Improvement of tuberculosis case detection and reduction of discrepancies between men and women by simple sputum-submission instructions: a pragmatic randomised controlled trial

Summary

Background

In several settings, women with suspected tuberculosis are less likely to test smear positive than are men. Submission of poor-quality sputum specimens by women might be one reason for the difference between the sexes. We did a pragmatic randomised controlled trial to assess the effect of sputum-submission instructions on female patients.

Methods

1494 women and 1561 men with suspected tuberculosis attending the Federal Tuberculosis Centre in Rawalpindi, Pakistan, were randomly assigned between May and July, 2005 either to receive sputum-submission guidance before specimen submission or to submit specimens without specific guidance, according to prevailing practice. Of enrolled patients, 133 (4%) declined to participate. The primary outcome measure was the proportion of instructed and non-instructed women testing smear positive. Intention-to-treat analysis was undertaken on the basis of treatment allocation. This study is registered with the International Standard Randomised Controlled Trial number 34123170.

Findings

Instructed women were more likely to test smear positive than were controls (Risk ratio 1·63 [95% CI 1·19–2·22]). Instructions were associated with a higher rate of smear-positive case detection (58 [8%] in controls vs 95 [13%] in the intervention group; p=0·002), a decrease in spot-saliva submission (p=0·003), and an increase in the number of women returning with an early-morning specimen (p=0·02). In men, instructions did not have a significant effect on the proportion testing smear positive or specimen quality.

Interpretation

In the Federal Tuberculosis Centre in Rawalpindi, lower smear positivity in women than in men was mainly a function of poor-quality specimen submission. Smear positivity in women was increased substantially by provision of brief instructions. Sputum-submission guidance might be a highly cost-effective intervention to improve smear-positive case detection and reduce the disparity between the sexes in tuberculosis control in low-income countries.

Introduction

In 2004, there were 8·9 million new cases of tuberculosis and 1·7 million deaths. Tuberculosis control remains a public health priority, as indicated by the Millennium Development Goals and by the World Health Assembly, whose targets included detection of 70% of new smear-positive cases by 2005. Although there has been progress in the geographical expansion of WHO's directly observed treatment short-course (DOTS) programme, estimates are that only 53% of the predicted smear-positive cases were notified under DOTS in 2004.1, 2 This low percentage shows that a great proportion of smear-positive cases are undetected within DOTS areas, and recent studies indicated that women, in particular, are at risk of underdetection. In developing countries, more men than women are diagnosed with tubercolosis.³ Studies in several settings, including Malawi, South Africa, and Bangladesh have shown that women attending tuberculosis diagnostic centres are less likely to test smear positive than are men.4, 5, 6, 7 In a recent study in Pakistan, we showed that, although there was little discrepancy in hospital attendance and specimen submission between the sexes, the rates of smear positivity of specimens submitted by men and women were 12% versus 6%.⁸ Whether sex differences in smear-positive detection occur because women have paucibacillary disease or because they face more barriers to diagnosis is unclear. Previous studies have suggested that cultural inhibitions about producing deep sputum, particularly in public places, and lack of knowledge about tuberculosis diagnosis in low-income countries might affect the quality of specimens submitted by women.⁹ However, provision of specific sputum-submission guidance is often not emphasised, and most diagnostic facilities do not provide such guidance. In Pakistan, which ranks seventh among the high-burden countries, about 26% of avoidable adult deaths are caused by tuberculosis.¹⁰ Pakistan faces many of the same hurdles in the control of this disease as other low-income countries. Although DOTS coverage increased rapidly from 9% in 2000 to 79% in 2004, only 27% of estimated smear-positive cases were detected with DOTS, which is far below the World Health Assembly target of 70%. The number of smear-positive case notifications in adult women (aged 15 years and over) is 10% lower than that in adult men; 15 275 women versus 16 790 men were notified in 2004.¹

Analysis of records from the Federal Tuberculosis Centre, one of the main tuberculosis hospitals in Pakistan, showed that women were more likely to be notified as smear negative and men more likely to be notified as smear positive. Non-participant observations at the Federal Tuberculosis Centre indicated that women, in particular, received inadequate guidance on how to produce good-quality sputum specimens. In-depth interviews revealed that most women were not aware that sputum rather than saliva has to be submitted for tuberculosis diagnosis.⁷ Therefore, one reason for lower smear positivity in women at the Federal Tuberculosis Centre might be that they are unaware of how to submit a good-quality sputum specimen. We tested this hypothesis in a pragmatic randomised controlled trial¹¹ to assess the effect of sputum-submission guidance on female patients testing smear positive.