To our best knowledge, this is the first study to address the identification of subgroups of weight evolutions and to determine factors associated with these subgroups.
Two profiles of BMI evolutions were identified: rapid and slow, with the average probability of belonging to the two LCM model being higher, ranging from 0.82 to 0.99, suggesting unambiguous classification (appendix). From a linear mixed (LM) model, we found that a BMI increase over time, with different evolution according to the treatment outcome. After controlling for lung cavities on X-ray, patients who were cured had gained on average 2.62 kg/m2 of BMI at the treatment end. A similar result was previously reported that patients who were cured had gained on average 3.9 kg at the end of the sixth month . Unlike the LM model, which shows an average gain BMI over time, our subgroup analysis showed that the speed of this weight gain was not identical for all patients. The most interesting finding was that the patients in the slow BMI evolution had poor response to the MDR-TB treatment, suggesting that weight may serve as a potential biomarker to monitor treatment outcome. These patients were characterized by a positive HIV infection, depression symptom, poor adherence to the MDR-TB treatment, and delay to the culture conversion. This is a relevant finding in public health, particularly in resource-limited settings because they allow a better targeting patient with high-risk to the treatment failure, and to focus the resources needed to improve treatment success rates. Strategies as close monitoring of these patients with therapeutic education to improve treatment adherence, the setting up of psychiatric consultations to manage depression will be contribute to improve the prognosis of these patients and increase their chance of success.
Furthermore, in patients with slow BMI progression, the chance of culture conversion was reduced by 65% (HR = 0.35, 95% CI [0.13—0.96]; p = 0.0087). This finding was higher than those reported from studies evaluating the impact of baseline weight loss (BMI < 18.5 kg/m2) and delay in culture conversion [4,5]. The reduce chances of culture conversion were 43% and 45% for Indonesian and South Korean patients respectively. In addition, 89% of our patients converted their culture in a median of 2 months, which was higher compared to the rates of culture conversion reported in Indonesia (80%)5 and South Korea (70%) , suggesting the reasonably well performance of our MDR-TB treatment program.
Recently, the superiority of the culture conversion than smear conversion in predicting MDR-TB treatment outcomes was demonstrated with an optimum times points between four and six months after treatment commencement. This conclusion supports the WHO recommendation to add culture examination to the sputum smear for the monitoring of MDR-TB patients for a better prediction of successful treatment outcomes . Nevertheless, in resources-constrained settings, the sputum culture is resource intensive, takes time to obtain, costly, requires specialized laboratories, equipment and trained staff. We found that in patient with MDR-TB, the stable or decreases weight between two visits is probably a sign of a poor response to treatment, especially in an HIV-infected, depressed woman with lung cavities on X-ray, and who had a poor treatment adherence. Since the measure of body weight is an easy, rapid, inexpensive method, and accessible everywhere, the association between a faster increase in BMI and shorter time-to initial culture conversion suggest the useful of weight assessment as a surrogate of the culture conversion to predict an early MDR-TB treatment response.
The mechanism underlying weight loss in patients with MDR-TB is well known . Poverty-induced malnutrition is one of the main causes of weight loss in countries with high prevalence of TB such as Guinea. By decreasing the concentration of immunoglobulins, interleukin–2 receptor, and T-cell subset (helper, suppressor-cytotoxic, and natural killer cells) , malnutrition further alters the immunity of patients with TB, making them vulnerable to infections such as HIV, and prone to severe clinical presentation and a higher proportion of positive sputum cultures. Effective poverty alleviation strategies such as reducing social inequalities, access to safe drinking water, and improving the nutritional status of patients will reduce the post-treatment community transmission and result in better success rates.
The current study has a number of strengths. First, patients were evaluated from a three-referral center for MDR-TB management in Guinea, which reduce selection bias and increase the validity of the extrapolation of our findings to the entire population of Guinean patients with MDR-TB. Second, unlike to the conventional mixed linear model used to describe the evolution of weight over time, our subgroup analysis identified a group of patients with poor prognosis (slow BMI evolution) as well as the characteristics of these patients. Third, we used a compromise criterion to select the best BMI subgroups evolutions instead of using only the Bayesian information criterion. As mentioned above, model with two classes has a higher average posterior probability up 0.80, suggesting unambiguous classification. Fourth, to account of informative dropout, we applied a sensitivity analysis using a joint model for longitudinal and time-to dropout . The results obtained from this joint model were similar to estimations using standard linear mixed model, suggesting an absence of bias in parameter estimations (data not shown). However, retrospective design, small sample size, some missing factors such as diabetes status, smoking and alcohol use, information on second-line drugs susceptibility, and other anthropometric measurements, such as skin-fold thickness or waist circumference, which could possibly serve proxy to weight assessment were limits of this study. Nevertheless, further prospective cohort study with large sample could be needed to confirm these findings.