Rickettsia typhi as Cause of Fatal Encephalitic Typhus in Hospitalized Patients, Hamburg, Germany, 1940-1944

Abstract

We evaluated formalin-fixed paraffin-embedded tissue specimens from 7 patients who died with encephalitic typhus in Hamburg, Germany, during World War II. The archived specimens included only central nervous system tissues >70 years old that had been stored at room temperature. We demonstrated successful detection of Rickettsia typhi DNA by a nested qPCR specific to prsA in 2 patients. These results indicate that R. typhi infections contributed to typhus outbreaks during World War II. Immunohistochemical analyses of brain tissue specimens of R. typhi DNA-positive and -negative specimens showed perivascular B-cell accumulation. Around blood vessels, nodular cell accumulations consisted of CD4-positive and CD8-positive T cells and CD68-positive microglia and macrophages; neutrophils were found rarely. These findings are similar to those of previously reported R. prowazekii tissue specimen testing. Because R. typhi and R. prowazekii infections can be clinically and histopathologically similar, molecular analyses should be performed to distinguish the 2 pathogens.

Keywords: CD4; CD8; Germany; Rickettsia prowazekii; Rickettsia typhi; T cells; World War II; bacteria; body louse; brain lesions; encephalitic typhus; endemic typhus; epidemic; fatality; flea; hospitalized patients; immunohistochemistry; murine typhus; nested PCR; outbreak; rat; rickettsiosis; typhus; typhus nodules; vector-borne infections.

Figure 1

Hematoxylin and eosin staining of typical typhus nodules in brain of typhus patients during World War II, Hamburg, Germany, 1940–1944. Most nodules were found in the pons and medulla oblongata. A) Loose nodule. B) Spongy nodule amid large neuronal cells. C) Compact typhus nodule along longitudinal blood vessel. Note hyperemia of other blood vessels nearby. D) Another compact nodule with hyperemic blood vessels nearby. Original magnifications ×40.

Figure 2

Immunohistochemical analyses of nodule cell compositions from typhus patients during World War II, Hamburg, Germany, 1940–1944. Tissue sections were incubated with specific antibodies and visualized with immunoperoxidase (brown) or immunophosphatase (blue) stains and lightly counterstained with hematoxylin. A) CD3 stain (brown) for T cells and CD20 stain (blue) for B cells. Only T cells are visible within the nodule. Original magnification ×40. B, C) CD4 stain (brown) and CD8 stain (blue) for T cell subsets. The nodules consist of a mixture of both cell types, with a predominance of CD8-positive cytotoxic T cells. Original magnifications ×40. D) CD68 stain (brown) for macrophages and microglia. A strong positivity is seen in the nodules and staining is also scattered in the surrounding brain parenchyma. Original magnification ×20.