# A prospective cohort study to describe the morphology of buboes in patients with bubonic plague using ultrasound imaging

## TL;DR

This study used ultrasound to examine buboes in bubonic plague patients and found that their size and shape don't reliably reflect treatment progress.

## Contribution

The first longitudinal ultrasound study of buboes in confirmed bubonic plague cases, revealing their morphology and measurement challenges.

## Key findings

- Bubo size and morphology did not correlate with clinical improvement during treatment.
- Digital calliper measurements significantly overestimated bubo size compared to ultrasound.
- Newly trained clinicians could reliably measure size but struggled with interpreting internal structures.

## Abstract

Bubonic plague, caused by Yersinia pestis, is characterised by painful, enlarged lymph nodes (“buboes”). Despite centuries of clinical recognition, bubo morphology has been described only through observation and palpation. This study aimed to characterise the sonographic features of buboes over time in confirmed bubonic plague and evaluate the validity of digital calliper measurements compared to ultrasound.

We conducted a prospective cohort study at three rural health centres in Madagascar between January and March 2024. Participants with suspected bubonic plague underwent ultrasound imaging and digital calliper measurements of enlarged lymph nodes at inclusion (D1), and follow-up on D4 and D11. Bubo size and morphology were assessed by clinicians – who received targeted ultrasound training for the study – using portable ultrasound devices, with expert radiologist oversight. Neither clinicians or radiologists were blind to clinical information or outcomes. Final diagnoses were retrospectively assigned using WHO criteria and national laboratory results. Of 16 enrolled participants, 12 were confirmed plague cases. Most buboes exhibited normal morphology on D1, with limited change over time despite clinical improvement. No association was found between bubo size or morphology and clinical status. Digital calliper measurements differed substantially from ultrasound. Study sonographers achieved good agreement with radiologists on bubo size, but lower agreement on structural features.

Bubo morphology and size do not appear to correlate with clinical status, challenging their use as indicators of treatment response. Digital callipers introduce significant measurement error. Newly trained clinicians can perform size measurements reliably, but further training is needed for accurate sonographic characterisation.

Bubonic plague, caused by Yersinia pestis, presents with painful, enlarged lymph nodes known as buboes. While their clinical significance has been recognised for centuries, existing descriptions rely on clinical evaluation alone. A recent systematic review reported buboes in 96% of confirmed cases, but provided little detail on their evolution and morphology. Imaging has been reported in a small number of case reports, usually at a single timepoint, and without radiological characterisation. This is the first study to describe the sonographic features of buboes in a cohort of confirmed bubonic plague cases using portable ultrasound. It provides longitudinal ultrasound data from a rural endemic setting in Madagascar and compares clinical and ultrasound bubo size measurements. We found that bubo morphology and size remained largely unchanged during treatment, despite clinical improvement, challenging the assumption that reduction in bubo size reflects clinical recovery. Calliper measurements also consistently overestimating size, and while newly trained clinicians showed strong agreement with radiologists for size, their interpretation of internal structures was less consistent. Overall, our findings indicate that bubo size and morphology are poor indicators of treatment response and may be unreliable endpoints for clinical trial or patient monitoring.