Secondary bacterial infection in plasma endotoxin levels and the acute‐phase response of mice infected withTrypanosoma brucei brucei

Abstract

Murine Trypanosoma brucei brucei infection leads to elevated plasma endotoxin-like activity levels not related to parasitaemia levels accompanied by the development of acute-phase response and increased plasma levels of serum amyloid P (SAP) and haptoglobin (Hp). To determine the source of the endotoxin-like activity and role of secondary bacterial infection in the pathogenesis of trypanosomosis, infected mice were treated with the antibiotic ciprofloxacin. Plasma endotoxin-like activity levels, irrespective of treatment, were elevated three- to fourfold, beginning 7 days after infection. Plasma protein concentrations increased markedly following infection from 7 days after infection (DAI). Peak Hp and SAP concentrations in ciprofloxacin-treated and -untreated infected mice were attained 7 and 14 DAI, respectively. Thereafter, both protein levels gradually declined until the end of the experiment, but Hp levels for non-treated mice declined up to 21 DAI and thereafter significantly increased on 28 and 35 DAI. Whole-trypanosome lysate and the membrane-enriched fraction demonstrated endotoxin-like activity, with the former having higher levels. The results suggest that the endotoxin-like activity in trypanosome fractions and plasma of infected mice is due to the trypanosome. Further elevation of haptoglobin during the late stages of infection in non-treated mice suggests the involvement of secondary bacterial infection.

The relationship of endotoxaemia to peripheral and central nervous system inflammatory responses in Human African Trypanosomiasis

“…Evidence has been presented that intestinal permeability of microbial products, which is the basis of baseline levels of serum endotoxin, is involved (Nyakundi et al 2002) and is consistent with the lack of correlation of endotoxaemia to parasitaemia. However, contradictory reports indicate a non-gut origin and an association with parasite membrane components (Ngure et al 2009 a , b ). …”

IFN‐γ mediates early B‐cell loss in experimental African trypanosomosis

“…However, the same study revealed that within one parasite population, many parasites do appear to ‘re‐use’ express VSGs during the chronic stage of infection, implying that the process of limited B‐cell destruction in a natural host could favour prolonged parasitemia. This would benefit the parasite in a direct manner, while negatively affecting host survival due to the increased susceptibility to secondary infections, even under vaccination conditions , as B‐cell destruction appears to result in non‐specific loss of B‐cell memory .…”