Salmonella infections: An update on epidemiology, management, and prevention

Travel Medicine and Infectious Disease (2011) 9, 263e277

Available online at www.sciencedirect.com

journal homepage: www.elsevierhealth.com/journals/tmid

Salmonella infections: An update on epidemiology, management, and prevention ´nchez-Vargas a, Maisam A. Abu-El-Haija b, Flor M. Sa ´mez-Duarte c,* Oscar G. Go a

Department of Internal Medicine, Saint Francis Hospital, Evanston, IL, USA Division of Pediatric Gastroenterology, University of Iowa Children’s Hospital, Iowa City, IA, USA c Division of Pediatric Infectious Diseases, University of Iowa Children’s Hospital, Iowa City, IA, USA b

Received 5 March 2011; received in revised form 30 September 2011; accepted 3 November 2011 Available online 25 November 2011

KEYWORDS Salmonella; Enteric fever; Gastroenteritis; Vaccine; Animal

Summary Salmonella species are a group of Gram-negative enterobacteria and known human pathogens in developing as well as industrialized countries. Despite significant advances in sanitation, provision of potable water, and highly controlled food chain surveillance, transmission of Salmonella spp. continues to affect communities, preferentially children, worldwide. This review summarizes updated concepts on typhoidal and non-typhoidal Salmonella infections, starting with a historical perspective that implicates typhoid Salmonella as a significant human pathogen since ancient times. We describe the epidemiology of this pathogen with emphasis on the most recent non-typhoidal Salmonella outbreaks in industrialized countries and continued outbreaks of typhoid Salmonella in underserved countries. An overview of clinical aspects of typhoid and non-typhoid infections in developing and industrialized countries, respectively, is provided, followed by a description on current treatment concepts and challenges treating multidrug-resistant Salmonella infections. We conclude with prevention recommendations, and recent research studies on vaccine prevention. ª 2011 Elsevier Ltd. All rights reserved.

Introduction

* Corresponding author. Present address: Division of Pediatric Infectious Diseases, Vanderbilt University, D6201 MCN, 1161 21st Avenue South, Nashville, TN 37232-2581, USA. Tel.: þ1 615 322 2250; fax: þ1 615 343 9723. E-mail address: [email protected] (O.G. Go ´mez-Duarte).

Salmonella species are Gram-negative bacilli (Fig. 1) associated with animal and human infections. Salmonella spp. infections lead to high morbidity rates not only in the developing world but also in industrialized countries and high mortality mainly in the poorest nations of the developing world. It is believed that epidemics caused by Salmonella spp. may have significantly affected the history

1477-8939/$ - see front matter ª 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tmaid.2011.11.001

264

F.M. Sa ´nchez-Vargas et al. Athens (448 BC to 429 BC).5 In fact, the premature death of Pericles and Alexander the Great, presumably due to S. Typhi, may have dramatically changed the fate of the magnificent Greek empire.6 In the 19th century and beginning of the 20th, enteric fever was a leading cause of mortality in several important American and European metropolitan areas such as London, Chicago, New York, among others. Death rates were as high as 174 per 100,000 inhabitants.7,8 After the mid-20th century, the reduction in morbidity and mortality in industrialized countries was not only the result of antibiotics availability but more importantly to improvement in water supply and sanitation. In 1948 the reported use of chloramphenicol in the treatment of enteric fever represented a significant milestone in Salmonella spp. infections management.9

Figure 1 Scanning electron microscopy of a Salmonella enterica, subsp. Enterica, serotype Typhimurium.

of humankind, even at present, the effect of Salmonella infections on entire communities result in economic burden to developing and also industrialized nations.1 The interest generated with Salmonella spp. as pathogens over the last decades and their implications on history, economics and biomedical science, is represented by close to 70,000 articles posted in Medline, and close to 15 million Internet entries. According to the most recent nomenclature adopted by the Centers for Disease Control (CDC), the genus Salmonella contains only two species, Salmonella enterica and Salmonella bongori.2 S. enterica subdivides into six subspecies named (or numbered) as follows: enterica (I), salamae (II), arizonae (IIIa), diarizonae (IIIb), houtenae (IV), and indica (VI), while S. bongori has no subspecies. Both Salmonella species and the subspecies are serotyped for further identification. Based on the clinical syndromes that Salmonella spp. cause in human subjects, we will limit our definitions to only two types of strains, typhoid Salmonella and non-typhoid Salmonella (NTS). The former species are the causative agents of enteric fever and they include S. enterica, subspecies enterica, serotypes Typhi and Paratyphi (Salmonella Typhi and Salmonella Paratyphi). The latter group includes the remaining strains (Table 1).

Epidemiology The epidemiology of Salmonella spp.-associated infections varies widely depending on the type of Salmonella spp. involved (Table 1). While enteric fever, caused by S. Typhi and S. Paratyphi, generally leads to a severe and lifethreatening disease that primarily affects communities in underserved nations, NTS infections tend to be self-limiting and to affect communities worldwide.10 The changing epidemiology of these infections is provided in separate sections below.

Enteric fever It is estimated that enteric fever causes 200,000 deaths and 22 millions of illness per year worldwide predominantly in low-income nations.11 The incidence of enteric fever, however, varies substantially between countries. High incidence estimates (more than 100 cases per 100.000 inhabitants per year) were calculated in south-central Asia and south-east Asia while low incidence (less than 10 cases per 100.000 per year) was reported in Europe, Australia and New Zealand and North America. In the US, the incidence of

Table 1 Comparison between typhoid Salmonella and non-typhoid Salmonella infections. Features

Typhoid Salmonella

NTSa

References

Serotypes

S. Typhi, S. Paratyphi Humans Predominantly water Developing countries Systemic

Remaining strains Animals Predominantly food Worldwide

18

Local or systemic Increased risk

42,110

<1%

120,126

Historic background S. Typhi have accompanied humankind since ancient times. Evolutionary evidence, based on phylogenetic analysis of S. Typhi strains, indicates that a common S. Typhi ancestor existed 15,000 to 150,000 year ago. Time when humans were still hunters and were spreading across the planet.3 While S. Typhi was not described as the etiologic agent of enteric fever until 1880 by Eberth, descriptions are recognized in Greek and Chinese texts dating back to hundreds of years BC.1,4 The term typhoid fever (enteric fever), derived from the Greek typhos, which translates as “putrid odor”, is proposed as the most likely cause of death among Athens inhabitants during the plague of Athens, a historic event that may have precipitated the end of the Golden Age of

Reservoir Transmission Location Disease

HIV Infection No higher risk risk Carrier rate 1-4% a

NTS: Non-typhoid Salmonella.

55 21 10

24,118

Salmonella infections: An update S. Typhi infections is low (400 per year) and, for the most part, it was related to travel, either, US travelers returning from developing countries, or foreigners traveling to the US.12 As in the US, enteric fever in UK and Canada is infrequent and most of the cases are imported from India or Pakistan.13,14 An epidemiological survey in Spain over a nine year period (1997e2005) reported an annual hospitalization rate of 0.31 cases per 100,000 inhabitants and a mortality rate of 0.003 cases per 100,000. The population at risk was travelers to the Indian Subcontinent and Africa.15 In Israel, the incidence of enteric fever decreased from 0.42 to 0.23 per 100,000 from 1995 to 2003, with 57.4% of cases imported, an increased number of S. Paratyphi isolated.16 Regions with medium incidence (10e100 cases per 100.000 inhabitants per year) included Africa, Latin America, the Caribbean and the rest of Asia and Oceania.11 In Asian countries the annual incidence of S. Typhi was higher in Pakistan (451.7 cases per 100,000) and India (214.2 cases per 100,000) compared with Viet Nam and China (21.3 and 15.3 cases per 100,000, respectively).17 The burden of enteric fever is poorly characterized in many developing countries because of limited availability of resources for diagnosis, surveillance tools and consequently epidemiologic data.18,19 In African countries, for instance, estimates have been difficult to calculate, in part, due the use of antibody testing as a measure of infection detection that may result in false positive episodes.20 S. Typhi and S. Paratyphi, have only humans as a reservoir (Table 1) and the route of transmission includes ingestion of contaminated food and water with patient’s and carrier’s feces.21 The main route of S. Paratyphi transmission is believed to be associated with consumption of street vendor’s food.18 S. Typhi has been a major global problem during most of the 20th century while S. Paratyphi was limited to a smaller proportion of enteric fever cases. Since the past decade, the incidence of S. Paratyphi A has increased worldwide and in south-central Asia and Southeast Asia countries where it appears to be responsible for up to 50% of Salmonella spp. blood stream enteric fever isolates.22 There is a need for epidemiological tools in countries with limited resources to follow the trend on S. Paratyphi infections. Epidemiological surveillance is essential to determine the impact of this pathogen on morbidity and mortality and on the burden of disease in the population at risk. Cases of enteric fever in endemic areas are generally more frequent in infants, pre-school age and school age children than in adults.23,24 In the last decade the annual incidence among children aged 2e5 years was around 27 per 100,000 in Viet Nam and China, and around 450 per 100,000 in Pakistan and India, with an incidence of bacteremia in children less 2 years of age of 443.1 per 100,000 child years.17,25 The prevalence in African children, calculated from 10 different studies, ranged from 0% to 4.23%, with one study from Egypt reporting a prevalence of 4.23%.20 The emergence of S. Typhi and S. Paratyphi antibiotic resistance is another important public health problem worldwide. Soon after antibiotics started to be used for treatment of enteric fever, cases of antibiotic resistance were reported. Antibiotic resistance was initially to

265 chloramphenicol and subsequently to beta-lactams, quinolones and azithromycin. At present, there is a significant concern with the extended spectrum B-lactamase resistance in the Asian continent.26,27 The frequency of multidrug-resistant S. Typhi (defined as resistance to ampicillin, chloramphenicol and trimethoprim-sulphamethoxazole) is high in Asian and African countries, with significant variation between regions.28 In a population-based surveillance in Asia, a high frequency of multidrug-resistant S. Typhi was reported in isolates from Pakistan (65%) and Viet Nam (22%) compared with China and Indonesia. Also, nalidixic resistance, considered a reliable indicator of decreased susceptibility to ciprofloxacin and other fluoroquinolones, was found in 59% of isolates from Pakistan, 57% from India and 44% from Viet Nam.17 A study conducted in eight Asian countries between 2003 and 2005 reported antibiotic resistance from 1774 typhoid Salmonella isolates.29 The frequency of multidrug resistance was variable between countries (16e37%), with a high incidence in Viet Nam, Nepal, Pakistan, India and Bangladesh and low incidence in China, Laos and Indonesia. Similar data was reported from seven Asian countries from 2002 to 2004, in which multidrug-resistant S. Typhi was found in 41.2% of isolates and 69.6% had reduced susceptibility to ciprofloxacin.30 High level quinolone resistance in S. Paratyphi isolates, compared with S. Typhi, has been reported in countries with high incidence of multidrug resistance.31,32 In the US, 13% of the isolates were multidrug-resistant, 38% were resistant to nalidixic acid and 97% had decreased susceptibility to ciprofloxacin (five of them resistant to ciprofloxacin). Patients with multi-resistant S. Typhi were more likely to have history of travel outside US, especially India, Bangladesh, Pakistan and Cambodia.33

Non-typhoid Salmonella (NTS) infections Despite the improvement in sanitation and hygiene, NTS illnesses continue to impose a significant burden on the population’s health in industrialized and underdeveloped countries.34e36 It is estimated that 93.8 million cases of gastroenteritis due Salmonella spp. occur worldwide leading to 155,000 deaths each year.34 According to SalmSurv (a World Health Organization (WHO) supported foodborne disease surveillance network) data from 2001 to 2005, S. Enteritidis was the most common serotype worldwide (65% of the isolates), followed by S. Typhimurium (12%) and S. Newport (4%).37 In Africa, S. Enteritidis and S. Typhimurium represented 26% and 25% of the isolates, respectively. In Asia, Europe and Latin America/Caribbean, S. Entiritidis was the most frequent isolate (38%, 87% and 31%, respectively). In North America S. Typhimurium was the most frequented reported (29%) followed by S. Enteritidis (21%) and other Salmonella spp. (21%).37 Sub-Saharan Africa hospital-based studies reported blood stream Salmonella spp. infections more frequently associated to NTS, particularly S. Enteritidis and S. Typhimurium, than S. Typhi or S. Paratyphi. In this region, invasive NTS is endemic and has elevated morbidity and mortality in children less 3 years and adults with human immunodeficiency virus (HIV) infection.38e40 In contrast,

266 NTS invasive disease is infrequent in Asia except in subjects with severe immunosupression.41,42 In industrialized countries the increasing incidence of NTS has become a public health concern.43 The estimated NTS-associated illnesses incidence in Europe is 690 per 100,000 inhabitants per year. This incidence varies between regions from 240 per 100,000 in Western Europe to 2390 per 100,000 person-years in Central Europe.34 The annual incidence in Israel ranges from 52 to 102 per 100,000.43 The incidence of NTS bacteremia in Finland, Australia, Denmark and Canada during 2000e2007 was estimated at 0.81 per 100,000 per year.44 In the US the Foodborne Diseases Active Surveillance Network (FoodNet) found that NTS infections were the most commonly reported (17.6 cases per 100,000 inhabitants) and the incidence has not declined since 1996, when the surveillance was initiated.45 FoodNet data from 1996 to 2005 reports that NTS infections have been the leading cause of death (39%) among foodborne bacterial pathogens with highest mortality among adults more 65 years and highest incidence among children less than 5 years of age (69.5 infections per 100,000 children).46 Childhood infections were associated with daycare center attendance and contact with cats or reptiles.47 FoodNet reported an incidence of invasive salmonellosis of 0.9 cases per 100,000 inhabitants with the highest risk among infants (7.8 cases per 100.000 inhabitants).48 From 2005 to 2010 the CDC reported an unusually high number of cases in the US as a result of several independent Salmonella outbreaks. Frequent factors associated with outbreaks included raw ingredients in contact with contaminated animal or people, improper storage or incomplete cooking of food products.49 The most recent outbreak leading to significant concern among health authorities, consumers and farms owners, was the January 2010 multistate outbreak that lasted one entire year. This outbreak caused by S. Enteritidisecontaminated eggs affected 16 states and resulted in an estimated number of 1939 cases.50 The estimated 380 million contaminated chicken eggs shipped across the US lead to a massive egg recall recommended by the US Food and Drug Administration to prevent further spread of the infection. NTS transmission to humans can occur by consumption of food animal products, non-animal food products, contaminated water, or by contact with animals. Food products mass production and distribution disseminates pathogens rapidly to communities. Furthermore, antibiotic resistance among NTS organisms makes more difficult the control and prevention of these infections.34 The complex ecologies linking NTS to animals and plants implies the need for concerted efforts in contamination prevention throughout the food chain supply.2,51e54 Farm animals are the major reservoir for NTS in industrialized countries with transmission by their contaminated products. NTS are naturally found in chickens, ducklings, sheep, goats, pigs, reptiles, amphibians, birds, pet rodents, dogs, cats, and in a variety of wild animals making infection control a challenge to public health authorities.55e60 NTS pet transmission to humans easily occurs by contact with animal feces. NTS infections associated to pet transmission may affect infants, and result in invasive disease and severe complications.61,62

F.M. Sa ´nchez-Vargas et al. The number of multidrug-resistant NTS has increased in many countries since the 1990 report of the multidrugresistant S. Typhimurium DT104 strain that spread around the globe.63 According to the National Antimicrobial Resistance Monitoring System (NARMS) 4.1% of the US isolates from 2005 to 2006 had decreased susceptibility to cephalosporins and 84% had multidrug resistance phenotypes.64 More comprehensive NARMS data from 1996 to 2007 showed also that invasive NTS were more likely to be multidrug resistant, but more importantly, it reported that isolates began to show resistance to nalidixic acid (2.7%) and ceftriaxone (2.5%), rising concern about clinical management and public health surveillance and prevention.65 A European survey from 2000 to 2004 on 135,000 isolates reported NTS resistance among 57e66% of them, including multidrug resistance in 15e18% and resistance to nalidixic acid in 14e20% during the same period.66 African and Asian countries have increased number of ciprofloxacin resistance strains, and reports of resistance to cephalosporins associated with extended spectrum beta-lactamase production.67e70

Salmonella infection and clinical syndromes Salmonella invasion A remarkable characteristic in Salmonella pathogenesis is the invasion of non-phagocytic cells. Salmonella will penetrate into the intestinal epithelial cells by inducing their own uptake, in a complex and active process that morphologically resembles phagocytosis.71,72 Virulence genes involved in invasion and required for intracellular survival are clustered in large chromosomal DNA regions designated Salmonella pathogenicity islands (SPIs).73,74 SPI1 and SPI-2 encode type III secretion systems, consisting of multiprotein complexes that build a contiguous channel across both the bacterial and epithelial cell membranes, resulting in efficient translocation of bacterial effectors directly into the epithelial cell cytoplasm. The secreted effectors interact with eukaryotic proteins to activate signal transduction pathways and rearrange the actin cytoskeleton and lead to membrane ruffling and bacterial engulfment.75e77 Once inside the host cell, these effectors are capable of altering host cellular functionsdsuch as cytoskeletal architecture, membrane trafficking, signal transduction, and cytokine gene expressiondthat result in bacterial intracellular survival and colonization.78,79

Intracellular survival Salmonella spp. can infect both warm and cold-blooded hosts; this wide range reflects the ability of this pathogen to sense and adapt to a range of different environments, including the interior of macrophages.80e82 Intracellular persistence in host cells is critical for pathogenesis and disease, because strains defective in this property are avirulent.83e85 Following invasion of host cells, Salmonella localize within a membrane compartment known as the Salmonella-containing vacuole.86 The bacteria actively remodel this compartment and establish a niche where they are capable of survival and replication.87,88 The

Salmonella infections: An update

267

capacity of virulent S. Typhi to avoid fusion of Salmonellacontaining vacuoles with dendritic cell lysosomes is the mechanism likely responsible for evasion of killing.89 By surviving within macrophages, S. Typhi is carried to the spleen, lymph nodes and throughout the reticuloendotelial system.90,91

myocarditis, endocarditis, pneumonia, and pleural effusion; iii. Renal complications: acute renal failure, glomerulonephritis, pyelonephritis; iv. Hematologic: disseminated intravascular coagulation, bone marrow suppression, thrombosis; v. Other: infection in bone, joints, liver, spleen, and musculoskeletal system.94,102e105

Enteric fever

NTS infections

Osler wrote a compelling description of typhoid fever that included incubation period, symptoms and signs of the disease, and convalescence. He described the rose-colored spots and splenomegaly, and emphasized the temperatureepulse relationship (relative bradycardia) and the apathetic face as key features of the disease.92 Clinical presentation and complications of enteric fever are similar between S. Typhi and S. Paratyphi.22,93 The incubation period is 7e14 days, with a range of 3e60 days.94,95 Before the onset of fever, patient’s symptoms may include headache, diarrhea or constipation and abdominal pain. Headache is a frequent symptom while diarrhea is most common in adults with HIV and children. Other nonspecific complaints include chills, loss of appetite, cough, or myalgias. An initial prolonged low-grade fever is followed by a high sustained fever in the second week. Fever may persist for up to 4 weeks if untreated.96e100 On examination, patient may have fever, coated tongue (typhoid tongue), bradycardia (less than 50% of the cases) and rose spots on abdomen and chest. Rose spots, blanching erythematous maculopapular 2e4 mm lesions, may be present in 30% of the cases. Other findings include splenomegaly, hepatomegaly, and mental status changes.93,95e97,101 The disease is more severe in children age less than 1 year and in patients with immunosuppression. Interestingly, studies conducted in Tanzania suggest that the HIV status may be protective against typhoid Salmonella bacteremia as HIV-infected patients were less likely to be bacteremic than HIV uninfected controls.38 Patients with infections caused by multidrug-resistant bacteria are often sicker and septic at onset of illness with high fever, hepatomegaly, splenomegaly and abdominal distension.28 Blood test findings may be unspecific with relative neutropenia, lymphopenia, thrombocytopenia, increased C-reactive protein, and increased erythrocyte sedimentation rate. Leukocytosis is less frequent. Abnormal liver function tests (increased in AST and ALT 2e3 times above the normal limit) could be observed in some patients.101 Complications may present in 10%e15% of the patients in endemic regions. The most common gastrointestinal complication is bleeding secondary to erosion of Peyer’s patches. Other complications include intestinal perforation (more frequent in the ileum), hepatitis, cholecystitis, pancreatitis and peritonitis. A sudden drop in temperature after several days of illness suggests intestinal perforation.93,95,102 Numerous extra-intestinal complications, although uncommon, may occur with S. Typhi infection and any organ may be involved, among them: i. Central nervous system complications: meningitis, hemorrhages, seizures, encephalopathy, Gillain-Barre ´ syndrome, and peripheral neuropathy; ii. cardio-respiratory complications:

NTS infections are associated with different clinical syndromes of variable severity, including gastroenteritis, bacteremia, endovascular infection and focal infection. The incubation period is usually 6e12 h.106 The most common initial symptoms are nausea, vomiting and no bloody diarrhea; other symptoms may include fever, chills, abdominal pain, myalgias, arthralgias and headache. These symptoms are usually self-limited and not associated with intestinal perforation. Other gastrointestinal signs such as hepatomegaly and splenomegaly, are less common. Serum C-reactive protein is frequently elevated, blood leukocyte count may be mildly elevated. Stool testing usually reveals leukocytes and less frequently erythrocytes.107 Gastrointestinal complications include appendicitis, pancreatitis, cholecystitis, cholangitis, and abdominal or perianal abscess.106 Systemic infection has variable clinical manifestations and it is more severe in immunocompromised patients.108 Bacteremia, the most common systemic presentation, occurs in 5% of the infected patients, and it may be associated with other extra-intestinal complications.42,109e111 Bacteremia and other invasive manifestations are associated with certain Salmonella serotypes, patient age (extremes of age) and immunosupression.23,109 In industrialized countries, adults with bacteremia are more likely to have predisposing conditions, higher incidence of extraintestinal complications and higher mortality compared to children.112 NST is endemic in sub-Saharan Africa and it is more frequent in HIV-infected adults and children less than 3 years. Clinical presentation includes fever, anemia and splenomegaly without gastrointestinal symptoms.39,40 In a study that included 401 invasive NST cases in Mozambican children, independent risk factors of death were young age, severe malnutrition, diarrhea and pneumonia.39 The most common extra-intestinal organ compromised is the lung. Other extra-intestinal manifestations are meningitis, encephalopathy, endocarditis, pneumonia, empyema, abscess, urinary tract infection, osteomyelitis, cellulitis or arthritis.109,112,113 In bacteremic children the risk of meningitis was 24% for infants between 0 and 6 months in one study in Thailand.114 Endovascular infections or infectious endarteritis are described in adults in industrialized countries and they localize in atherosclerotic plaques or aneurysms, yet the infection may result in a mycotic aneurism in any arterial vessel.40,115 Other risk factors predisposing the host to NTS infection include immunosuppression, decreased gastric acidity, recent use of antibiotics, changes in the intestinal flora, hemoglobinopathies, and extremes of age.40,106 Salmonella and HIV co-infections have been reported and the role of the HIV status in susceptibility to Salmonella infection is currently a subject of investigation. Overall, HIV positive

268 patients, including those with acquired immunodeficiency syndrome (AIDS), are more frequently infected with NTS than with S. Typhi (Table 1).116,117 NTS infections in AIDS patients are associated with high mortality and high recrudescence rates.118 Although decreased NTS infection incidence among HIV patients has been associated with antiretroviral therapy and treatment with trimethoprimsulfamethoxazole, an increased NTS infection morbidity in HIV-AIDS patients is observed regardless of antiretroviral therapy.117

Chronic carrier S. Typhi carrier status defined as positive culture in stools for more that 12 months after acute infection or acute illness is a public health concern. Carriers may shed and infect individual with S. Typhi for decades, in fact, they are responsible for all human infections in endemic areas and during outbreaks. S. Typhi transmission commonly occurs when chronic carrier’s feces contaminate food products or water sources. Since S. Typhi has only humans as a reservoir, searching for chronic carriers and eliminating the carrier status is essential for transmission elimination and disease prevention. S. Typhi carrier status among food vendors is implicated in enteric fever spread in the community (Feglo et a., 2004).119 One to 4% of patients with enteric fever may become chronic carriers, as well as people who have no history of the disease.95,120 Carrier state tends to be more frequent in women, infants and elderly, and in cholelithiasis patients. Interestingly, precise estimations of the number of S. Typhi carriers were actually obtained by evaluating individuals with known cholecystitis.121 It is suggested that the liver is the organ where S. Typhi persists and it is intermittently excreted into the gallbladder. There are several reports suggesting the association of carcinoma of the gallbladder with chronic typhoid carriage.122e125 NTS carriage is less frequent, and it occurs in 0.1e1% of individuals with laboratory confirmed NTS infection.126 NTS carrier state is as concerning as S. Typhi carriage because NTS chronic carriers are not responsible for most human infections worldwide. Animals, instead, are more frequently colonized by NTS than humans. Risks factors associated with NTS carriage include young age, female gender, and presence of gallstones or kidney stones as described for S. Typhi.23

Diagnosis Salmonella spp. may be isolated from blood, bone marrow aspirates, urine, stool and other sterile sites. Blood or stool cultures followed by conventional microbiological identification and serology are the mainstay salmonella infection diagnostic testing.127 Blood cultures have low sensitivity as only 40e60% are positive in enteric fever cases, in contrast, the sensitivity of bone marrow aspirate cultures is more than 80%, making this type of culture the gold standard for diagnosis of enteric fever.128e131 In resource-limited countries, however, blood cultures or bone marrow aspirate for diagnosis may not be possible due to expense and limited trained personnel.132e134

F.M. Sa ´nchez-Vargas et al. Stool cultures are positive in only 30%e35% of the cases. This low sensitivity, due in part to the intermittent bacterial shedding, requires multiple testing samples for the evaluation of Salmonella spp carriers.131,135 The urine culture sensitivity is also low and it may range from 7% to 10%. Positive cultures in urine or stools need may indicate an acute infection or may occur in chronic carriage.135 Serologic tests have been used for diagnosis for more than 100 years. The Widal test developed in 1896, utilizes a suspension of killed S. typhi as antigen to detect serum antibodies against the flagellar and somatic antigens that on positive samples results in agglutination during the acute and convalescent phases of disease. In developing countries the Widal test could be the only laboratory tool available for diagnosis. Its role in diagnosis is controversial as it has a low sensitivity and specificity and requires two samples one in the acute phase and other in the convalescent phase taken approximately 10 days apart. The diagnosis based only in Widal test is frequently inaccurate as false positive and false negative results are common. There is also high variability between commercial preparations and lack of standardization.134,136 In contrast, rapid diagnostic testing using PCR stools and blood specimens were reported to have high specificity and sensitivity.137e141 In addition to microbiologic identification of Salmonella spp. and serologic testing for determination of species and serovars, other techniques are available as epidemiological tools to investigate outbreaks, to evaluate bacterial genetic diversity, and to study the evolution and population structure of strains coming from different sources and geographic regions. The most common methods currently in use are the pulse-field gel electrophoresis (PFGE) and multiple loci sequencing typing (MLST). PFGE is based on the separation of chromosomal DNA fragments after restriction enzymatic digestion. MLST, based on sequencing analysis of chromosomally located house-keeping genes, has higher discriminatory power, excellent data analysis capability and, in contrast to PFGE, it has higher reproducibility between laboratories.142e144

Antibiotic treatment Enteric fever treatment For more than 40 years, chloramphenicol was the antibiotic of choice to treat enteric fever. Ciprofloxacin became the first line therapy after the spread of chloramphenicol resistance was reported in the 1970s.145,146 Treatment of enteric fever in the 21st century is challenging due to develop of multidrug resistance, decreased susceptibility to ciprofloxacin and development of expanded-spectrum beta-lactamase resistance. Antimicrobial selection depends on local patterns of antimicrobial resistance and other factors such as severity of the disease, availability and cost.18,127 In uncomplicated enteric fever secondary to sensitive strains the treatment of choice is a fluoroquinolone (ciprofloxacin, gatifloxacin, levofloxacin or ofloxacin) for 5e7 days. Alternative antimicrobials are chloramphenicol, amoxicillin or trimethoprim-sulfamethoxazole.127,146 Results of a Cochrane Review that included 38 trials

Salmonella infections: An update

269

showed that in adults, fluoroquinolones were similar in efficacy compared with chloramphenicol, co-trimoxazole, or azithromycin. In children with nalidixic acid-resistant strains, fluoroquinolones had more clinical failures compared with azithromycin, although data in children for comparison were limited.147 Although fluoroquinolones have limited use in children because of potential joint toxicity observed in animal models, they are used safely in children with enteric fever.148 In adults, fluoroquinolones may be better than chloramphenicol for preventing clinical relapse.147 Chloramphenicol is still used in developing countries due to availability, low cost and strain sensitivity. Disadvantages associated to the use of chloramphenicol are the side effects, the need for long courses of treatment, and development of carrier state.127,149,150 The first line of therapy in uncomplicated cases in the presence of multidrug resistance is 5e7 days of a fluoroquinolone given at high doses. The alternative therapy includes azithromycin or third generation cephalosporins.95,151,152 Quinolones remain the best choice for patients from areas where isolates with decreased susceptibility to ciprofloxacin is uncommon, such as Africa, South America and Central America.153 Azithromycin advantages are a prolonged intracellular concentration, oral route of administration and safety in pediatric patients. Cefixime is also safe and effective in pediatric patients.146,154,155 Quinolones should be avoided in many parts of Asia because the high frequency of strains with decreased susceptibility or full resistance to ciprofloxacin.153 Ceftriaxone is the first line of treatment in the presence of quinolone resistance or decreased susceptibility to ciprofloxacin, while cefixime or azithromycin are used as alternatives.18,93,153 Azithromycin and carbapenems are treatment options in cases of full resistance to ciprofloxacin and cephalosporins and tigecycline has emerged as an option in ceftriaxone resistant isolates.146,156 The treatment of choice for severe disease secondary to sensitive strains is also a fluoroquinolone for 10e14 days with chloramphenicol, amoxicillin or trimethoprimsulfametoxazol as alternative. In the presence of multidrug resistance a fluoroquinolone is the first line of therapy and a third generation cephalosporins is the second choice. In the setting of quinolone resistance a third generation

Table 2

cephalosporin such as (ceftriaxone, cefotaxime o cefoperazone) is the treatment of choice.127 For the treatment of the carrier state, amoxicillin or ampicillin plus probenecid, trimethoprimsulfamethoxazole, or ciprofloxacin are recommended in adults or children (Table 2). Treatment course is generally for several months and in some cases a cholecystectomy is necessary, especially if there are gallbladder stones.97,127

Treatment of NTS infections Antimicrobial therapy of uncomplicated gastroenteritis is not indicated in patients without underlying diseases because this condition is generally self-limiting and there is no evidence of clinical benefit. Furthermore, treatment with antibiotics may increase adverse effects and tend to prolong the carrier state.156e158 However, therapy should be considered in patients with invasive disease risk, such as neonates, adults older than 50 years, immunosuppressed patients, and patients with vascular abnormalities or prosthetic valves, grafts or joints.23,106,159 In these cases a fluoroquinolone is the first line therapy and azithromycin, cephalosporins, trimethoprim-sulfamethoxazole, or ampicillin are alternatives. In bacteremia, a third generation cephalosporin or intravenous fluoroquinolone are recommended for 7e14 days. Localized infections require surgical debridement and endovascular infections surgical resection.40,115,160 Treatment concerns are rising globally with the increasing number of expanded-spectrum B-lactamase NTS detected.161e163 Feeding of stock animal with food containing antibiotics plays a significant role in the development of multidrug-resistant Salmonella.157,164 Studies in US cattle have shown a concerning spread of multidrug-resistant Salmonella among commercial dairy herds.165 Studies in Denmark pig farms have also shown the increase number of multidrug-resistant Salmonella strains in association with the use of antibiotics.166 Increased number of multidrug-resistant Salmonella strains raises significant concerns because infections secondary to these strains may be difficult to treat with conventional antibiotics and as a consequence lead to higher mortality.167,168

Treatment and prevention of Salmonella infections.

Measures

Enteric fever

NTS infections

References

Safe water, sanitation, education Measures during outbreaks

Recommended

Recommended

127,172

Search for cases/carriers Eliminate contaminated food Chlorinate suspected water Immunize people at risk Recommended

Eliminate food handling errors Eliminate contaminated food Recommended for systemic disease Not recommended Not available

172

Antibiotic treatment Treatment of carriers Salmonella vaccine

Recommended In endemic areas, during outbreaks and for travelers

146,150,159,191 97,127,169,170 127,176,177

270

F.M. Sa ´nchez-Vargas et al.

Treatment of the NTS carrier state is not recommended (Table 2) because antibiotic treatment is not superior to placebo for eradication of intestinal carriage in asymptomatic adults.169,170 Chronic carriage treatment has been tried by given three months of amoxicillin or trimethoprimsulfamethoxazole or one month of ciprofloxacin.171

or people living in high risk areas where disease is endemic (Table 3). Vaccine in these areas should target high risk groups based in local epidemiology, with priority to children over two years old.28,127,156 The main limitations of currently licensed typhoid vaccines are that they do not protect infants and they do not protect against S. Paratyphi or NTS, for which there are no license vaccines.18,178

Prevention and vaccines Parenteral vaccines The most important measures for enteric infection prevention are provision of safe water access, safe food handling practices, sanitation measures, public education and vaccination.127,172 For NST, measures to limit the number of infections from animals may include proper hand washing after being in contact with animals in general and contact avoidance with all animals especially amphibians known to be 90% colonized with Salmonella spp.173 Measures to limit infections from food products include proper cooking of food likely to be contaminated with Salmonella spp.12 or elimination of contaminated food products. Irradiation of food products including meat, vegetables, eggs, and dairy products may significantly decrease the load of live organisms in high risk food products. Irradiation has been promoted in many countries but it has also unleashed debate about the risk of radioactivity to food handlers or the remote risk of the food itself. Irradiation technology has been approved by several health agencies, including the World Health Organization, the CDC, and the European commission’s Scientific Committee on Food. Food irradiation is currently being partially implemented in some European countries and in the US.174 The improvement in safe water and sanitation, the primary goal for prevention, is difficult to achieve in developing countries. Chlorination of water sources suspected to be contaminated is also recommended during enteric fever outbreaks (Table 2). Another essential measure to prevent the increased number of antibiotic resistant NTS strains is the restriction to the indiscriminate use of antibiotics in livestock animal food, along with improved farm-based infection control measures.175 The high morbidity and mortality associated to Salmonella spp. infections and the emergence of multidrug resistance strains highlights the importance of vaccination. While no vaccines are available for human NTS infections, two types of vaccines are approved for typhoid fever prevention, the oral live attenuated vaccines and the inactivated or subunit parenteral vaccines.176,177 The World Health organization recommends vaccination to travelers

Table 3

Parenteral vaccination against typhoid fever has been used since the 19th century. The whole-killed cell vaccine has high reactogenicity and efficacy between 50 and 94%. The high rate of side effects with this vaccine has limited its use.179 Side effects include fever, severe headache, and pain at the site of the injection. The parenteral Vi vaccine, a significantly less reactogenic vaccine, was licensed in 1990 and it is based on a capsular polysaccharide antigen of S. Typhi. This vaccine, widely used in developing and industrialized countries, is licensed for adults and children more than 2 years.180 Vi vaccine is safe in immunocompromised host and administrated in a single parenteral dose with a booster recommended every two years. The protection starts seven days after vaccination with maximal protection after 28 days. The parenteral Vi vaccine has an efficacy between 61 and 80%% with protection that last only 2 years and it’s well tolerated.181e183 In a cluster-randomized study in India with 37,673 subjects, who were 2 years of age or older, one single dose of Vi vaccine conferred 61% total protection. Children between 2 and 5 years of age had a higher level of protection (80%) and side effects were minimal.184 The Vi capsular polysaccharide vaccine is a T cell-independent vaccine, does not generate immunological memory and is not immunogenic in children below 2 years of age. Other limitations include the need for refrigeration and trained personnel for administration.185 To improve capsular polysaccharide immunogenicity it was bound to the recombinant Pseudomonas aeruginosa exoprotein A (Vi-rEPA). This conjugation switches the response from T cell-independent response to T celldependent response and as a consequence it induces immunological memory that may result in prolong protection.185 In a double blind, randomized trial, Lin et al, evaluated in Viet Nam the Vi-rEPA in 11,091 children two to five years old who were followed 27 months. The efficacy with two vaccine doses was 91.5%. The Vi-rEPA conjugate vaccine was safe and immunogenic with

Human Salmonella Typhi vaccines.

Vaccine

Administration

Number of doses

Percent protection

Duration of protection

Safety

Approval

References

Live Ty21a Vi capsular Vi-conjugate Heat-phenol inactivated

Oral IM IM SC

3 to 4 Single Single 2

60-80% 61-80% 89% 6-94%

4 to 7 years 1 to 2 years Unknown 7 years

Well tolerated Well tolerated Well tolerated Reactogenic

Licenseda Licensedb Not licensed Discontinued

188e190 181e184 185e187 179

a b

Licensed for individuals above 5 years of age. Licensed for individuals above 2 years of age.

Salmonella infections: An update significant persistence of antibodies at two years of vaccination.178 At over 46 months of follow up, the efficacy in the vaccinated group was 89%.186 Most recently the Vi-rEPA tested in healthy infants ages 2 months and above demonstrated safety, protective immunity, and compatibility with the expanded program on immunization vaccines from the WHO.187 Vi capsular polysaccharide based vaccines, however, are unlikely to provide effective protection against S. Paratyphi, since they lack of Vi antigen, similarly this vaccine may be ineffective against S. Typhi strains not expressing the Vi polysaccharyde (Vinegative strains).28,134

Attenuated life oral Salmonella vaccine Ty21a The currently approved oral live attenuated S. Typhi Ty21a vaccine was derived from the wild-type Ty2 S. Typhi strain after chemical mutagenesis.188 Oral administration mimics the infection route that the wild-type strain would take and it induces not only humoral and cellular immune responses at the mucosal level but also systemically. Oral live attenuated S. Typhi vaccine is proven to induce sufficient immune response to protect individuals against infections with wild-type S. Typhi infections, with an efficacy of 50%e 80%.189,190 The live attenuated S. Typhi Ty21a vaccine is given orally in three to four doses for optimal immunogenicity. The vaccine elicits protection from 10 to 14 days after the third dose. This vaccine is well tolerated, and field studies in school age children in Egypt and Chile have demonstrated significant protection. The duration of protection is at least five years at which time boost is recommended. It is licensed in the United States for use in adults and children more than 6 years of age. Side effects are mild, infrequent and limited to gastrointestinal discomfort or fever.179 Concern remains with the use of live attenuated Salmonella vaccines for typhoid fever prevention in the immunosuppressed population including HIV-AIDS population. The American Academy of Pediatrics does not recommend live attenuated Salmonella vaccines to immunosuppressed individuals, including HIV-infected individuals.191 Other disadvantages of this vaccine include the need for multiple doses, cold chain dependence and poor immunogenicity in younger children. New vaccine development research concepts are necessary in response to the need for enteric fever prevention against both S. Typhi and S. Paratyphi. New vaccine candidate proposals should also consider cost, single rather than multiple doses, and optimal immunogenicity in all age groups.

Salmonella vaccines for livestock animals Because food industry and zoonotic infections represent a major source of NTS infections in humans, animal vaccines against Salmonella spp. may represent an effective measure to prevent or limit the transmission of these microorganisms from animals to humans. Different vaccine strategies are currently being used on livestock for NTS infection prevention. They include live attenuated Salmonella vaccines, killed Salmonella vaccines, and a combination of both. Live attenuated S. Gallinarum vaccine orally

271 delivered to chickens was able to prevent not only wildtype infections by S. Gallinarum but also infections by S. Enteritidis.192 A killed vaccine containing three different Salmonella serogroups (B, C, and E) administered to chickens resulted in significant reduction in carriage of Salmonella serogroups B and C when compared to the unvaccinated groups.193 Administration of live attenuated S. Typhimurium vaccine followed by a killed Salmonella serovars Berta and Kentucky into chickens it was shown to significantly decrease Salmonella spp. prevalence in the vaccinated animal in comparison to the unvaccinated group.194 Salmonella vaccines have also been used in pigs to protect against infection. A promising role for vaccines given to pregnant sows has been the protection of piglets from Salmonella infections.195 Vaccination using live attenuated S. Typhimurium vaccine in pigs holds promise not only to prevent disease in animals, but also to prevent transmission from animals to humans.196,197 Furthermore, animal NTS vaccines may also help prevent animal colonization with multidrug-resistant Salmonella strains, a particular obstacle when treating invasive Salmonella infection in humans.165,166 While many Salmonella animal vaccines are still under development in the US, no commercially available vaccines are used in the United States for Salmonella infection prevention in livestock or pet animals, significant sources of human infection. This is in contrast, with the widespread use of commercially available Salmonella animal vaccines in some European countries that have resulted in a dramatic decrease in human salmonellosis and NTSassociated foodborne outbreaks.198

Summary Salmonella infections remain a significant worldwide public health concern that affect children and adults not only in developing countries but also in the industrialized world. The genetic make-up of Salmonella spp. allows the bacteria to adapt to a variety of environments, including mammalian and non-mammalian hosts as well as non-animated reservoirs, making their eradication by conventional means difficult. Furthermore, the high frequency of multidrugresistant Salmonella strains is making treatment of focal and disseminated infections a medical challenge. At present there is a great need for strategies to limit the indiscriminate use of antimicrobial agents in livestock animals as a way to stop the spread of multidrug-resistant Salmonella strains and their transmission to the people worldwide. Research on epidemiologic surveillance by the implementation of affordable detection testing to rapidly assess infection in developing countries is essential as a way to guide public heath preventive measures. Continuing research on vaccine development for prevention of Salmonella infections in human populations will benefit affected communities in both the developing and industrialized world. Research on the use of NTS vaccines for animals, including cost-benefit analyses, may provide valuable information on the potential impact these vaccines may have on the food industry and public health worldwide.

272

F.M. Sa ´nchez-Vargas et al.

Financial support The writing of this paper was supported in part by a Pilgrims Foundation Grant and by the Department of Pediatrics, University of Iowa, to Oscar G. Gomez-Duarte.

16.

17.

Conflict of interest No conflict of interest is reported by the authors.

18. 19.

Acknowledgments We are grateful with Dr. Charles Grose for critically reading the manuscript. We are in debt with Mr. Paul Cassela for helpful advice on this manuscript. We thank Jing Bai for technical assistance with electron microscopy imaging.

20. 21.

22.

References 23. 1. Cunha BA. The death of Alexander the Great: malaria or typhoid fever? Infect Dis Clin North Am 2004;18(1):53e63. 2. Center for Disease Control (CDC). Salmonella surveillance: annual summary. Available at: http://www.cdc.gov/ncidod/ dbmd/phlisdata/salmtab/2006/SalmonellaIntroduction2006. pdf; 2006. 3. Kidgell C, Reichard U, Wain J, Linz B, Torpdahl M, Dougan G, et al. Salmonella typhi, the causative agent of typhoid fever, is approximately 50,000 years old. Infect Genet Evol 2002; 2(1):39e45. 4. August C, Konert J. Awarded the honorary chair for anatomy in Halle 100 years ago: Carl Joseph Eberthediscoverer of the typhus pathogen. Pathologe 1993;14(4):234e6. 5. Papagrigorakis MJ, Yapijakis C, Synodinos PN, BaziotopoulouValavani E. DNA examination of ancient dental pulp incriminates typhoid fever as a probable cause of the Plague of Athens. Int J Infect Dis 2006;10(3):206e14. 6. Wood M. We’ll say our goodbyes in Babylon. In: In the footsteps of Alexander the Great: a journey from Greece to Asia. Berkeley: University of California Press; 1997. p. 223e32. 7. Budd W. Typhoied fever: its nature, mode of spreading, and prevention. London: Longmans, Green, and Co; 1873. 8. Sedgwick WT, Hazen A. Typhoid fever in Chicago. Eng News Am Rail J 1892:1e21. 9. Woodward TE, Smadel JE, Ley Jr HL, Green R, Mankikar DS. Preliminary report on the beneficial effect of chloromycetin in the treatment of typhoid fever. 1948. Wilderness Environ Med 2004;15(3):218e20. 10. Hardy A. Salmonella: a continuing problem. Postgrad Med J 2004;80(947):541e5. 11. Crump JA, Luby SP, Mintz ED. The global burden of typhoid fever. Bull World Health Organ 2004;82(5):346e53. 12. Nguyen TQ, Reddy V, Sahl S, Kornstein L, Balter S. Importance of travel in domestically acquired typhoid fever infections: opportunities for prevention and early detection. J Immigr Minor Health 2009;11(2):139e42. 13. Cooke FJ, Day M, Wain J, Ward LR, Threlfall EJ. Cases of typhoid fever imported into England, Scotland and Wales (2000e2003). Trans R Soc Trop Med Hyg 2007;101(4):398e404. 14. Morris SK, Richardson SE, Sauve LJ, Ford-Jones EL, Jamieson F. Increasing fluoroquinolone resistance in Salmonella typhi in Ontario, 2002e2007. Am J Trop Med Hyg 2009; 80(6):1012e3. 15. Gil Prieto R, Alejandre CG, Meca AA, Barrera VH, de Miguel AG. Epidemiology of hospital-treated Salmonella

24.

25.

26.

27.

28. 29.

30.

31.

32.

33.

34.

35.

infection; data from a national cohort over a ten-year period. J Infect 2009;58(3):175e81. Meltzer E, Yossepowitch O, Sadik C, Dan M, Schwartz E. Epidemiology and clinical aspects of enteric fever in Israel. Am J Trop Med Hyg 2006;74(4):540e5. Ochiai RL, Acosta CJ, Danovaro-Holliday MC, Baiqing D, Bhattacharya SK, Agtini MD, et al. A study of typhoid fever in five Asian countries: disease burden and implications for controls. Bull World Health Organ 2008;86(4):260e8. Crump JA, Mintz ED. Global trends in typhoid and paratyphoid fever. Clin Infect Dis 2010;50(2):241e6. Kothari A, Pruthi A, Chugh TD. The burden of enteric fever. J Infect Dev Ctries 2008;2(4):253e9. Mweu E, English M. Typhoid fever in children in Africa. Trop Med Int Health 2008;13(4):532e40. Linam WM, Gerber MA. Changing epidemiology and prevention of Salmonella infections. Pediatr Infect Dis J 2007;26(8): 747e8. Fangtham M, Wilde H. Emergence of Salmonella paratyphi A as a major cause of enteric fever: need for early detection, preventive measures, and effective vaccines. J Travel Med 2008;15(5):344e50. Crump JA, Ram PK, Gupta SK, Miller MA, Mintz ED. Part I. Analysis of data gaps pertaining to Salmonella enterica serotype Typhi infections in low and medium human development index countries, 1984e2005. Epidemiol Infect 2008;136(4): 436e48. Kariuki S. Typhoid fever in sub-Saharan Africa: challenges of diagnosis and management of infections. J Infect Dev Ctries 2008;2(6):443e7. Owais A, Sultana S, Zaman U, Rizvi A, Zaidi AKM. Incidence of typhoid bacteremia in infants and young children in southern coastal Pakistan. Pediatr Infect Dis J 2010;29(11):1035e9. Kumar S, Rizvi M, Berry N. Rising prevalence of enteric fever due to multidrug-resistant Salmonella: an epidemiological study. J Med Microbiol 2008;57(Pt 10):1247e50. Molloy A, Nair S, Cooke FJ, Wain J, Farrington M, Lehner PJ, et al. First report of Salmonella enterica serotype paratyphi A azithromycin resistance leading to treatment failure. J Clin Microbiol 2010;48(12):4655e7. Zaki SA, Karande S. Multidrug-resistant typhoid fever: a review. J Infect Dev Ctries 2011;5(5):324e37. Chau TT, Campbell JI, Galindo CM, Van Minh Hoang N, Diep TS, Nga TTT, et al. Antimicrobial drug resistance of Salmonella enterica serovar typhi in asia and molecular mechanism of reduced susceptibility to the fluoroquinolones. Antimicrob Agents Chemother 2007;51(12):4315e23. Chuang C-H, Su L-H, Perera J, Carlos C, Tan BH, Kumarasinghe G, et al. Surveillance of antimicrobial resistance of Salmonella enterica serotype Typhi in seven Asian countries. Epidemiol Infect 2009;137(2):266e9. Harish BN, Madhulika U, Parija SC. Isolated high-level ciprofloxacin resistance in Salmonella enterica subsp. enterica serotype Paratyphi A. J Med Microbiol 2004;53(Pt 8):819. Hasan R, Zafar A, Abbas Z, Mahraj V, Malik F, Zaidi A. Antibiotic resistance among Salmonella enterica serovars Typhi and Paratyphi A in Pakistan (2001e2006). J Infect Dev Ctries 2008;2(4):289e94. Lynch MF, Blanton EM, Bulens S, Polyak C, Vojdani J, Stevenson J, et al. Typhoid fever in the United States, 19992006. J Am Med Assoc 2009;302(8):859e65. Majowicz SE, Musto J, Scallan E, Angulo FJ, Kirk M, O’Brien SJ, et al. The global burden of nontyphoidal Salmonella gastroenteritis. Clin Infect Dis 2010;50(6):882e9. Su L-H, Chiu C-H, Wu T-L, Chu C, Chia J-H, Kuo A-J, et al. Molecular epidemiology of Salmonella enterica serovar Enteritidis isolated in Taiwan. Microbiol Immunol 2002; 46(12):833e40.

Salmonella infections: An update 36. Westrell T, Ciampa N, Boelaert F, Helwigh B, Korsgaard H, Chrı´el M, et al. Zoonotic infections in Europe in 2007: a summary of the EFSA-ECDC annual report. Euro Surveill(3). Available at: http://www.ncbi.nlm.nih.gov/pubmed/19161723, 2009;14 [accessed 28.09.11]. 37. Galanis E, Lo Fo Wong DMA, Patrick ME, Binsztein N, Cieslik A, Chalermchikit T, et al. Web-based surveillance and global Salmonella distribution, 2000e2002. Emerging Infect Dis 2006;12(3):381e8. 38. Crump JA, Ramadhani HO, Morrissey AB, Saganda W, Mwako MS, Yang L-Y, et al. Invasive bacterial and fungal infections among hospitalized HIV-infected and HIVuninfected adults and adolescents in northern Tanzania. Clin Infect Dis 2011;52(3):341e8. 39. Mandomando I, Macete E, Sigau ´ L, ´que B, Morais L, Quinto Sacarlal J, et al. Invasive non-typhoidal Salmonella in Mozambican children. Trop Med Int Health 2009;14(12): 1467e74. 40. Morpeth SC, Ramadhani HO, Crump JA. Invasive non-Typhi Salmonella disease in Africa. Clin Infect Dis 2009;49(4):606e11. 41. Dhanoa A, Fatt QK. Non-typhoidal Salmonella bacteraemia: epidemiology, clinical characteristics and its’ association with severe immunosuppression. Ann Clin Microbiol Antimicrob 2009;8:15. 42. Khan MI, Ochiai RL, von Seidlein L, Dong B, Bhattacharya SK, Agtini MD, et al. Non-typhoidal Salmonella rates in febrile children at sites in five Asian countries. Trop Med Int Health 2010;15(8):960e3. 43. Weinberger M, Keller N. Recent trends in the epidemiology of non-typhoid Salmonella and antimicrobial resistance: the Israeli experience and worldwide review. Curr Opin Infect Dis 2005;18(6):513e21. 44. Laupland KB, Schønheyder HC, Kennedy KJ, Lyytika ¨inen O, Valiquette L, Galbraith J, et al. Salmonella enterica bacteraemia: a multi-national population-based cohort study. BMC Infect Dis 2010;10:95. 45. Center for Disease Control (CDC). Vital signs: incidence and trends of infection with pathogens transmitted commonly through foodefoodborne diseases active surveillance network, 10 U.S. sites, 1996e2010. MMWR Morb Mortal Wkly Rep 2011;60(22):749e55. 46. Barton Behravesh C, Jones TF, Vugia DJ, Long C, Marcus R, Smith K, et al. Deaths associated with bacterial pathogens transmitted commonly through food: foodborne diseases active surveillance network (FoodNet), 1996e2005. J Infect Dis 2011;204(2):263e7. 47. Younus M, Hartwick E, Siddiqi AA, Wilkins M, Davies HD, Rahbar M, et al. The role of neighborhood level socioeconomic characteristics in Salmonella infections in Michigan (1997e2007): assessment using geographic information system. Int J Health Geogr 2007;6(56). 48. Vugia DJ, Samuel M, Farley MM, Marcus R, Shiferaw B, Shallow S, et al. Invasive Salmonella infections in the United States, FoodNet, 1996e1999: incidence, serotype distribution, and outcome. Clin Infect Dis 2004;38(Suppl. 3): S149e156. 49. Lynch M, Painter J, Woodruff R, Braden C. Surveillance for foodborne-disease outbreakseUnited States, 1998e2002. MMWR Surveill Summ 2006;55(10):1e42. 50. Center for Disease Control (CDC). CDC e Outbreak of Enteritidis Infections e December 2, 2010-Salmonella. Available at: http:// www.cdc.gov/salmonella/enteritidis/. [accessed 28.09.11]. 51. Center for Disease Control (CDC). Preliminary FoodNet data on the incidence of infection with pathogens transmitted commonly through foode10 States, United States, 2005. MMWR Morb Mortal Wkly Rep 2006;55(14):392e5. 52. Center for Disease Control (CDC). Multistate outbreak of human Salmonella infections associated with exposure to

273

53.

54.

55.

56.

57.

58.

59.

60.

61.

62.

63.

64.

65.

66.

67.

68.

69.

turtleseUnited States, 2007e2008. MMWR Morb Mortal Wkly Rep 2008;57(3):69e72. Fisher IST. Dramatic shift in the epidemiology of Salmonella enterica serotype Enteritidis phage types in western Europe, 1998e2003 e results from the Enter-net international salmonella database. Euro Surveill 2004;9(11):43e5. Stevens MP, Humphrey TJ, Maskell DJ. Molecular insights into farm animal and zoonotic Salmonella infections. Philos Trans R Soc Lond, B, Biol Sci 2009;364(1530):2709e23. Dione MM, Ikumapayi UN, Saha D, Mohammed NI, Geerts S, Ieven M, et al. Clonal differences between Non-Typhoidal Salmonella (NTS) recovered from children and animals living in close contact in the Gambia. PLoS Negl Trop Dis 2011;5(5):e1148. Kikuvi GM, Ombui JN, Mitema ES. Serotypes and antimicrobial resistance profiles of Salmonella isolates from pigs at slaughter in Kenya. J Infect Dev Ctries 2010;4(4):243e8. Jardine C, Reid-Smith RJ, Janecko N, Allan M, McEwen SA. Salmonella in raccoons (Procyon lotor) in southern Ontario, Canada. J Wildl Dis 2011;47(2):344e51. Siembieda JL, Miller WA, Byrne BA, Ziccardi MH, Anderson N, Chouicha N, et al. Zoonotic pathogens isolated from wild animals and environmental samples at two California wildlife hospitals. J Am Vet Med Assoc 2011;238(6):773e83. Swanson SJ, Snider C, Braden CR, Boxrud D, Wu ¨nschmann A, Rudroff JA, et al. Multidrug-resistant Salmonella enterica serotype Typhimurium associated with pet rodents. N Engl J Med 2007;356(1):21e8. Wacheck S, Fredriksson-Ahomaa M, Ko ¨nig M, Stolle A, Stephan R. Wild boars as an important reservoir for foodborne pathogens. Foodborne Pathog Dis 2010;7(3):307e12. Aiken AM, Lane C, Adak GK. Risk of Salmonella infection with exposure to reptiles in England, 2004e2007. Euro Surveill 2010;15(22):19581. Mermin J, Hutwagner L, Vugia D, Shallow S, Daily P, Bender J, et al. Reptiles, amphibians, and human Salmonella infection: a population-based, case-control study. Clin Infect Dis 2004; 38(Suppl. 3):S253e261. Helms M, Ethelberg S, Mølbak K. International Salmonella Typhimurium DT104 infections, 1992e2001. Emerging Infect Dis 2005;11(6):859e67. Sjo ¨lund-Karlsson M, Rickert R, Matar C, Pecic G, Howie RL, Joyce K, et al. Salmonella isolates with decreased susceptibility to extended-spectrum cephalosporins in the United States. Foodborne Pathog Dis 2010;7(12):1503e9. Crump JA, Medalla FM, Joyce KW, Krueger AL, Hoekstra RM, Whichard JM, et al. Antimicrobial resistance among invasive nontyphoidal Salmonella enterica isolates in the United States: National Antimicrobial Resistance Monitoring System, 1996 to 2007. Antimicrob Agents Chemother 2011;55(3): 1148e54. Meakins S, Fisher IST, Berghold C, Gerner-Smidt P, Tscha ¨pe H, Cormican M, et al. Antimicrobial drug resistance in human nontyphoidal Salmonella isolates in Europe 2000e2004: a report from the Enter-net International Surveillance Network. Microb Drug Resist 2008;14(1):31e5. Akinyemi KO, Bamiro BS, Coker AO. Salmonellosis in Lagos, Nigeria: incidence of Plasmodium falciparum-associated coinfection, patterns of antimicrobial resistance, and emergence of reduced susceptibility to fluoroquinolones. J Health Popul Nutr 2007;25(3):351e8. Jabeen K, Zafar A, Irfan S, Khan E, Mehraj V, Hasan R. Increase in isolation of extended spectrum beta lactamase producing multidrug resistant non typhoidal Salmonellae in Pakistan. BMC Infect Dis 2010;10:101. Kruger T, Szabo D, Keddy KH, Deeley K, Marsh JW, Hujer AM, et al. Infections with nontyphoidal Salmonella species producing TEM-63 or a novel TEM enzyme, TEM-131, in South Africa. Antimicrob Agents Chemother 2004;48(11):4263e70.

274 70. Ran L, Wu S, Gao Y, Zhang X, Feng Z, Wang Z, et al. Laboratory-based surveillance of nontyphoidal Salmonella infections in China. Foodborne Pathog Dis 2011;8(8):921e7. 71. Hansen-Wester I, Stecher B, Hensel M. Type III secretion of Salmonella enterica serovar Typhimurium translocated effectors and SseFG. Infect Immun 2002;70(3):1403e9. 72. Takaya A, Suzuki M, Matsui H, Tomoyasu T, Sashinami H, Nakane A, et al. Lon, a stress-induced ATP-dependent protease, is critically important for systemic Salmonella enterica serovar typhimurium infection of mice. Infect Immun 2003;71(2):690e6. 73. Gerlach RG, Ja ¨ckel D, Geymeier N, Hensel M. Salmonella pathogenicity island 4-mediated adhesion is coregulated with invasion genes in Salmonella enterica. Infect Immun 2007; 75(10):4697e709. 74. Grassl GA, Finlay BB. Pathogenesis of enteric Salmonella infections. Curr Opin Gastroenterol 2008;24(1):22e6. 75. Dieye Y, Dyszel JL, Kader R, Ahmer BMM. Systematic analysis of the regulation of type three secreted effectors in Salmonella enterica serovar Typhimurium. BMC Microbiol 2007;7:3. 76. Gala ´n JE, Wolf-Watz H. Protein delivery into eukaryotic cells by type III secretion machines. Nature 2006;444(7119):567e73. 77. Winnen B, Schlumberger MC, Sturm A, Schu ¨pbach K, Siebenmann S, Jenny P, et al. Hierarchical effector protein transport by the Salmonella Typhimurium SPI-1 type III secretion system. PLoS ONE 2008;3(5):e2178. 78. Haraga A, Ohlson MB, Miller SI. Salmonellae interplay with host cells. Nat Rev Microbiol 2008;6(1):53e66. 79. Kichi Uchiya, Groisman EA, Nikai T. Involvement of Salmonella pathogenicity island 2 in the up-regulation of interleukin-10 expression in macrophages: role of protein kinase A signal pathway. Infect Immun 2004;72(4):1964e73. 80. Humphreys S, Stevenson A, Bacon A, Weinhardt AB, Roberts M. The alternative sigma factor, sigmaE, is critically important for the virulence of Salmonella typhimurium. Infect Immun 1999;67(4):1560e8. 81. Prost LR, Miller SI. The Salmonellae PhoQ sensor: mechanisms of detection of phagosome signals. Cell Microbiol 2008;10(3): 576e82. 82. Prost LR, Sanowar S, Miller SI. Salmonella sensing of antimicrobial mechanisms to promote survival within macrophages. Immunol Rev 2007;219:55e65. 83. Coburn B, Grassl GA, Finlay BB. Salmonella, the host and disease: a brief review. Immunol Cell Biol 2007;85(2):112e8. 84. Coburn B, Li Y, Owen D, Vallance BA, Finlay BB. Salmonella enterica serovar Typhimurium pathogenicity island 2 is necessary for complete virulence in a mouse model of infectious enterocolitis. Infect Immun 2005;73(6):3219e27. 85. Raupach B, Kurth N, Pfeffer K, Kaufmann SHE. Salmonella typhimurium strains carrying independent mutations display similar virulence phenotypes yet are controlled by distinct host defense mechanisms. J Immunol 2003;170(12):6133e40. 86. Bakowski MA, Braun V, Brumell JH. Salmonella-containing vacuoles: directing traffic and nesting to grow. Traffic 2008; 9(12):2022e31. 87. Fields PI, Swanson RV, Haidaris CG, Heffron F. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci U.S.A 1986; 83(14):5189e93. 88. Ramsden AE, Holden DW, Mota LJ. Membrane dynamics and spatial distribution of Salmonella-containing vacuoles. Trends Microbiol 2007;15(11):516e24. 89. Fink RC, Evans MR, Porwollik S, Vazquez-Torres A, JonesCarson J, Troxell B, et al. FNR is a global regulator of virulence and anaerobic metabolism in Salmonella enterica serovar Typhimurium (ATCC 14028s). J Bacteriol 2007;189(6): 2262e73.

F.M. Sa ´nchez-Vargas et al. 90. Monack DM, Mueller A, Falkow S. Persistent bacterial infections: the interface of the pathogen and the host immune system. Nat Rev Microbiol 2004;2(9):747e65. 91. Wyant TL, Tanner MK, Sztein MB. Potent immunoregulatory effects of Salmonella typhi flagella on antigenic stimulation of human peripheral blood mononuclear cells. Infect Immun 1999;67(3):1338e46. 92. Osler W. Typhoid fever. In: The principles and practice of medicine. 1st ed. New York: Appleton and Company; 1892. p. 2e39. 93. Connor BA, Schwartz E. Typhoid and paratyphoid fever in travellers. Lancet Infect Dis 2005;5(10):623e8. 94. Bhan MK, Bahl R, Bhatnagar S. Typhoid and paratyphoid fever. Lancet 2005;366(9487):749e62. 95. Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ. Typhoid fever. N Engl J Med 2002;347(22):1770e82. 96. Patel TA, Armstrong M, Morris-Jones SD, Wright SG, Doherty T. Imported enteric fever: case series from the hospital for tropical diseases, London, United Kingdom. Am J Trop Med Hyg 2010;82(6):1121e6. 97. Pegues DA, Ohl ME, Miller SI. Salmonella species, including Salmonell Typhi. In: Mandell, Douglas and Bennett’s principles and practice of infectious diseases. 6th ed. New York [u.a.]: Churchill Livingstone; 2005. 98. Pohan HT. Clinical and laboratory manifestations of typhoid fever at Persahabatan Hospital, Jakarta. Acta Med Indones 2004;36(2):78e83. 99. Thielman NM, Guerrant RL. Clinical practice. Acute infectious diarrhea. N Engl J Med 2004;350(1):38e47. 100. Thisyakorn U, Mansuwan P, Taylor DN. Typhoid and paratyphoid fever in 192 hospitalized children in Thailand. Am J Dis Child 1987;141(8):862e5. 101. Kuvandik C, Karaoglan I, Namiduru M, Baydar I. Predictive value of clinical and laboratory findings in the diagnosis of the enteric fever. New Microbiol 2009;32(1):25e30. 102. Box CR. Typhoid fever: its chief complications. Br Med J 1935; 1(3871):538e40. 103. Feldman LS. Salmonella septic sacroiliitis: case report and review. Pediatr Infect Dis J 2006;25(2):187e9. 104. Naithani R, Rai S, Choudhry VP. Septic arthritis of hip in a neutropenic child caused by Salmonella typhi. J Pediatr Hematol Oncol 2008;30(2):182e4. 105. Saphra I, Winter JW. Clinical manifestations of salmonellosis in man; an evaluation of 7779 human infections identified at the New York Salmonella Center. N Engl J Med 1957;256(24): 1128e34. 106. Hohmann EL. Nontyphoidal salmonellosis. Clin Infect Dis 2001;32(2):263e9. 107. Crump JA, Kretsinger K, Gay K, Hoekstra RM, Vugia DJ, Hurd S, et al. Clinical response and outcome of infection with Salmonella enterica serotype Typhi with decreased susceptibility to fluoroquinolones: a United States foodnet multicenter retrospective cohort study. Antimicrob Agents Chemother 2008; 52(4):1278e84. 108. Gordon MA. Salmonella infections in immunocompromised adults. J Infect 2008;56(6):413e22. 109. Fisker N, Vinding K, Mølbak K, Hornstrup MK. Clinical review of nontyphoid Salmonella infections from 1991 to 1999 in a Danish county. Clin Infect Dis 2003;37(4):e47e52. 110. Huang DB, DuPont HL. Problem pathogens: extra-intestinal complications of Salmonella enterica serotype Typhi infection. Lancet Infect Dis 2005;5(6):341e8. 111. Zaidenstein R, Peretz C, Nissan I, Reisfeld A, Yaron S, Agmon V, et al. The epidemiology of extraintestinal nontyphoid Salmonella in Israel: the effects of patients’ age and sex. Eur J Clin Microbiol Infect Dis 2010;29(9):1103e9. 112. Shimoni Z, Pitlik S, Leibovici L, Samra Z, Konigsberger H, Drucker M, et al. Nontyphoid Salmonella bacteremia: age-

Salmonella infections: An update

113.

114.

115.

116.

117.

118.

119.

120.

121.

122.

123.

124.

125.

126.

127.

128. 129.

130.

131.

related differences in clinical presentation, bacteriology, and outcome. Clin Infect Dis 1999;28(4):822e7. Arii J, Tanabe Y, Miyake M, Mukai T, Matsuzaki M, Niinomi N, et al. Clinical and pathologic characteristics of nontyphoidal salmonella encephalopathy. Neurology 2002; 58(11):1641e5. Sirinavin S, Chiemchanya S, Vorachit M. Systemic nontyphoidal Salmonella infection in normal infants in Thailand. Pediatr Infect Dis J 2001;20(6):581e7. Nielsen H, Gradel KO, Schønheyder HC. High incidence of intravascular focus in nontyphoid Salmonella bacteremia in the age group above 50 years: a population-based study. Acta Pathol Microbiol Immunol 2006;114(9):641e5. Kankwatira AM, Mwafulirwa GAK, Gordon MA. Non-typhoidal salmonella bacteraemiaean under-recognized feature of AIDS in African adults. Trop Doct 2004;34(4):198e200. Larsen IK, Gradel KO, Helms M, Hornstrup MK, Ju ¨rgens G, Mens H, et al. Non-typhoidal Salmonella and Campylobacter infections among HIV-positive patients in Denmark. Scand J Infect Dis 2011;43(1):3e7. Gordon MA, Banda HT, Gondwe M, Gordon SB, Boeree MJ, Walsh AL, et al. Non-typhoidal salmonella bacteraemia among HIV-infected Malawian adults: high mortality and frequent recrudescence. AIDS 2002;16(12):1633e41. Feglo PK, Frimpong EH, Essel-Ahun M. Salmonellae carrier status of food vendors in Kumasi, Ghana. East Afr Med J 2004; 81(7):358e61. Gonzalez-Escobedo G, Marshall JM, Gunn JS. Chronic and acute infection of the gall bladder by Salmonella Typhi: understanding the carrier state. Nat Rev Microbiol 2011;9(1): 9e14. Levine MM, Black RE, Lanata C. Precise estimation of the numbers of chronic carriers of Salmonella typhi in Santiago, Chile, an endemic area. J Infect Dis 1982;146(6):724e6. Nath G, Singh H, Shukla VK. Chronic typhoid carriage and carcinoma of the gallbladder. Eur J Cancer Prev 1997;6(6): 557e9. Nath G, Singh YK, Kumar K, Gulati AK, Shukla VK, Khanna AK, et al. Association of carcinoma of the gallbladder with typhoid carriage in a typhoid endemic area using nested PCR. J Infect Dev Ctries 2008;2(4):302e7. Nath G, Singh YK, Maurya P, Gulati AK, Srivastava RC, Tripathi SK. Does Salmonella Typhi primarily reside in the liver of chronic typhoid carriers? J Infect Dev Ctries 2010;4(4): 259e61. Vaishnavi C, Kochhar R, Singh G, Kumar S, Singh S, Singh K. Epidemiology of typhoid carriers among blood donors and patients with biliary, gastrointestinal and other related diseases. Microbiol Immunol 2005;49(2):107e12. Buchwald DS, Blaser MJ. A review of human salmonellosis: II. Duration of excretion following infection with nontyphi Salmonella. Rev Infect Dis 1984;6(3):345e56. World Health Organization (WHO). Background document: the diagnosis, treatment and prevention of typhoid fever. Geneva: World Health Organization; 2003. 1e38. Baker S, Favorov M, Dougan G. Searching for the elusive typhoid diagnostic. BMC Infect Dis 2010;10:45. Guerra-Caceres JG, Gotuzzo-Herencia E, Crosby-Dagnino E, Miro-Quesada M, Carrillo-Parodi C. Diagnostic value of bone marrow culture in typhoid fever. Trans R Soc Trop Med Hyg 1979;73(6):680e3. Parry CM, Wijedoru L, Arjyal A, Baker S. The utility of diagnostic tests for enteric fever in endemic locations. Expert Rev Anti Infect Ther 2011;9(6):711e25. Vallenas C, Hernandez H, Kay B, Black R, Gotuzzo E. Efficacy of bone marrow, blood, stool and duodenal contents cultures for bacteriologic confirmation of typhoid fever in children. Pediatr Infect Dis 1985;4(5):496e8.

275 132. Farooqui BJ, Khurshid M, Ashfaq MK, Khan MA. Comparative yield of Salmonella typhi from blood and bone marrow cultures in patients with fever of unknown origin. J Clin Pathol 1991;44(3):258e9. 133. Nga TVT, Karkey A, Dongol S, Thuy HN, Dunstan S, Holt K, et al. The sensitivity of real-time PCR amplification targeting invasive Salmonella serovars in biological specimens. BMC Infect Dis 2010;10:125. 134. Wain J, Hosoglu S. The laboratory diagnosis of enteric fever. J Infect Dev Ctries 2008;2(6):421e5. 135. Gilman RH, Terminel M, Levine MM, Hernandez-Mendoza P, Hornick RB. Relative efficacy of blood, urine, rectal swab, bone-marrow, and rose-spot cultures for recovery of Salmonella typhi in typhoid fever. Lancet 1975;1(7918):1211e3. 136. Olopoenia LA, King AL. Widal agglutination test e 100 years later: still plagued by controversy. Postgrad Med J 2000; 76(892):80e4. 137. Go ´mez-Duarte OG, Bai J, Newell E. Detection of Escherichia coli, Salmonella spp., Shigella spp., Yersinia enterocolitica, Vibrio cholerae, and Campylobacter spp. enteropathogens by 3-reaction multiplex polymerase chain reaction. Diagn Microbiol Infect Dis 2009;63(1):1e9. 138. Gordon MA. Invasive nontyphoidal Salmonella disease: epidemiology, pathogenesis and diagnosis. Curr Opin Infect Dis 2011;24(5):484e9. 139. Hatta M, Ratnawati. Enteric fever in endemic areas of Indonesia: an increasing problem of resistance. J Infect Dev Ctries 2008;2(4):279e82. 140. Hatta M, Smits HL. Detection of Salmonella typhi by nested polymerase chain reaction in blood, urine, and stool samples. Am J Trop Med Hyg 2007;76(1):139e43. 141. Tennant SM, Diallo S, Levy H, Livio S, Sow SO, Tapia M, et al. Identification by PCR of non-typhoidal Salmonella enterica serovars associated with invasive infections among febrile patients in Mali. PLoS Negl Trop Dis 2010;4(3):e621. 142. Foley SL, White DG, McDermott PF, Walker RD, Rhodes B, Fedorka-Cray PJ, et al. Comparison of subtyping methods for differentiating Salmonella enterica serovar Typhimurium isolates obtained from food animal sources. J Clin Microbiol 2006;44(10):3569e77. 143. Kotetishvili M, Stine OC, Kreger A, Morris Jr JG, Sulakvelidze A. Multilocus sequence typing for characterization of clinical and environmental salmonella strains. J Clin Microbiol 2002;40(5):1626e35. 144. Sangal V, Harbottle H, Mazzoni CJ, Helmuth R, Guerra B, Didelot X, et al. Evolution and population structure of Salmonella enterica serovar Newport. J Bacteriol 2010;192(24):6465e76. 145. Butler T, Islam A, Kabir I, Jones PK. Patterns of morbidity and mortality in typhoid fever dependent on age and gender: review of 552 hospitalized patients with diarrhea. Rev Infect Dis 1991;13(1):85e90. 146. Capoor MR, Nair D. Quinolone and cephalosporin resistance in enteric fever. J Glob Infect Dis 2010;2(3):258e62. 147. Thaver D, Zaidi AK, Critchley JA, Azmatullah A, Madni SA, Bhutta ZA. Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). Cochrane Database Syst Rev 2008;(4). CD004530. 148. Gendrel D, Chalumeau M, Moulin F, Raymond J. Fluoroquinolones in paediatrics: a risk for the patient or for the community? Lancet Infect Dis 2003;3(9):537e46. 149. Arjyal A, Basnyat B, Koirala S, Karkey A, Dongol S, Agrawaal KK, et al. Gatifloxacin versus chloramphenicol for uncomplicated enteric fever: an open-label, randomised, controlled trial. Lancet Infect Dis 2011;11(6):445e54. 150. Arjyal A, Pandit A. Treatment of enteric fever. J Infect Dev Ctries 2008;2(6):426e30. 151. Alam MN, Haq SA, Das KK, Baral PK, Mazid MN, Siddique RU, et al. Efficacy of ciprofloxacin in enteric fever: comparison of

276

152.

153. 154.

155.

156.

157.

158.

159.

160.

161.

162.

163.

164.

165.

166.

167.

168.

169.

170.

F.M. Sa ´nchez-Vargas et al. treatment duration in sensitive and multidrug-resistant Salmonella. Am J Trop Med Hyg 1995;53(3):306e11. Singh CP, Singh N, Brar GK, Lal G, Kumar H. Efficacy of ciprofloxacin and norfloxacin in multidrug resistant enteric fever in adults. J Indian Med Assoc 1993;91(6):156e7. Parry CM, Beeching NJ. Treatment of enteric fever. Br Med J 2009;338:b1159. Effa EE, Bukirwa H. Azithromycin for treating uncomplicated typhoid and paratyphoid fever (enteric fever). Cochrane Database Syst Rev 2008;(4). CD006083. Memon IA, Billoo AG, Memon HI. Cefixime: an oral option for the treatment of multidrug-resistant enteric fever in children. South Med J 1997;90(12):1204e7. Parry CM, Threlfall EJ. Antimicrobial resistance in typhoidal and nontyphoidal salmonellae. Curr Opin Infect Dis 2008; 21(5):531e8. Mølbak K. Human health consequences of antimicrobial drugresistant Salmonella and other foodborne pathogens. Clin Infect Dis 2005;41(11):1613e20. Sirinavin S, Jayanetra P, Thakkinstian A. Clinical and prognostic categorization of extraintestinal nontyphoidal Salmonella infections in infants and children. Clin Infect Dis 1999; 29(5):1151e6. Ruiz M, Rodrı´guez JC, Escribano I, Royo G. Available options in the management of non-typhi Salmonella. Expert Opin Pharmacother 2004;5(8):1737e43. Graham SM, English M. Non-typhoidal salmonellae: a management challenge for children with communityacquired invasive disease in tropical African countries. Lancet 2009;373(9659):267e9. Dunne EF, Fey PD, Kludt P, Reporter R, Mostashari F, Shillam P, et al. Emergence of domestically acquired ceftriaxoneresistant Salmonella infections associated with AmpC betalactamase. J Am Med Assoc 2000;284(24):3151e6. Gupta A, Fontana J, Crowe C, Bolstorff B, Stout A, Van Duyne S, et al. Emergence of multidrug-resistant Salmonella enterica serotype Newport infections resistant to expandedspectrum cephalosporins in the United States. J Infect Dis 2003;188(11):1707e16. Sow AG, Wane AA, Diallo MH, Boye CS-B, Aı¨dara-Kane A. Genotypic characterization of antibiotic-resistant Salmonella enteritidis isolates in Dakar, Senegal. J Infect Dev Ctries 2007;1(3):284e8. Mølbak K. Spread of resistant bacteria and resistance genes from animals to humansethe public health consequences. J Vet Med B Infect Dis Vet Public Health 2004;51(8e9):364e9. Adhikari B, Besser TE, Gay JM, Fox LK, Davis MA, Cobbold RN, et al. Introduction of new multidrug-resistant Salmonella enterica strains into commercial dairy herds. J Dairy Sci 2009; 92(9):4218e28. Emborg H-D, Baggesen DL, Aarestrup FM. Ten years of antimicrobial susceptibility testing of Salmonella from Danish pig farms. J Antimicrob Chemother 2008;62(2):360e3. Varma JK, Greene KD, Ovitt J, Barrett TJ, Medalla F, Angulo FJ. Hospitalization and antimicrobial resistance in Salmonella outbreaks, 1984e2002. Emerging Infect Dis 2005; 11(6):943e6. Varma JK, Molbak K, Barrett TJ, Beebe JL, Jones TF, RabatskyEhr T, et al. Antimicrobial-resistant nontyphoidal Salmonella is associated with excess bloodstream infections and hospitalizations. J Infect Dis 2005;191(4):554e61. Sirinavin S, Pokawattana L, Bangtrakulnondh A. Duration of nontyphoidal Salmonella carriage in asymptomatic adults. Clin Infect Dis 2004;38(11):1644e5. Sirinavin S, Thavornnunth J, Sakchainanont B, Bangtrakulnonth A, Chongthawonsatid S, Junumporn S. Norfloxacin and azithromycin for treatment of nontyphoidal salmonella carriers. Clin Infect Dis 2003;37(5):685e91.

171. Crum-Cianflone NF. Salmonellosis and the gastrointestinal tract: more than just peanut butter. Curr Gastroenterol Rep 2008;10(4):424e31. 172. Heymann D. Control of communicable diseases manual: an official report of the American Public Health Association. Washington DC: American Public Health Assoc; 2004. 173. National Association of State Public Health Veterinarians, Inc. (NASPHV). Compendium of measures to prevent disease associated with animals in public settings, 2007: National Association of State Public Health Veterinarians, Inc. (NASPHV). MMWR Recomm Rep 2007;56(RR-5):1e14. 174. Maki DG. Coming to grips with foodborne infectionepeanut butter, peppers, and nationwide salmonella outbreaks. N Engl J Med 2009;360(10):949e53. 175. Talbot EA, Gagnon ER, Greenblatt J. Common ground for the control of multidrug-resistant Salmonella in ground beef. Clin Infect Dis 2006;42(10):1455e62. 176. Guzman CA, Borsutzky S, Griot-Wenk M, Metcalfe IC, Pearman J, Collioud A, et al. Vaccines against typhoid fever. Vaccine 2006;24(18):3804e11. 177. Whitaker JA, Franco-Paredes C, del Rio C, Edupuganti S. Rethinking typhoid fever vaccines: implications for travelers and people living in highly endemic areas. J Travel Med 2009; 16(1):46e52. 178. Lin FY, Ho VA, Khiem HB, Trach DD, Bay PV, Thanh TC, et al. The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children. N Engl J Med 2001;344(17): 1263e9. 179. Paterson GK, Maskell DJ. Recent advances in the field of Salmonella Typhi vaccines. Hum Vaccin 2010;6(5):379e84. 180. Khan MI, Ochiai RL, Clemens JD. Population impact of Vi capsular polysaccharide vaccine. Expert Rev Vaccines 2010; 9(5):485e96. 181. Klugman KP, Gilbertson IT, Koornhof HJ, Robbins JB, Schneerson R, Schulz D, et al. Protective activity of Vi capsular polysaccharide vaccine against typhoid fever. Lancet 1987;2(8569):1165e9. 182. Yang HH, Kilgore PE, Yang LH, Park JK, Pan YF, Kim Y, et al. An outbreak of typhoid fever, Xing-An County, People’s Republic of China, 1999: estimation of the field effectiveness of Vi polysaccharide typhoid vaccine. J Infect Dis 2001;183(12): 1775e80. 183. Yang HH, Wu CG, Xie GZ, Gu QW, Wang BR, Wang LY, et al. Efficacy trial of Vi polysaccharide vaccine against typhoid fever in south-western China. Bull World Health Organ 2001; 79(7):625e31. 184. Sur D, Ochiai RL, Bhattacharya SK, Ganguly NK, Ali M, Manna B, et al. A cluster-randomized effectiveness trial of Vi typhoid vaccine in India. N Engl J Med 2009;361(4):335e44. 185. Szu SC, Taylor DN, Trofa AC, Clements JD, Shiloach J, Sadoff JC, et al. Laboratory and preliminary clinical characterization of Vi capsular polysaccharide-protein conjugate vaccines. Infect Immun 1994;62(10):4440e4. 186. Mai NL, Phan VB, Vo AH, Tran CT, Lin FYC, Bryla DA, et al. Persistent efficacy of Vi conjugate vaccine against typhoid fever in young children. N Engl J Med 2003;349(14):1390e1. 187. Thiem VD, Lin F-YC, Canh DG, Son NH, Anh DD, Mao ND, et al. The Vi conjugate typhoid vaccine is safe, elicits protective levels of IgG anti-Vi, and is compatible with routine infant vaccines. Clin Vaccine Immunol 2011;18(5):730e5. 188. Germanier R, Fu ¨er E. Isolation and characterization of Gal E mutant Ty 21a of Salmonella typhi: a candidate strain for a live, oral typhoid vaccine. J Infect Dis 1975;131(5):553e8. 189. Levine MM, Ferreccio C, Black RE, Germanier R. Large-scale field trial of Ty21a live oral typhoid vaccine in enteric-coated capsule formulation. Lancet 1987;1(8541):1049e52. 190. Levine MM, Ferreccio C, Cryz S, Ortiz E. Comparison of enteric-coated capsules and liquid formulation of Ty21a

Salmonella infections: An update

191.

192.

193.

194.

typhoid vaccine in randomised controlled field trial. Lancet 1990;336(8720):891e4. American Academy of Pediatrics, Pickering L. Red book: 2009 report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village IL: American Academy of Pediatrics; 2009. Penha Filho RAC, de Paiva JB, da Silva MD, de Almeida AM, Berchieri Jr A. Control of Salmonella Enteritidis and Salmonella Gallinarum in birds by using live vaccine candidate containing attenuated Salmonella Gallinarum mutant strain. Vaccine 2010;28(16):2853e9. Pavic A, Groves PJ, Cox JM. Utilization of a novel autologous killed tri-vaccine (serogroups B [Typhimurium], C [Mbandaka] and E [Orion]) for Salmonella control in commercial poultry breeders. Avian Pathol 2010;39(1):31e9. Do ´rea FC, Cole DJ, Hofacre C, Zamperini K, Mathis D, Doyle MP, et al. Effect of Salmonella vaccination of breeder chickens on contamination of broiler chicken carcasses in integrated poultry operations. Appl Environ Microbiol 2010; 76(23):7820e5.

277 195. Hur J, Lee JH. Immunization of pregnant sows with a novel virulence gene deleted live Salmonella vaccine and protection of their suckling piglets against salmonellosis. Vet Microbiol 2010;143(2e4):270e6. 196. Denagamage TN, O’Connor AM, Sargeant JM, Rajic A, McKean JD. Efficacy of vaccination to reduce Salmonella prevalence in live and slaughtered swine: a systematic review of literature from 1979 to 2007. Foodborne Pathog Dis 2007; 4(4):539e49. 197. Selke M, Meens J, Springer S, Frank R, Gerlach G-F. Immunization of pigs to prevent disease in humans: construction and protective efficacy of a Salmonella enterica serovar Typhimurium live negative-marker vaccine. Infect Immun 2007; 75(5):2476e83. 198. Collard JM, Bertrand S, Dierick K, Godard C, Wildemauwe C, Vermeersch K, et al. Drastic decrease of Salmonella enteritidis isolated from humans in Belgium in 2005, shift in phage types and influence on foodborne outbreaks. Epidemiol Infect 2008;136(6):771e81.