Neutropenic Fever (Children)

Neutropenic Fever is defined as a single temperature above 38.3°C taken in the mouth or a body temperature greater than 38.0°C sustained for more than one hour in a child with neutropenia¹. Neutropenia commonly occurs post chemotherapy because the number of neutrophils (a type of white blood cell) in the bloodstream decreases after a child receives chemotherapy. A child has neutropenia when his or her Absolute Neutrophil Count (ANC) is less than 1500/mm3.

Our white blood cells are the soldiers of our body against invaders such as bacteria, fungi and viruses. Amongst them is an important soldier - neutrophil.

When a child undergoes chemotherapy and radiation therapy, these agents cause the bone marrow function to become poorer. In addition, certain cancers that invade the bone marrow cause a decrease in the number of blood cells.

When the effect of the cancer or the therapeutic agents is severe enough, the number of soldiers in our body including neutrophils is greatly reduced and the child becomes vulnerable to infection. The risk of a serious infection in a child receiving treatment for cancer is related to the degree and duration of neutropenia.

A normal ANC is more than 1500/mm3. Children with brief periods of neutropenia (ANC 200/mm3 to 500/mm3) and fever for less than 7 days respond better than those with severe neutropenia (ANC less than or equal to 200/mm3) lasting more than 7 days. Lung infections, skin infections and blood infections occur more frequently when the ANC falls below 500/mm3. The risk of a life-threatening infection increases further when the ANC is less than 200/mm3.

Neutropenia and its nadir (lowest point that one's blood cell count will reach) often occur between 7 and 14 days after a child receives chemotherapy. This period can be different depending on the underlying condition and chemotherapy received. Depending on the chemotherapy regimen given, the immune system is suppressed to varying degrees. For example, patients with acute myeloid leukaemia may have periods of severe neutropenia for up to 4 weeks as compared to patients with standard risk acute lymphoblastic leukaemia in which the neutrophil counts usually recover by day 10.

Neutropenic Fever is the most common side effect from cancer treatment. Fever in a neutropenic child should be managed as a medical emergency as he or she is at risk of bacterial sepsis (bacterial infection) if left untreated. Children who have any form of immunodeficiency or recently received chemotherapy are at risk of developing Neutropenic Fever and hence a full blood count (FBC) should be performed urgently in these patients at the onset of fever.

Source:¹Infectious Diseases Society of America

A child may experience one or more of these warning signs of infection:

• Fever (temperature over 38°C)
• Chills or shaking
• Burning feeling when passing urine; more frequent urination
• Redness, heat, swelling or drainage from a wound
• Cough and shortness of breath
• Sore throat with fever
• Mouth ulcers
• Vomiting and/or diarrhoea with fever
• Skin rashes, especially round blisters

It is recommended that you keep a reliable axillary or tympanic (ear) thermometer at home to monitor your child's temperature.

The doctor will perform a thorough history check and do a complete physical exam to find out what is causing the fever and where the infection comes from.

Common areas that infections may arise from are:

• Upper respiratory tract (Otitis Media or Sinusitis)
• Oropharynx (Dental Abscess or Mucositis)
• Lower respiratory tract (Pneumonia, including Pneumocystis Jirovecii Pneumonia)
• Gastrointestinal tract (Clostridium Difficile Colitis or Typhlitis)
• Skin (Cellulitis, Chicken Pox or Herpes Virus Infection)
• Perineum and perianal area (Anal Fissure or Abscess)
• Central catheter sites (Tunnel or Exit Site Infection)

The following laboratory tests and diagnostic imaging may be performed for a child with Neutropenic Fever:

• Full blood count
• Tests to look at degree of inflammation in the body that may indicate a serious bacterial infection
• Blood cultures from central venous lines, if any
• Samples from other sites (urine, sputum, wound, stool and others) will be collected and sent for testing if we suspect that there may be an infection from these sites
• Chest X-ray if symptomatic (displaying symptoms of a disease i.e. cough, breathlessness or low oxygen saturations)
• Respiratory Viral Immunofluorescence or Multiplex Polymerase Chain Reaction, if there are symptoms of upper respiratory tract infection
• Imaging studies (CT scan, ultrasound, 2D-echo etc.) will be considered as guided by the doctors' physical findings

Education of patients and their caregivers is crucial to the outcome of treatment as they need to be aware of the possible signs, symptoms and dangers of neutropenic fever. This will empower them to seek necessary treatment early and also to be prepared for the possible complications.

Broad spectrum antibiotics will be quickly initiated once the appropriate investigations are obtained. If there is evidence of a specific viral infection such as Herpes Simplex Virus or Cytomegalovirus, we may choose to initiate antiviral drugs as well. For children with prolonged Neutropenic Fever, we may initiate antifungal treatment if we think the child is at risk.

How fast a child can be discharged is dependent on the type of bacteria, fungus or virus, source of infection and how well the child recovers.

The child needs to fulfil all these criteria before he or she is allowed to be discharged:

• Evidence of marrow recovery - ANC more than 500/mm3 and rising
• No fever for at least 24 hours
• Low probability of having a blood infection caused by bacteria or fungi after 48 hours
• Clinically well i.e. haemodynamically stable (blood pressure, heart rate, oxygen saturation and respiratory rate within normal ranges)
• Adequate care and monitoring can be provided at home
• Able to eat and drink adequately

Bring your child to the nearest Children's Emergency if he or she has Neutropenic Fever or infection.

While Neutropenic Fever cannot be entirely prevented, there are some measures that can be put in place to reduce the risk of getting infections:

• Maintain hand hygiene by cleaning your child's hands as frequently as possible.
• Avoid crowded places.
• Avoid public transportation. If necessary, use it during off peak hours.
• Avoid contact with people who are sick.
• Do not share food, drinks, cups, utensils or personal items such as toothbrushes.
• Shower or bathe daily.
• Cook meat and eggs thoroughly to kill any germs.
• Carefully wash raw fruits and vegetables.
• Avoid eating raw food.
• Clean teeth and gums regularly with a soft toothbrush.
• Keep all household surfaces clean.
• Vaccinate all household members with varicella and influenza vaccines if possible.