1.1 Presentation

1.2 Investigations

1.3 Management

1.4 Discharge and follow‐up

1.1 Presentation

Suspect malaria in any child with fever and travel to a malaria‐endemic area. Be aware that while the risk of falciparum malaria is highest in the first few weeks after exposure, it can present up to 6 months later. Non-falciparum malaria can rarely present years after travel to an endemic country https://travelhealthpro.org.uk/countries

Uncomplicated malaria:

Non‐specific symptoms - fever, lethargy, malaise, nausea, abdominal pain, vomiting and diarrhoea. Often no distinct fever pattern. Patient may also have hepatosplenomegaly. Please note children can appear well, especially new migrants from endemic countries who have some malarial immunity.

Indicators of severe or complicated malaria: 

• Impaired consciousness or seizures
• Respiratory distress or acidosis (pH less than 7.3)
• Hypoglycaemia (blood glucose less than 2.2mmol/l)
• Severe anaemia (haemoglobin less than 80g/l)
• Prostration (inability to stand or sit)
• Parasitaemia greater than 2% (red blood cells parasitized)

1.2 Investigations

• Malaria antigen tests & thick and thin blood films (“malaria parasite” order on Trakcare covers both). The haematology laboratory BMS will need to contact the haematologist on call to examine the films to confirm the results of antigen testing and provide an estimate of parasitaemia. 
• If initial tests are negative, arrange to repeat. Three negative tests over a period of 24-48 hours are recommended to exclude malaria. These tests should be no less than 12 hours apart, and ideally no longer than 24 hours apart. It may be logistically easier for families, and clinically safer, to admit children to the Clinical Decision Unit to complete at least the first two tests. If the child recovers clinically and is afebrile for at least 24 hours, and the country risk of malaria is low, then a third test may not be required. This should be a general paediatric consultant decision, discussed with ID if required.
• Blood gas including glucose.
• Full Blood Count. Thrombocytopenia is highly suggestive of malaria.
• LFT’s, U&E’s, blood glucose and clotting studies.
• G6PD screen (required prior to giving primaquine in case of vivax and P.ovale ). This should be checked in all children with clinical signs of severe malaria at baseline, and in all other children once a positive malaria test is confirmed. Samples for G6PD testing need to be taken before blood transfusion for the test to be valid.
• Do not forget appropriate investigations for other infections as detailed in Fever in the returning paediatric traveller, in particular blood and stool cultures for typhoid.  

1.3 Management

• Discuss all patients with confirmed malaria with the ID consultant on call and admit under the ID team.
• Perform four hourly observations and blood sugar monitoring. 
• If the patient has features of severe malaria consider admission to PICU.
• In severe malaria, repeat thick films for parasitaemia after 12‐24 hours or sooner if there is clinical deterioration (“malaria parasite” order on Trakcare).

Uncomplicated malaria:

Treatment of choice is oral artemether with lumefantrine (Riamet) (Table 1).

• To increase absorption, give with food or a milky drink.
• Tablets may be crushed immediately prior to administration.
• Use with caution in patients with severe hepatic impairment, severe renal impairment, electrolyte disturbance e.g. hypokalaemia or hypomagnesemia, concomitant drugs that prolong the QT interval. Monitor ECG and electrolytes. Discuss with the antimicrobial pharmacist.
• Contraindicated in patients with a history of arrhythmia, clinically relevant bradycardia, congestive heart failure accompanied by reduced left ventricular ejection fraction, family history of congenital QT interval prolongation and family history of sudden death.
• Avoid in patients with acute porphyria.
• There are a number of significant drug interactions with Riamet, please refer to SPC for further information. Search ‘Riamet’ on the homepage.

Table 1: Riamet dosing

If under 5kg, please discuss dosing with the antimicrobial pharmacist.

If oral artemether with lumefantrine is unavailable or if contra-indicated, use oral atavoquone with proguanil hydrochloride (Malarone®) (Table 2)

• To increase absorption, give with food or a milky drink. 

• Tablets may be crushed immediately prior to administration. 

Table 2: Malarone dosing

If under 5kg, please discuss dosing with the antimicrobial pharmacist.

Severe or complicated malaria: 

The first line treatment for severe/complicated malaria is IV artesunate (Table 3). After 24 hours of IV treatment this can be switched to oral Artemether with lumefantrine (Riamet®) if the patient is improving. Give a full oral treatment course, as detailed above. 

• No necessary adjustments are required for renal or hepatic impairment. 
• Monitor for hypersensitivity reactions. 
• Risk of haemolysis – follow-up at 2 weeks post treatment with FBC. 
• Co-administration of Artesunate with strong inhibitors of UGT enzymes (e.g. Axitinib, Vandetanib, Imatinib, diclofenac) & UGT inducers (e.g. nevirapine, ritonavir, rifampicin, carbamazepine, phenytoin) should be avoided. See SPC for more details. 
• See Medusa IV monograph for reconstitution, dilution and administration information.
• Once reconstituted, the solution must be used within 1.5 hours (If licensed product unavailable see Medusa for reconstitution advice on other products as this may differ)

If artesunate is unavailable then discuss with the ID team. IV quinine may be used as an alternative treatment only after discussion.  

Table 3: IV Artesunate dosing

1.4 Discharge and follow‐up: 

If the child is a recent migrant, then consider screening for other infections. Refer to Refugee and asylum seeking children and young people guideline for further information. 

Patients with severe malaria may be discharged when they show clinical improvement, have falling parasitaemia (less than 2%) and stable blood parameters. Children with uncomplicated malaria may be discharged after discussion with the consultant on call for ID. 

For follow up, FBC and malaria film will be arranged by the ID team after 2 weeks if the patient has been treated with an anti‐malarial. 

For patient receiving IV artesunate additional follow-up at 4-6 weeks may be required.  

If P.vivax or P.ovale, treat to eradicate parasite in hepatocytes with primaquine, doses are as per BNFc. If patient is less than 6 months of age or has G6PD deficiency discuss with ID before commencing treatment.  

Advise parents/carers: 

• To re‐present if patient has fever in the following 3 months.
• To use anti‐malarial prophylaxis if future travel to malaria‐endemic area (GP, travel clinic).

Pregnancy increases the risk of malaria infection, and the risk of severe disease. Malaria parasites can adversely affect the placenta and increase the risk of stillbirth, prematurity and intra-uterine growth retardation. Prompt treatment of malaria in pregnancy reduces these risks. Congenital malaria (direct infection of an infant with malaria parasites via the placenta or during birth) can occur, and is best avoided by antenatal treatment.

The overall risk of congenital malaria after  antenatal treatment is very low. The risk will be higher in untreated malaria or where treatment is close to the time of delivery. Symptomatic congenital malaria is likely to present in the first month of life. 

Investigation of infants born following malaria in pregnancy is recommended by the RCOG to exclude the possibility of congenital malaria. 

The following guidance has been agreed for investigation and management of these infants in NHS GGC: 

2.1 Informing paediatric/neonatal teams 

2.2 Testing of samples from cord and placenta at birth

2.3. Management of the infant

2.4. Follow-up

2.1 Informing paediatric/neonatal teams 

Adult infectious diseases/obstetric teams should inform the neonatal and paediatric infectious diseases consultants on call when malaria is diagnosed in pregnancy. This should be in hours unless delivery of the infant is imminent. A Clinical Portal note should be made to highlight malaria in pregnancy and link to this guideline for actions after delivery.

2.2 Testing of samples from cord and placenta at birth

a) Cord samples

Once the infant is born, cord blood should be sampled (usual technique), placed in an EDTA tube and sent to the haematology laboratory using the Trakcare request "malarial parasites" using the  infant CHI. Sample should be labelled with the INFANT's CHI number. For clinical details on the request please write "Please process as per Congenital Malaria SOP. To be sent ASAP for PCR even if malaria film/RDT negative". Phone the haematology laboratory staff to explain and confirm this plan before sending the samples. Haematology laboratory staff will take enough sample for a blood film, and send the rest to the Malaria Reference Laboratory for urgent PCR testing. 

b) Placental blood samples

Once the placenta is delivered, take placental blood sample as outlined in appendix 3 of the RCOG guideline as follows: Placental blood can be obtained by placing the placenta maternal surface upward. Choose a site midway between the edge of the placenta and the cord, wipe it clean with gauze, make an incision about 1 cm deep and 3–4 cm in length with a scalpel blade (do not pierce the fetal surface) and use a syringe and needle (or haematocrit tube) to withdraw blood that pools in the incised area.  Put this blood directly into an EDTA tube (do not put on slides as in the RCOG guidance) and send to the haematology laboratory using the Trakcare request “Malarial parasites” from maternal CHI. Label with MATERNAL CHI. For clinical details on the request form write "Process as per Congenital Malaria SOP. PLACENTAL BLOOD. To be sent ASAP for PCR even if malaria film/RDT negative". The haematology laboratory staff will be responsible for sending the samples onwards to the Malaria Reference Laboratory as per our usual process. 

The haematology laboratory staff will aim to complete the blood film on the same day received, including weekends, but this does not need to be done overnight. 

Please phone the SmiRL Malaria Reference Laboratory on 0141 242 9631 during working hours once samples are sent, to request urgent PCR. The SmiRL reference lab will process the samples on the same day if they arrive before 13.00, otherwise processing will be on the next working day. Samples will not be processed for PCR over a weekend. 

Results for blood film and PCR should be phoned to the neonatal registrar on call (contact via switchboard). 

c) Placenta for pathology

The whole placenta should sent to histology as per usual processes, although please include "Malaria in pregnancy. Please look for evidence of placental malaria parasite sequestration" on the clinical details. Placental tissue should not be sent to microbiology or the malaria reference lab.  

Clinicians (obstetric and neonatal) should be aware that a positive RDT or PCR test on the placenta does not necessarily indicate ongoing malaria infection, as it would likely reflect dead parasites sequestered in the placenta. The purpose of testing is to assess the risk of malaria being transmitted to the infant via the placenta earlier in pregnancy. If in doubt (i.e. if there has been further travel since the last episode of malaria or patient is unwell) send peripheral bloods for a malaria parasite screen and discuss with the adult ID team if necessary. The risk of recurrent malaria is low, if infection was treated, but is higher in pregnant than in non-pregnant people. 

2.3. Management of the infant

If placenta/cord blood malaria tests are positive, send infant blood for malaria by microscopy and urgent PCR (not rapid antigen test) (“malaria parasite” order on Trakcare, request additional ‘PCR’ and contact the Malaria Reference Laboratory at the SmiRL to discuss as above), then test the infant weekly for 1 month by blood film microscopy/PCR (not rapid antigen test). The infant should be treated if post-birth blood tests are positive or they have symptoms suggestive of sepsis/congenital malaria. 

If the infant is unwell with suspected infection they should also be investigated and treated for bacterial sepsis as per our standard guidelines. 

Malaria treatment would be with IV artesunate with dosing outlined as per Table 3. Please inform the paediatric ID team if treatment is started. 

While our standard malaria guidance allows a switch to oral Riamet after 24 hours, Riamet dosing is difficult under 5kg, therefore the practicalities of this would depend on the age and size of the infant at time of treatment and should be discussed with the ID team, including the antimicrobial pharmacist. 

Side effects of artesunate in neonates are uncommon for short courses but can increase with ongoing use.  Adverse drug reactions include: bradycardia (risk reduced with slower administration), allergy (very uncommon in infants, presents with rash), reduced WCC, renal toxicity (reduced urine output as early indicator), jaundice,  gastrointestinal disturbance. 

2.4. Follow-up 

If placenta/cord blood are negative on microscopy or PCR then the infant is at very low risk of malaria, and no formal testing of the infant is required. However, the family should be safety-netted and told to present for medical review and test for malaria if febrile or other malaria symptoms any time in the first 3 months of life. A Trakcare alert and clinical note should be placed on Clinical Portal on the infant’s record by the neonatal team, to highlight this plan before discharge. Infants presenting with fever under 3 months old should also be investigated and managed as per our usual guidelines for bacterial infection.

Please let the paediatric ID team know at time of delivery if the infant is unwell (although this should not delay starting artesunate), or once test results known if well.  

If the infant is treated for malaria, follow-up should be as outlined in the section on ‘Discharge and follow-up’ above.

The Consultant on call for Infectious Diseases at the Royal Hospital for Children, Glasgow can be reached through hospital switchboard (0141 201 0000) 24 hours a day.