Spreading of Persistent Infections in Heterogeneous Populations

Up to now, the effects of having heterogeneous networks of contacts have been studied mostly for diseases which are not persistent in time, i.e., for diseases where the infectious period can be considered very small compared to the lifetime of an individual. Moreover, all these previous results have been obtained for closed populations, where the number of individuals does not change during the whole duration of the epidemics. Here, we go one step further and analyze, both analytically and numerically, a radically different kind of diseases: those that are persistent and can last for an individual's lifetime. To be more specific, we particularize to the case of Tuberculosis' (TB) infection dynamics, where the infection remains latent for a period of time before showing up and spreading to other individuals. We introduce an epidemiological model for TB-like persistent infections taking into account the heterogeneity inherent to the population structure. This sort of dynamics introduces new analytical and numerical challenges that we are able to sort out. Our results show that also for persistent diseases the epidemic threshold depends on the ratio of the first two moments of the degree distribution so that it goes to zero in a class of scale-free networks when the system approaches the thermodynamic limit.Comment: 12 pages and 2 figures. Revtex format. Submitted for publication

Optimal control strategies for tuberculosis treatment: a case study in Angola

We apply optimal control theory to a tuberculosis model given by a system of ordinary differential equations. Optimal control strategies are proposed to minimize the cost of interventions. Numerical simulations are given using data from Angola.Comment: This is a preprint of a paper whose final and definite form will appear in the international journal Numerical Algebra, Control and Optimization (NACO). Paper accepted for publication 15-March-201

Annual Risk of Tuberculous Infection Using Different Methods in Communities with a High Prevalence of TB and HIV in Zambia and South Africa

BACKGROUND: The annual risk of tuberculous infection (ARTI) is a key epidemiological indicator of the extent of transmission in a community. Several methods have been suggested to estimate the prevalence of tuberculous infection using tuberculin skin test data. This paper explores the implications of using different methods to estimate prevalence of infection and ARTI. The effect of BCG vaccination on these estimates is also investigated. METHODOLOGY/PRINCIPAL FINDINGS: Tuberculin surveys among school children in 16 communities in Zambia and 8 in South Africa (SA) were performed in 2005, as part of baseline data collection and for randomisation purposes of the ZAMSTAR study. Infection prevalence and ARTI estimates were calculated using five methods: different cut-offs with or without adjustments for sensitivity, the mirror method, and mixture analysis. A total of 49,835 children were registered for the surveys, of which 25,048 (50%) had skin tests done and 22,563 (90%) of those tested were read. Infection prevalence was higher in the combined SA than Zambian communities. The mirror method resulted in the least difference of 7.8%, whereas that estimated by the cut-off methods varied from 12.2% to 17.3%. The ARTI in the Zambian and SA communities was between 0.8% and 2.8% and 2.5% and 4.2% respectively, depending on the method used. In the SA communities, the ARTI was higher among the younger children. BCG vaccination had little effect on these estimates. CONCLUSIONS/SIGNIFICANCE: ARTI estimates are dependent on the calculation method used. All methods agreed that there were substantial differences in infection prevalence across the communities, with higher rates in SA. Although TB notification rates have increased over the past decades, the difference in cumulative exposure between younger and older children is less dramatic and a rise in risk of infection in parallel with the estimated incidence of active tuberculosis cannot be excluded

Low tuberculosis notification in mountainous Vietnam is not due to low case detection: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Studies show that tuberculosis notification declines with increasing altitude. This can be due to declining incidence or declining case detection. In Vietnam notification rates of new smear-positive tuberculosis in the central mountainous provinces (26/100,000 population) are considerably lower than in Vietnam in general (69/100,000 population). In order to clarify whether this is explained by low incidence or low case detection, we aimed to assess the prevalence of new smear-positive tuberculosis among adults with prolonged cough in three mountainous provinces in central Vietnam.</p> <p>Methods</p> <p>A house-to-house survey of persons (≥ 15 years) was carried out in twelve randomly selected districts in 2003. Three sputum specimens were microscopically examined of persons reporting a prolonged cough (≥ 3 weeks). Case detection was assessed by the ratio between notification and prevalence.</p> <p>Results</p> <p>Of 68,946 included persons (95% response), 1,298 (1.9% 95%CI 1.8–2.2) reported a prolonged cough. Of these, eighteen were sputum smear-positive of whom two had had anti-tuberculosis treatment. The prevalence of new smear-positive tuberculosis was 27/100,000 (95%CI 11–44/100,000) and the notification rate was 44/100,000 among persons ≥ 15 years. The estimated case detection rate was 76%.</p> <p>Conclusion</p> <p>Low tuberculosis notification in this mountainous setting is probably a true reflection of low tuberculosis incidence. Possible causes for low incidence in mountainous areas include low transmission rates or altitude-related differences in pathology.</p

Delays in the diagnosis and treatment of tuberculosis patients in Vietnam: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Treatment delay is an important indicator of access to tuberculosis diagnosis and treatment. Analyses of patient delay (i.e. time interval between onset of symptoms and first consultation of a health care provider) and health care delay (i.e. time interval between first consultation and start of treatment) can inform policies to improve access. This study assesses the patient, health care provider and total delay in diagnosis and treatment of new smear-positive pulmonary tuberculosis patients, and the risk factors for long delay, in Vietnam.</p> <p>Methods</p> <p>A cross-sectional survey of new patients treated by the National Tuberculosis Control Programme was conducted in 70 randomly selected districts in Vietnam. All consecutively registered patients in one quarter of 2002 were interviewed using a pre-coded structured questionnaire.</p> <p>Results</p> <p>Median (range) delay was 4 weeks (1–48) for total, 3 (1–48) weeks for patient and 1 (0–25) week for health care delay. Patients with long total delay (≥ 12 weeks, 15%) accounted for 49% of the cumulative number of delay-weeks. Independent risk factors (p < 0.05) for long total delay were female sex, middle age, remote setting, residence in the northern or central area, and initial visit to the private sector. For long patient delay (≥ 6 weeks) this was female sex, belonging to an ethnic minority, and living at > 5 km distance from a health facility or in the northern area. For long health care delay (≥ 6 weeks) this was urban setting, residence in the central area and initial visit to a communal health post, TB hospital or the private sector.</p> <p>Conclusion</p> <p>Analyses of patient and treatment delays can indicate target groups and areas for health education and strengthening of the referral system, in particular between the private sector and the NTP.</p

ESAT-6/CFP10 Skin Test Predicts Disease in M. tuberculosis-Infected Guinea Pigs

Background: Targeted preventive chemotherapy of individuals with progressive subclinical (incipient) disease before it becomes contagious would break the chain of tuberculosis transmission in high endemic regions. We have studied the ability of a skin test response to ESAT-6 and CFP10 (E6/C10) to predict later development of tuberculosis disease in the guinea pig model. Methods and Findings: Guinea pigs, either vaccinated with BCG or unvaccinated, were infected with a low dose of Mycobacterium tuberculosis by the aerosol route and the development of delayed type hypersensitivity responses to E6/C10 and to purified protein derivative (PPD) were followed until the onset of clinical disease. We demonstrated a negative correlation between the size of the skin test response and the time to the onset of clinical disease; a large E6/C10 skin test response correlated to a shorter survival time post skin testing, while a small E6/C10 skin test reaction correlated with a longer survival time (r = 20.6 and P,0.0001). No correlation was found using PPD. Conclusions: Our data suggest that it may be possible to develop a prognostic skin test based on E6/C10 that will allow the identification of individuals with incipient disease, who have the highest risk of developing active tuberculosis in the near future

Nutrition, Diabetes and Tuberculosis in the Epidemiological Transition

BACKGROUND: Diabetes prevalence and body mass index reflect the nutritional profile of populations but have opposing effects on tuberculosis risk. Interactions between diabetes and BMI could help or hinder TB control in growing, aging, urbanizing populations. METHODS AND FINDINGS: We compiled data describing temporal changes in BMI, diabetes prevalence and population age structure in rural and urban areas for men and women in countries with high (India) and low (Rep. Korea) TB burdens. Using published data on the risks of TB associated with these factors, we calculated expected changes in TB incidence between 1998 and 2008. In India, TB incidence cases would have increased (28% from 1.7 m to 2.1 m) faster than population size (22%) because of adverse effects of aging, urbanization, changing BMI and rising diabetes prevalence, generating an increase in TB incidence per capita of 5.5% in 10 years. In India, general nutritional improvements were offset by a fall in BMI among the majority of men who live in rural areas. The growing prevalence of diabetes in India increased the annual number of TB cases in people with diabetes by 46% between 1998 and 2008. In Korea, by contrast, the number of TB cases increased more slowly (6.1% from 40,200 to 42,800) than population size (14%) because of positive effects of urbanization, increasing BMI and falling diabetes prevalence. Consequently, TB incidence per capita fell by 7.8% in 10 years. Rapid population aging was the most significant adverse effect in Korea. CONCLUSIONS: Nutritional and demographic changes had stronger adverse effects on TB in high-incidence India than in lower-incidence Korea. The unfavourable effects in both countries can be overcome by early drug treatment but, if left unchecked, could lead to an accelerating rise in TB incidence. The prevention and management of risk factors for TB would reinforce TB control by chemotherapy

Evaluation of the Association between Arsenic and Diabetes: A National Toxicology Program Workshop Review

Background: Diabetes affects an estimated 346 million persons globally, and total deaths from diabetes are projected to increase > 50% in the next decade. Understanding the role of environmental chemicals in the development or progression of diabetes is an emerging issue in environmental health. In 2011, the National Toxicology Program (NTP) organized a workshop to assess the literature for evidence of associations between certain chemicals, including inorganic arsenic, and diabetes and/or obesity to help develop a focused research agenda. This review is derived from discussions at that workshop