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.

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.

Climate change and malaria: temperatures without fevers?

As the world gets warmer, the predictions about the spread of vector-based diseases such as malaria get gloomier. However, in their timely Perspective, Dye and Reiter explain the implications of a new climate model (Randolph and Rogers), which predicts that the distribution of malaria is unlikely to change dramatically in the next 50 years even if the world does get hotter.

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.

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 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.

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.

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.

Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness.

BACKGROUND: BCG vaccine has shown consistently high efficacy against childhood tuberculous meningitis and miliary tuberculosis, but variable efficacy against adult pulmonary tuberculosis and other mycobacterial diseases. We assess and compare the costs and effects of BCG as an intervention against severe childhood tuberculosis in different regions of the world. METHODS: We calculated the number of tuberculous meningitis and miliary tuberculosis cases that have been and will be prevented in all children born in 2002, by combining estimates of the annual risk of tuberculosis infection, the proportion of infections that lead to either of these diseases in unvaccinated children, the number of children vaccinated, and BCG efficacy. FINDINGS: We estimated that the 100.5 million BCG vaccinations given to infants in 2002 will have prevented 29,729 cases of tuberculous meningitis (5th-95th centiles, 24,063-36,192) in children during their first 5 years of life, or one case for every 3435 vaccinations (2771-4177), and 11,486 cases of miliary tuberculosis (7304-16,280), or one case for every 9314 vaccinations (6172-13,729). The numbers of cases prevented would be highest in South East Asia (46%), sub-Saharan Africa (27%), the western Pacific region (15%), and where the risk of tuberculosis infection and vaccine coverage are also highest. At US2-3 dollars per dose, BCG vaccination costs US206 dollars (150-272) per year of healthy life gained. INTERPRETATION: BCG vaccination is a highly cost-effective intervention against severe childhood tuberculosis; it should be retained in high-incidence countries as a strategy to supplement the chemotherapy of active tuberculosis.

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.

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 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.

Targets for global tuberculosis control.

The United Nations Millennium Development Goals (MDGs) have added to the suite of targets and indicators used to evaluate progress in tuberculosis (TB) control. This paper reviews the history of target setting for TB control and lays out the complete set of indicators and targets that will guide TB control through to 2015, the target year for all MDGs.

Tuberculosis deaths in countries with high HIV prevalence: what is their use as an indicator in tuberculosis programme monitoring and epidemiological surveillance?

Although the reduction of tuberculosis deaths is one of the aims of tuberculosis control, it has not always been a priority for National Tuberculosis Programmes (NTPs). The usual explanation is that death as a treatment outcome not associated with ongoing tuberculosis transmission is not relevant to the public health objective of cutting the cycle of disease transmission. However, death as an adverse outcome for tuberculosis patients and their families is an important indicator in NTP monitoring. Global health targets agreed as part of the Millennium Development Goals include the reduction of tuberculosis deaths. Tuberculosis deaths as an indicator of the impact of tuberculosis control measures are therefore important in the epidemiological surveillance of progress towards these targets. These considerations are particularly important in countries with high human immunodeficiency virus (HIV) prevalence where HIV has exacerbated the tuberculosis epidemic and is now the single best predictor of tuberculosis incidence. Tuberculosis deaths are also closely linked to HIV prevalence. Routine NTP data on tuberculosis cohort deaths are important in programme monitoring, and improvements in recording and reporting of deaths would help to overcome limitations in their accuracy. As routine NTP data on tuberculosis cohort deaths are insufficient as an indicator in epidemiological surveillance regarding the impact of NTPs on tuberculosis mortality, measuring progress towards targets for reduced tuberculosis deaths depends on improved national vital registration systems for a more accurate determination of tuberculosis mortality.

Preliminary study using an indirect ELISA for the detection of serum antibodies to Alternaria in domestic cats.

Alternaria is a saprophytic fungus that is widespread in the environment; it is an opportunistic pathogen and causes disease in human beings and domestic animals. Fungal spores gain entry to the host through skin lesions and cause slow-growing, soft to firm, subcutaneous swellings, either with or without ulcers. An indirect ELISA was developed for the detection of anti-Alternaria immunoglobulin G (IgG) antibodies in serum to determine the prevalence of Alternaria exposure in domestic cats. Fifty-two of 63 cats had detectable levels of anti-Alternaria IgG antibody. There were no correlations between the concentration of antibody and the sex, breed or living environment of the cats, but cats less than two years of age had significantly lower concentrations than older cats. The cats with disease caused by culture-confirmed Alternaria infections did not have significantly higher concentrations of antibody than the healthy cats or cats with other diseases.

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.

Extensive polymorphism at the Gp63 locus in field isolates of Leishmania peruviana.

Genetic diversity within and between tandemly arrayed copies of the Gp63 gene occurs in laboratory isolates of Leishmania spp., but the extent to which this represents natural genetic diversity has not been assessed. Here, the Gp63 locus is examined in 58 fresh isolates of L. peruviana, and clones derived from them, collected throughout the Peruvian Andes. Extensive polymorphism is observed, both in size of Gp63 containing chromosomes, and for restriction-fragment-length polymorphisms (RFLPs) at the Gp63 locus. All clones within an isolate are identical, including those with two distinct Gp63-hybridising chromosomal-sized pulsed-field gel electrophoresis (PFGE) bands, consistent with diploidy but with size differences in homologous chromosomes. For RFLP analysis, three enzymes were selected to cut within the coding region (PstI), in the intergenic region (SalI) and outside (EcoRI) the Gp63 gene cluster. PstI gave identical banding patterns across all isolates/clones. For EcoRI and SalI, all clones within an isolate were identical, but isolates were polymorphic for fragments at 13 (2-30 kb) and 8 (2.6-8.8 kb) different molecular mass locations generating 19 and 16 distinct RFLP patterns or genotypes for each enzyme, respectively. EcoRI restriction patterns, analysed by PFGE, were consistent with the presence of two clusters of Gp63 genes on each homologous chromosome, one contained within EcoRI fragments large enough to carry from 3 to 10 copies of the Gp63 gene, the second on fragments which could carry 1 or 2 copies of the gene. SalI patterns indicated variable restriction sites within clusters, but not within every intergenic region. A hierarchical analysis of variance of allele frequencies, expressed in terms of Wright's F-statistic, indicated significant barriers to gene flow at all levels, valleys within regions (north/south), villages within valleys, and individuals within villages. This extreme polymorphism at the Gp63 locus of L. peruviana demonstrates the great potential for generation of genetic diversity in parasite populations.

Intra and inter-specific microsatellite variation in the Leishmania subgenus Viannia.

Leishmania species of the subgenus Viannia are responsible for a large proportion of New World leishmaniasis. Here we report the development of a set of microsatellite markers which are able to discriminate between all species within the subgenus Viannia, including the closely related species pairs: Leishmania (V.) braziliensis and Leishmania (V.) peruviana; Leishmania (V.) panamensis and Leishmania (V.) guyanensis. Potential species hybrids were uncovered in the analysis. These markers are sufficiently polymorphic such that within-species epidemiological, population and genetic studies are theoretically possible for all species analyzed.