02 Aug 2017 12 Sep 2017
A 22 year old male whom had just returned from the malarial endemic region of Nigeria from a visit to friends was admitted to A/E at Queen Elizabeth Hospital Nottingham presenting with symptoms of cerebral malaria (severe malaria)
The five protozoa plasmodium endo-parasite species that result in malaria disease in human hosts are: Falciparum, Vivax, Malariae, Ovale and Knowlesi - a particular cause of 70% of malarial cases in Southeast Asia. These species all belong to the Plasmodium genus with Falciparum being the most virulent- accounting for 80% of all cases and 90% of all deaths (Moore, Knight, and Blann, 2010) along with being the only plasmodium species causing severe malaria where cerebral malaria (a multi system disease) is a known complication. Transmission of Falciparum is through bites from female anopheles' mosquitoes, of which the anopheles gambiae is best for known, during their blood meals to nourish their eggs (Moore, Knight, and Blann, 2010) Falciparum infection in relation to this case was the likely diagnosis due to observed clinical manifestation of cerebral malaria in the patient. Cerebral malaria is considered a pediatric disease from the endemic region (Nigeria) where patient was returning from, however Falciparum has been shown to have a wide epidemiological reach. The endo parasite is endemic in tropical and subtropical regions (non-arid climate optimal survival conditions for vector) such as aforementioned many parts of sub Saharan Africa with Nigeria having the highest morbidity and mortality in regards to malaria in the world.class="table table-bordered" America (central and northern half of south America mainly) and Asia (south east Asia particularly, where main body of information on the clinical features, course and prognosis of infection with Falciparum, leading to cerebral malaria, in particularly young adults such as the patient is derived) are also regions of high transmission. (Idro et al., 2005)
Table 1: Clinical features of Falciparum infection
Early clinical features/ symptoms Falciparum infection
Later symptoms and Neurological manifestations of infection
Other Neurological signs/ Major complications (worsening of symptoms)
After a few days infected patients typically present with-any combo of:
Without treatment of Falciparum infection these early features can manifest into cerebral malaria with common features of:
Patients typically have symmetrical upper neuron signs/brainstem signs such as:
Table 2: Outcomes/ Prognosis of cerebral malaria in adults with treatment
Recovery of consciousness
Slower in Adults occurs within 48 hours
Around 20% (50% of mortality cases occur within 24hrs without treatment)
Neurological/ neurocognitive sequelae
Very rare in adults range from <1%- <5% (Encephalopathy and psychosis following cerebral malaria observed in 5% of cases taking mefloquine drug as follow on oral treatment (Dondorp, 2006)
Behavioural difficulties/ the post malarial neurological syndrome (acute psychosis, inappropriate speech and behaviour, convulsions/seizures (catatonic) and hallucinations is a long term sequel sometimes observed in adults!
The Patient FBC results were as follows:
WHITE BLOOD CELL COUNT= 7.0 x 109/L -class="table table-bordered" normal according to standardised adult reference ranges
PLATELET COUNT = 90 x 109/L -class="table table-bordered" This very low platelet count according to standardised adult reference ranges suggest thrombocytopenia likely due to severe Red cell destruction (haemolytic anaemia) a typical symptom of Falciparum (as well as other plasmodium spp.) infection, this result therefore supports diagnosis of parasitic infection however does not specify by which species similarly
HAEMOGLOBIN= 98class="table table-bordered" g/L- very low value according to standardised adult MALE reference ranges suggests and suggest low haemoglobin is due to RBC destruction via endoparasite action. This further supports diagnosis of parasitic infection however as aforementioned does specify by which species
To successfully confirm diagnosis of an infection with Falciparum of this patient the ideal "gold standard" lab test would be a blood smear/film. For a blood smear a drop of blood is applied (containing infected RBC) and spread on a glass slide, stained (R66 Giemsa for Thin films/ Field stain for Thick films) at a ph of 7.2 to ensure optimal results and visualised under a light microscope. Thick films are used to detect presence of intraerythocyte malarial parasites and thin films are used for identification of infecting parasite species, therefore both were required in this case to confirm presence of parasitic infection and identity of the infection cause. Microscopy of stained films should be at a magnification of 1000 to allow identification and counting of intraerythrocytic parasites to determine presence and degree of infection (Dondorp, 2006). Patient was already exhibiting symptoms of severe infection (cerebral malaria) in this case developmental stage and % of infected neutrophils should also have been noted in microscopy to confirm degree of infection and aid in the provision of proper treatment (Dondorp, 2006)
The blood smear results in both thick and thin films in this case should have been positive to confirm malarial diagnosis. A negative blood smear makes diagnosis very unlikely however to rule out parasitic infection the test should have been repeated every 12 to 48 hours to account for the classic attack cycles (induced by cyclic release of merozoites) characteristic of malarial parasite infection. At least 3 negative blood smears on microscopy required before the diagnosis can be excluded (Idro et al., 2005) Ideally 4 of each film should have been produced to allowclass="table table-bordered" 2 of each to be stained and spares to be sent off for further study at a reference centre if difficulty with diagnosis should occur. all malarial films should have been observed by two observers to avoid human error.
Although laboratories with appropriate expertise prefer microscopy of blood films as the main diagnostic tool. In the absence of a positive blood smear result and with the need of a quick diagnosis so appropriate treatment can be initiated (as patient in this case was already displaying symptoms of severe malaria), Immunochromatographic tests (dipstick/cassette) based on use of monoclonal antibodies for identification of parasite antigens from patient peripheral blood can/should have been used. In Falciparum the main antigens produced by this species of malaria are the pfHPR2 (produced by young gametocytes in asexual stages of parasitical lifecycle) and pDHL (produced in the sexual and asexual stages of parasite) (moody, 2002) .The main antigen tests towards these are; the CareStartâ„¢ Malaria HRP-2/pLDH (Pf/pan) Combo Test, targeting HRP2 and pDHL of Falciparum and Vivax. ICT Malaria Pf (targets pfHRP2) OptiMAL (targets pDHL) , Parasight-F capture assay (dipstick test that targets pfHRP2) similar to microscopy is highly sensitive and specific ,sensitivity of 88% and a specificity of 97% in comparison to other diagnostic tests (Humar et al., 1997). antigen tests are a good indicator of presence and species of malarial parasite in the blood, however do not quantify and are poor at low parasitemia. RDT's also cannot give clear parasite stages (i.e pDHL can be produced at any stage of Falciparum life cycle) all Factors needed to determine stage and severity of infection. RDT's can also generate false positive results; PfHRP2 has been shown to circulate weeks after treatment and cure (Dondorp, 2006).
If both slide examinations and RDT results were negative in this case malaria being the cause of cerebral manifestation was highly unlikely and other causes of this symptom should have been investigated (World Health Organization 2015). Also a positive diagnosis using antigen tests requires microscopy to confirm reliability of diagnosis and so this may have been an inappropriate test in this case as further tests delay treatment.Microscopy with fluorescent staining of the buffy coat (QBC) has a higher sensitivity to detect low parasitemia, (Dondorp, 2006) and does not require a further test to confirm result as with RDT's, along with PCR these are sometimes referred to as Microscopic RDT techniques and can be used to enhance detection of malarial parasites in blood in the absence of a positive blood smear in our patient/ if light microscopy fails to produce a positive result in our patient and if RDT's are viewed as unreliable!
Once diagnosis was confirmed appropriate treatment should have been administered promptly as Mortality approaches 100% if severe malaria (particularly cerebral malaria) is left untreated, whereas that rate falls to around 10-20% with prompt and effective antimalarial treatment (World Health Organization, 2015) Primary objectives of treatment of severe malaria are to prevent death whereas secondary objectives are prevention of Neurological/ physical sequelae and a recurrence of infection (World Health Organization, 2015). WHO recommends Treatment of severe malaria in all (adults and children) such as in this case should be with administration of parenteral antimalarial drugs (Artesunate) for a minimum of 24hrs until patient can tolerate oral medication, after which treatment should be completed with 3 days of administration of ACT; a combination of effective oral antimalarial drugs (World Health Organization, 2015) which is what should have been done.
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