Answer to Q1

1. Malaria: Recrudescence of P falciparum. This could not be a newly acquired infection as there is no malaria on the Highveld. (Except ‘taxi’ malaria….) Both recrudescent and relapsing infections manifest as return of disease after its apparent cessation. Recrudescence occurs most often within days or weeks; relapse occurs within weeks or months. In recrudescence, parasites remain in the bloodstream undetected due to ineffective treatment or host immunological response (or both). In relapse, new hypnozoites are released from liver cells causing another parasitaemia. P. falciparum is the usual cause of recrudescent infections, although P. malariae can remain dormant for years; P. vivax and P. ovale may cause relapse months after the primary blood stage infection is cured, as these species have hypnozoite forms.
2. Malaria: Relapse of P vivax or ovale (If he had had a mixed infection previously. P falciparum is responsible for 95% of the malaria in Sub-Saharan Africa).
3. Trypanosomiasis: This is not known to occur in the Nampula area of Mozambique but could occur in the region. He had however been to the Zambezi Valley where Sleeping Sickness does occur. There are two forms of the disease, one of which occurs mainly in East Africa and is caused by the parasite Trypanosoma brucei rhodesiense. The other arises mainly in West and Central Africa and is caused by Trypanosoma brucei gambiense. They are both transmitted by the tsetse fly and have identical morphologic appearances. However, the clinical infections differ in presentation and prognosis. Both are characterized by an early stage, during which trypanosomes are found circulating in the blood or in lymph nodes, and a late stage in which there is prominent involvement of the central nervous system (CNS). T. b. gambiense is a slowly progressive infection, and the asymptomatic phase can last for months or years. In contrast, T. b. rhodesiense tends to progress rapidly, and CNS involvement is often detectable within weeks of infection. Both infections are fatal if untreated. In T. b. gambiense, early symptoms include intermittent headache, fevers, malaise and arthralgias. These symptoms are frequently intermittent, corresponding with successive waves of parasitaemia and antibody production. Organomegaly, in particularly splenomegaly, is a common finding. Generalized lymphadenopathy is also often present. Other nonspecific symptoms may be present, including pruritus, rash, weight loss and facial swelling. Neuroendocrine disturbances leading to amenorrhea in women or impotence in men may also be seen. In the later stages of T. b. gambiense disease, progressive diffuse meningoencephalitis and parenchymal edema of the brain develop. Perivascular and meningeal inflammatory infiltrates, cerebral hemorrhages, and widespread multifocal white matter demyelination occur. Symptoms include: headache, difficulty concentrating, personality changes, psychosis, sensory disorders, tremor and ataxia. Meningismus and focal neurologic signs may occur but are unusual. An alteration of the circadian sleep/wake cycle leading to daytime somnolence also frequently develops. Convulsions may occur, especially in children. Progressive deterioration occurs until the patient is in a stuporous state. A similar sequence of events is seen with T. b. rhodesiense, but the presentation and progression are typically much more rapid. Rather than asymptomatic periods and slow deterioration, Rhodesian trypanosomiasis causes an acute, severe febrile disease that rapidly progresses to involve the CNS over weeks to a few months. Worsening coma and death ultimately occur in both infections. Infections in tourists, which are usually acquired in game parks in East Africa, may have an incubation period as short as a few days. Individuals develop fever, headache, and malaise. Rash is also common. Progressive neurologic involvement will develop if the infection is not treated. Since T. b. gambiense can present years after exposure, a thorough travel history should be obtained in patients who present with chronic neurologic symptoms, since the diagnosis can be missed when the index of suspicion is low. Several nonspecific laboratory findings may be associated with infection. Anemia is common and is thought to be due at least in part to immune-mediated haemolysis. Leukocytosis may be seen. Thrombocytopenia may be present, possibly related to splenic sequestration. Hypergammaglobulinaemia, largely related to raised levels of polyclonal IgM, is also characteristic. Hypoalbuminemia, elevated erythrocyte sedimentation rate, and low levels of complement are frequently found. Patients with neurologic involvement often have abnormal electroencephalograms (EEGs), usually demonstrating slow wave oscillations (delta waves). A definitive diagnosis of infection requires the demonstration of the parasite, usually from the blood, lymph node aspirate or cerebrospinal fluid (CSF).
4. Drug associated neurocognitive disorder: Psychosis may result from ingestion of prescribed medications, alcohol, or illicit drugs, or from withdrawal of alcohol or sedative/hypnotic drugs such as barbiturates or benzodiazepines. In most instances the presence of offending substances is detectable; however, cases of persistent psychosis for days or weeks after a drug is cleared from the body have been described, especially with hallucinogens and amphetamines.
5. Herpes simplex encephalitis: Herpes simplex encephalitis (HSE) is a severe viral infection of the human central nervous system. It affects at least 1 in 500,000 individuals per year. About a third of cases result from primary HSV-1 infection, predominantly affecting individuals under the age of 18; 2 in 3 cases occur in seropositive persons, few of whom have history of recurrent orofacial herpes. Approximately half of individuals that develop HSE are over 50 years of age. Most cases of HSE show a decrease in their level of consciousness and an altered mental state presenting as confusion and personality changes. Increased numbers of white blood cells can be found in patient's cerebrospinal fluid, without the presence of pathogenic bacteria and fungi. Patients are usually febrile and may present with convuslions. The electrical activity of the brain changes as the disease progresses, first showing abnormalities in one temporal lobe of the brain, which spread to the other temporal lobe 7–10 days later. Without appropriate treatment the disease results in rapid death in approximately 70% of cases. HSE is deadly in around 20% of treated cases causing serious long-term neurological sequelae in the majority of survivors.
6. Acute psychosis: Psychosis is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality". It is one of the more severe forms of psychiatric disorder during which hallucinations and delusions and impaired insight may occur. Psychotic patients may report hallucinations or delusional beliefs and may exhibit personality changes and thought disorder. This may be accompanied by unusual or bizarre behaviour as well as difficulty with social interaction and impairment in carrying out the daily life activities. A variety of central nervous system diseases caused by external toxins and / and internal physiologic illness may produce symptoms of psychosis. Both patients demonstrated abnormal cognitive and emotional behaviour as their primary presenting symptoms but neither had a prior psychiatric history and the natural progress of their respective illness was not in keeping with psychosis and cleared up spontaneously without further psychiatric intervention.
7. Chronic subdural haematoma: A subdural subdural haematoma follows on traumatic brain injury in which blood gathers within the outermost meningeal layer between the dura and arachnoid mater enveloping the brain. Acute subdural haematomas are often life-threatening but chronic subdural hematomas are usually not deadly if treated. Chronic subdural bleeds develop over the period of days to weeks, often after minor, even unnoticed head trauma. They may not be discovered until they present clinically months or years after a head injury. They may present with the classical signs of raised intracranial pressure or any of the following: Other signs and symptoms of subdural hematoma can include any combination of the following: Loss of consciousness or fluctuating levels of consciousness, irritability, epilepsy, numbness, headache (either constant or fluctuating), dizziness, disorientation, amnesia, weakness or lethargy, nausea and / or vomiting, loss of appetite, personality changes, speech disturbance, ataxia, difficulty walking, vision disturbance, abnormal breathing patterns, abnormal gaze or ocular movement. Both subjects had normal CT and MRI scans of the cranium and brain excluding this option as a diagnosis.
8. HIV Encephalopathy: Changes in memory, mood, attention, and motor skills are common in HIV-infected patients and present a diagnostic challenge to the clinician. Since these symptoms can represent a wide variety of disorders, accurate diagnosis is critical for patient treatment. HIV associated dementia (HAD) typically presents with the classic triad of symptoms of subcortical dementia: memory and psychomotor speed impairment, depressive symptoms and movement disorders. Early symptoms — At the onset, patients usually experience subtle symptoms that may be overlooked or attributed to fatigue or other illness, such as slight difficulty with reading, comprehension, memory, and mathematical skills. Early motor symptoms include unsteady gait, leg weakness, and tremor. Other early manifestations may include apathy, lethargy, loss of sexual drive, and diminished emotional responsiveness. Early language deficits are uncommon. Both subjects were HIV negative.

Question 2: What is your differential diagnosis in Case 2?

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?