Typhoid fever is a bacterial infection caused by the Gram-negative bacterium Salmonella enterica subspecies enterica serovar Typhi (S. Typhi), prevalent in many low- and middle-income countries. In high-income territories, typhoid fever is predominantly travel-related, consequent to travel in typhoid-endemic regions; however, data show that the level of typhoid vaccination in travellers is low. Successful management of typhoid fever using antibiotics is becoming increasingly difficult due to drug resistance; emerging resistance has spread geographically due to factors such as increasing travel connectivity, affecting those in endemic regions and travellers alike. This review provides an overview of: the epidemiology and diagnosis of typhoid fever; the emergence of drug-resistant typhoid strains in the endemic setting; drug resistance observed in travellers; vaccines currently available to prevent typhoid fever; vaccine recommendations for people living in typhoid-endemic regions; strategies for the introduction of typhoid vaccines and stakeholders in vaccination programmes; and travel recommendations for a selection of destinations with a medium or high incidence of typhoid fever.

Melarsoprol administration for the treatment of late-stage human African trypanosomiasis (HAT) is associated with the development of an unpredictable and badly characterized encephalopathic syndrome (ES), probably of immune origin, that kills approximately 50% of those affected. We investigated the characteristics and clinical risk factors for ES, as well as the association between the Human Leukocyte Antigen (HLA) complex and the risk for ES in a case-control study. Late-stage Gambiense HAT patients treated with melarsoprol and developing ES (69 cases) were compared to patients not suffering from the syndrome (207 controls). Patients were enrolled in six HAT treatment centres in Angola and in the Democratic Republic of Congo. Standardized clinical data was obtained from all participants before melarsoprol was initiated. Class I (HLA-A, HLA-B, HLA-Cw) and II (HLA-DR) alleles were determined by PCR-SSOP methods in 62 ES cases and 189 controls. The principal ES pattern consisted in convulsions followed by a coma, whereas ES with exclusively mental changes was not observed. Oedema, bone pain, apathy, and a depressed humour were associated with a higher risk of ES, while abdominal pain, coma, respiratory distress, and a Babinski sign were associated with higher ES-associated mortality. Haplotype C*14/B*15 was associated with an elevated risk for ES (OR: 6.64; p-value: 0.008). Haplotypes A*23/C*14, A*23/B*15 and DR*07/B*58 also showed a weaker association with ES. This result supports the hypothesis that a genetically determined peculiar type of immune response confers susceptibility for ES.