Invasive Salmonella infections in Africa.

Although Salmonella enterica is a leading cause of communityacquired bloodstream infection in Africa, these infections are frequently neglected as a target for public health intervention. The typhoidal Salmonella, serovars Typhi and Paratyphi A, cause enteric fever. Areas with high levels of endemic and epidemic typhoid fever are increasingly reported in Africa, and paratyphoid fever is described in some locations. Furthermore, in many sub-Saharan African countries, non-typhoidal Salmonella, primarily serovars Typhimurium and Enteritidis, cause bloodstream infections with incidence levels rarely seen elsewhere in the world. Efforts to control other important invasive bacterial infections such as Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis with conjugate vaccines are likely to leave S. enterica as a prominent next target for prevention. However, efforts to address invasive Salmonella infections in the region face a range of challenges. Burden of disease data are an essential first step towards building a case for intervention yet data to underpin estimates for both typhoidal and invasive non-typhoidal Salmonella disease are particularly scant in Africa. Lack of investment in clinical microbiology services and in invasive bacterial disease surveillance in many parts of Africa contribute to this problem. Even at sentinel hospital sites where facilities for blood culture are available, ascertainment of cases, and the understanding of patterns of healthcare utilization and of the size and structure of the catchment population, are frequently insufficient to accurately estimate more than minimum disease incidence. Strengthening long-term routine surveillance, ensuring that existing datasets are made widely available and developing novel surveillance tools would all contribute to progress in refining disease burden estimates. Beyond incidence, measuring outcomes of greatest interest, such as severe or complicated disease and death, is challenging. Invasive Salmonella infections are difficult to distinguish clinically from other febrile illnesses, risking misattribution of deaths to other diseases. Disease complications and death may occur in the community and not reach the attention of facility based surveillance. Furthermore, outcomes may be modified by the early detection, and correct diagnosis, of cases inherent and appropriate in high quality disease surveillance systems. New approaches to improving these estimates are needed. Managing patients with invasive Salmonella infections in lowresource areas continues to be problematic. In addition to challenges with clinical diagnosis, conventional diagnosis by blood culture is insensitive, slow and may not be available, and so can rarely inform acute management. Developing rapid diagnostic tests for invasive Salmonella infections has proved challenging. For invasive non-typhoidal Salmonella, comorbidities and late presentation contribute to high case fatality ratios. Multiple-drug resistant non-typhoidal and typhoidal Salmonella is established in Africa. The emergence of decreased fluoroquinolone susceptibility among typhoidal Salmonella and extended-spectrum cephalosporin resistance among nontyphoidal Salmonella threaten existing regimens for management of sepsis, leaving limited antimicrobial treatment options and, potentially, leading to worse outcomes. Therefore, the continuing emergence of antimicrobial resistance among invasive Salmonella should focus the attention of the research and public health community on strategies for control and prevention. Despite many decades of research we have only a rudimentary understanding of sources, modes of transmission and risk factors for infection that, alongside disease burden estimates, are crucial to the design of non-vaccine prevention programs. Human feces are the ultimate source of typhoidal Salmonella, and the host risk factors for invasive non-typhoidal Salmonella, including malaria, malnutrition and HIV, are well appreciated. Research in industrialized nations indicate that non-human vertebrate animals are the major reservoir of non-typhoidal Salmonella and that transmission to humans is usually via the consumption of foods of animal origin, produce contaminated by animal feces, and occasionally via water or direct contact with animals and their environments. However, genomic studies suggest human– host adaptation of epidemic invasive non-typhoidal Salmonella in Africa raising the possibility of transmission cycles that do not involve animals. An understanding of the relative contribution of waterborne, foodborne and other routes of transmission of both typhoidal and non-typhoidal Salmonella remains elusive. Although the few risk factor studies that have been conducted in Africa have provided few clues, novel molecular epidemiological tools implemented together with high quality field epidemiology now provide an exciting opportunity to make real progress.