In animals, effective immune responses against malignancies and against several infectious pathogens, including malaria, are mediated by T cells. Here we show that a heterologous prime-boost vaccination regime of DNA either intramuscularly or epidermally, followed by intradermal recombinant modified vaccinia virus Ankara (MVA), induces high frequencies of interferon (IFN)-gamma-secreting, antigen-specific T-cell responses in humans to a pre-erythrocytic malaria antigen, thrombospondin-related adhesion protein (TRAP). These responses are five- to tenfold higher than the T-cell responses induced by the DNA vaccine or recombinant MVA vaccine alone, and produce partial protection manifest as delayed parasitemia after sporozoite challenge with a different strain of Plasmodium falciparum. Such heterologous prime-boost immunization approaches may provide a basis for preventative and therapeutic vaccination in humans.

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Lesson of the month 2: A case of coma in a Parkinson's patient: a combination of fatigue, dehydration and high protein diet over the New Year period?Although motor fl uctuation can often be severe in Parkinson's disease (PD), it is rare for an 'off period' to result in coma. The case presented here is of a patient with longstanding PD who was admitted to our hospital with a Glasgow Coma Scale of three after missing just one or two doses of her medication. Investigation for infective, neurovascular and metabolic causes of coma were negative and the patient recovered very rapidly following reinstitution of dopaminergic therapy via nasogastric tube. This case highlights how fl orid the presentation of motor fl uctuations in PD can be and the importance of restarting treatment as quickly as possible. Guidance is provided on how to administer dopaminergic medications in patients who are unable to swallow. KEYWORDS:Parkinson's disease, coma, wearing off, acute akinesia, high protein diet Case presentationA 67-year-old retired doctor, Dr N, with a 23-year history of Parkinson's disease (PD) and type 2 diabetes, presented to the emergency department (ED) on New Year's Day. She had hosted a large New Year's Eve party the preceding evening and recalled taking her medication at 10pm on New Year's Eve, although it was unclear whether she had taken her tablets at 11am that morning. Since diagnosis, she had led a reasonably independent life on dopaminergic medication, although she no longer drove a car. Shortly prior to admission, Dr N had experienced an increased frequency of falls. She modulated her own treatment according to symptoms: Sinemet Plus (co-careldopa) 25/100 mg four times daily, pramipexole modifi ed release 0.7 mg three times daily (TDS) and amantadine 100 mg TDS, in addition to omeprazole and metformin. She had consumed less fl uid than usual over the New Year period, causing dehydration and constipation. On New Year's Day she had gone to sleep at 11am after cooking lunch. At 2pm her son (also a doctor) could not rouse her and called an ambulance. Paramedics excluded hypoglycaemia (blood sugar 9.0 mmol/l) and arranged transfer to hospital. In the ED at 5pm, Dr N had a Glasgow Coma Scale (GCS) score of 5/15 (E1 M3 V1). Her blood pressure was 130/78 mmHg, pulse 84 beats per minute and blood oxygen saturation 98% on room air. There was no focal neurological defi cit. A computerised tomographic (CT) head scan revealed a mild degree of cerebral atrophy, but was otherwise normal. Routine haematology and biochemistry investigations were normal. After exclusion of an intracranial haemorrhage, she was referred to the medical team. What is the differential diagnosis and the most likely diagnosis?A subdural haemorrhage was ruled out by a normal CT head scan. While acute ischaemic stroke was a possibility in view of the patient's age and the presence of type 2 diabetes, the absence of focal neurology made this unlikely. Normal peripheral white cell count and C-reactive protein made bacterial meningitis unlikely; intraveno...