Salmonella and Sickle Cell: Why?

Q: Why is Salmonella a common cause of joint infections in patients with sickle cell disease? Any particular reason?
A: Salmonella is the most common cause of osteomyelitis (over 70%) in patients of sickle cell disease especially varieties like Salmonella enteritidis, Salmonella typhimurium, Salmonella paratyphi B, Salmonella choleraesuis and Salmonella aureus followed by Staphylococcus aureus, which is seen in 10% of patients suffering from sickle cell-related osteomyelitis. The majority of Salmonella infections in sickle cell patients involve bones (especially long bones) and joints and occur most frequently in early childhood. Multiple sites, often symmetrical, are usually involved. The following are the proposed/hypothesized reasons for the same:

1. At portal of entry: Capillary occlusion secondary to intravascular sickling may devitalize and infarct the gut, permitting Salmonella invasion.

2. In the blood: saturation of the macrophage system with red cell breakdown products of chronic haemolysis. Also, reduced function of the liver and spleen (asplenia due to autosplenectomy) suppresses clearance of these encapsulated organisms from the bloodstream. Abnormal opsonization and complement function probably also play a role.

3. In the bone: The multiple infarcts in bone (caused by vaso-occlusive crises) became infected either by transient bacteraemia or by activation of dormant foci of salmonella in bone marrow when tissues are devitalised. Also, the expanded bone marrow seen in sickle cell anemia (due to increased erythropoiesis) with sluggish flow leads to an ischemic focus for salmonella localization. The adjoining joints may also get affected. 

Salmonella osteomyelitis in a child with sickle cell disease. Bilateral radii symmetrically affected with pathological fractures at place of infection.
Q: How can we reduce invasive Salmonella infection in sickle cell disease ?

A: One way is by prevention: For example, look at how the pneumococcal vaccine reduced the burden of invasive pneumococcal disease in sickle cell patients: showing rates of invasive pneumococcal disease (IPD; cases per 100,000 person-years) among individuals with sickle cell disease who were enrolled in Tennessee Medicaid and lived in selected counties in Tennessee


Reported p-values are from the comparison of rates for the periods 1995–1999 (prior to introduction of the pneumococcal conjugate vaccine; shaded) and 2001–2004 (following vaccine introduction; not shaded), stratified for individuals aged <2 years, <5 years, and ≥5 years. Reference: Natasha B. Halasa, Sadhna M. Shankar, Thomas R. Talbot, Patrick G. Arbogast, Ed F. Mitchel, Winfred C. Wang, William Schaffner, Allen S. Craig, Marie R. Griffin; Incidence of Invasive Pneumococcal Disease among Individuals with Sickle Cell Disease before and after the Introduction of the Pneumococcal Conjugate Vaccine, Clinical Infectious Diseases, Volume 44, Issue 11, 1 June 2007, Pages 1428–1433, https://doi.org/10.1086/516781


Although there are vaccines available for Salmonella, their efficacy, risks and benefits in sickle cell disease patients have not been documented and thus, they are not routinely administered in sickle cell disease. Hopefully, this will change in the future. A simpler (in theory) yet much tougher (in practice!) guideline to implement is to reduce the feco-oral transmission of Salmonella species by hand hygiene and safe eating/drinking practices through public health education. References: 1. Salmonella osteomyelitis and arthritis in sickle cell disease. Anand AJ, et al. Semin Arthritis Rheum. 1994. 2. Global Burden of Sickle Cell Anaemia in Children under Five, 2010–2050: Modelling Based on Demographics, Excess Mortality, and Interventions Frédéric B. Piel , Simon I. Hay, Sunetra Gupta, David J. Weatherall, Thomas N. Williams July 16, 2013 https://doi.org/10.1371/journal.pmed.1001484 3. Invasive non-typhoidal Salmonella in sickle cell disease in Africa: is increased gut permeability the missing link? Seah H. Lim1,5* , Barbara A. Methé, Bettina M. Knoll, Alison Morris and Stephen K. Obaro Journal of Translational Medicine201816:239 https://doi.org/10.1186/s12967-018-1622-4   4. Salmonella osteomyelitis in childhood : A report of 63 cases seen in Nigerian children of whom 57 had sickle cell anaemia A A ADEYOKUNNU AND R G HENDRICKSE Archives of Disease in Childhood, 1980, 55, 175-184  





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