Case 1-2011 : A 60 years Old Male with Coma and Fever with Recent Travel to South Sudan

The patient had history of recent travel to Juba, south of Sudan 2 weeks befor admission. 5 days after return from Sudan , he noticed fatigue and mild fever.He was given non-specific treatment. 5 days later jaundice appeared on his skin , he was admitted to private hospital in Zagazig .The investigation showed total bilirubin :10 mg/dl , direct 7 mg/dl , ALT:150 , AST :120,Hg :10 gm/dl ,platelets :110000 / dl .The patient was managed as having acute liver disease. Later on malaria parasite test (MP test) was done and revealed P. falciparum in thick and thin blood films.The patient was referred to Zagazig Fever Hospital with deterioration of conscious level , quinine was given intravenously without improvement . In the next day , the patient was referred to Tropical Medicine Intensive Care Unit. The patient was deeply comatose ,deeply jaundiced and pale, splenomegaly was found , bubbling chest crepitations were auscultated.The urine was black and the skin showed echymosis .The investigations showed total bilirubin :32 mg /dl, direct bilirubin 22 mg/dl, Hg :6 gm /dl ,platelets : 15000/dl , creatinin: 6 mg/dl , INR :7 ,PH: 7.31 , bicarbonate :12 mmol/l and glucose : 350 mg/dl. Hemoglobin was found in urine. Quinine was given by intravenous infusion in the dose of 20mg /kg loading dose then 10mg/ kg every 8 hours. Doxycyclin 100 mg /12 hours was given through the Ryle . Intravenous frusemide was given as well as oxygen inhalation as a measure against pulmonary edema , also chest consultation for the possibility of mechanical ventilation was requested.Transfusion of platelets, fresh frozen plasma ,and backed red blood cells were given . Intravenous fluids as glucose 10% with 15 unit regular insulin and Ringer lactate solution were given according to the CVP. Regular insulin according to blood glucose level was given every 6 hours subcutaneously. The patient showed no response after one day of extensive care and death was the the end due to multiple organ failure .

The patient had history of recent travel to Juba, south of Sudan 2 weeks befor admission.5 days after return from Sudan , he noticed fatigue and mild fever.He was given non-specific treatment.5 days later jaundice appeared on his skin , he was admitted to private hospital in Zagazig .The investigation showed total bilirubin :10 mg/dl , direct 7 mg/dl , ALT:150 , AST :120,Hg :10 gm/dl ,platelets :110000 / dl .The patient was managed as having acute liver disease.Later on malaria parasite test (MP test) was done and revealed P. falciparum in thick and thin blood films.The patient was referred to Zagazig Fever Hospital with deterioration of conscious level , quinine was given intravenously without improvement .In the next day , the patient was referred to Tropical Medicine Intensive Care Unit.The patient was deeply comatose ,deeply jaundiced and pale, splenomegaly was found , bubbling chest crepitations were auscultated.The urine was black and the skin showed echymosis .The investigations showed total bilirubin :32 mg /dl, direct bilirubin 22 mg/dl, Hg :6 gm /dl ,platelets : 15000/dl , creatinin: 6 mg/dl , INR :7 ,PH: 7.31 , bicarbonate :12 mmol/l and glucose : 350 mg/dl.Hemoglobin was found in urine.Quinine was given by intravenous infusion in the dose of 20mg /kg loading dose then 10mg/ kg every 8 hours.Doxycyclin 100 mg /12 hours was given through the Ryle .Intravenous frusemide was given as well as oxygen inhalation as a measure against pulmonary edema , also chest consultation for the possibility of mechanical ventilation was requested.Transfusion of platelets, fresh frozen plasma ,and backed red blood cells were given .Intravenous fluids as glucose 10% with 15 unit regular insulin and Ringer lactate solution were given according to the CVP.Regular insulin according to blood glucose level was given every 6 hours subcutaneously.The patient showed no response after one day of extensive care and death was the the end due to multiple organ failure .
Fever with jaundice: Fever accompanied by jaundice is caused by viral hepatitis, falciparum malaria , paratyphoid B, infectious mononucleosis , Weil 's disease , hemolytic crises, septic cholangitis, acute leukaemia, yellow fever and other viral hemorrhagic fevers as rift valley fever [1].

Discussion:
The above case is a case of severe malaria according to WHO definition of severe malaria [2] due to presence of coma , renal failure, pulmonary edema, high INR ,hemoglobinuria and acidemia .1. Cerebral malariaunrousable coma not attributable to any other cause in a patient with falciparum malaria.The coma should persist for at least 30 min (1 h in the 2000 definition) after a generalized convulsion to make the distinction from transient postictal coma.Coma should be assessed using the Blantyre coma scale in children or the Glasgow coma scale in adults.

2.
Severe anaemianormocytic anaemia with haematocrit <15% or haemoglobin <5 g/dL in the presence of parasitaemia more than 10 000/μL.Note that finger prick samples may underestimate the haemoglobin concentration by up to 1 g if the finger is squeezed.If anaemia is hypochromic and/or microcytic, iron deficiency and thalassaemia/haemoglobinopathy must be excluded.(These criteria are rather generous; and would include many children in high transmission areas.A parasitaemia of >100 000/μL might be a more appropriate threshold.)3. Renal failuredefined as a urine output of <400 mL in 24 h in adults, or 12 mL/kg in 24 h in children, failing to improve after rehydration, and a serum creatinine of more than 265 μmol/L (>3.0 mg/dL).(In practice for initial assessment, the serum creatinine alone is used.) 4. Pulmonary oedema or adult respiratory distress syndrome.5. Hypoglycaemiadefined as a whole blood glucose concentration of less than 2.2 mmol/L (40 mg/dL).6. Circulatory collapse or shockhypotension (systolic blood pressure <50 mmHg in children aged 1-5 years or <70 mmHg in adults), with cold clammy skin or core-skin temperature difference >10°C.(The more recent review declined to give precise definitions, but noted the lack of sensitivity or specificity of core-peripheral measurements.)Capillary refill time is not mentioned but recent studies indicate this simple test provides a good assessment of severity.7. Spontaneous bleeding from gums, nose, gastrointestinal tract, etc. and/or substantial laboratory evidence of DIC.
(This is relatively unusual.)8. Repeated generalized convulsionsmore than two observed within 24 h despite cooling.(In young children, these may be febrile convulsions, and the other clinical and parasitological features need to be taken into account.)Clinical evidence of seizure activity may be subtle (e.g.tonic clonic eye movements, profuse salivation, delayed coma recovery).9. Acidaemiadefined as an arterial or capillary pH <7.35 (note temperature corrections are needed as most patients are hotter than 37°C; add 0.0147 pH unit per degree Celsius (°C) over 37°C), or acidosis defined as a plasma bicarbonate concentration <15 mmol/L or a base excess >10.(Operationally, the clinical presentation of 'respiratory distress' or 'acidotic breathing' is focused upon in the 2000 recommendations.Abnormal breathing patterns are a sign of severity indicating severe acidosis, pulmonary oedema or pneumonia.)10.Macroscopic hemoglobinuriaif definitely associated with acute malaria infection and not merely the result of oxidant antimalarial drugs in patients with erythrocyte enzyme defects such as G6PD deficiency.(This is difficult to ascertain in practice: if the G6PD status is checked following massive haemolysis, the value in the remaining red cells may be normal even in mild G6PD deficiency.This part of the definition is not very useful.)11.Postmortem confirmation of diagnosis.In fatal cases a diagnosis of severe falciparum malaria can be confirmed by histological examination of a postmortem needle necroscopy of the brain.The characteristic features, found especially in cerebral grey matter, are venules/capillaries packed with erythrocytes containing mature trophozoites and schizonts of P. falciparum.(These features may not be present in patients who die several days after the start of treatment, although there is usually some residual pigment in the cerebral vessels.) The 2000 recommendations also include the following: 12. Impairment of consciousness less marked than unrousable coma.(Any impairment of consciousness must be treated seriously).(Assessment using the Glasgow Coma Scale is straightforward, but the Blantyre Scale needs careful local standardization particularly in younger children.) 13. Prostration: Inability to sit unassisted in a child who is normally able to do so.In a child not old enough to sit, this is defined as an inability to feed.This definition is based on examination not history.14.Hyperparasitaemiathe relation of parasitaemia to severity of illness is different in different populations and age groups, but in general very high parasite densities are associated with increased risk of severe disease, e.g.>4% parasitaemia is dangerous in non-immunes, but may be well tolerated in semi-immune children.In non-immune children studied in Thailand a parasitaemia ≥4% carried a 3% mortality (30 times higher than in all uncomplicated malaria) but in areas of high transmission values much higher may be tolerated well.Many use a threshold definition of 10% parasitaemia in higher transmission settings.The followings were not considered criteria of severe malaria: Jaundicedetected clinically or defined by a serum bilirubin concentration >50 μmol/L (3.0 mg/dL).This is only a marker of severe malaria when combined with evidence of other vital organ dysfunction such as coma or renal failure.Hyperpyrexiaa rectal temperature above 40°C in adults and children is no longer considered a sign of severity.
The above case was treated by quinine infusion with doxycyclin by the Ryle as well as by supportive measures for severe malaria.

Treatment of Severe P. falciparum Malaria[3]:
Specific antimalarial treatment: Regimen 1: 1 st drug Artesunate 2.4 mg/kg iv or im on admission; then at 12 h and 24 h, then once a day for at least 24 hours, followed by full course of ACT(artimisinin combined therapy) , and 2 nd drug Doxycycline 100mgs BID (2.2mg/kg BID for <45kgs) for 7 days OR Clindamycin 20mg base/kg/day divided in three doses for 7 days in pregnancy OR Malaron 4 tab daily for 3 days OR Mefloquine 4 tab in 1 st day , 2 tab in 2 nd day.

Regimen2:
1 st drug Artemether 3.2 mg/kg i.m. given on admission then 1.6 mg/kg per day for at least 24 hours, followed by full course of ACT , and As above.
Regimen3: The above case is an imported malaria because malaria is eradicated from Egypt except small focus in Elfayoum Governorate .In 2007, Zaher et al ,reported a case of imported malaria died by cerebral malaria due to delayed diagnosis before admission to Almaza Military Fever Hospital , Cairo.[4].Also Birnbaumer concluded that death of imported malaria cases was due to miss or delay diagnosis [5].

Conclusion:
Malaria in travelers typically manifests days or weeks after patients left the endemic area.Malaria symptoms are non specific and rapid diagnosis and treatment are needed .Specific chemoprophylaxis for travelers to chloroquine resistant areas should be given.