Typhoid fever and malaria co-infection alters brain structures and impairs spatial working memory in Wistar rats

Typhoid fever and malaria co-infection have been documented since the 19th century in addition to its significant impact on global population. The aim of the present study was to investigate the potential neurological damages of typhoid fever-malaria co-infection in rats. To perform this, 34 Wistar strain rats were divided into five groups, including a control group which received distilled water, an immunosuppressed group treated only with cyclophosphamide, a group mono-infected with Salmonella typhimurium; a group mono-infected with Plasmodium berghei, and a co-infected one which received both Salmonella typhimurium and Plasmodium berghei. Spatial working memory rats was assessed via T-maze testing 12 days post-infection. Two days after T-maze test, the animals were sacrificed, brain and other organs collected and weighed. A part of the brain was used to prepare homogenates and the other part for histological sections. In the brain, stress markers, GABA and its catabolic enzyme (GABA transaminase) activity were evaluated. It emerges from this work that typhoid fever and malaria infections significantly (p < 0.05) impaired the exploratory behavior of rats with an emphasis on co-infected animals. When co-infected animals succeeded to move, they spent more time in their preferred arm in T-maze compared to the other groups. It was noticed a high level of oxidative stress markers (malondialdehyde, nitrites) as well as GABA transaminase in co-infected animals. Conversely, a low concentration of GABA, reduced glutathione, and a low activity of catalase were registered in the same group. In addition, marked alterations in the structure of the brain were recorded in these co-infected animals. Collectively, these findings indicate that Salmonella and Plasmodium infections exacerbated oxidative stress, disrupted working memory processes and induced neuroinflammation in experimental animals. When both pathogens are present in the same organism, their combined effect is worse than the effect of each pathogen alone. All these show a severe negative effect of Salmonella-Plasmodium co-infection in the nervous system.