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Malaria Chemoprevention for the Post-Discharge Management of Paediatric Severe Anaemia in Malaria Endemic Areas of Africa

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Kwambai, Titus (2019) Malaria Chemoprevention for the Post-Discharge Management of Paediatric Severe Anaemia in Malaria Endemic Areas of Africa, Thesis (Doctoral), Liverpool School of Tropical Medicine.

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Abstract

Children hospitalised with severe anaemia in malaria-endemic areas are at high risk of readmission or death within six months post-discharge. No strategy specifically addresses this post-discharge period. This thesis aims to provide evidence of the burden of post-discharge mortality and morbidity among children less than five years of age who are admitted with all-cause severe anaemia and other syndromes and living in malaria-endemic areas of Africa. We also report the results of a malaria chemoprevention trial for the post-discharge management of severe anaemia.
In the first study, we conducted a retrospective cohort analysis using data collected between 2008 and 2013 from continuous paediatric in-hospital surveillance and population-based surveillance in western Kenya. During this period, 3,639 hospital admissions involving 4,423 different diagnoses were recorded. Overall, in-hospital mortality was 2.8% and the post-discharge mortality by three, six and twelve months among the 3,538 survivors was 7.6%, 9.4%, and 12.4%, respectively. Admissions with severe acute malnutrition and severe anaemia were associated with the highest post-discharge mortality in the first six months. Severe anaemia was associated with a significantly higher odds of six-month post-discharge mortality than in-hospital mortality (Mantel-Haenszel odds ratio [MHOR]=2.02, 95% CI 1.19-4.05, p=0.011).
In the second study, we conducted a systematic review and meta-analysis to determine the pooled risks of morbidity and mortality in the post-discharge period among children admitted with severe anaemia versus other syndromes in malaria-endemic areas in Africa. Children admitted with severe anaemia were found to have higher odds of dying within six months post-discharge than during the in-hospital stay (N=4, MHOR=1.44, 95% CI 1.07-1.92, p<0.0157, I2=0.8%) and they were twice as likely to die by 6 months post-discharge compared with children admitted without severe anaemia (N=4, Relative Risk [RR]=2.80, 95% CI 1.61-4.86, p<0.0001, I2=73.1%). Severe acute malnutrition was also associated with increased post-discharge mortality compared to children admitted without severe anaemia or malnutrition (N=2, RR=4.27, 95% CI 2.42-7.55, p<0.0001, I2=76.8). The risk of readmission was also higher among children admitted with severe anaemia compared to other syndromes (RR=3.05, 95% CI 1.12-8.35, p<0.001, I2=0.0%).
The third study was a randomised placebo-controlled trial in nine hospitals in Kenya and Uganda to determine if three months of post-discharge malaria chemoprevention (PMC) with monthly 3-day treatment courses of dihydroartemisinin-piperaquine (DP) reduced the rate of all-cause readmissions and deaths by six months post-discharge (primary outcome). Children aged <5 years with admission haemoglobin of <5g/dL were eligible. A 3-day course with artemether-lumefantrine was given to all children at discharge. Children were then randomised to receive DP or placebo-DP at two, six, and ten weeks post-discharge and followed until week 26 inclusive. There were 184 primary outcome events in the PMC arm and 316 in the placebo arm (HR=0.65, 95% CI 0.54-0.78, p<0.001). The HR was 0.30 (95% CI 0.22-0.42, p<0.001) during the PMC-intervention period (2-14 weeks) and 1.13 (95% CI 0.87-1.47, p=0.35) during the post-intervention period (15-26 weeks), p<0.001).
This thesis shows that children admitted with severe anaemia and other acute conditions are at a high risk of post-discharge mortality and morbidity. Admission with all-cause severe anaemia in this setting is associated with a doubling of the risk of post-discharge mortality compared to other acute conditions. Malaria chemoprevention with three monthly courses of DP is a promising tool for post-discharge management of children recently admitted with severe anaemia in malaria-endemic areas.

Item Type: Thesis (Doctoral)
Subjects: WA Public Health > Preventive Medicine > WA 108 Preventive health services. Preventive medicine. Travel Medicine.
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 155 Anemia
WS Pediatrics > Diseases of Children and Adolescents > By System > WS 300 Hemic and lymphatic system
Faculty: Department: Biological Sciences > Vector Biology Department
Depositing User: Lynn Roberts-Maloney
Date Deposited: 16 Apr 2020 10:31
Last Modified: 16 Apr 2020 10:31
URI: https://archive.lstmed.ac.uk/id/eprint/14203

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