Sickle Cell Symptom #2 - Infections

HI

My name is Lea and I have Sickle Cell Disease.

Ever since I was born i was handled with the utmost care so as ot to "break"

This meant, I never was allowed to do anything crazy like swimming, hiking, standing in the sun, eating outside home etc. While sometimes I may look back and think "wow! my parents were crazy paranoid" , I always feel a sence of gratiude for the best they did with the information they had at that particular time.

When you have Sickle Cell, your body is compromised from the get go. What do i mean? Okay, its quite simple. Knowing the nature of the disease; the sickling , destruction of red blood cells, anemia, reduced supply of oxygen and not to mention the extra amount of work the body has to do to ensure proper growth and development with its very little and stretched resources, the body is left defenseless. From the first doctors visit, a dose of penicillin is prescribed to up those defenses. However, this still doesnt hide the fact that Sickle Cell Warriors are quite suceptible to infections. 

From an article by Catherine Booth, Baba Inusa, Stephen K. Obaro on the International Journal Of Infectious Diseases , this is what I found out.

Infection is a significant contributor to morbidity and mortality in sickle cell disease (SCD). The sickle gene confers an increased susceptibility to infection, especially to certain bacterial pathogens, and at the same time infection provokes a cascade of SCD-specific pathophysiological changes. Historically, infection is a major cause of death in SCD, particularly in children, and it was implicated in 20–50% of deaths in prospective group studies over the last 20 years. Worldwide, it remains the leading cause of death, particularly in less developed nations. In developed countries, measures to prevent and effectively treat infection have made a substantial contribution to improvements in survival and quality of life, and are continually being developed and extended. However, progress continues to lag in less developed countries where the patterns of morbidity and mortality are less well defined and implementation of preventive care is poor.  SCD increases susceptibility to infections and the underlying mechanisms for susceptibility to specific pathogens.

Since you all know the clinical manifestations of SCD result from two key processes: vaso-occlusion (blood vessel obstruction by sickled red blood cells) and hemolysis (break down of red blood cells). Sickle cells, along with non-sickled RBCs, leukocytes, and platelets, form cell groups, which adhere to the vascular endothelium, causing obstruction of small blood vessels. This tiny circulatory obstructions lead to acute and chronic tissue damage and death, with multisystem effects, particularly in bone, lungs, brain, kidneys, and spleen.

Causes of Infection in SCD #10003 

Causes of Infection in Sickle Cell Disease

Impaired Spleen Function

The spleen has a key role in the increased susceptibility to certain bacterial infections seen in SCD. It functions as a phagocytic (protective cells i.e. white blood cells) filter, removing old and damaged cells and blood-borne microorganisms, and also produces antibodies. Individuals with SCD typically suffer from reduced and in some cases, lack of splenic function. The sluggish circulation through the spleen, high rates of O2 extraction, and local acidosis cause deoxygenation of HbS, promoting sickling, which leads to congestion and swelling of the sinusoids of the spleen with sickled cells. This can cause diversion of blood within the spleen, bypassing the normal filtering mechanisms. Macrophages (large stationary white blood cell) engulfing the abnormally shaped cells may become ‘blocked’, impairing their phagocytosis (ingestion of bacteria) of other particles.

Individuals with SCD hence they cannot mount a rapid specific response to captured organisms. Local infections can readily become systemic and this, in combination with the loss of the spleen's filtering function, can permit overwhelming sepsis (presence in tissues of harmful bacteria and their toxins, typically through infection of a wound) to develop. The main pathogen of concern is S. pneumoniae, though severe and systemic infections with H. influenzae, Neisseria meningitidis, and salmonellae also occur. Before preventive measures, children with SCD were 30–600 times more likely to develop invasive pneumococcal disease (IPD), including pneumonia, meningitis, and septicemia. Overwhelming sepsis can develop rapidly with no obvious primary source of infection, resulting in shock, disseminated intravascular coagulation, adrenal hemorrhage, and death within 24 to 48 hours. Mortality can reach 35–50% from septicemia and 10% in meningitis. The risk is confined almost exclusively to young children, with a reported incidence of 5.8 per 100 in children aged less than 3 years, 1.1 per 100 in those aged 5–9 years, and 0.6 per 100 in those aged over 10 years in the pre-treatment era.

While it is theoretically conceivable that children affected by SCD in malaria hyper-endemic settings like Kenya may be at increased risk of death from other pathogens such as malaria and invasive salmonellosis, poor diagnostic facilities and the high childhood mortality rates call this assertion into question. Well-planned longitudinal cohort studies to define the etiologic agents that predominate in SCD morbidity and mortality in this region are urgently needed.

Deficiencies in Micronutrients

Zinc is known to be important for immune function, so low levels in SCD have been suggested as a contributory factor in susceptibility to infection. Zinc deficiency is associated with lymphopenia (abnormally low levels of immune building white blood cells). Zinc deficiency may affect 60–70% of SCD patients. High protein turnover increases requirements, while hemolysis releases zinc, which is lost via the kidneys as renal tubular damage impairs reabsorption. At the same time poor diet and inadequate intestinal absorption could reduce intake. A study in 21 zinc deficient children suggested that giving supplements reduced the incidence of bacterial infections and cut hospital admissions.

Genetic Factors

Despite sharing the same underlying genetic mutation, the range of severity in SCD patients is striking, with some patients disabled by frequent crises and long-term complications while others live virtually normal lives. Individuals are also differently predisposed to particular pathological manifestations of the disease. This suggests that the SCD phenotype is multi-genic: since many unlinked genes are involved in the underlying extreme processes in SCD (such as destruction of sickled cells or endothelial adhesion), variation in genes at multiple locus points may modify outcome. Complexities in a number of genes involved in the immune response have been suggested as contributing to increased susceptibility to infection in SCD.

Mechanical Factors

The pathological effects of SCD can themselves create an environment supporting infection. Children with SCD are predisposed to osteomyelitis (inflammation of bone/bone marrow). The bone marrow space is expanded to accommodate the increased hematopoiesis (formation of blood/blood cells) needed to compensate for chronic hemolysis (red blood cell destruction), and oxygen demand is high. At the same time circulation is sluggish. Together these factors render bone vulnerable to vaso-occlusive (obstruction of blood vessel) episodes and infarction (tissue death). Areas of necrotic (dead) bone act as focus for infection, which becomes established via hematogenous (bloodstream) spread.

Edwardsiella tarda is another enterobacterium that has been reported with increased incidence in SCD. Increased gut permeability and biliary sludging in SCD is likely to be responsible for this association. It may be that patchy ischemia and infarction of bowel secondary to micro vascular occlusion permits gut bacteria to invade the intestinal wall and enter the bloodstream.

Another consequence of micro vascular disease is its association with acute chest syndrome. SCD carries an increased risk of prolonged and severe respiratory infections due to Mycoplasma, Chlamydia and other pathogens, particularly in children prone to pain or micro vascular sequestration, such as those with SCD.

Finally, SCD patients may be predisposed to certain iatrogenic (illness caused by medical examination or treatment) infections as a result of therapeutic interventions. Blood transfusion is commonly used to treat complications, particularly aplastic crisis or splenic sequestration (when Hb falls acutely) and acute chest syndrome, priapism, or strokes (when exchange transfusion is used to reduce the proportion of HbS). In general such programs are potentially associated with increased risk of blood-borne infections, particularly hepatitis B and C and HIV. Although all blood products in developed countries are screened for these viruses, standards in other countries may not be so exacting, so early hepatitis B immunization is recommended as a preventive measure. 

Now it is clear as day that my parents weren't crazy in being vigilant. As a sickle cell warrior speaking from experience, it is better to prevent than to treat. Sickle Cell is an expensive disease, however, it is way cheaper and less stressful to manage than to treat and bring the body back to balance when in crisis.

Next week we look at the effects of the infection on Sickle Cell Warriors and how we can prevent them. Until next time.

Love Life!

Lea