Table 1.
Annual Pigbel cases and deaths reported to the Papua New Guinea Paediatric Hospital Reporting program: https://pngpaediatricsociety.org/reports/annual-child-morbidity-and-mortality-reports/.
Table 2.
Enteritis necroticans (confirmed or presumed Clostridium perfringens type C associated) reported outside of Papua New Guinea since 2000.
Fig 1.
Abdominal CT scan of a 15-year-old girl with abdominal sepsis 1 week after a bone marrow transplant.
Hemorrhagic necrosis of the small bowel is seen in addition to extensive pneumatosis intestinalis, ascites and the periportal pneumatosis in the liver. Clostridium perfringens was recovered from the blood and ascitic fluid.
Table 3.
Enteric disease in animals due to Clostridium perfringens type C.
Fig 2.
Proposed pathogenesis of enteritis necroticans.
(1) Healthy intestine with microbiota; (2) colonization with Clostridium perfringens type C, beta-toxin degradation through trypsin; (3) proliferation and toxin secretion of C. perfringens type C, potentially due to disbalanced microbiota, uptake of large numbers of pathogen, trypsin inhibitors preventing beta-toxin degradation, or other factors that may facilitate proliferation and toxin elaboration; (4) initial epithelial barrier alteration (through additional clostridial virulence factors or other co-pathogens), diffusion of beta-toxin into lamina propria, local endothelial damage with plasma extravasation and small hemorrhages, lesions macroscopically most likely not yet visible; (5) increased nutrient supply for C. perfringens through vascular leakage, increased proliferation and upregulation of toxin secretion leads to acceleration of damage, lesions become macroscopically visible and extend rapidly; (6) vicious cycle of clostridial proliferation, toxin secretion, vascular damage and nutrient supply leads to rapidly progressing hemorrhagic transmural jejunitis with peritonitis, lesions potentially extend into distal small and also large intestine, death can occur at this stage; (7) in more protracted cases patchy lesions develop and there is marked inflammatory response in affected intestinal segment, lesions become macroscopically less hemorrhagic and more fibrinous, severe peritonitis can develop. Figure created with BioRender.com.
Fig 3.
Clostridium perfringens beta-toxin targets endothelial cells of mucosal vasculature during early stages of lesion development in an experimental porcine infection model.
(A) Histopathology of an early jejunal lesions of necrotic enteritis induced by C. perfringens type C in a porcine ileal loop model showing hemorrhage in the tips of villi and epithelial cell sloughing. Magnification 400× (B) Immunohistochemistry for beta-toxin of a serial section from A. Note that beta-toxin signal (red) stains the vascular outline (endothelial cells) in the lamina propria. (Samples derived from study by Schumacher and colleagues [70]).