Cerebral malaria in children M. Chiara Stefanini Catholic University - Rome
Malaria: epidemiology Global distribution of malaria transmission risk,, 2003 World malaria report, WHO, 2005
Estimated incidence of clinical malaria episodes caused by any species resulting from local transmission, country level averages (2004) World malaria report, WHO, 2005
Drug resistance to P. Falciparum from studies in sentinel sites (2004) World malaria report, WHO, 2005
Malaria: epidemiology M. is the world s s most important tropical parasitic disease, and kills more people that any other communicable disease. In Africa, M. exacts an enormous toll in lives, in medical costs,, and in days of labour lost.
Malaria: epidemiology M.. is a public health problem in >90 countries, inhabited by 40% of the world s s population, and is endemic in a total of 101 countries. The worldwide prevalence of the M. is estimated to be in the order of 300-500 million clinical cases each year.
Malaria: epidemiology >90% of all cases are in sub-saharan Africa. >1 million deaths/year The vast majority (>75%) of deaths occur in african children <5y Source: WHO, 2003 RBM (WHO, UNDP, UNICEF, World Bank)
Rest of the world Age (years) Africa Deaths (thousands Deaths (thousands)
Roll Back Malaria (RBM) was launched in 1998 with the declared objective of halving the global burden of malaria by 2010. Its founding partners the United Nations Development Programme, UNICEF, the World Bank and WHO - agreed to share their expertise and resources in a concerted effort to tackle malaria worldwide, with a particular focus on Africa.
The rapid spread of resistance to antimalarial drugs, coupled with widespread poverty,, weak health infrastructure and, in some countries, civil unrest,, means that mortality from malaria in Africa continues to rise. The tragedy is that the vast majority of these deaths are preventable. www.rbm.who.int (2005)
The life cycle of malaria parasites 5 The mosquito inoculates another human 1 An infected female Anopheles gambiae mosquito bites, injecting Plasmodium parasites into the blood. They pass quickly into the liver 2 The parasites multiplies in the liver cells over the next 7-107 days, causing no symptoms. 3 Parasites bursts from the liver cells to invade erythrocytes and multiply again. The parasites invade more erythrocytes. This cycle is repeated, causing fever each time parasites break free and invade. 4 If a female Anopheles mosquito feeds on this patient, parasites will multiply in her stomach wall. Thousands of new parasites migrate to her salivary glands, to be injected in saliva during next feed.
Cerebral Malaria (CM) CM is the most severe clinical form of Malaria Very young children (1-2 2 years old) are the the group population at higher risk for CM, because they have not yet acquired adequate clinical immunity
Cerebral Malaria: clinical picture It is characterized by 3 primary symptoms: 1. Fever non-specific high grade fever with impaired consciousness
2. Epileptic seizures occur in >70% of affected children as first symptom most seizures are partial motor,, with EEG spike-and and-wave activity arising from the posterior temporo-parietal parietal region
EEG focus on the left central region. Seizures: repeated clonic seizures of the right arm
2. Epileptic seizures occur in >70% of affected children as first symptom most seizures are partial motor, with EEG spike-and and-wave activity arising from the posterior temporo-parietal parietal region 25% of affected children show also subtle, only electrographic seizures. >30% of patients have an episode of status epilepticus
Left occipital status epilepticus SE manifested by contralateral conjugate eye deviation and nystagmus
2. Epileptic seizures occur in >70% of affected children as first symptom most seizures are partial motor, with EEG spike-and and-wave activity arising from the posterior temporo-parietal parietal region *A seizure occurring in infancy or 25% of affected children show also subtle, only electrographic childhood seizures. (3 m. childhood (3 m. 5 a.), associated with fever, without evidence of >30% of patients have an episode of status epilepticus intracranial or defined cause in young children simple *febrile seizures must be differentiated from epileptic seizures due to CM in >50% of patients seizures mark the onset of coma
3. Coma lasts 6-90 hours,, usually shorter in children neurological signs: : brain stem disturbances, decerebrate or decorticate postures if coma persists >30 min after a generalized seizure, CM must be suspected 4. Other symptoms Cerebral oedema Retinal haemorrhages Hepatosplenomegaly Vomiting + failure to eat Severe anaemia (commonest complication) Bronchopneumonia (common complication)
Clinical manifestations of Malaria in adults and in children
Clinical manifestations Duration of illness prior to complications Convulsions Abnormal brain stem reflexes C.S.F. pressure Resolution of coma Adults Children 5-77 days 1-22 days Common Rare Usually normal Very common More common Variable, often raised 2-44 days 1-22 days Neurological sequelae <5% >10% Cough Anemia Jaundice Pre-treatment hypoglycemia Pulmonary oedema Renal failure Bleeding/clotting disturbances Uncommon Common Common Uncommon Common Common Up to 10% Common More common and more severe Uncommon Common Rare Rare Rare
Dysconiugate gaze (mesenchephalon( mesenchephalon)
The contrast between the palm of a child with anaemia and that of his mother
Crawley et Al., 2001 Cerebral Malaria: treatment Antimalarial chemotherapy: : quinine dihydrochloride (10-15 15 mg/kg i.v., every 12 h) ATTENTION! MEFLOQUINE may cause neuropsychiatric adverse effects: anxiety, depression, hallucinations and epileptic seizures Antipyretics: paracetamol,, if BT>38 C C (15 mg/kg every 6 h) Anticonvulsants to prevent and treat seizures: PB (5-10 mg/kg) to treat status epilepticus: DZP (0.3-0.5 0.5 mg/kg i.v.) or PHT (15 mg/kg i.v.) Osmotic diuretics: : to reduce brain oedema
The majority of deaths for malaria occurs in young children Why?
Malaria kills young children in three different ways Infection in pregnancy Acute febrile illness Chronic, repeated infection Low birth weight Preterm delivery Cerebral malaria Severe anaemia Respiratory distress Hypoglycaemia Death Source: WHO, 2003
Cerebral Malaria: sequelae Approximately >10% of children who survive CM are left with permanent neurological problems: motor impairment: - hemiplegia - spastic quadriplegia cognitive impairment epilepsy with remote seizures and visual impairement Crawley et al., 2000
Congenital Malaria Occurs in <5% of affected pregnancies Placental barrier and maternal Ig G antibodies (which cross the placenta) may protect the foetus It is much more common in non-immune population and the incidence goes up during epidemics of M
Congenital Malaria The newborn child can manifest with fever, irritability, feeding problems,hepato- splenomegaly, anemia,, jaundice etc. Differential diagnoses include Rh incompatibility, infections with CMV, Herpes, Rubella, Toxoplasmosis, and syphilis.
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