Skeletal muscle, cachexia and tuberculosis: a scoping review following the PRISMA-ScR framework

Abstract 
Background 
Cachexia, a multifactorial syndrome characterized by skeletal muscle wasting, remains under-studied in tuberculosis 
(TB), despite TB historically being regarded as the archetypal wasting disease, once termed “consumption”. 
Methods 
We conducted a scoping review of pulmonary TB (pTB), cachexia, and skeletal muscle, following Arksey and 
O’Malley’s framework and PRISMA-ScR guidelines. Searches of Medline, Embase, Web of Science, and Africa 
Journals Online, as well as grey literature, were performed from inception to September 2025. 
Results 
Of 4,677 records screened, 44 studies met inclusion criteria (42 primary studies, 1 systematic review, 1 narrative 
review) comprising > 16,500 individuals with TB. Africa was the best-represented region in studies of skeletal muscle 
followed by Asia; most research was in urban hospital outpatient settings. Most studies were observational and 
focused on anthropometric of muscle mass, with limited use of gold-standard diagnostic methods. No studies directly 
defined or measured TB-cachexia. pTB was consistently associated with reduced skeletal muscle mass and function, 
and low muscle mass at TB diagnosis was associated with increased mortality. Although few studies reported 
prevalence, skeletal muscle deficits were common when assessed. Muscle mass only partially improves during 
treatment, remaining below levels observed in in healthy controls, with evidence suggesting that weight gain was 
predominantly due to fat rather than muscle accretion. No studies investigated the short or long-term real-world 
consequences of musculoskeletal deficits among pTB survivors. Mechanistic studies were scarce, but available data 
indicated that deficits were more pronounced in men, individuals of low socioeconomic status, and those with severe 
TB or advanced HIV. Interventions targeting muscle mass and function primarily focused on nutritional or protein 
supplementation with mixed often transient effects. 
Conclusions 
Despite frequent reports of wasting in pTB, cachexia has not been clearly defined or phenotyped. Skeletal muscle 
deficits, central to cachexia, are common in pTB and appear to resolve only partially with treatment, potentially 
contributing to long-term morbidity. Research is urgently needed to define TB-associated cachexia, elucidating 
mechanisms of muscle loss, standardize muscle measurement, and evaluate multimodal interventions beyond 
nutrition to improve survival and recovery.