Persistent fever and serious recurrent infections

Persistent Fever and Pyrexia of Unknown Origin

Pyrexia of unknown origin (PUO) refers to prolonged fever (more than 1 week in young children and 2–3 weeks in adolescents). Often the diagnosis becomes apparent or the fever resolves within a short period of time. The cause is usually an atypical presentation of a common illness such as urine infection or pneumonia, but more significant causes include endocarditis, collagen vascular diseases, malignancy and inflammatory bowel disease. Sometimes no diagnosis is made, but the fever abates spontaneously.

The child should be hospitalized for careful observation. Antipyretics should not be given as they obscure the pattern of fever. Blood cultures should be obtained at the time of fever peaks when the yield is higher.

Kawasaki’s Disease

Kawasaki’s disease should be considered particularly in younger children and in infants with pyrexia beyond five days. Raised inflammatory markers and platelet count are sometimes seen, complications of coronary artery anuerysms.

Infective Endocarditis

Infective endocarditis usually occurs as a complication of congenital heart disease. The commonest causal organism is Streptococcus viridans which may be introduced during dental or other surgery. Endocarditis can also be seen in children with indwelling central venous catheters (e.g. for parenteral nutrition or chemotherapy).

The child presents with fever, malaise and anorexia. Signs include clubbing, splinter haemorrhages in the nails and splenomegaly, and the pre-existing heart murmur may change in character. Microscopic haematuria may be found. The diagnosis is made on blood culture, and echocardiography, which shows vegetations on the heart valves. Intravenous antibiotics are required for 6 weeks.


Osteomyelitis affects long bone metaphyses. Organisms are Staphylococcus aureus, Haemophilus influenzae, enterobacter species and Streptococcus pyogenes. Although the child may present with PUO, more usually the infected limb is obviously painful and held immobile. Swelling and redness eventually appear, and the adjacent joint may contain a sterile ‘sympathetic’ effusion. Repeated blood culture or direct aspiration of the bone abscess determines the causative organism. Radiographs are not helpful at presentation, as changes only become apparent after 10 days, but bone scans or MRI may be diagnostic. High-dose antibiotics are needed for up to 6 weeks, with surgical drainage if there is no immediate response. Inadequate treatment leads to bone necrosis, chronic discharge and limb deformity.

Serious Recurrent Infection and Immunodeficiency

Most children experience recurrent trivial infections. These are commonly respiratory and peak on starting school or nursery. Despite parental concern they do not require investigation. However, recurrent serious infections or recurrent infections in an unusual site need to be thoroughly evaluated. There may be an anatomical cause (e.g. a fistula causing recurrent urinary tract infection, or splenectomy) or an inherited or acquired immunodeficiency.

Splenectomy and Hyposplenism

Children who lack an effective spleen are at increased risk of sepsis, especially pneumococcal septicaemia. Hyposplenism may occur as a result of sickle cell disease (autoinfarction of the spleen) or after splenectomy for trauma, metabolic and haematological conditions (e.g. severe idiopathic thrombocytopenia purpura (ITP)). The risk of bacterial infection is especially high in children under 5 years old, and pneumococcal vaccination and prophylaxis with penicillin is recommended.

Congenital Immunodeficiency

Most immunodeficiency disorders present in early childhood with recurrent infections and failure to thrive. In DiGeorge’s syndrome there is cell-mediated immunodeficiency due to thymic aplasia, cardiac abnormality and hypoparathyroidism. Severe combined immunodeficiency (SCID) affects 1 in 100 000 and presents with opportunistic infection failure to thrive.

Acquired Immunodeficiency

This is often due to side effects of chemotherapy or immunosuppressants following a transplant. It is important that those treating the child (e.g. primary care doctors) are aware of the risk of infections. Care should be taken to avoid contact with chickenpox, herpes simplex and other common infections.


By far the commonest acquired immunodeficiency worldwide is HIV-1 infection leading to AIDS. 2.3 million children live with HIV, either infants born to infected mothers or adolescents who acquire infection sexually or by intravenous drug abuse. Young children usually present by the age of 3 years with failure to thrive, diarrhoea, recurrent oral candidiasis, hepatosplenomegaly, or severe bacterial infections.

Diagnosis is made by the detection of HIV antibody or viral load by PCR Techniques. Treatment uses combination highly active antiretroviral therapy (HAART), antibiotic prophylaxis with co-trimoxazole and appropriate viral vaccination. In developing countries affected children often die in infancy or early childhood, but in the UK, with early diagnosis and treatment, the prognosis is good, with most children achieving viral suppression (an undetectable viral load by HIV PCR tests).

Without intervention, vertical transmission is 20–30%. Viral load should be reduced in pregnancy with HAART and with use of zidovudine in labour and for 4 weeks after birth, delivery by caesarean section and avoidance of breast-feeding, it can be reduced to <2%. Breast-feeding doubles the risk of infection. Because maternal anti-HIV IgG antibody crosses the placenta, a standard HIV test is not reliable in the first 18 months of life, and a quantitative RNA/DNA must be used.


  • A thorough history and repeat physical examinations are required. This may save the child from multiple investigations.
  • The characteristics of the fever may give a clue to diagnosis.
  • Samples for culture should be taken at the peak of the fever.
  • In severe, unusual or recurrent infections, consider immunodeficiency.
< div class='tao-gold-member'>

Only gold members can continue reading. Log In or Register to continue

Jul 2, 2016 | Posted by in PEDIATRICS | Comments Off on Persistent fever and serious recurrent infections
Premium Wordpress Themes by UFO Themes