Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The abnormal susceptibility towards certain infections in SCD patients has a partial explanation in the well described functional defects of the spleen and of the alternative complement pathway; such defects probably account for the etiology of fulminant, often fatal, childhood infections with encapsulated organisms (Streptococcus pneumoniae, Haemophilus influenzae). On the other hand, the frequent systemic infections with enteric organisms in SCD patients, particularly of the salmonella species, and also with Staphylococcus aureus, are more difficult to explain. We therefore reviewed the potential contribution of neutrophil (PMN) dysfunctions to the increased infective tendency of SCD patients and included some previously unpublished data from our laboratory. While notable discrepancies still exist--and need further clarification--a tentative working hypothesis can be extracted from the available data: dysfunctions of neutrophils affect their locomotion (as reflected by decreased chemotaxis and in vivo migration), their phagocytic processes and their bactericidal performance. The latter concerns the ineffective killing of Staphylococcus aureus, Candida albicans, and Streptococcus pneumoniae. Dysfunctional bactericidal activity, in turn, apparently relates to a poor or at times non-existent PMN oxidative activity, which prevents the prompt disposal of microorganisms. Under certain circumstances salmonella species seem to further paralyze the oxidative machinery of PMNs in SCD. Serum from some patients contains a poorly defined inhibitor, or lacks an enhancing factor, and such serum abnormalities aggravate the existing defects just described. Interestingly recent findings suggest that dysfunctional PMNs may originate from the mandatory demargination of leukocytes secondary to the functional asplenia of SCD; a predominance of non-rosetting (EA-) PMNs among such leukocytes could produce the operational explanation for an exaggerated representation of dysfunctional PMNs in SCD patients with leukocytis.
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PMID:Neutrophil dysfunctions in sickle cell disease. 220 48

Children with SCD are prone to invasive infections caused by S. pneumoniae and H. influenzae. Osteomyelitis is caused most often by Salmonella species and less often by S. aureus. The chest syndrome and its associated microvascular disease carry a risk of prolonged and severe infections for Mycoplasma, Chlamydia, and probably other lower respiratory pathogens, particularly in the group of children with SCD prone to pain or microvascular sequestration, such as those with SC hemoglobinopathy. Despite three decades of investigation, the immunopathologic mechanisms leading to these increased risks is not completely clear. Bone infarction and microvascular disease probably play a part in the predisposition to osteomyelitis. Dysfunctional IgG and IgM antibody response, a lack of splenic clearance, defects in alternative pathway fixation of complement, and opsonophagocytic dysfunction play a role in the predisposition to invasive infection from polysaccharide-encapsulated organisms. Immunization with the conjugate Haemophilus vaccines has largely controlled infections caused by this pathogen. Early recognition of SCD through neonatal screening allows early and vigorous antibiotic management of febrile episodes in children with SCD and has perhaps provided the greatest benefit. Treatment of acute febrile episodes should include antibiotics active against regional strains of S. pneumoniae and H. influenzae, whereas treatment of febrile lower respiratory infections should include macrolide antibiotics that are active against Chlamydia and Mycoplasma, as well as pneumococci and Haemophilus. To date, no convincing evidence exists for the efficacy of pneumococcal polysaccharide vaccines in children with SCD, but preliminary data with the conjugate pneumococcal vaccines in normal children and those with SCD suggest that they may be as successful as Haemophilus vaccines in controlling this infection once they are available. Prophylaxis with daily penicillin administration is recommended and is well founded on clinical trials. However, problems with pneumococcal penicillin resistance and the association of failure with a lack of compliance to antibiotic regimens will dictate continued reexamination of this modality for the prevention of pneumococcal infections.
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PMID:Infections and immunizations of children with sickle cell disease. 1007 55