Browsing by Author "Cheaveau, James"

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    Active case detection of malaria in pregnancy using loop-mediated amplification (LAMP): a pilot outcomes study in South West Ethiopia
    (2020-08-27) Tadesse, Guluma; Kamaliddin, Claire; Doolan, Cody; Amarasekara, Ranmalee; Legese, Ruth; Mohon, Abu N; Cheaveau, James; Yewhalaw, Delenasaw; Pillai, Dylan R
    Abstract Background 125 million women are pregnant each year in malaria endemic areas and are, therefore, at risk of Malaria in Pregnancy (MiP). MiP is the direct consequence of Plasmodium infection during pregnancy. The sequestration of Plasmodium falciparum parasites in the placenta adversely affects fetal development and impacts newborn birth weight. Importantly, women presenting with MiP commonly develop anaemia. In Ethiopia, the Ministry of Health recommends screening symptomatic women only at antenatal care visits with no formal intermittent preventive therapy. Since MiP can display low-level parasitaemia, current tests which include microscopy and RDT are challenged to detect these cases. Loop mediated isothermal Amplification (LAMP) technology is a highly sensitive technique for DNA detection and is field compatible. This study aims to evaluate the impact of active malaria case detection during pregnancy using LAMP technology in terms of birth outcomes. Methods A longitudinal study was conducted in two health centres of the Kafa zone, South West Ethiopia. Both symptomatic and asymptomatic pregnant women were enrolled in the first or second trimester and allocated to either Standard of Care (SOC—microscopy and RDT) or LAMP (LAMP, microscopy and RDT). Women completed at least three visits prior to delivery, and the patient was referred for treatment if Plasmodium infection was detected by any of the testing methods. The primary outcome was to measure absolute birth weight, proportion of low birth weight, and maternal/neonatal haemoglobin in each arm. Secondary outcomes were to assess the performance of microscopy and RDT versus LAMP conducted in the field. Results One hundred and ninety-nine women were included and assigned to either LAMP or SOC. Six were lost to follow up. In this cohort, 66.8% of women did not display any clinical symptoms and 70.9% were multi-parous. A reduced proportion of low birth weight newborns was observed in the LAMP group (0%) compared to standard of care (14%) (p <0.001). Improved neonatal haemoglobin was observed in the LAMP (13.1 g/dL) versus the SOC (12.8 g/dL) (p = 0.024) arm. RDT and microscopy had an analytical sensitivity of 66.7% and 55.6% compared to LAMP as a reference standard. Conclusions These results support the use of highly sensitive tools for rapid on-site active case detection of MiP which may improve birth outcomes in the absence of IPT. However, further large-scale studies are required to confirm this finding.
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    Application of Epidemiology and Biostatistics to Malaria Diagnosis in Returning Travellers
    (2019-07-04) Cheaveau, James; Pillai, Dylan; Deardon, Rob; Gregson, Dan
    Today, malaria elimination is back on the agenda but for this to be feasible, there must be a coordinated global effort utilizing all available tools. Portable, sensitive diagnostics with a low limit of detection are required to detect the malaria reservoir, and novel antimalarials are required to combat the threat of artemisinin resistance. Returning travellers are a good population in which to investigate malaria physiology and diagnostics because there is a good supply of study participants and an abundance of easily available data. In Canada, a combination of microscopy and rapid diagnostic tests are used to diagnose malaria, but these lack sensitivity and require repeated testing to rule out the condition. A prospective diagnostic trial of the illumigene Malaria, loop-mediated isothermal amplification (LAMP) assay, manufactured by Meridian Bioscience was conducted in symptomatic returning travellers between June 2017 and January 2018. After discrepant resolution with RT-PCR, LAMP had a sensitivity of 100% (95% CI; 95.8-100) and a specificity of 100% (95% CI; 98.7-100). In symptomatic returning travellers, LAMP has the potential to replace traditional malaria diagnostics, allowing for malaria to be ruled out in a timely manner. It is unclear if uncomplicated malaria causes deranged liver enzymes, which has implications for antimalarial drug development. A retrospective cohort study was evaluated in returning travellers (n=4548) who underwent a malaria test and had liver enzymes measured within 31 days from 2010-2017. After adjusting for gender, age, and use of hepatotoxic medications, returning travellers testing positive for malaria had higher odds of having an abnormal TB [(OR: 12.64, 95% CI: 6.32 – 25.29), p<0.001] but not ALP [(OR: 0.32, 95% CI: 0.09 – 1.10), p=0.072], ALT [(OR: 1.01, 95% CI: 0.54 – 1.89), p=0.978] or AST [(OR: 1.26, 95% CI: 0.22 – 7.37), p=0.794], compared to those who tested negative. This is most likely to be due to haemolysis, which normalizes following treatment. LAMP can be used in the diagnosis of malaria in returning travellers, and it may have a role in malaria elimination. Uncomplicated malaria does not appear to cause raised aminotransferases in returning travellers, and consideration must be given to this in antimalarial drug development.