Model-consistent estimation of the basic reproduction number from the incidence of an emerging infection

We investigate the merit of deriving an estimate of the basic reproduction number \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} $$\mathcal{R}_0$$ \end{document} early in an outbreak of an (emerging) infection from estimates of the incidence and generation interval only. We compare such estimates of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} $$\mathcal{R}_0$$ \end{document} with estimates incorporating additional model assumptions, and determine the circumstances under which the different estimates are consistent. We show that one has to be careful when using observed exponential growth rates to derive an estimate of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} $$\mathcal{R}_0$$ \end{document} , and we quantify the discrepancies that arise

What has Karonga taught us? Tuberculosis studies over three decades

This paper summarises tuberculosis (TB) research over almost 30 years in Karonga District, northern Malawi, an area typical of much of rural Africa. The dominant factor has been the human immunodeficiency virus (HIV), which arrived in the district about 1980, leading to an increase in TB incidence to a peak of approximately 65 smear-positive pulmonary cases per 100000 population in 2000. Tuberculin surveys indicate annual risks of Mycobacterium tuberculosisinfection of approximately 1%; thus, most of the population is uninfected and at risk of primary infection and disease. Molecular epidemiological studies demonstrate that about two thirds of TB arises from recent infection, but recognisable recent contact is responsible for only about 10% of disease. By 2001, 57% of TB was directly attributable to HIV, implying that it would have declined were it not for HIV. HIV infection increases the risk of TB most among young adults, and greatly increases the risk of recurrence from new infection after treatment. Mortality rates in the HIV-infected are high, but there is no association of HIVwith drug resistance. Other risk factors with relatively smaller effects include age and sex, contact, several genetic polymorphisms and area. Neither one nor two doses of the bacille Calmette-Guérin (BCG) vaccine provides protection against adult pulmonary TB, despite protecting against leprosy. Skin test surveys, cohort studies and comparative immunological studies with the UK suggest that exposure to environmental mycobacteria provides some protection against TB and that BCG's failure is attributable partly to this widespread heterologous exposure masking effects of the vaccine. Drug resistance has remained constant (<10%) over more than 20 years. Immunotherapy with M. vaccae provided no benefits, but treatment of HIV-positive patients with cotrimoxazole reduced mortality. The Karonga programme illustrates the value of long-term population-based studies to investigate the natural history of TB and to influence TB control policy. Current studies focus on immunological markers of infection, disease and protection, and on elucidating the impact of antiretroviral treatment on TB incidence at population level

Tuberculosis: associations with HIV and socioeconomic status in rural Malawi

Tuberculosis (TB) is associated with human immunodeficiency virus (HIV) infection, increasing age and male sex, but less is known about other risk factors in developing countries. As part of the Karonga Prevention Study in northern Malawi, we conducted a retrospective cohort study in the general population to assess risk factors for the development of TB. Individuals were identified in 1986–1989 and TB cases diagnosed up to 1996 were included. TB was confirmed in 62/11059 (0·56%) HIV negative individuals and 7/182 (3·9%) HIV positive individuals (relative risk 7·1, 95% confidence interval 3·2–15·7). This association was little altered by adjustment for age, sex or socioeconomic factors. The risk of TB was higher in those aged over 30 years than in younger individuals, in men than in women, in those engaged in occupations other than farming than in subsistence farmers, in those living in households with burnt brick dwellings than in those with less well built dwellings, and in those with some schooling than in those with none. These associations persisted after adjusting for age, sex, HIV status and population density. The absolute risks of TB were low in this study due to the passive follow-up and strict diagnostic criteria. The relative risk with HIV was of a similar magnitude to that measured elsewhere. Increased risks of TB with age and in men are expected. Associations with measures of higher socioecomomic status were unexpected. They may reflect a greater likelihood of diagnosis in this group

On the oxygen consumption of white adipose tissue

From population-based surveys in the 1980s in Karonga district, northern Malawi, 197 'index individuals' were identified as HIV-positive. 396 HIV-negative 'index individuals' were selected as a comparison group. These individuals, and their spouses and children, were followed up in 1998-2000. 582 of 593 index individuals were traced. 487 children of HIV-positive, and 1493 children of HIV-negative, parents were included in analyses. Rates of paternal, maternal, and double orphanhood among children with one or both parents HIV-positive were respectively 6, 8, and 17 times higher than for children with HIV-negative parents. Around 50% of children living apart from both parents had a grandparent as their guardian; for most of the rest the guardian was an aunt, uncle, or sibling. There were no child-headed households. Almost all children aged 6-14 were attending primary school. There was no evidence that parental HIV affected primary school attainment among children <15 years old. Children of HIV-positive parents were less likely to have attended secondary school than those of HIV-negative parents. The extended family has mitigated the impact of orphanhood on children, but interventions to reduce the incidence of orphanhood, and/or which strengthen society's ability to support orphans, are essential, especially as the HIV epidemic matures and its full impact is felt

Tuberculosis and gender: exploring the patterns in case control study in Malawi

Background: In many populations there is an excess of tuberculosis in young women and older men. We explored possible explanations for these patterns, concentrating on human immunodeficiency virus (HIV) status, pregnancy, smoking, cooking smoke exposure, contact with tuberculosis cases within the household or outside, and gender differences in health service usage and diagnostic delay. Design: Case control study in Karonga District, Malawi. Methods: Cases were new tuberculosis patients with bacteriological or histological evidence of tuberculosis. Controls were selected in the community using field-based random sampling. Results: The study included 598 tuberculosis cases and 992 controls, with an excess of tuberculosis in young females and older males. This was more marked in HIV-positive individuals. HIV infection was a similarly strong risk factor for tuberculosis in both men and women. Tuberculosis was associated with having a family or household contact with tuberculosis for both men and women. For women, but not men, contacts outside the close family and household were also a risk factor for tuberculosis. Tuberculosis was not associated with current or recent pregnancy, or with smoking or smoke exposure. There were no differences between men and women in health service usage or delay. Conclusions: In this population, HIV infection and contacts with known tuberculosis patients are important determinants of the gender distribution of cases