Dr Philip Botha, Infectious Diseases Specialist, Tygerberg Hospital
Dr Albie de Frey and Lee Baker – South African Society of Travel Medicine
We describe two clinical cases, one originating from South Africa and the other from Australia. Both cases demonstrate the importance of a good history including a good travel history, meticulous attention to detail and the importance of good laboratory facilities to back the clinical diagnosis.
A previously fit and healthy, self-employed, middle aged South African engineer was admitted to a private hospital on the Highveld. He presented with erratic ‘soft’ neurological symptoms including inconsistent disorientation for time and place, inappropriate humour and mildly anti-social behaviour drawing the attention of the nursing supervisor on night duty. He did not have any obvious motor loss. He complained about a headache and there was mention of a low grade fever. All other vital signs and physical examination were normal.
He had a history of admission for ‘cerebral malaria’ to the ICU of the same hospital approximately three weeks before. He spent about a week in ICU and responded well to IV Quinine followed by oral doxycycline for seven days. He did not require mechanical ventilation nor renal dialysis.
In the period in-between admissions he was well with normal behaviour only complaining of a degree of fatigue ascribed to his infection and stay in ICU.
It had been assumed that he had contracted Plasmodium falciparum malaria in Nampula, Mozambique but he had travelled to the north of Zimbabwe for business a few weeks earlier. There was no other travel history.
This resembled a similar case that had occurred previously. See Case 2.
A sixty year old Australian Camp manager returned to work on a mine in West Africa two months after being admitted to a hospital in Australia for what had been diagnosed as P falciparum malaria whilst on home leave.
He was a well controlled, known insulin independent diabetic and other than having lost approximately 10kg he was considered fit and well. The weight loss had been ascribed to his spat with malaria including a week long stay in ICU.
Approximately ten days after his return to site he presented to the mine clinic with confusion, memory loss and disorientation for time and place.
He was thought to have malaria again in spite of the absence of a documented fever and a negative malaria antigen test. He was sent to Johannesburg, South Africa for further investigation and management.
Question 1: What is your differential diagnosis in Case 1?
Answer to Q1
Question 2: What is your differential diagnosis in Case 2?
Answer to Q2
Question 3: What important question, absent from the history above must be answered?
Answer to Q3
Have either one of them recommenced on malaria prophylaxis and if so, what? One of three WHO acknowledged malaria prophylactics might have been commenced: Mefloquine may have been commenced in either case in anticipation of return to Mozambique and prior to actually returning to Senegal. Mefloquine is known to cause neuropsychiatric illness. Severe neuropsychiatric reactions (psychosis, convulsions) are infrequent with prophylactic doses and occur in approximately 1/10 000 to 1/13 000 persons. The frequency of mild neuropsychiatric effects is probably much higher. Malanil® has been associated with neuropsychiatric illness, but only in exceptional cases. Doxycycline is an acknowledged malaria prophylactic as well but not associated with neuropsychiatric side-effects.
Question 4: Which special investigations would you call for?
Answer to Q4
The patient was transferred to a tertiary care facility in Pretoria and submitted to a battery of tests and investigations similar to that of Case 2 earlier on. Everything proved negative or normal and he showed good neurocognitive improvement over a period of about one week.
The neurologist elected to administer a short course of high dose steroids.
The patient was discharged with a diagnosis of organic brain syndrome in the context of malaria illness
In a Johannesburg Hospital he had normal vital signs and a non-remarkable physical examination but was still disorientated for time and place and did not recognise persons well known to him. An MRI scan which was normal. A Iumbar puncture demonstrated an elevated protein of 0.96 and 2 lymphocytes but all other investigations including repeat malaria smears were normal. EEG was normal. He returned to his home country with an escort for further assessment and was subsequently admitted to hospital in his home town.
The patient could not remember much of the past 6-8 weeks. He felt febrile, was lethargic and admitted to being confused. On examination he was mildly drowsy. He was able to say the day and year but not the date or month. Registration was normal. The digit span was normal. He was not able to spell the word 'WORLD' backwards. He could remember 0 to 3 objects at 3 minutes. He was able to follow a three stage command and the speech was normal. He had retrograde amnesia for the previous 8 weeks.
There were no focal motor or sensory signs. There was no neck stiffness and Kernig's & Brudzinki's signs were negative. The cranial nerves were normal. General examination was again within normal limits. A repeat MRI scan was normal. A cerebral blood flow study was normal. An EEG was normal. The CRP was less than 1 and the white cell count was 5.7. The malarial blood film was negative.
At follow-up for several weeks later he was noted to have a limited concentration span and memory lapses.
The final diagnosis was post-malaria Neurological Syndrome.
The two cases bear witness to a complication of malaria that is seldom described in the South African context. A literature search provided no documented case studies from South Africa.
Two cases from Africa were described in the French literature.
Although uncommon this complication is debilitating in the context of the patient and his family who are dependent on him as an expatriate breadwinner who may be incapable of working for a period of several weeks.
Neurological symptoms in acute malaria are usually associated with severe Plasmodium falciparum infection, when sequestration of parasitized red blood cells within the cerebral vessels can result in local ischaemic damage. The presence of impaired consciousness, seizures and visual and auditory problems can also be associated with hypoglycaemia (malaria- or quinine-induced) or with the toxicity of antimalarials. More recently however, a discreet transient neurological syndrome after recovery from severe malaria infections has been described: Post-malaria neurologic syndrome (PMNS). PMNS is a rare neurological complication that occurs after the successful treatment of Plasmodium falciparum malaria. It presents as an acute onset of neurological or neuro-psychiatric syndrome. What distinguishes it from cerebral malaria is that the patient has already recovered from the malaria infection and the blood smear is negative for parasites. In cerebral malaria, the neurological symptoms occur during the parasitaemia period. Clinical features that have been reported include: generalized convulsions, an acute confusional state, psychosis, tremors, cerebellar ataxia, motor aphasia and generalized myoclonus. The first description of a post-infectious neurological complication of malaria was cerebellar ataxia, identified in Sri Lanka in 1984, and it has been described a number of times since then. The pathogenesis is unknown but is probably immunologically mediated. Symptoms usually manifest any time from a few days to nine weeks after parasite clearance, continue for a few days, and resolve spontaneously, without any treatment. Patients with severe encephalopathy may however require corticosteroid therapy. The diagnosis of PMNS is therefore largely one of exclusion. The diagnostic criteria currently are:
A prospective study on PMNS was conducted in Vietnam over 4 years, and of 18,124 patients with P. falciparum malaria, (1176 of whom had severe infections), 19 adults and 3 children had subsequent PMNS. The overall incidence was 1.2 per 1000 and in 21 of the 22 patients, the syndrome followed severe malaria. (Relative risk after severe vs uncomplicated malaria was 299). The syndrome was self-limiting with a median duration of 60 hours (range 24-240 hours) Whereas clinicians in tropical disease and travel health practice should consider this as a diagnosis in the correct setting it is equally important to exclude, inter alia, the various diagnoses listed earlier on as many of these require urgent medical or surgical intervention that may mean the difference between life and death. By contrast PMNS is a self-limiting condition with no specific treatment other than re-assurance and emotional support as it may be disruptive to careers and normal daily life. This is particularly true if the patient is employed as an expatriate in a region with limited medical and psycho-social support.
FIDSSA Members can earn CPD points by logging into the secure section of the website and visiting the MyCPD section.