1. Introduction

Human Listeriosis, the infection caused by Listeria spp has been traditionally known as a food-borne illness. Listeria spp are a group of saprophytic gram positive bacilli present in the environment (soil, water, effluents etc.,) as well as colonized in alimentary tract of human and animals ^[1]. Infection with Listeria spp was first discovered as a cause of septicemia in laboratory animals (rabbits and guinea pigs) and later isolated from a patient suffering from meningitis ^{[2, 3, 4]}. Human listeriosis is normally acquired by the consumption of food (milk, milk products, meat, fish and vegetables etc.,) and close contact with animals is considered as a predisposing factor ^[5]. Gastrointestinal infections, mastitis and abortions are usually associated with listeriosis in animals. Currently there are six species of Listeria identified among which L monocytogenes and L ivanovii are considered as pathogenic strains to humans and animals respectively ^[6]. Human infections of Listeria spp normally occur following ingestion of contaminated food as evidenced from most of the previous outbreaks world wide ^[7]. Recent reports have also confirmed the association of human listeriosis with geriatric age population ^{[8, 9]}. Human listeriois was confined to a select group of population including the pregnant women, neonates, individuals with weakened immune system ^{[10, 11, 12]}. Reports of Listeria spp infection among the pediatric age children who are immunologically competent, invasive infections in adult population with and without underlying causes, the occurrence of nosocomial listeriosis and community acquired Listeria meningitis should be considered as a cause of serious concern ^{[13, 14, 15, 16]}.

2. Epidemiology of Human Listeriosis

Incidence of human listeriosis varies with geographical region ^[17]. It has been estimated that 0.24 per one lakh people suffer from infection with Listeria in America annually. A recent report from center for disease control and prevention (CDC) has noted that among the 147 infected during an outbreak after consumption of cantaloupe 33 (22.5%) had died and a pregnant women suffered miscarriage ^[18]. Report from Rio d Janeiro (Brazil) by Martins et al., revealed that there was an outbreak of human listeriosis affecting six elderly hospitalized patients ^[19]. A study by Brouwer MC et al among the human listeriosis cases that included 30 immunocompromised patients has revealed a mortality rate of 17% ^[20]. An Israeli study by Seigman-Igra Y et al which reviewed 161 cases and 1808 reported cases showed that 74% of the infected patients were immunosuppressed with a mortality rate of 30% ^[21]. Consumption of fresh cheese contaminated with Listeria monocytogenes was attributed to an outbreak in Spain ^[22]. A recent study from north India by Soni DK et al have characterized Listeria spp based on the serotype, antimicrobial susceptibility patterns and presence of virulence determinant genes. This study which included Listeria spp isolated from various sources (human clinical samples, milk and ganges river water) has revealed occurrence of different serogroups that included 1/2a, 1/2b, 1/2c, 3a, 3b, 3c, 4b, 4d and 4e. The same report also demonstrated that the Listeria spp isolated from human source and other sources (milk and water) belonged to two different clones ^[23]. Another study by Orsi RH et al have revealed that serotypes of Listeria spp belong to 4 lineages (lineage I, II, III, IV) where in Listeria monocytogenes, the most common human pathogen belonged to lineages I and II (serotypes 1/2a, 1/2b and 4b) ^[24].

3. Clinical Presentation

Listeriosis in human is mainly characterized as perinatal listeriosis, neonatal listeriosis and adult listeriosis. Most cases of human listeriosis present as brain abscess or meningitis confirming the dissemination hematogenously from a local area (gastrointestinal tract) to central nervous system (CNS). Skin infections caused by Listeria spp have been noted among the farmers, agricultural workers and veterinarians presenting as pyogranulomatous rash ^[25]. Atypical clinical presentation of human listeriosis includes endocarditis, myocarditis, arteritis, pneumonia, pleuritis, cholecystitis, peritonitis, arthritis, osteomyelitis, sinusitis, otitis, conjunctivitis, ophthalmitis. Clinical presentation of human listeriosis is influenced by the physiological, pathological and immunological (T cell immunity) status of the host. Predisposing factors for human infections with Listeria spp include pregnant women, neonates, old age (>50 years), immunocompromised and debilitated individuals. Other predisposing factors for human listeriosis are malignancy, patients on cancer chemotherapy, immunosuppressive therapy, chronic kidney disease (CKD), and chronic liver disease. Metabolic disorders like diabetes mellitus and autoimmune diseases may also predispose to Listeria spp infections ^{[11, 26, 27]}.

4. Pathogenicity and Virulence Determinants

Listeria monocytogenes are facultative intracellular bacterial pathogens, which pose a potential public health problem related to consumption of contaminated food that is facilitated by their ability to tolerate high concentrations of salt and able to survive and multiply in refrigeration temperatures ^[25]. It was only in the early 1980’s Listeria spp have been recognized as a threat to food industry that later led to further studies on its virulence factors and potential to cause serious human infections. Previous studies have elaborated on the probable mode of entry and the nature of dissemination of Listeria spp using murine model experiments and have confirmed that acute infection of Listeria spp usually starts after ingestion of contaminated food ^{[28, 29]}. Listeria spp, then get colonized intracellularly in the intestinal epithelial cells before invading to the nearest lymph nodes and then disseminating through blood first to liver and then to other organs ^[30]. Immunologically competent host is sufficient to eliminate Listeria spp before it establishes and that could be the main reason for less number reports of human listeriosis ^[31]. Other significant factor attributed to under reporting and missed diagnosis of human listeriosis is the long incubation periods ranging from few days to months as noted by a recent study ^[32]. The profile of human listeriosis has shown a significant change from a bacterium that is responsible for gastrointestinal infections and meningitis, to a pathogen that has capability to cause invasive infections not only confined to immunosuppressed and debilitated patients but also in immunocompetent individuals ^[33]. The virulence factors associated with invasive Listeria infections include hemolysin (Hly), similar to the streptolysin O produced by Streptococcus pyogenes and is called as listeriolysin O (LLO), phospholipase (PLC) (PlcA and PlcB) similar to the one secreted by Staphylococcus aureus, Cholesterol dependent pore-forming toxin (CDTX), lecithinase, ActA (Actin-based intracellular motility) and internalins (InlA and InlB) that facilitate invasion ^{[1, 34]}.

5. Laboratory Identification Methods

Listeria spp are a group of non-sporing gram positive bacilli that have been recognized as established pathogens in animals including the cattle, sheep, wild animals, birds and other mammals ^[1]. Isolation rates of Listeria spp in traditional clinical microbiological laboratories are negligible when compared to other pathogenic bacteria. Studies have impressed on the importance of use of Listeria enrichment broth for increased chances of isolation from various samples ^{[35, 36]}. Food processing industry has been identified as the most susceptible and possible source of Listeria spp contaminating food and food products ^[37]. Reports from studies including the Listeria spp isolated from such industries have identified that biofilm formation and resistance to the chemical preservative benzalkonium chloride is attributed to Listeria spp food contamination ^{[38, 39]}. Studies have also stressed on the significance of molecular methods in the tracking of Listeria spp in food industry ^{[40, 41]}. Human listeriosis is under reported and only few studies are available in literature, mostly from developed nations ^{[42, 43]}. Use of rapid, advanced and molecular laboratory testing methods including the polymerase chain reaction (PCR) have been instrumental in the diagnosis as well as epidemiological characterization of human listeriosis. Novel techniques facilitating the study on serotypes, virulence determinants, colonization and invasive characters, clone identification and surveillance include optimized Multilocus variable-number tandem-repeat analysis assay (MLVA) (VNTR), pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and Fluorescence amplified fragment length polymorphism (fAFLP). Only few studies in the existing literature are available that report the predominant serotype prevalent and their association with a particular type of clinical illness ^{[44, 45, 46]}.

6. Antimicrobial Chemotherapy

A evidenced from the available literature it is clear that most listerial infections in human are subclinical and clinical infections are usually associated with immunosuppressed and debilitated conditions. Ampicillin, amoxicillin and gentamicin were successfully tried among pregnant women and the management of severe invasive infections in immunocompromised patients require long term antimicrobial therapy. Listeria spp are known to show resistance to cephalosporins and erythromycin and co-trimoxazole are other antimicrobial agents effective against human listerial infections ^{[47, 48, 49]}.

7. Discussion including Preventive and Control Measures

Clinical presentation of human listeriosis is complex and is believed to be influenced by the physiological, clinical and immunological status of an individual. Mode of entry of the bacilli, its virulence factors also play an important role in the outcome of the disease. Gastrointestinal symptoms following food contamination is the most common presentation followed by neurological complications when Listeria spp invade the central nervous system (CNS). Existing literature also indicate that Listeria spp may be excreted through feces of immunocompetent host without contributing to any clinical symptoms, thus acting as transmission vehicles for further food contamination and spread to susceptible population (pregnancy, old age) and may contribute to community acquired human listeriosis. Previous studies have also noted that it is very difficult to analyze on the probable source and entry of Listeria spp in human. Adults aged > 65 years and pregnant women who are considered as high risk groups have to be carefully evaluated and they should be advised to pay attention to the various food sources of Listeria (milk and milk products: both raw and pasterurized, meat and processed meat products) to prevent infection. Thorough cleaning of vegetables, implementation of effective hand washing technique, avoiding consumption of soft cheese and consuming thoroughly cooked and steamed food may be helpful in control of human listeriosis.

8. Conclusion

The inclusion of human listeriosis in the notifiable infectious agent list would allow determination of the distribution and characteristics of this infection and molecular epidemiological studies concentrating on the clonal group identification associated with colonization and invasive infections will help in evolving effective prevention and control measures. Clinical microbiology laboratories and health care professionals should play a pro-active role in suspecting and diagnosing human listeriosis. Conventional microbiological methods, improved selective culture methods for Listeria when assisted with rapid, advanced and molecular techniques would facilitate increased identification of Listeria spp and help in understanding the epidemiology, demographic and clinical characteristics of human listeriosis. Sporadic reports of human infection with Listeria spp should not undermine its public health impact.

Acknowledgement

I Express my sincere gratitude to the management, Prathima Institute of Medical Sciences, Karimnagar, India.

Competing Interest

None.

Source of support

None.

References

[1]	Jose´ A. VA´ zquez-Boland, Michael Kuhn, Patrick Berche, Trinad Chakraborty, Gustavo Dom´inguez-Bernal, Werner Goebel. Listeria Pathogenesis and Molecular Virulence Determinants Clin Microbiol Rev 2001; 14(3): 584-640.
	In article
[2]	Murray, E. G. D., R. A. Webb, and M. B. R. Swann. 1926. A disease of rabbits characterised by a large mononuclear leukocytosis, caused by a hitherto undescribed bacillus Bacterium monocytogenes (n. sp.). J. Pathol. Bacteriol. 29:407-439.
	In article		CrossRef
[3]	Nyfelt, A. 1929. Etiologie de la mononucl´eose infectieuse. C. R. Soc. Biol. 101:590-591.
	In article
[4]	Dumont, J., and L. Cotoni. 1921. Bacille semblable `a celui du rouget du porc rencontr´e dans le L.C.R. d’un m´eningitique. Ann. Inst. Pasteur 35: 625-633.
	In article
[5]	Centers for Disease Control and Prevention (CDC). Multistate outbreak of listeriosis associated with Jensen Farms cantaloupe-United States, August-September 2011. MMWR Morb Mortal Wkly Rep 2011; 60:1357-1358.
	In article		PubMed
[6]	Whittaker P. Evaluating the use of fatty acid profiles to differentiate human pathogenic and nonpathogenic Listeria species. J AOAC Int. 2012 Sep-Oct; 95(5):1457-9.
	In article		CrossRef PubMed
[7]	Hasbún J, Sepúlveda-Martínez A, Haye MT, Astudillo J, Parra-Cordero M. Chorioamnionitis caused by Listeria monocytogenes: a case report of ultrasound features of fetal infection. Fetal Diagn Ther. 2013; 33(4):268-71.
	In article		CrossRef PubMed
[8]	Teodor A, Teodor D, Miftode E, Prisăcaru D, Leca D, Petrovici C, Dorneanu O, Dorobăt CM. Severe invasive listeriosis--case report. Rev Med Chir Soc Med Nat Iasi. 2012 Jul-Sep; 116(3):808-11.
	In article		PubMed
[9]	Descy J, De Mol P, Hayette MP, Huynen P, Meex C, Melin P. Acute cholecystitis with Listeria monocytogenes. Acta Clin Belg. 2012 Jul-Aug; 67(4):295-7.
	In article		PubMed
[10]	Delvallée M, Ettahar N, Loïez C, Decoene C, Courcol R, Wallet F. An unusual case of fatal pericarditis due to Listeria monocytogenes. Jpn J Infect Dis. 2012 Jul; 65(4):312-4.
	In article		CrossRef PubMed
[11]	Spyros I Papadoulas, Stavros K Kakkos, Pantelis A Kraniotis, Maria E Manousi, Markos N Marangos, and Ioannis A Tsolakis. Listeriosis Infection of an Abdominal Aortic Aneurysm in a Diabetic Patient. J Glob Infect Dis. 2013 Jan-Mar; 5(1): 31-33.
	In article		CrossRef PubMed
[12]	Clauss HE, Lorber B: Central nervous system infection with Listeria monocytogenes. Curr Infect Dis Rep 2008.
	In article		CrossRef PubMed
[13]	Ianick Souto Martins, Flavia Cristina da Conceição Faria, Marco Antônio Lemos Miguel, Manuela Pereira de Sá Colaço Dias, Fernando Luís Lopes Cardoso, Ana Cristina de Gouveia Magalhães, et al. A cluster of Listeria monocytogenes infections in hospitalized Adults. Am J Infect Control 2010; 38(9): e31-e36
	In article		CrossRef PubMed
[14]	Dinic M, Stankovic S. Neonatal listeriosis followed by nosocomial infection. Indian J Med Microbiol. 2013 Apr-Jun; 31(2):187-9.
	In article		PubMed
[15]	Huan-ling Wang, Khalil G. Ghanem, Peng Wang,Shuang Yang, and Tai-sheng Li. Listeriosis at a tertiary care hospital at Beijing, China: High prevalence of nonclustered healthcare- associated cases among adult patients clinical Infectious Diseases 2013;56(5):666-76.
	In article		CrossRef PubMed
[16]	Brouwer MC et al: Community-acquired Listeria monocytogenes meningitis in adults. Clin Infect Dis 2006; 43:1233.
	In article		CrossRef PubMed
[17]	Dulcinéa Blum-Menezes, Ivânia Deliberalli, Najara Carneiro Bittencourt, Carlus Augustu Tavares do Couto, Liana Nunes Barbosa, Alessandro Marques dos Santos and Gabriel Godinho Pinto. Listeriosis in the far South of Brazil: neglected infection? Revista da Sociedade Brasileira de Medicina Tropical 46(3):381-383, May-Jun, 2013.
	In article		CrossRef PubMed
[18]	Centers for Disease Control and Prevention (CDC). Multistate outbreak of listeriosis associated with Jensen Farms cantaloupe-United States, August-September 2011. MMWR Morb Mortal Wkly Rep 2011; 60:1357-1358.
	In article		PubMed
[19]	Martins IS, Faria FC, Miguel MA, Dias MP, Cardoso FL, Magalhães AC, et al. A cluster of Listeria monocytogenes infections in hospitalized adults. Am J Infect Control 2010; 38:e31-6. Epub 2010 Jun 8. Rebello, Renata Fernandes [corrected to Rabello, Renata Fernandes]. Erratum in: Am J Infect Control 2010; 38:849.
	In article		CrossRef PubMed
[20]	Brouwer MC et al: Community-acquired Listeria monocytogenes meningitis in adults. Clin Infect Dis 2006; 43:1233.
	In article		CrossRef PubMed
[21]	Siegman-Igra Y et al: Listeria monocytogenes infection in Israel and review of cases worldwide. Emerg Infect Dis 8:305, 2002.
	In article		CrossRef PubMed
[22]	de Castro V, Escudero J, Rodriguez J, Muniozguren N, Uribarri J, Saez D, Vazquez J. Listeriosis outbreak caused by Latin-style fresh cheese, Bizkaia, Spain, August 2012. Euro Surveill. 2012 Oct 18; 17(42). pii: 20298.
	In article
[23]	Soni DK, Singh RK, Singh DV, Dubey SK. Characterization of Listeria monocytogenes isolated from Ganges water, human clinical and milk samples at Varanasi, India. Infect Genet Evol. 2013 Mar; 14:83-91.
	In article		CrossRef PubMed
[24]	Orsi RH, den Bakker HC, Wiedmann M. Listeria monocytogenes lineages: Genomics, evolution, ecology, and phenotypic characteristics. Int J Med Microbiol. 2011 Feb;301(2):79-96.
	In article		CrossRef PubMed
[25]	Lorber B; Listeria monocytogenes; Chapter 195 IN: Principles & Practice of Infect Dis, Mandell G, Bennett J & Dolin R. 5th Ed, Churchill Livingston; pp. 2208.
	In article
[26]	McLauchlin, J., and J. C. Low. Primary cutaneous listeriosis in adults: an occupational disease of veterinarians and farmers. Vet. Rec. 1994; 135: 615-617.
	In article		PubMed
[27]	Farber, J. M., and P. I. Peterkin. Listeria monocytogenes, a food-borne pathogen. Microbiol. Rev. 1991; 55:476-511.
	In article		PubMed
[28]	Schlech, W. F., III, D. P. Chase, and A. Badley. 1993. A model of food- borne infection Listeria monocytogenes infection in the Sprague-Dawley rat using gastric inoculation: development and effect of gastric acidity on infective dose. Int. J. Food Microbiol. 18:15-24.
	In article		CrossRef
[29]	J. A. Melton-Witt, S. M. Rafelski, D. A. Portnoy, and A. Bakardjiev, “Oral infection with signature-tagged Listeria monocytogenes reveals organ-specific growth and dissemination routes in guinea pigs,” Infection and Immunity, vol.80, no. 2, pp. 720-732, 2012.
	In article		CrossRef PubMed
[30]	Marco, A. J., N. Prats, J. A. Ramos, V. Briones, M. Blanco, L. Dom´ınguez, and M. Domingo. A microbiological, histopathological and immuno- histological study of the intragastric inoculation of Listeria monocytogenes in mice. J. Comp. Pathol. 1992; 107:1-9.
	In article		CrossRef
[31]	Sherrid AM, Kollmann TR. Age-dependent differences in systemic and cell-autonomous immunity to L. monocytogenes. Clin Dev Immunol. 2013; 2013:917198.
	In article
[32]	Goulet et al.: What is the incubation period for listeriosis? BMC Infectious Diseases 2013 13:11.
	In article		CrossRef PubMed
[33]	B. Pron, C.Boumaila, F. Jaubertetal., “Dendritic cells are early cellular targets of Listeria monocytogenes after intestinal delivery and are involved in bacterial spread in the host,” Cellular Microbiology,vol.3,no.5,pp.331-340,2001.
	In article		CrossRef PubMed
[34]	Travier L, Guadagnini S, Gouin E, Dufour A, Chenal-Francisque V, Cossart P, Olivo-Marin JC, Ghigo JM, Disson O, Lecuit M. ActA. promotes Listeria monocytogenes aggregation, intestinal colonization and carriage. PLoS Pathog. 2013 Jan;9(1):e1003131.
	In article		CrossRef PubMed
[35]	Jayasinghe S, Connor M, Donaldson S, Austin H, Foster A. Spontaneous bacterial peritonitis due to Listeria monocytogenes: importance of enrichment culture. J Clin Pathol. 2010 Sep;63(9):835-6.
	In article		CrossRef PubMed
[36]	Kristóf K, Barcs I, Cziniel M, Ghidán A, Nagy K. Connatal listeriosis--a case report and the possibilities of microbiological diagnosis. Acta Microbiol Immunol Hung. 2008 Mar;55(1):63-72.
	In article		CrossRef PubMed
[37]	Lamden KH, Fox AJ, Amar CF, Little CL. A case of foodborne listeriosis linked to a contaminated food production process. J Med Microbiol. 2013 Jun 20.
	In article		CrossRef PubMed
[38]	Nakamura H, Takakura K, Sone Y, Itano Y, Nishikawa Y. Biofilm Formation and Resistance to Benzalkonium Chloride in Listeria monocytogenes Isolated from a Fish Processing Plant. J Food Prot. 2013 Jul;76(7):1179-86.
	In article		CrossRef PubMed
[39]	Rivoal K, Fablet A, Courtillon C, Bougeard S, Chemaly M, Protais J. Detection of Listeria spp. in liquid egg products and in the egg breaking plants environment and tracking of Listeria monocytogenes by PFGE. Int J Food Microbiol. 2013 Jun 20;166(1):109-116.
	In article		CrossRef PubMed
[40]	Jin D, Luo Y, Zhang Z, Fang W, Ye J, Wu F, Ding G. Rapid molecular identification of Listeria species by use of real-time PCR and high-resolution melting analysis. FEMS Microbiol Lett. 2012 May; 330(1):72-80.
	In article		CrossRef PubMed
[41]	Shalaby MA, Mohamed MS, Mansour MA, Abd El-Haffiz AS. Comparison of polymerase chain reaction and conventional methods for diagnosis of Listeria monocytogenes isolated from different clinical specimens and food stuffs. Clin Lab. 2011; 57(11-12):919-24.
	In article		PubMed
[42]	Valero FP, Rafart JV. Incidence study of listeriosis in Spain. Gac Sanit. 2013 Jun 4. pii: S0213-9111(13)00053-8.
	In article
[43]	Morbidity and Mortality Weekly Report (MMWR). Vital Signs: Listeria Illnesses, Deaths, and Outbreaks — United States, 2009-2011. June 7, 2013 / 62(22);448-452.
	In article
[44]	Chenal-Francisque V, Diancourt L, Cantinelli T, Passet V, Tran-Hykes C, Bracq-Dieye H, Leclercq A, Pourcel C, Lecuit M, Brisse S. Optimized Multilocus variable-number tandem-repeat analysis assay and its complementarity with pulsed-field gel electrophoresis and multilocus sequence typing for Listeria monocytogenes clone identification and surveillance. J Clin Microbiol. 2013 Jun;51(6):1868-80.
	In article		CrossRef PubMed
[45]	Roussel S, Félix B, Grant K, Dao TT, Brisabois A, Amar C. Fluorescence amplified fragment length polymorphism compared to pulsed field gel electrophoresis for Listeria monocytogenes subtyping. BMC Microbiol. 2013 Jan 24;13:14. doi: 10.1186/1471-2180-13-14.
	In article		CrossRef
[46]	Wang Y, Zhao A, Zhu R, Lan R, Jin D, Cui Z, Wang Y, Li Z, Wang Y, Xu J, Ye C. Genetic diversity and molecular typing of Listeria monocytogenes in China. BMC Microbiol. 2012 Jun 22;12:119.
	In article		CrossRef PubMed
[47]	Janakiraman V; Listeriosis in pregnancy: diagnosis, treatment, and prevention. Rev Obstet Gynecol. 2008 Fall; 1(4):179-85.
	In article		PubMed
[48]	Safdar A, Armstrong D; Antimicrobial activities against 84 Listeria monocytogenes isolates from patients with systemic listeriosis at a comprehensive cancer center (1955-1997). J Clin Microbiol 2003; 41 (1): 483-485.
	In article		CrossRef PubMed
[49]	Marco F et al: In vitro activities of 22 antimicrobial agents against Listeria monocytogenes strains isolated in Barcelona, Spain. The Collaborative Study Group of Listeriosis of Barcelona. Diagn Microbiol Infect Dis 38:259, 2000.
	In article		CrossRef