Severe Vivax Malaria Research Articles

Severe Vivax Malaria: Newly Recognised or Rediscovered?

Malignant tertian” and “benign tertian” are terms that have long been used for two of the major diseases we recognise as malaria. The former is generally considered to be synonymous with Plasmodium falciparum and the latter with P. vivax infection. As the names “malignant” and “benign” suggest, the current dogma is that P. falciparum can be severe and life-threatening while P. vivax tends to be mild. However, two studies published in this issue of PLoS Medicine challenge this dogma.

Demographic Risk Factors for Severe and Fatal Vivax and Falciparum Malaria Among Hospital Admissions in Northeastern Indonesian Papua

Between January 1998 and December 2000, the Jayapura Provincial Public Hospital in northeastern Indonesian New Guinea (Papua) admitted 5,936 patients with a diagnosis of malaria. The microscopic diagnosis at admission was Plasmodium falciparum (3,976, 67%), Plasmodium vivax (1,135, 19%), Plasmodium malariae (8, < 1%), and mixed species infections (817, 14%). Approximately 9% (367) of patients were classified as having severe malaria (277 P. falciparum, 36 P. vivax, 53 mixed infections, and 1 P. malariae) and 88 died (79 P. falciparum/mixed infections and 9 P. vivax). Risk of fatal outcomes among severe malaria patients was indistinguishable between those with falciparum versus vivax malaria (OR = 0.89; P = 0.771). Compared with non-pregnant women, pregnant women showed no higher risk of severe malaria (P = 0.643) or death caused by severe malaria (P = 0.748). This study compares admissions per population (based on census data), parasitemia, morbidity, and mortality among children versus adults, pregnant versus non-pregnant women, and urban/suburban versus rural residents.

An unexpected cause of fever and seizures

In June, 2007, a 27-year-old man was brought to our emergency department by ambulance, having regained consciousness after a generalised tonic-clonic seizure. He had been having fever, chills, and rigors, on alternate days, for the previous 8 days. He had no past history of convulsions, head injury, febrile convulsions during infancy, birth trauma, meningitis, encephalitis, or psychiatric illness. There was no other past medical history of note. Until he fell ill, he had been working in a jewellery shop in Surat, Gujarat—a city where both falciparum and vivax malaria are endemic. On examination, nothing abnormal was found. The patient’s full blood count was normal; biochemistry tests, including a blood glucose measurement, also gave unremarkable results. Electrocardiography, ophthalmoscopy, examination of the cerebrospinal fl uid, and CT of the head all showed nothing of note. However, examination of the blood fi lm showed trophozoites of Plasmodium vivax, at a density of 16 200 per μL (fi gure). A rapid diagnostic test (FalciVax, Zephyr Biomedical Systems, Goa, India) indicated the presence of parasite lactate dehydrogenase, specifi c to P vivax, and the absence of histidine-rich protein 2, specifi c to P falciparum. 6 h after he arrived, the patient had another generalised seizure. He was immediately given intravenous quinine, as per the WHO guidelines for severe vivax malaria; in addition, anticonvulsant drugs were given. Over the next 12 h, the patient had a total of eight generalised seizures, with intervals of 30–120 min, without regaining full consciousness. 48 h after treatment began, the fever subsided, and the patient became fully conscious. Further blood tests—for dengue fever, leptospirosis, and HIV—gave negative results; repeat CT of the head, and electroencephalography, showed nothing remarkable. PCR, which was done as described by Kochar and colleagues, confi rmed that the patient had been infected by P vivax, but not P falciparum. The patient was discharged 8 days after his arrival. When last seen, in August, 2007, he was entirely well. P falciparum is known to cause cerebral malaria, which can manifest with seizures. The parasite multiplies in red blood cells, which adhere to the walls of small blood vessels, causing reduced cerebral blood fl ow. P vivax is less likely than P falciparum to cause severe illness— indeed, the typical 48 h interval between fevers, and benign course, have led to vivax malaria being termed “benign tertian malaria”. Classically, P vivax has not been thought to cause cerebral malaria. However, it is now known that severe P vivax infection can cause cerebral malaria—although, to our knowledge, this is the fi rst case in which the cause of seizures has been confi rmed as P vivax alone. How P vivax causes cerebral malaria is unclear, but recent studies indicate that the mechanism may be similar to that triggered by P falciparum. Other causes of seizures in malaria include hypoglycaemia, hyponatraemia, lactic acidosis—and other illnesses, such as epilepsy.