Increased tuberculosis case detection in Tanzanian children and adults using African giant pouched rats

Abstract

Background: African giant pouched rats, trained by Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling (APOPO), have demonstrated their ability to detect tuberculosis (TB) from sputum. We assessed rat-based case detection and compared the mycobacterium bacillary load (MTB-load) in children versus adults.

Methods: From January-December 2022, samples were collected prospectively from 69 Directly Observed Therapy (DOT) facilities' presumed TB patients. Using an average of five rats, APOPO re-evaluated patients with bacteriologically negative (sputum-smear microscopy or Xpert MTB/RIF) results. Rat-positive samples were tested using concentrated smear light-emitting diode microscopy to confirm TB detection before treatment initiation. The rats' identification of pulmonary TB is based on smelling TB-specific volatile organic compounds (VOCs) in sputum. Using STATA, Chi-square for odds ratio and confidence interval was calculated and evaluated: (1) the yield of rat-based TB detection compared to that of the health facilities; (2) rat-based TB detection in children versus adults; and (3) rats' ability to detect TB across MTB-loads and between children and adults.

Results: From 35,766 patients, 5.3% (1900/35,766) were smear-positive and 94.7% (33,866/35,766) were smear or Xpert-negatives at DOTS facility. Of those with negative results, 2029 TB cases were detected using rats, contributing to 52% (2029/3929 of total TB identified), which otherwise would have been missed. Compared to DOT facilities, rats were six-fold more likely to detect TB among Acid Fast Bacilli (AFB) 1+/scanty [90% (1829/2029) versus 60% (1139/1900), odds ratio, OR = 6.11, 95% confidence interval, CI: 5.14-7.26]; twice more likely to identify TB cases among children [71% (91/129) versus 51% (1795/3542), OR = 2.3, 95% CI: 1.59-3.42]; and twice more likely to identify TB cases among children with AFB 1+/scanty than adults with the same MTB-load [5% (86/1703) versus 3% (28/1067), OR = 2.0, 95% CI: 1.28-3.03].

Conclusions: Rats contributed over half of the TB cases identified in program settings, and children, especially those with a lower MTB-load, were more likely to be diagnosed with TB by rats. The chemical signatures, VOCs, were only available for adults, and further research describing the characteristics of VOCs in children versus adults may pave the way to enhance TB diagnosis in children.

Keywords: APOPO; Mycobacterium bacillary load; Pulmonary TB; Rat-based TB detection.

Fig. 1

APOPO tuberculosis detection model using rats. Reproduced with permission [12]

Fig. 2

A Rat indication and tuberculosis cases after LED smear confirmation among presumptive tuberculosis patients in Tanzania study sites from January to December 2022. Note: *Since the samples were not tested by culture, 17.8% does not truly represent sensitivity. Since the LED smear is not good enough in sensitivity, nor does 81.9% represent a true false positive. B Presumptive tuberculosis and bacteriologically confirmed tuberculosis cases in Tanzania study sites from January to December 2022. Note: *Children versus adults bacteriologically confirmed TB: 5% (129/2508) versus 12% (3542/30,735), odds ratio 0.42, 95% confidence interval: 0.35–0.50, p value, 0.001

Fig. 3

Tuberculosis cases among children and adults identified using rats by Mycobacterium bacillary load

Fig. 4

Tuberculosis cases detected by smear microscopy at DOTs and by rats at APOPO and confirmed by LED smear microscopy in Tanzania study sites from January to December 2022

Fig. 5

Average rat indication by Mycobacterium Tuberculosis bacillary load