A Decline in the Incidence of Invasive Non-Typhoidal Salmonella Infection in the Gambia Temporally Associated with a Decline in Malaria Infection

Mackenzie, Grant; Ceesay, Serign J.; Hill, Philip C.; Walther, Michael; Bojang, Kalifa; Satoguina, Judith; Enwere, Godwin; D’Alessandro, Umberto; Saha, Debasish; Ikumapayi, Usman N.; O’Dempsey, Tim; Mabey, David; Corrah, Tumani; Conway, David J.; Adegbola, Richard A.; Greenwood, Brian

doi:10.1371/journal.pone.0010568

Cited by 80 publications

(66 citation statements)

References 21 publications

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“…In recent epidemiological studies in Malawi, the prevalence of invasive NTS (iNTS) infections was found to be intrinsically entwined with rates of HIV, malaria, and malnutrition (133). This supports earlier reports from the Gambia and Kenya, where decreases in iNTS infections were noted upon implementation of effective malaria interventions (134,135). As such, determining the safety and efficacy of vaccines in populations with these underlying conditions represents a new challenge.…”

Section: Comorbidity Modelssupporting

confidence: 74%

Animal Models for Salmonellosis: Applications in Vaccine Research

Higginson

Simon

Tennant

2016

Clin Vaccine Immunol

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Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are generally ineffective against other Salmonella serovars. Vaccines that target paratyphoid and nontyphoidal Salmonella serovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for various Salmonella serovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models for Salmonella infection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development.A nimal models are indispensable tools for assessing candidate vaccines, with preclinical animal safety, immunogenicity, and efficacy data being prerequisite for regulatory agencies such as the U.S. Food and Drug Administration (FDA) prior to undertaking early-stage clinical trials. However, not all animal models are created equal. While some models are highly robust and closely mimic clinical infection, others are contrived and far removed from clinical relevance. Choosing the right animal model for the vaccine under investigation is imperative in determining its safety and/or effectiveness.Salmonella spp. are often used as model organisms to study bacterial pathogenesis and host-microbe interactions, due to the ability of certain Salmonella serovars to readily infect animals. As such, there are a myriad of animal models available to vaccine developers. These range from colonization or lethality models to those involving complex surgical techniques (Table 1). The choice of model is often related not only to relevance but also cost, ethics, housing requirements, and the availability of appropriate technical expertise. While most researchers utilize one model or another, integration of data from multiple animal models can provide a more complete understanding of the safety of a candidate vaccine and/or predict how a potential vaccine may perform in humans. In this minireview, we provide background on Salmonella clinical syndromes and pathogenesis and then summarize the various animal models that have been used for Salmonella vaccine research. We include a brief discussion of the technical aspects, advantages, and limitations of each model, followed by a review of the literature surrounding its use in vaccine evaluation. While there has been considerable development for veterinary Salmonella vaccines, here we will focus solely on vaccines and models for human salmonellosis.

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Section: Comorbidity Modelssupporting

confidence: 74%

Animal Models for Salmonellosis: Applications in Vaccine Research

Higginson

Simon

Tennant

2016

Clin Vaccine Immunol

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“…Malaria predisposes children to bacteremia in areas where malaria is endemic (6). The incidence of NTS bacteremia has also been associated with recent malaria (18) and has decreased with decreasing malaria prevalence in areas of endemicity (19). However, a lack of correlation between severe malaria and bacteremia has also been reported (20).…”

Section: Discussionmentioning

confidence: 99%

Bacterial Coinfections in Travelers with Malaria: Rationale for Antibiotic Therapy

et al. 2013

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e Malaria predisposes children in areas where malaria is endemic to concurrent bacteremia, often with severe outcomes. The importance of bacterial coinfections in patients diagnosed with malaria in nonendemic settings has, however, not been reported. A retrospective analysis of microbiology data was performed in 755 travelers diagnosed with malaria in Sweden. Bacterial cultures from blood and other locations were correlated to clinical outcome and antibiotic treatment. Blood cultures were drawn from 417 (55%) patients (88% of whom were >15 years old), and bacterial isolates of clinical relevance (Salmonella enterica serovar Enteritidis and Escherichia coli) were detected in 2 patients (0.3%). Cultures from other locations (mainly urine, nasopharyngeal, and fecal samples) were obtained from 44% of the patients with 4.9% positivity. Of the 38 patients given antibiotics, 47% had neither severe malaria nor positive cultures and/or radiology signs indicative of treatment. C-reactive protein levels were associated with bacterial infections but had only a fair predictive value. Bacterial coinfections are uncommon among travelers with malaria. These data suggest a weaker association between malaria and bacteremia than previously described in endemic settings and might indicate different patient populations with different pathophysiological mechanisms and microbial environments. The study supports a restrictive antibiotic policy in returning travelers with malaria.

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“…Recent malaria [40], acute severe malaria [47] and severe malarial anaemia, but not cerebral malaria [48], have all been specifically described as risk factors for iNTS disease. Several groups have also described temporal-spatial relationships of malaria and iNTS disease among children [49–51].…”

Section: Invasive Non-typhoidal Salmonella (Ints) Diseasementioning

confidence: 99%

Antimicrobial resistance and management of invasive Salmonella disease

Kariuki¹,

Gordon²,

Feasey³

et al. 2015

Vaccine

245

202

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Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20–30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50–75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries.

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A Decline in the Incidence of Invasive Non-Typhoidal Salmonella Infection in the Gambia Temporally Associated with a Decline in Malaria Infection

Cited by 80 publications

References 21 publications

Animal Models for Salmonellosis: Applications in Vaccine Research

Animal Models for Salmonellosis: Applications in Vaccine Research

Bacterial Coinfections in Travelers with Malaria: Rationale for Antibiotic Therapy

Antimicrobial resistance and management of invasive Salmonella disease

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