We have shown that untargeted periodic active case finding for symptomatic smear-positive tuberculosis repeated once every 6 months made a substantial contribution to diagnosis of smear-positive tuberculosis in an urban population with high HIV prevalence, and to control of infectious tuberculosis (panel
). The mobile van delivery strategy significantly outperformed door-to-door enquiry for chronic cough, especially in neighbourhoods with high HIV prevalence. By the start of intervention round six, infectious tuberculosis in the community had fallen by more than 40% from rates before intervention, to rates well below those reported elsewhere in the region.5–9
This major improvement in tuberculosis control in a population with high HIV prevalence suggests that such an intervention could provide rapid reductions in tuberculosis transmission in the community, and could lead to declining rates of new tuberculosis cases in individuals with and without HIV infection within a few years.
Panel. Research in context
Before the study started, we searched PubMed for relevant articles with search terms including “tuberculosis AND case finding” as MeSH headings, “tuberculosis” and “case finding” as search terms, “tuberculosis AND (community OR population OR household)”, “tuberculosis AND case-finding AND clinical trial”, and “(active OR enhanced OR intensified) AND tuberculosis AND (case-finding OR case finding)”. References in relevant articles were also screened. In view of the long history of active case finding, we did not set any criteria for assessing quality to avoid exclusion of articles published before standard reporting guidelines were developed.
Findings of our study show that the mobile van method was substantially more effective than was door-to-door enquiry for identification of patients with previously undiagnosed smear-positive tuberculosis. Repeated implementation of periodic active case finding can substantially reduce undiagnosed infectious tuberculosis in the community, which is likely to be associated with reduced transmission rates.
Active case finding has been an integral part of tuberculosis control in industrialised countries since the 1920s.11,12,15
Early programmes used radiological screening of otherwise untargeted adults, reporting yields as high as 30 cases of previously undiagnosed tuberculosis per 1000 screened in New York City during the early 1930s.11
Intensive interventions in native Alaskans in the 1950s, in whom prevalence was extremely high, led to rapid and major reductions in tuberculosis incidence, mortality, and transmission in the population within a few years.25
Elsewhere, however, the effect is difficult to discern from pre-existing downward trends.11,25
Policy from the 1970s recommended targeted screening of close contacts of patients with tuberculosis, recent immigrants, prisoners, homeless people, and people with HIV infection, but not general populations.15
In these high-prevalence groups, active case finding can reduce tuberculosis incidence through prevention of secondary cases.13,26
During the past 15 years, global scale-up of facility-based tuberculosis diagnostic and treatment services has greatly improved treatment success rates, but has had disappointingly little effect on tuberculosis incidence.15
Failure to adequately control undiagnosed tuberculosis in poor communities, together with an increasing prevalence of factors favouring tuberculosis transmission and disease, seem to be the key issues and enhanced case finding is being reconsidered as a possible next step in global control.15
However, little evidence is available to guide contemporary choices about who should be screened, how screening should be done and with what frequency, and how to deliver services effectively.11,15
We chose to use fluorescence microscopy to screen sputum samples from adults volunteering symptoms, rather than the more sensitive alternative of radiological screening of all adults, because smear-positive patients are by far the most infectious and decentralised microscopy is already well supported globally and has low unit costs. Between three and eight per 1000 adults surveyed in four African countries from 2002 to 2009 were smear positive, about half of whom reported chronic cough, providing a simple target linked to infectiousness that has a high positive predictive value for smear positivity at community level, and consistency with facility-based approaches.5,8,9,11,27
Moreover failure to provide diagnosis at subclinical stages is not necessarily a long-term barrier to tuberculosis control.10,28
In our study, active case finding provided the first investigation for 77% of smear-positive participants, despite the fact that all participants were symptomatic and lived within 2 km of a primary clinic. This finding adds to accumulating evidence that the slow rate at which patients with tuberculosis report to health facilities is a major rate-limiting step in global efforts to control tuberculosis.5,15,29–31
Competing priorities for time and money, fear of diagnosis with an HIV-related disease, and the hope of spontaneous resolution all contribute to this delay.31,32
The finding that the mobile van attracted significantly more smear-positive participants than did door-to-door enquiry for chronic cough was counterintuitive, but especially striking in clusters with high HIV prevalence that were also the poorest and most crowded. This finding was associated with a higher rate of smear positivity in the mobile van group than in the door-to-door group, not an increased rate of participation. Reporting of symptoms is more proactive than is response to direct enquiry, and more participants in the mobile van group reported previous consultations with health-care providers than did those in the door-to-door group. The mobile van group was potentially associated with stigma because consultation for an HIV-related disease was done in front of neighbours, but this intervention provided increased opportunity for encouragement from others, and time to decide to seek the intervention and find a convenient moment to do so.32
Follow-up house-to-house enquiry added little to case finding through a mobile clinic in Thailand,20
but the study did not investigate the possibility that mobile clinics were more effective than was house-to-house enquiry. Mobile services are often used to provide outreach services, including HIV testing, and report high participation.33
Unannounced door-to-door enquiries for chronic cough are likely to be less sensitive than are more intensive approaches to home-based case finding (for example, face-to-face interview and screening of adult members of randomly selected households detected additional tuberculosis cases in the door-to-door group, despite this survey immediately following the last round of intervention in our study), but contributed 40% of all cases of smear-positive tuberculosis diagnosed in South Korea during the 1970s.15
Assessment of the combined effect of our two intervention strategies through prevalence surveys provides a clearer measure of the effect on tuberculosis control than could be obtained from our primary outcome alone: counting cases diagnosed provides little insight into how much smear-positive person-time has been averted, and does not capture potentially important indirect effects from reduced tuberculosis transmission and more timely reporting of tuberculosis symptoms to routine health-care providers between intervention rounds. By contrast with the case finding outcome, the effect of intervention on prevalence was very similar between the mobile van and door-to-door groups. Subanalyses for prevalence had very low power and the 95% CIs are widely overlapping. But, if these overlaps truly indicate absence of difference, then patients in the door-to-door group were on average at an earlier stage in their health-seeking process than were those diagnosed through the mobile van and so were further in time from routine diagnosis, in which case the two intervention groups will have had equivalent effect on tuberculosis transmission.
The prevalence data also suggest suboptimal intervention effect in men and in individuals with HIV infection. Although neither interaction was significant, men tend to have a higher prevalence of undiagnosed tuberculosis than do women,5,22,34
and health-seeking behaviour varies substantially by sex.31
In the active case-finding component of this study, participation, but not diagnosis, was higher in women than in men. For HIV infection, we anticipated that the 6-monthly intervals of intervention might be intrinsically more likely to affect HIV-negative tuberculosis (low incidence but typical delay to diagnosis or death of ≥1 year) than HIV-positive tuberculosis (high incidence but a brief delay to diagnosis or death).4,10,22
Our intervention clusters were fairly homogeneous, with no slums or rural clusters, and we assessed only two of many case-finding approaches.11
High-density urban populations are the obvious target for active case finding in view of their accessibility and high tuberculosis burden,5,9
but effective rural strategies have also been described.35
Other limitations of our study include the separation of clusters by areas receiving no intervention to avoid cross-contamination, which will have diluted any effect on transmission rates. Our secondary outcome was an uncontrolled before-and-after comparison, vulnerable to coincidental time trends. However, we believe that such trends are unlikely to explain the striking reduction in infectious tuberculosis because population characteristics remained similar during the intervention period, with little change in coverage of antiretroviral therapy36
and deterioration rather than strengthening of routine health and tuberculosis services during the study period. Last, suboptimal participation by men in the prevalence surveys could have biased our subanalysis by sex, although the substantial reduction in infectious tuberculosis in women strongly supports our conclusions about the effectiveness of active case finding.
Active case finding for tuberculosis in the general community was discouraged for several decades because of high costs of implementation and insufficient strength of treatment programmes.11,12,15
With the successful global scale-up of effective tuberculosis treatment, however, our results suggest that active case finding needs re-evaluation in general populations wherever tuberculosis incidence or prevalence is high. Effectiveness should ideally be assessed as cases averted or reduction in prevalence, and these outcomes, not cases found, should be used for cost-effectiveness analysis together with capture of transmission dynamics.37
In countries with severe generalised epidemics of HIV infection and tuberculosis, including the middle-income countries of South Africa and Botswana, the affordability of active case finding in the general population needs to be weighed against the extremely high financial and societal costs of allowing the dual epidemic to rage on.1,38
The effect on HIV-negative tuberculosis that we report is in the range needed for countries to meet the Millennium Development Goal relating to tuberculosis prevalence,15
and was achieved in under 3 years. Interventions should aim to effectively engage men, and, in settings of high HIV prevalence, should ideally be accompanied by interventions promoting HIV diagnosis linked to intensified tuberculosis prevention with antiretroviral therapy and isoniazid preventive therapy.4