, something which cannot be levelled against the SDGs. But might the warning of the High-Level Panel that originally drafted the framework document have been ignored—"The international community will need to ensure that a single, sustainable framework agenda is not overloaded with too many priorities. A product of compromise rather than decisions…"? (p 14) [5]. The post-2015 vision—as articulated through the SDGs—is to create a single universal agenda in which the social, economic, and environmental dimensions of sustainability are integrated. Whereas the MDGs were criticised for targeting the low-hanging fruit, the post-2015 agenda is underpinned by the tenet “leave no one behind.” As the UN summit drew closer in 2015, we noted how this principle, coupled with the post-2015 focus on environmental issues, provided a number of advocacy issues behind which the NTD lobby began to position itself: equity, poverty, water sanitation and hygiene (WASH), climate change, quality education, NTD-related disability, and nutrition. In this paper, we reflect on the NTD lobby’s efforts to gain traction in the wide-ranging post-2015 agenda by making the case that NTDs are crosscutting and by lobbying for NTD indicators.

An unfused tetanus of a motor unit (MU) evoked by a train of pulses at variable interpulse intervals is the sum of non-equal twitch-like responses to these stimuli. A tool for a precise prediction of these successive contractions for MUs of different physiological types with different contractile properties is crucial for modeling the whole muscle behavior during various types of activity. The aim of this paper is to develop such a general mathematical algorithm for the MUs of the medial gastrocnemius muscle of rats. For this purpose, tetanic curves recorded for 30 MUs (10 slow, 10 fast fatigue-resistant and 10 fast fatigable) were mathematically decomposed into twitch-like contractions. Each contraction was modeled by the previously proposed 6-parameter analytical function, and the analysis of these six parameters allowed us to develop a prediction algorithm based on the following input data: parameters of the initial twitch, the maximum force of a MU and the series of pulses. Linear relationship was found between the normalized amplitudes of the successive contractions and the remainder between the actual force levels at which the contraction started and the maximum tetanic force. The normalization was made according to the amplitude of the first decomposed twitch. However, the respective approximation lines had different specific angles with respect to the ordinate. These angles had different and non-overlapping ranges for slow and fast MUs. A sensitivity analysis concerning this slope was performed and the dependence between the angles and the maximal fused tetanic force normalized to the amplitude of the first contraction was approximated by a power function. The normalized MU contraction and half-relaxation times were approximated by linear functions depending on the normalized actual force levels at which each contraction starts. The normalization was made according to the contraction time of the first contraction. The actual force levels were calculated initially from the recorded tetanic curves and subsequently from the modeled curves obtained from the summation of all models of the preceding contractions (the so called “full prediction”). The preciseness of the prediction was verified by two coefficients estimating the error between the modeled and the experimentally recorded curves. The proposed approach was tested for 30 MUs from the database and for three additional MUs, not included in the initial set. It was concluded that this general algorithm can be successfully used for modeling of a unfused tetanus course of a single MU of fast and slow type.

Background The British Columbia (BC) Hepatitis Testers Cohort (BC-HTC) was established to assess and monitor hepatitis C (HCV) epidemiology, cost of illness and treatment effectiveness in BC, Canada. In this paper, we describe the cohort construction, data linkage process, linkage yields, and comparison of the characteristics of linked and unlinked individuals. Methods The BC-HTC includes all individuals tested for HCV and/or HIV or reported as a case of HCV, hepatitis B (HBV), HIV or active tuberculosis (TB) in BC linked with the provincial health insurance client roster, medical visits, hospitalizations, drug prescriptions, the cancer registry and mortality data using unique personal health numbers. The cohort includes data since inception (1990/1992) of each database until 2012/2013 with plans for annual updates. We computed linkage rates by year and compared the characteristics of linked and unlinked individuals. Results Of 2,656,323 unique individuals available in the laboratory and surveillance data, 1,427,917(54%) were included in the final linked cohort, including about 1.15 million tested for HCV and about 1.02 million tested for HIV. The linkage rate was 86% for HCV tests, 89% for HCV cases, 95% for active TB cases, 48% for HIV tests and 36% for HIV cases. Linkage rates increased from 40% for HCV negatives and 70% for HCV positives in 1992 to ~90% after 2005. Linkage rates were lower for males, younger age at testing, and those with unknown residence location. Linkage rates for HCV testers co-infected with HIV, HBV or TB were very high (90–100%). Conclusion Linkage rates increased over time related to improvements in completeness of identifiers in laboratory, surveillance, and registry databases. Linkage rates were higher for HCV than HIV testers, those testing positive, older individuals, and females. Data from the cohort provide essential information to support the development of prevention, care and treatment initiatives for those infected with HCV.

Objective This study was aimed to find out epidemiologic characteristic of tuberculosis (TB) cases, and Human Immunodeficiency Virus (HIV) positive cases among TB patients (TB/HIV co-infection) through demographic, temporal, and spatial study in Urumqi. Methods Descriptive statistics and multivariate logistic regression were applied to identify the epidemiologic characteristics and risk factors of TB epidemic and TB/HIV co-infection epidemic. All addresses of each TB case, TB/HIV co-infection case, and administrative street were transformed into geographical coordinate. Subsequently, the geocoded address for 82 streets was transformed into a dot map used as the basis of spatial datasets. In addition, the paper also used quantile map and the spatial scan statistic in order to identify the spatial distribution and spatial clusters of TB epidemic and TB/HIV co-infection epidemic. Result There was a declining trend of the notification rates of TB epidemic from 2007 to 2009, as well as a rising trend from 2010 to 2013. However, the notification rates of TB/HIV co-infection epidemic showed a rising trend from 2007 to 2010, and a declining trend from 2011 to 2013. Moreover, a significant share of TB epidemic and TB/HIV co-infection epidemic happened between the age of 15 to 45 years old, indicating an increase in risk of TB and TB/HIV infection. It is worth noting that the risk of HIV infection for male TB patients was 2.947 times (95% CI [2.178, 3.988]) than that of female patients. Han ethnicity and Uygur ethnicity in urban region accounted for a large proportion of total TB and TB/HIV co-infection cases. Most of the TB cases of minorities in Urumqi showed a statistically significant increase in risk of HIV infection than Han ethnicity in Urumqi. In addition, the spatial distribution of TB epidemic and TB/HIV co-infection epidemic was highly skewed. Most of the local clusters were located in urban area and rural-urban continuum where showed an increase in risk of TB and TB/HIV infection. Conclusion The epidemiologic and spatial-temporal analysis of TB epidemic and TB/HIV co-infection epidemic demonstrates a potential connection between TB and HIV in Urumqi. Demographic, temporal, geographic factors are the reasons of causing TB and TB/HIV co-infection epidemic.

Soil is considered to be a major reservoir of Burkholderia pseudomallei in the environment. This paper investigates soil physicochemical properties that may influence presence of B. pseudomallei in soil samples from small ruminant farms in Peninsular Malaysia. Soil samples were collected from the farms and cultured for B. pseudomallei. The texture, organic matter and water contents, pH, elemental contents, cation exchange capacities, carbon, sulfur and nitrogen contents were determined. Analysis of soil samples that were positive and negative for B. pseudomallei using multivariable logistic regression found that the odds of bacterial isolation from soil was significantly higher for samples with higher contents of iron (OR = 1.01, 95%CI = 1.00–1.02, p = 0.03), water (OR = 1.28, 95%CI = 1.05–1.55, p = 0.01) and clay (OR = 1.54, 95%CI = 1.15–2.06, p = 0.004) compared to the odds of isolation in samples with lower contents of the above variables. These three factors may have favored the survival of B. pseudomallei because iron regulates expression of respiratory enzymes, while water is essential for soil ecology and agent’s biological processes and clay retains water and nutrients.

Introduction South Africa has the highest reported rates of multi-drug resistant TB in Africa, typified by poor treatment outcomes, attributable mainly to high default and death rates. Concomitant HIV has become the strongest predictor of death among MDR-TB patients, while anti-retroviral therapy (ART) has dramatically reduced mortality. TB Case fatality rate (CFR) is an indicator that specifically reports on deaths due to TB. Aim The aim of this paper was to investigate causes of death amongst MDR-TB patients, the contribution of conditions other than TB to deaths, and to determine if causes differ between HIV-uninfected patients, HIV-infected patients receiving ART and those without ART. Methods We carried out a retrospective review of data captured from the register of the MDR-TB programme of the North West Province, South Africa. We included 671 patients treated between 2000–2008; 59% of the cohort was HIV-infected and 33% had received ART during MDR treatment. The register contained data on treatment outcomes and causes of death. Results Treatment outcomes between HIV-uninfected cases, HIV-infected cases receiving ART and HIV-infected without ART differed significantly (p

Tuberculosis (TB) is highly infectious and one of the leading killers globally. Several studies from sub-Saharan Africa highlight health systems challenges that affect ability to cope with existing disease burden, including TB, although most of these employ survey-type approaches. Consequently, few address community or patient perspectives and experiences. At the same time, understanding of the mechanisms by which the health systems challenges translate into seeking or avoidance of formal health care remains limited. This paper applies the notion of human agency to examine the ways people who have symptoms suggestive of TB respond to and deal with the symptoms vis-à-vis major challenges inherent within health delivery systems. Empirical data were drawn from a qualitative study exploring the ways in which notions of masculinity affect engagement with care, including men’s well-documented tendency to delay in seeking care for TB symptoms. The study was carried out in three high-density locales of urban Blantyre, Malawi. Data were collected in March 2011 –March 2012 using focus group discussions, of which eight (mixed sex = two; female only = three; male only = three) were with 74 ordinary community members, and two (both mixed sex) were with 20 health workers; and in-depth interviews with 20 TB patients (female = 14) and 20 un-investigated chronic coughers (female = eight). The research process employed a modified version of grounded theory. Data were coded using a coding scheme that was initially generated from the study aims and subsequently progressively amended to incorporate concepts emerging during the analysis. Coded data were retrieved, re-read, and broken down and reconnected iteratively to generate themes. A myriad of problems were described for health systems at the primary health care level, centring largely on shortages of resources (human, equipment, and drugs) and unprofessional conduct by health care providers. Participants consistently pointed out how the problems could drive patients from promptly reporting symptoms at primary healthcare centres. The accounts suggest that in responding to illness symptoms including those suggestive of TB, patients navigate their options taking into cognisance past and current experiences with formal health systems. Understanding and factoring in the mediating role of such ‘agency’ is critical when implementing efforts to promote timely response to TB-suggestive symptoms.

Objectives Kyrgyzstan is one of the 27 high multidrug-resistant tuberculosis (MDR-TB) burden countries listed by the WHO. In 2012, Medecins Sans Frontieres (MSF) started a drug-resistant tuberculosis (DR-TB) project in Kara Suu District. A qualitative study was undertaken to understand the perception of TB and DR-TB in order to improve the effectiveness and acceptance of the MSF intervention and to support advocacy strategies for an ambulatory model of care. Methods This paper reports findings from 63 interviews with patients, caregivers, health care providers and members of communities. Data was analysed using a qualitative content analysis. Validation was ensured by triangulation and a ‘thick’ description of the research context, and by presenting deviant cases. Results Findings show that the general population interprets TB as the ‘lungs having a cold’ or as a ‘family disease’ rather than as an infectious illness. From their perspective, individuals facing poor living conditions are more likely to get TB than wealthier people. Vulnerable groups such as drug and alcohol users, homeless persons, ethnic minorities and young women face barriers in accessing health care. As also reported in other publications, TB is highly stigmatised and possible side effects of the long treatment course are seen as unbearable; therefore, people only turn to public health care quite late. Most patients prefer ambulatory treatment because of the much needed emotional support from their social environment, which positively impacts treatment concordance. Health care providers favour inpatient treatment only for a better monitoring of side effects. Health staff increasingly acknowledges the central role they play in supporting DR-TB patients, and the importance of assuming a more empathic attitude. Conclusions Health promotion activities should aim at improving knowledge on TB and DR-TB, reducing stigma, and fostering the inclusion of vulnerable populations. Health seeking delays and adherence problems will be countered by further implementation of shortened treatment regimens. An ambulatory model of care is proposed when convenient for the patient; hospitalisation is favoured only when seen as more appropriate for the respective individual.

Background Knowledge of tuberculosis incidence and associated factors is required for the development and evaluation of strategies to reduce the burden of HIV-associated tuberculosis. Methods Systematic literature review and meta-analysis of tuberculosis incidence rates among HIV-infected individuals taking combination antiretroviral therapy. Results From PubMed, EMBASE and Global Index Medicus databases, 42 papers describing 43 cohorts (32 from high/intermediate and 11 from low tuberculosis burden settings) were included in the qualitative review and 33 in the quantitative review. Cohorts from high/intermediate burden settings were smaller in size, had lower median CD4 cell counts at study entry and fewer person-years of follow up. Tuberculosis incidence rates were higher in studies from Sub-Saharan Africa and from World Bank low/middle income countries. Tuberculosis incidence rates decreased with increasing CD4 count at study entry and duration on combination antiretroviral therapy. Summary estimates of tuberculosis incidence among individuals on combination antiretroviral therapy were higher for cohorts from high/intermediate burden settings compared to those from the low tuberculosis burden settings (4.17 per 100 person-years [95% Confidence Interval (CI) 3.39–5.14 per 100 person-years] vs. 0.4 per 100 person-years [95% CI 0.23–0.69 per 100 person-years]) with significant heterogeneity observed between the studies. Conclusions Tuberculosis incidence rates were high among individuals on combination antiretroviral therapy in high/intermediate burden settings. Interventions to prevent tuberculosis in this population should address geographical, socioeconomic and individual factors such as low CD4 counts and prior history of tuberculosis.

Multi-drug resistant tuberculosis (MDR-TB) represents a threat to health and development in countries with high TB burden. China’s MDR-TB prevalence rate of 6.8% is the highest in the world. Interventions to remove barriers against effective TB control, and prevention of MDR-TB are urgently needed in the country. This paper reports a cross-sectional questionnaire survey of 513 pulmonary TB (PTB) patients, and qualitative interviews of 10 healthcare workers (HCWs), and 15 PTB patients. The objective was to assess barriers against effective control of PTB and prevention of MDR-TB by elucidating the perspectives of patients and healthcare providers. Results showed that more than half of the patients experienced patient delay of over 12.5 days. A similar proportion also experienced detection delay of over 30 days, and delay in initiating treatment of over 31 days. Consulting a non-TB health facility ≥3 times before seeking care at TB dispensary was a risk factor for both detection delay [AOR (95% CI): 1.89(1.07, 3.34) and delay in initiating treatment[AOR (95% CI): 1.88 (1.06, 3.36). Results revealed poor implementation of Directly Observed Therapy (DOT), whereby treatment of 34.3% patients was never monitored by HCWs. Only 31.8% patients had ever accessed TB health education before their TB diagnosis. Qualitative data consistently disclosed long patient delay, and indicated that patient’s poor TB knowledge and socioeconomic barriers were primary reasons for patient delay. Seeking care and being treated at a non-TB hospital was an important reason for detection delay. Patient’s long work hours and low income increased risk for treatment non-adherence. Evidence-based measures to improve TB health seeking behavior, reduce patient and detection delays, improve the quality of DOT, address financial and system barriers, and increase access to TB health promotion are urgently needed to address the burgeoning prevalence of MDR-TB in China.

Summary Mycobacterium abscessus is a rapidly growing non-tuberculous mycobacterial species that has been associated with a wide spectrum of human infections. As the classification and biology of this organism is still not well understood, comparative genomic analysis on members of this species may provide further insights on their taxonomy, phylogeny, pathogenicity and other information that may contribute to better management of infections. The MabsBase described in this paper is a user-friendly database providing access to whole-genome sequences of newly discovered M. abscessus strains as well as resources for whole-genome annotations and computational predictions, to support the expanding scientific community interested in M. abscessus research. The MabsBase is freely available at http://mabscessus.um.edu.my.

We establish a mathematical framework for studying immune interactions with Shigella, a bacteria that kills over one million people worldwide every year. The long-term goal of this novel approach is to inform Shigella vaccine design by elucidating which immune components and bacterial targets are crucial for establishing Shigella immunity. Our delay differential equation model focuses on antibody and B cell responses directed against antigens like lipopolysaccharide in Shigella’s outer membrane. We find that antibody-based vaccines targeting only surface antigens cannot elicit sufficient immunity for protection. Additional boosting prior to infection would require a four-orders-of-magnitude increase in antibodies to sufficiently prevent epithelial invasion. However, boosting anti-LPS B memory can confer protection, which suggests these cells may correlate with immunity. We see that IgA antibodies are slightly more effective per molecule than IgG, but more total IgA is required due to spatial functionality. An extension of the model reveals that targeting both LPS and epithelial entry proteins is a promising avenue to advance vaccine development. This paper underscores the importance of multifaceted immune targeting in creating an effective Shigella vaccine. It introduces mathematical models to the Shigella vaccine development effort and lays a foundation for joint theoretical/experimental/clinical approaches to Shigella vaccine design.

There is growing concern over the welfare of animals used in research, in particular when these animals develop pathology. The present study aims to identify the main sources of animal distress and to assess the possible implementation of refinement measures in experimental infection research, using mouse models of tuberculosis (TB) as a case study. This choice is based on the historical relevance of mouse studies in understanding the disease and the present and long-standing impact of TB on a global scale. Literature published between 1997 and 2009 was analysed, focusing on the welfare impact on the animals used and the implementation of refinement measures to reduce this impact. In this 12-year period, we observed a rise in reports of ethical approval of experiments. The proportion of studies classified into the most severe category did however not change significantly over the studied period. Information on important research parameters, such as method for euthanasia or sex of the animals, were absent in a substantial number of papers. Overall, this study shows that progress has been made in the application of humane endpoints in TB research, but that a considerable potential for improvement remains., Nuno H. Franco is funded by Fundação para a Ciência e Tecnologia (SFRH/BD/38337/2007). This work is funded by FEDER funds through the Operational Competitiveness Programme - COMPETE and by national funds through FCT - Fundação para a Ciência e Tecnologia under the project FCOMP-01-0124-FEDER-022718 (PEst-C/SAU/LA0002/2011.

BACKGROUND: The introduction of sophisticated treatment of bladder dysfunction and hydrocephalus allows the majority of SB patients to survive into adulthood. However, no systematic review on urological outcome in adult SB patients is available and no follow-up schemes exist. OBJECTIVES: To systematically summarize the evidence on outcome of urinary tract functioning in adult SB patients. METHODS: A literature search in PubMed and Embase databases was done. Only papers published in the last 25 years describing patients with open SB with a mean age >18 years were included. We focused on finding differences in the treatment strategies, e.g., clean intermittent catheterization and antimuscarinic drugs versus early urinary diversion, with regard to long-term renal and bladder outcomes. RESULTS: A total of 13 articles and 5 meeting abstracts on urinary tract status of adult SB patients were found describing a total of 1564 patients with a mean age of 26.1 years (range 3-74 years, with a few patients

BackgroundStreptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of life-threatening neonatal meningitis and survivors often suffer permanent neurological damage. How this organism interacts with the meninges and subsequently with astrocytes that constitute the underlying cortical glia limitans superficialis is not known.Methodology/principal findingsIn this paper, we demonstrate dose-dependent adherence of GBS over time to human meningioma cells and fetal astrocytes in vitro, which was not influenced by expression of either β-haemolysin/cytolysin (β-h/c) toxin, different capsule serotypes or by absence of capsule (p>0.05). Internalization of GBS by both cell types was, however, a slow and an infrequent event (only 0.02-0.4% of associated bacteria were internalised by 9 h). Expression of β-h/c toxin did not play a role in invasion (p>0.05), whereas capsule expression lead to a reduction (pConclusions/significanceThis study has described key events in the interactions of GBS with meningeal cells and astrocytes in vitro and a major virulence role for β-h/c toxin. Understanding the mechanisms involved will help to identify potential therapies for improving patient survival and for reducing the incidence and severity of neurological sequelae.

JC has an unpaid relationship with the World Health Organization in the Department of Global Alert and Response (Infection Prevention and Control Unit). All other authors have declared that no competing interests exist. The authors received no specific funding to write this paper. JC received financial support for a sabbatical leave from the University of Calgary, Calgary, Canada. Provenance: Not commissioned; externally peer reviewed.