Diseases caused by S. enterica serovars are especially prevalent in developing areas, such as Southeast Asia, Africa, and South America. Challenges such as antibiotic-resistant Salmonella strains pose a significant threat to the development of reliable therapies. In this section, we highlight the work of groups that presented research dedicated to understanding the prevalence, spread, and control of both typhoidal and nontyphoidal salmonelloses in the developing world.
serovars, such as Salmonella enterica
serovars Typhi and Paratyphi, cause systemic illness that leads to an estimated 20 million cases and 200,000 deaths worldwide each year (5
). In Southeast Asian countries, such as Vietnam, the prevalence of typhoidal salmonellosis is high, and patients often suffer from recurrent or relapsed infections (5
). Why the immune system is unable to mount a lasting protective response against typhoidal Salmonella
species remains unknown. The work of Lucinda Thompson (Stanford University, Stanford, CA) aimed to address this issue by examining transcriptional signatures in the peripheral blood of serovar Typhi-infected patients from Vietnam. She described how salmonellosis patients in the acute, chronic, or convalescent stage of infection displayed distinct and temporal transcriptional profiles of immune genes. For example, profiles from acute typhoid cases had large upregulation of genes associated with increased neutrophil activity, while antiproliferative genes were downregulated. Over time, the acute signature approached that of uninfected individuals; however, some patients retained transcription profiles that indicated a more long-term effect of typhoid infection.
One of the foremost obstacles to administering effective treatment against Salmonella
infection is antibiotic resistance among disease-causing strains (37
). Studies conducted in the 1990s revealed significant increases in resistance to the most frequent antibiotic used against Salmonella
, nalidixic acid (48
). As the clinical outcome for patients infected with resistant strains is poor (13
), new therapies must be sought out. In her talk, “Clinical Aspects of Enteric Fever,” Christine Dolecek (University of Oxford, Oxford, United Kingdom) described how her group is developing a new evidence-based approach to testing anti-Salmonella
drugs in clinical trials in Vietnam. Their primary goal is to make local clinical drug trials standardized, reproducible, and easily executed. In addition, information obtained from trials should be accessible, and sharing of information between groups should be encouraged. With these principles in mind, clinical trials are under way to determine drug efficacy and to establish dosing regimes for azithromycin and gatifloxacin—new-generation antibiotics effective against drug-resistant Salmonella
Antibiotic resistance is also of critical concern in African countries, where multidrug-resistant nontyphoidal salmonellosis is one of the most common causes of bacteremia in children (13
). Nontyphoidal salmonellosis is caused by Salmonella enterica
serovars Typhimurium, Enteritidis, Newport, and Heidelberg and typically presents as self-limiting gastroenteritis, although in immunocompromised individuals, serious complications can ensue (20
). In recently published work, Sam Kariuki (KEMRI, Nairobi, Kenya) and colleagues presented data showing trends of drug resistance in nontyphoidal Salmonella
(NTS) isolated from children in Kenya (25
). At the meeting, Kariuki described these results, showing that while drug resistance is on the rise in urban populations, NTS isolated from patients in rural areas was decreasingly resistant to amoxicillin and cotrimoxazole. In addition, Kariuki described epidemiological studies aimed at tracking the prevalence and presentation of nontyphoidal salmonellosis in various populations to determine a reservoir for these infections. The data highlighted the influence of socioeconomic factors in disease, as invasive NTS incidence was significantly higher in children from slum populations.
Human immunodeficiency virus (HIV)/AIDS patients in Africa are another high-risk population for contracting NTS infections. The mortality rate for HIV patients infected with NTS can be as high as 60%, and bacterial recrudescence occurs in up to 45% of these individuals (11
). In her talk, Melita Gordon (Liverpool University, Liverpool, United Kingdom) described how her group is investigating the intracellular persistence of NTS in macrophages derived from HIV patients. Her results show that, while macrophages from HIV patients show no defects in bacterial internalization or killing, macrophages primed with gamma interferon hyperproduce tumor necrosis factor alpha, interleukin 10 (IL-10), and IL-12 in response to NTS. Gordon's previously published results demonstrating the importance of gamma interferon in human monocyte-derived macrophages support her current findings and highlight the importance of using human cells for in vitro studies (12
). Currently, Gordon's group is conducting further research to determine the mechanisms by which NTS-infected macrophages produce altered cytokine profiles in the context of HIV infection.
Molecular genotyping of NTS strains is fundamental to tracking disease-associated and drug-resistant strains in various populations. Currently, serotyping techniques and pulsed-field gel electrophoresis are used; however, the accuracy of these techniques is controversial (55
). At the meeting, Mark Achtman (Max-Planck Institute for Infection Biology, Munich, Germany) addressed this issue and highlighted the difficulties associated with molecular typing of Salmonella
isolates. According to Achtman, serotyping libraries are unreliable and no distinction can be made between serotypes isolated from different disease pathologies and hosts. Multilocus sequence typing (MLST) was described by Achtman as an alternative option to more accurately define Salmonella
isolates. While MLST of closely related Salmonella
isolates that share housekeeping genes can be problematic, the technique can be fine tuned to discriminate between sequences derived from stable temperate phages, which are more uniquely scattered throughout the genome (45
). Strain discrimination also is more accurate when MLST is used in combination with pulsed-field gel electrophoresis or other typing techniques (17
). While Achtman did point out that MLST should ultimately be replaced with even more sensitive techniques, such as small nucleic polymorphism identification, MLST has longevity in epidemiological research and is invaluable in studies such as those ongoing in Kenya and Malawi.