Discussion
TB, death, fatigue, HIV infection, TB-HIV co-infection, sweats, malnutrition, Fatigue
HIV INFECTION, DISEASE TRANSMISSION, SEVERE MALNUTRITION, MALNUTRITION
The overall prevalence of TB-HIV co-infection was 14% among children under age five years diagnosed with TB in our study. Studies from Cameroon and Kenya have found estimates in children less than five years of age with TB-HIV co-infection to be between 41 and 52% [In this study, CLHIV did not necessarily have a wider variety of clinical presentations, but they did present with acute malnutrition more frequently compared to those living without HIV. This exploratory analysis had limited power and did not determine a statistically significant difference in the case-fatality rate among the two populations. In published studies, TB manifestations have been shown to be more severe and progression to death more rapid among CLHIV compared to those living without HIV, with overall high rates of mortality, specifically amongCLHIV under the age five years [The importance of considering malnutrition as a key element in TB case finding, especially among CLHIV, is highlighted by two findings in this study. The first is the significant association found between HIV infection and acute malnutrition among children diagnosed with TB. The second is that malnutrition was independently associated with a significant delay in TB diagnosis, both in HIV-infected and uninfected populations. Delayed TB diagnosis and treatment initiation is associated with higher disease transmission [The other determinants of time from symptom onset to TB diagnosis were fatigue and existence of a household contact diagnosed with TB, which reduced the time to diagnosis, while night sweats and older age increased the time to diagnosis. Having a household contact with TB was associated with a faster TB diagnosis, which may reflect efficient contact tracing in these households. Fatigue and younger age may have been significant prompting caregivers to bring their child to healthcare facilities more rapidly. We are not able to explain why children with night sweats were diagnosed significantly later than other children.Although most cases were diagnosed clinically, CLHIV tended to have more bacteriologic confirmations compared to children living without HIV. Obtaining sputum in children, especially those under the age of five years, irrespective of HIV status, is difficult and it is clear from our results that LF-LAM diagnostic test performed on urine samples contributed a lot to bacteriologic confirmation among CLHIV. This sub-analysis highlights and stresses the importance of the newly updated WHO recommendations on the use of currently commercially available LF-LAM to aid in the diagnosis of TB among the people living with HIV [Rapid, non-sputum-based diagnostic tools such as urine LF-LAM, urine Xpert Ultra or stool Xpert have shown value for TB diagnosis in people living with HIV and in the general pediatric population including the outpatient setting [Limitations of our study included the small number of CLHIV which limited our ability to draw generalizable conclusions, and the number of children with an unknown HIV status. Among fifteen children presenting at enrollment with an unknown status, a HIV test was performed in seven by the time of TB diagnosis, and was found to be negative. The eight children with remaining unknown HIV status were grouped with the cohort of children living without HIV, which may have contributed to a decreased co-infection rate. Among them, one was born from an HIV-positive mother. This child was in very critical condition at baseline and died soon after TB diagnosis was made, but before HIV testing. The seven other children were born from HIV-negative (n = 5) or unknown (n = 2) mothers, making it less likely that they would have been HIV-positive.Because we did not collect the weight-for-age z-score or mid-upper arm circumference but only determined if moderate or severe acute malnutrition was present (as per indicated in facility records), we were not able to assess if the classification of children with moderate and severe malnutrition was accurate based on standardized definitions. This potential inaccuracy is the reason why we decided to group children with reported moderate and acute severe malnutrition together in our analyses.Despite these limitations, this study gives important insights into specific clinical presentations and pathways to diagnosis of TB in CLHIV.