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    Lactoferrin Against Strep A

    Lactoferrin Against Strep A
    17 January 2023 Stephanie Drax
    How Lactoferrin helps against Strep A

    Lactoferrin Against Strep A

    This winter has seen a surge in Streptococcus A infections. While most people do not get extremely ill, the highly contagious bacterium has had tragic consequences for several children. We spoke to Dr Hamid Merchant, a pharmaceutical scientist at the University of Huddersfield and Leapfrog’s consultant, about Strep-A – the symptoms, how to help prevent infection, and what role lactoferrin might play.

    What is Strep-A?

    Group A Streptococcus (GAS; Streptococcus pyogenes) is a bacterium which can colonise the throat, skin and anogenital tract. When it ‘colonises’ GAS can cause a diverse range of skin, soft tissue and respiratory tract infections, including tonsillitis, pharyngitis, scarlet fever, impetigo, erysipelas, cellulitis and pneumonia.

    What are the possible implications of a Strep-A infection?

    GAS can occasionally cause infections that are extremely severe and in rare cases patients may go on to develop post-streptococcal complications, such as rheumatic fever and glomerulonephritis. Invasive GAS (iGAS) is an infection where the bacteria are isolated from a normally sterile body site, such as the blood. Any GAS manifestation can be associated with development of streptococcal toxic shock syndrome, although patients with necrotising fasciitis are at highest risk.

    How might we contract Strep-A?

    GAS is spread by close contact between individuals, through respiratory droplets and direct skin contact. It can also be transmitted environmentally, through contact with contaminated objects, such as towels or bedding, or ingestion of food inoculated by a carrier.

    What are the symptoms to look out for?

    Symptoms of GAS include a sore throat, swollen tonsils and neck glands and a skin rash. The bacterium can also cause any of the following: tonsillitis, pharyngitis, scarlet fever (swollen red tongue) skin infections like impetigo or erysipelas, cellulitis and pneumonia. In most cases, the GAS infection starts with an infection of oropharyngeal cavity, and common symptoms such as sore throat (tonsillitis and/or pharyngitis), high temperature, and inflamed tongue. The early manifestation of GAS involves symptoms of common cold and upper respiratory tract infection before the skin rash peculiar to scarlet fever is manifested in most patients.

    What steps can we take if we notice those symptoms?

    Like any upper respiratory tract infection, the most important strategy to combat GAS is to treat it in the early stages, reduce the bacterial load in the oral cavity and the upper respiratory tract and prevent the vertical transmission of infection down the lower respiratory (lungs) and a more systemic infection (iGAS). Good hand and oral hygiene can help reduce the bacterial load, together with mouth washes, throat rinses and nutritional supplements to support the immune system such as zinc, vitamin C and lactoferrin. Combined, these can be very useful in preventing catching the infection in the first place. These can also help in the recovery from GAS and prevent progression to a more severe form of the disease.

    What are the key mechanisms by which lactoferrin may help?

    Lactoferrin has a multitude of biological functions (including antibacterial, antiviral and anti-inflammatory) and is getting significant clinical attention due to its multifactorial immunomodulatory properties. Lactoferrin exerts its biological effects primarily by binding with receptors on target cells and preventing viral or bacterial entry. Lactoferrin’s advantage is also its iron-binding ability: Iron supports bacterial growth, and iron transfer from ceruloplasmin to the lactoferrin prevents iron being used by pathogenic bacteria. Lactoferrin also disrupts the bacterial cell membrane, preventing a proinflammatory cascade and cellular damage. You can refer to a meta-analysis I co-authored (published in 2021) entitled “Lactoferrin reduces the risk of respiratory tract infections”.

    And what is the latest science?

    One study confirmed that bovine lactoferrin was able to bind to three different strains of Streptococcus bacterial cells [3]. Other studies have shown that lactoferrin in its iron-free state is capable of a direct bactericidal effect on Streptococcus mutans, commonly found in the human oral cavity [4]. In an in-vivo study in mice, it was further confirmed that endogenous LF was able to protect against Streptococcus mutans-induced infections [5].
    In another in-vitro study, lactoferrin produced a bactericidal effect against Streptococcus pneumoniae (pneumococcus), and also downregulated genes involved in the pathogenicity of pneumococcus, thus demonstrating potential as new agents for the treatment of pneumococcal infections [6]. Another study showed that lactoferrin treatment helped to clear Streptococcus mutans from the blood and organs of bacteremic mice. Moreover, prophylaxis treatment of Lf also reduced the serum CRP levels and decreased IFN-γ, TNF-α, IL-1β, IL-6, MPO and iNOS in spleen and liver. The results indicated that Lf treatment protects the hosts from Streptococcus-induced bacteremia [7]. More research is needed into lactoferrin’s potential to combat Group A Streptococcus, but initial studies and lactoferrin’s widely accepted biological functions make it a promising candidate.

    References:
    (1) UK Health Security Agency’s infectious diseases collection: Information and guidance on group A streptococcal infections. Last updated: 16th December 2022. Available at: https://www.gov.uk/government/collections/group-a-streptococcal-infections-guidance-and-data
    (2) Ali AS, Hasan SS, Kow CS, Merchant HA. Lactoferrin reduces the risk of respiratory tract infections: A meta-analysis of randomized controlled trials. Clin Nutr ESPEN. 2021 Oct; 45:26-32. doi: 10.1016/j.clnesp.2021.08.019.
    (3) Park HM, Almeida RA, Luther DA, Oliver SP. Binding of bovine lactoferrin to Streptococcus dysgalactiae subsp. dysgalactiae isolated from cows with mastitis. FEMS Microbiol Lett. 2002 Feb 19;208(1):35-9. doi: 10.1111/j.1574-6968.2002.tb11057.x.
    (4) Arnold RR, Brewer M, Gauthier JJ. Bactericidal activity of human lactoferrin: sensitivity of a variety of microorganisms. Infect Immun. 1980 Jun;28(3):893-8. doi: 10.1128/iai.28.3.893-898.1980.
    (5) Velusamy SK, Markowitz K, Fine DH, Velliyagounder K. Human lactoferrin protects against Streptococcus mutans-induced caries in mice. Oral Dis. 2016 Mar;22(2):148-54. doi: 10.1111/odi.12401.
    (6) León-Sicairos N, Angulo-Zamudio UA, Vidal JE, López-Torres CA, Bolscher JG, Nazmi K, Reyes-Cortes R, Reyes-López M, de la Garza M, Canizalez-Román A. Bactericidal effect of bovine lactoferrin and synthetic peptide lactoferrin chimera in Streptococcus pneumoniae and the decrease in luxS gene expression by lactoferrin. Biometals. 2014 Oct;27(5):969-80. doi: 10.1007/s10534-014-9775-y.
    (7) Velusamy SK, Fine DH, Velliyagounder K. Prophylactic effect of human lactoferrin against Streptococcus mutans bacteremia in lactoferrin knockout mice. Microbes Infect. 2014 Sep;16(9):762-7. doi: 10.1016/j.micinf.2014.07.009. Epub 2014 Aug 11. PMID: 25124544; PMCID: PMC4252812.

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