Scale-free dynamics of COVID-19 in a Brazilian city.

A common basis to address the dynamics of directly transmitted infectious diseases, such as COVID-19, are compartmental (or SIR) models. SIR models typically assume homogenous population mixing, a simplification that is convenient but unrealistic. Here we validate an existing model of a scale-free fractal infection process using high-resolution data on COVID-19 spread in São Caetano, Brazil. We find that transmission can be described by a network in which each infectious individual has a small number of susceptible contacts, of the order of 2-5. This model parameter correlated tightly with physical distancing measured by mobile phone data, such that in periods of greater distancing the model recovered a lower average number of contacts, and vice versa. We show that the SIR model is a special case of our scale-free fractal process model in which the parameter that reflects population structure is set at unity, indicating homogeneous mixing. Our more general framework better explained the dynamics of COVID-19 in São Caetano, used fewer parameters than a standard SIR model and accounted for geographically localized clusters of disease. Our model requires further validation in other locations and with other directly transmitted infectious agents.

Computed tomographic findings in dogs with suspected aspiration pneumonia: 38 cases (2014-2019).

OBJECTIVES: To describe computed tomographic (CT) findings in dogs diagnosed with aspiration pneumonia and to assess for any correlation with patient outcome. MATERIALS AND METHODS: Retrospective analysis of 38 cases with a presumptive diagnosis of aspiration pneumonia at two UK referral centres. Medical records were reviewed for signalment, history, physical examination and clinicopathologic data. CT examinations of the thorax were reviewed by the European College of Veterinary Diagnostic Imaging board-certified radiologist for all dogs to describe the characteristics and distribution of the pulmonary lesions. RESULTS: The most common CT findings were lung lobe consolidation associated with air bronchograms (100%) followed by ground-glass attenuation (89.4%), bronchial wall thickening (36.8%), bronchiolectasis (31.5%) and bronchiectasis (15.7%). Large-breed dogs were overrepresented. Duration of hospitalisation ranged between 0 and 8 days (mean 3 days). Overall, 89.4% of dogs survived the aspiration event and were discharged from the hospital. The four dogs that did not survive to discharge had five or more lobes affected on CT. CLINICAL SIGNIFICANCE: CT findings in dogs with aspiration pneumonia are described. CT is a useful imaging modality to diagnose aspiration pneumonia.

Accelerating progress towards tuberculosis elimination: the need for combination treatment and prevention.

Although estimated tuberculosis (TB) incidence is now falling globally, we are unlikely to achieve the Millennium Development Goal (MDG) TB targets without changing the emphasis of the global TB response in high human immunodeficiency virus prevalence settings. Two independent modelling exercises using South African data with different structures and assumptions conclude that, until new drugs, diagnostics and vaccines are available, a fully funded and accessible combination approach to anti-tuberculosis treatment and prevention, based on knowledge of local TB epidemiology and evidence-informed policy, is essential to accelerate progress towards zero new tuberculous infections, zero TB deaths and zero suffering from TB.

Mass treatment to eliminate tuberculosis from an island population.

SETTING: The global target of tuberculosis (TB) elimination by 2050 requires new approaches. Active case finding plus mass prophylactic treatment has been disappointing. We consider mass full anti-tuberculosis treatment as an approach to TB elimination in Kiribati, a Pacific Island nation, with a persistent epidemic of high TB incidence. OBJECTIVE: To construct a mathematical model to predict whether mass treatment with a full course of anti-tuberculosis drugs might eliminate TB from the defined population of the Republic of Kiribati. METHODS: We constructed a seven-state compartmental model of the life cycle of Mycobacterium tuberculosis in which active TB disease arises from the progression of infection, reinfection, reactivation and relapse, while distinguishing infectious from non-infectious disease. We evaluated the effects of 5-yearly mass treatment using a range of parameter values to generate outcomes in uncertainty analysis. RESULTS: Assuming population-wide treatment effectiveness for latent tuberculous infection and active TB of ⩾90%, annual TB incidence is expected to fall sharply at each 5-yearly round of treatment, approaching elimination in two decades. The model showed that the incidence rate is sensitive to the relapse rate after successful treatment of TB. CONCLUSION: Mass treatment may help to eliminate TB, at least for discrete or geographically isolated populations.

How can mathematical models advance tuberculosis control in high HIV prevalence settings?

Existing approaches to tuberculosis (TB) control have been no more than partially successful in areas with high human immunodeficiency virus (HIV) prevalence. In the context of increasingly constrained resources, mathematical modelling can augment understanding and support policy for implementing those strategies that are most likely to bring public health and economic benefits. In this paper, we present an overview of past and recent contributions of TB modelling in this key area, and suggest a way forward through a modelling research agenda that supports a more effective response to the TB-HIV epidemic, based on expert discussions at a meeting convened by the TB Modelling and Analysis Consortium. The research agenda identified high-priority areas for future modelling efforts, including 1) the difficult diagnosis and high mortality of TB-HIV; 2) the high risk of disease progression; 3) TB health systems in high HIV prevalence settings; 4) uncertainty in the natural progression of TB-HIV; and 5) combined interventions for TB-HIV. Efficient and rapid progress towards completion of this modelling agenda will require co-ordination between the modelling community and key stakeholders, including advocates, health policy makers, donors and national or regional finance officials. A continuing dialogue will ensure that new results are effectively communicated and new policy-relevant questions are addressed swiftly.

Data needs for evidence-based decisions: a tuberculosis modeler's 'wish list'.

Infectious disease models are important tools for understanding epidemiology and supporting policy decisions for disease control. In the case of tuberculosis (TB), such models have informed our understanding and control strategies for over 40 years, but the primary assumptions of these models--and their most urgent data needs--remain obscure to many TB researchers and control officers. The structure and parameter values of TB models are informed by observational studies and experiments, but the evidence base in support of these models remains incomplete. Speaking from the perspective of infectious disease modelers addressing the broader TB research and control communities, we describe the basic structure common to most TB models and present a 'wish list' that would improve the evidence foundation upon which these models are built. As a comprehensive TB research agenda is formulated, we argue that the data needs of infectious disease models--our primary long-term decision-making tools--should figure prominently.

[Triple cutaneous mycosis (Cunninghamella bertholletiae, Phomopsis spp. and Paraconiothyrium spp.) in an immonucompromised patient: a Martinican case report]. / Mycoses cutanées àCunninghamella bertholletiae, Phomopsis sp. et Paraconiothyrium sp. chez un patient immunodéprimé : à propos d'un cas martiniquais.

INTRODUCTION: Patients from hematology department, with a weak immune system, can develop opportunist infections due to environment moulds that proliferate without notion of accidental inoculation or pre-existent lesion. CASE REPORT: We report a triple cutaneous infection case caused by Cunninghamella bertholletiae, Phomopsis spp. and Paraconiothyrium spp. on three different anatomic sites in a 68-years-old Martinican patient treated with high-dose chemotherapy and long-term corticotherapy for B-cell lymphoma and who also developed necrotic placards of legs. The patient's condition improved after stopping corticotherapy, treatment by voriconazole and medullary restoration. DISCUSSION: We will discuss about cases described in literature about those rare and different kinds of pathogenic agents while considering evolution, topography of lesions in our case, in order to focus on specificities. We shall emphasize the necessity to be careful about cutaneous hurt in immunocompromised patients.

Trends in tuberculosis incidence and their determinants in 134 countries.

OBJECTIVE: To determine whether differences in national trends in tuberculosis incidence are attributable to the variable success of control programmes or to biological, social and economic factors. METHODS: We used trends in case notifications as a measure of trends in incidence in 134 countries, from 1997 to 2006, and used regression analysis to explore the associations between these trends and 32 measures covering various aspects of development (1), the economy (6), the population (3), behavioural and biological risk factors (9), health services (6) and tuberculosis (TB) control (7). FINDINGS: The TB incidence rate changed annually within a range of +/-10% over the study period in the 134 countries examined, and its average value declined in 93 countries. The rate was declining more quickly in countries that had a higher human development index, lower child mortality and access to improved sanitation. General development measures were also dominant explanatory variables within regions, though correlation with TB incidence trends varied geographically. The TB incidence rate was falling more quickly in countries with greater health expenditure (situated in central and eastern Europe and the eastern Mediterranean), high-income countries with lower immigration, and countries with lower child mortality and HIV infection rates (located in Latin America and the Caribbean). The intensity of TB control varied widely, and a possible causal link with TB incidence was found only in Latin America and the Caribbean, where the rate of detection of smear-positive cases showed a negative correlation with national incidence trends. CONCLUSION: Although TB control programmes have averted millions of deaths, their effects on transmission and incidence rates are not yet widely detectable.

The decline of tuberculosis in Yemen: evaluation based on two nationwide tuberculin surveys.

SETTING: Yemen. OBJECTIVE: To review the epidemiological situation of tuberculosis (TB) in Yemen by conducting a tuberculin survey and by comparing the results obtained with those of a previous tuberculin survey from 1991. DESIGN: A nationwide tuberculin survey enrolling 31,276 schoolchildren aged between 7 and 12 years. RESULTS: Skin indurations were recorded for 28,499 schoolchildren, of whom 16,927 (59.4%) had no bacille Calmette-Guérin (BCG) scar. Analysis of the distribution of indurations was difficult as it did not show any bimodal pattern. Prevalence of infection and annual risk of tuberculosis infection (ARTI) were thus estimated using the mirror image and mixture methods, and not the cut-off point method. The two methods indicated similar results: respectively 0.45% and 0.51% for prevalence of infection, and 0.05% and 0.05% for ARTI. In comparison with the 1991 tuberculin survey, the average annual decline of ARTI was 9.0% by the mirror method and 5.5% by the mixture method. CONCLUSION: Yemen seems to have a low ARTI (0.05%), and TB infection seems to be declining considerably. Analysis of the survey results highlighted the limitations of tuberculin surveys in countries with comparable epidemiological situations.

Modelling local and global effects on the risk of contracting Tuberculosis using stochastic Markov-chain models.

For some diseases, the transmission of infection can cause spatial clustering of disease cases. This clustering has an impact on how one estimates the rate of the spread of the disease and on the design of control strategies. It is, however, difficult to assess such clustering, (local effects on transmission), using traditional statistical methods. A stochastic Markov-chain model that takes into account possible local or more dispersed global effects on the risk of contracting disease is introduced in the context of the transmission dynamics of tuberculosis. The model is used to analyse TB notifications collected in the Asembo and Gem Divisions of Nyanza Province in western Kenya by the Kenya Ministry of Health/National Leprosy and Tuberculosis Program and the Centers for Disease Control and Prevention. The model shows evidence of a pronounced local effect that is significantly greater than the global effect. We discuss a number of variations of the model which identify how this local effect depends on factors such as age and gender. Zoning/clustering of villages is used to identify the influence that zone size has on the model's ability to distinguish local and global effects. An important possible use of the model is in the design of a community randomised trial where geographical clusters of people are divided into two groups and the effectiveness of an intervention policy is assessed by applying it to one group but not the other. Here the model can be used to take the effect of case clustering into consideration in calculating the minimum difference in an outcome variable (e.g. disease prevalence) that can be detected with statistical significance. It thereby gauges the potential effectiveness of such a trial. Such a possible application is illustrated with the given time/spatial TB data set.

The measurement and estimation of tuberculosis mortality.

Tuberculosis (TB) ranks among the 10 principal causes of death and disability worldwide, largely on the basis of mortality estimates. These estimates have been derived by a variety of methods, from a limited database. Here we review the data and methods used to measure and estimate TB mortality in adults, assess the strengths and weaknesses of each and suggest ways to improve current mortality statistics. In principle, deaths attributable to TB can be obtained directly from national vital registration (VR) systems. However, only 59 of 213 countries in 2005 (including three in the World Health Organization Africa Region and one in the South-East Asia Region) had VR systems that reported TB deaths, corresponding to just 10% of all estimated deaths attributable to TB. Until comprehensive, national VR systems are established, an interim solution is to carry out verbal autopsies within sample VR schemes. The number of TB deaths from VR should ultimately converge with deaths recorded in national TB control programmes. At present, deaths in treatment cohorts cover a small subset of all estimated TB deaths (<13% in 2006), as deaths are missed among patients who are never diagnosed, who default or fail treatment, and among patients with untreated recurrent TB or TB sequelae. In contrast, some deaths recorded during treatment are not due to TB. To ensure convergence between cohort monitoring and VR, definitions of causes of death--including TB as an associate cause in deaths from human immunodeficiency virus/acquired immune-deficiency syndrome--should be standardised, so that both systems adhere to the International Classification of Diseases.

The design effect and cluster samples: optimising tuberculosis prevalence surveys.

Cross-sectional surveys of disease prevalence, including for tuberculosis (TB), often use a two (or more) stage sampling procedure. By choosing clusters of people randomly from all possible clusters, the logistic costs of doing the survey can be reduced. However, this increases the statistical uncertainty in the estimate of prevalence, and we need to balance the reduction in cost against the increase in uncertainty. Here we describe cluster sampling and consider ways to determine the optimal survey design as well as the extent to which deviations from the optimal design matter. We illustrate the results using data from a recent survey in Cambodia in which TB was diagnosed using sputum smears, cultures and X-rays.

Tuberculosis prevalence surveys: rationale and cost.

This article is the first of the educational series 'Assessing tuberculosis (TB) prevalence through population-based surveys'. The series will give overall guidance in conducting cross-sectional surveys of pulmonary TB (PTB) disease. TB prevalence surveys are most valuable in areas where notification data obtained through routine surveillance are of unproven accuracy or incomplete, and in areas with an estimated prevalence of bacteriologically confirmed TB of more than 100 per 100,000 population. To embark on a TB prevalence survey requires commitment from the national TB programme, compliance in the study population, plus availability of trained staff and financial resources. The primary objective of TB prevalence surveys is to determine the prevalence of PTB in the general population aged >or=15 years. Limitations of TB prevalence surveys are their inability to assess regional or geographic differences in prevalence of TB, estimate the burden of childhood TB or estimate the prevalence of extra-pulmonary TB. The cost of a prevalence survey is typically US$ 4-15 per person surveyed, and up to US$ 25 per person with radiographic screening. A survey of 50,000 people, of limited precision, would typically cost US$ 200,000-1,250,000.

From suspect to patient: tuberculosis diagnosis and treatment initiation in health facilities in South Africa.

SETTING: Thirteen primary health care (PHC) facilities in the Stellenbosch District, South Africa. OBJECTIVE: To assess the use of a sputum register to evaluate the tuberculosis (TB) diagnostic process and the initiation of TB treatment in selected PHC facilities in a country with a centralised laboratory system. DESIGN: This prospective study was conducted between April 2004 and March 2005. The names of all individuals submitting sputum samples for TB testing were noted in a newly introduced sputum register. We classified all TB suspects with two positive smears as TB cases and consulted TB treatment registers until 3 months after sputum submission to determine how many had started treatment. RESULTS: A total of 4062 persons aged > or =15 years submitted sputum samples, of whom 2484 were TB suspects. There were 2037 suspects with at least two results, 367 (18%) had at least two positive smears and 64 (17%) of these did not start treatment (initial defaulters). Over the entire diagnostic process, up to 5% of TB cases were missed, and up to 26% did not start treatment and were not reported. CONCLUSION: By correcting diagnostic weaknesses identified in the sputum register, PHC facilities will be able to detect, treat and cure a higher percentage of TB patients.

Measuring tuberculosis burden, trends, and the impact of control programmes.

The targets for tuberculosis control, framed within the United Nations' Millennium Development Goals, are to ensure that the incidence per head of tuberculosis is falling by 2015, and that the 1990 prevalence and mortality per head are halved by 2015. In monitoring progress in tuberculosis control, the ultimate aim for all countries is to count tuberculosis cases (incidence) accurately through routine surveillance. Disease prevalence surveys are costly and laborious, but give unbiased measures of tuberculosis burden and trends, and are justified in high-burden countries where many cases and deaths are missed by surveillance systems. Most countries in which tuberculosis is highly endemic do not yet have reliable death registration systems. Verbal autopsy, used in cause-of-death surveys, is an alternative, interim method of assessing tuberculosis mortality, but needs further validation. Although several new assays for Mycobacterium tuberculosis infection have recently been devised, the tuberculin skin test remains the only practical method of measuring infection in populations. However, this test typically has low specificity and is therefore best used comparatively to assess geographical and temporal variation in risk of infection. By 2015, every country should be able to assess progress in tuberculosis control by estimating the time trend in incidence, and the magnitude of reductions in either prevalence or deaths.

The decline of tuberculosis epidemics under chemotherapy: a case study in Morocco.

BACKGROUND: Tuberculosis (TB) case notifications per capita fell by only 3-4% per year in Morocco between 1996 and 2005, despite implementation of the World Health Organization (WHO) DOTS strategy since the early 1990s. At the current pace of epidemic decline, there will be more than 10,000 new cases in 2050, the target year for global elimination. METHODS: Analysis of cases reported by the National TB Control Programme, disaggregated by age, sex, clinical form of TB and region, for years 1996-2005. The validity of observed patterns was judged using four criteria: statistical validity, precision of measurement, biological plausibility and the consistency and strength of different lines of evidence. RESULTS: TB incidence (case numbers and rates) is higher in urban than in rural areas and higher in adult men than in women. The most infectious (smear-positive) form of the disease is more frequent in men with TB than women. Men aged 15-44 years accounted for half of all smear-positive cases in 2005. TB incidence has fallen more slowly than average among men, but the decline was also unexpectedly slow among women. CONCLUSIONS: In Morocco, men living in cities should be a focus for prevention and control. Globally, routine surveillance data should be more fully exploited to guide TB control activities.

Tuberculosis in European cities: establishment of a patient monitoring system over 10 years in Paris, France.

BACKGROUND: Tuberculosis (TB) is a persistent public health problem in European cities. France has been unable to report on treatment outcomes until now, and it is not known whether the World Health Organization (WHO) target cure rate of 85% has been met. METHODS: All patients placed under treatment in four hospitals and five out-patient Social Medical Centres in Paris were followed up between 1996 and 2005. Patient monitoring and evaluation were performed using a new software programme, TB-INFO. RESULTS: In a cohort of 1127 patients, 76% had pulmonary TB, of whom 39% were smear-positive, 81% were foreign-born and 9.3% were human immunodeficiency virus positive. At the end of the follow-up, 16% were cured and 54% had completed treatment. Among the 1118 non-multidrug-resistant patients, these percentages were 17% and 46%, respectively, for smear-positive pulmonary patients. Some patients died (1.9%) or failed treatment (0.1%), but many more defaulted (20.5%) as they interrupted treatment (1.5%), were lost to follow-up (19.5%) or were transferred out (7.9%). CONCLUSIONS: This 10-year follow-up of TB patients, managed with TB-INFO software, shows that a patient monitoring system can be implemented in France, providing essential information. Treatment success in this cohort of patients was far below the WHO target.

Three-fold reduction in the prevalence of tuberculosis over 25 years in Indonesia.

BACKGROUND: Tuberculosis (TB) remains the principal cause of death from a curable infectious disease. Indonesia is estimated to have the third highest case load worldwide, but TB prevalence has not been measured for 25 years. METHODS: In 2004, 20000 households were selected in all 30 provinces. All adults (aged >/=15 years) in every household were screened for symptoms of pulmonary tuberculosis (PTB). Among those with symptoms, TB was diagnosed by sputum smear microscopy and sputum culture. RESULTS: Eighty adults were positive on at least two sputum smears (104 per 100000 population, 95%CI 66-142). Prevalence was lower in Central Indonesia (Java-Bali, 59/100000) than in the Western (Sumatra, 160/100000) or Eastern regions (189/100000), but the estimated 225000 prevalent cases were distributed evenly among the three regions. The national per capita prevalence in 2004 was lower than in 1979-1982 by a factor of three (3.1, 95%CI 1.2-4.9), and the total number of cases was lower by a factor of two. CONCLUSIONS: Although the 2004 national survey may have underestimated the prevalence of smear-positive TB in Indonesia, there is strong evidence that it fell markedly between 1979-1982 and 2004.

Tuberculosis.

Tuberculosis (TB) is a disease of antiquity, caused by Mycobacterium tuberculosis, which principally affects the lungs. It is a major public-health problem, with around 9 million new cases and 2 million deaths estimated to occur each year. Patients with pulmonary TB whose sputum is smear-positive for M. tuberculosis form the main source of infection in communities. About 5%-10% of infected individuals are likely to develop symptomatic TB during their lives but the risk of developing the clinical manifestations of the disease is greatly increased by HIV co-infection. The strong association between HIV and TB in sub-Saharan Africa is responsible for the massive increase in the incidence of TB observed in that region in the last 20 years. Diagnosis of TB in resource-poor countries is largely based on sputum-smear microscopy and chest radiography, although these methods lack sensitivity or specificity, especially when used on HIV-infected patients. Effective treatment has existed for 40 years but TB-attributable mortality remains high among HIV-infected patients in Africa, who are also particularly likely to develop TB again after receiving drug treatment for the disease. In Eastern Europe it is drug resistance in the local M. tuberculosis that makes the treatment of TB relatively ineffective. The approach to TB control that is now internationally recommended is the DOTS ('directly-observed treatment, short-course') strategy, which aims to prevent the transmission of M. tuberculosis, and the related illness and death, by using combinations of anti-TB drugs to treat patients with the active disease. Unfortunately, countries in sub-Saharan Africa are falling short of the World Health Organization's targets for case detection and treatment. This failure is, in turn, making the achievement of the Millennium Development Goals for TB--to ensure that the incidence of TB is falling by 2015 and to halve the prevalence of TB and the annual number of TB-attributable deaths between 1990 and 2015--less likely. To improve the performance and impact of TB-control programmes, in the face of HIV co-infection and other constraints on DOTS, the World Health Organization has launched the revised 'Stop TB Strategy'. The new strategy, to be implemented via the Global Plan to Stop TB (2006-2015), includes intensified TB-case finding, treatment of latent TB infection with isoniazid, prevention of HIV infection, cotrimoxazole preventive therapy, and antiretroviral therapy.