In this retrospective cohort study of 747 adult patients with pulmonary tuberculosis in urban Uganda, most deaths occurred in HIV-infected persons. Wasting was associated with poor survival, but the effect varied by method of body composition measurement and gender. The impact of wasting varied little between men and women when using the BMI; however, when using the LMI as defined by BIA, the effect of wasting was dramatic in women with reduced lean tissue mass, but not in men. Fat mass wasting appears not to predict survival regardless of gender. This study demonstrates that loss of body mass, especially lean tissue mass, affects the survival of tuberculosis patients, especially when HIV-infected.
Our findings suggest that survival is influenced by BMI in both men and women, but that lean tissue mass is associated with survival only in women. For BMI, the magnitude of effect was similar among men and women and indicated that wasting increased the risk of death by about 80%. We interpret this to mean that loss of body mass in general as measured by BMI is a marker of poor survival. With BIA, we gain insight into potential mechanism that may explain the heightened risk, at least among women. In women, there is preferential loss of fat mass in order to preserve the limited lean tissue as previously described (20
). When the energy reserve is spent, the body resorts to the muscle component for survival. Since we did not see any effect of lean tissue on survival in men, we surmise that they had sufficient lean tissue to meet the additional energy requirements of their illness.
Our findings also suggest that the effects of malnutrition on survival are accentuated by co-morbidities (5
). In the face of co-morbidities such as HIV, the effects of malnutrition become detectable. HIV sero-positive patients with reduced BMI at time of tuberculosis diagnosis had poor survival compared to HIV sero-positive patients with normal BMI. Yet there was a minimal effect on survival among HIV sero-negative patients with reduced BMI, though the number of deaths in this group were few. Previous studies have also reported similar effect that underweight BMI is associated with increased risk of mortality whereas obese and overweight BMI have reduced risk of both mortality and tuberculosis (27
). It is known that malnutrition can cause immune-suppression (28
); and thus, tuberculosis in the presence of malnutrition might further exacerbate HIV-associated immune-suppression. These interrelated effects may explain why both tuberculosis and malnutrition are associated with reduced survival among HIV-infected patients (29
). It may also account, in part, for the effect of tuberculosis on the natural history of HIV infection.
In this study, most deaths occurred during the first year of follow-up. There are several potential reasons for the early deaths. First, many presented with severe and extensive tuberculosis. More than 75% had moderate/or far advanced disease on chest x-ray. Second, most deaths were HIV-related, indicating that HIV-tuberculosis co-infection may be associated with additional nutritional alterations that lead to poor outcomes. The extra burdens on nutritional status include increased energy expenditure, nutrient malabsorption, reduced intake, micronutrient malnutrition, and increased production of inflammatory cytokines with lipolytic and proteolytic activity (31
). Third, about a quarter of the study population presented with anemia, which is an HIV-related complication associated with poor outcome (34
). Finally, there was substantial wasting at time of tuberculosis diagnosis in our population, yet wasting is associated with increased risk of early death.
The interpretation of findings in this study should be made with caution because the BIA method that was used in measuring body composition is not the reference standard, and the BIA prediction method used has not yet been validated in the local population. As a result, findings of body composition may be biased because of variations in hydration across ethnic groups (10
). However, the prediction equations that were used in this study were previously cross-validated in individuals of different races and among men and women who were HIV sero-negative healthy controls and HIV sero-positive patients (18
). Moreover, the equations have been used widely in other studies in Africa with meaningful findings (19
). Our findings are also limited by lack of information on dietary intake. This may contribute to some of the observed difference in body composition and survival by gender. Another limitation is that we did not have data on CD4+ T cell counts to comment on effect of HIV disease severity; however, our findings are consistent with previous studies of mortality in HIV-infected patients in Africa in which the rate of mortality was higher in men than in women (36
In conclusion, findings in this study indicate that body wasting exerts greatest effect on observed survival among HIV-infected tuberculosis patients with body wasting, and that the effect of wasting on survival varies by gender. A reduced BMI at presentation with tuberculosis is associated with increased risk for death among both men and women whereas reduced lean tissue mass is among women. These observations may need further investigations in other settings, and it may be important to consider use of LMI as part of nutritional assessment to achieve early identification of patients at risk for poor outcomes.