Severe anaemia associated with Plasmodium falciparum infection in children: consequences for additional blood
Laura Maria Francisca Kuijpers1,2, Jessica Maltha3,4, Issa Guiraud5
1Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. lkuijpers@itg.be.
Insights
Blood draws for malaria research in children can exceed safe limits, especially in younger children and those with anemia. Researchers and ethics committees must carefully consider blood volume guidelines to protect child participants.
Area of Science:
- Pediatrics
- Infectious Diseases
- Hematology
Background:
- Plasmodium falciparum infection is a major cause of severe anemia in children.
- Diagnostic studies in sub-Saharan Africa require careful consideration of safe blood sampling volumes.
- Previous guidelines recommended limiting blood sampling to 3.8% of total blood volume (TBV).
Purpose of the Study:
- To evaluate the impact of the 3.8% TBV safety guideline on intended blood sampling volumes in children suspected of severe malaria.
- To assess the risk of exceeding safe blood sampling volumes in a pediatric cohort in Burkina Faso.
Main Methods:
- A simulation exercise was conducted using data from 666 children (2 months to 12 years) in Burkina Faso.
- Estimated Total Blood Volume (TBVe) was calculated based on weight and corrected for anemia to determine Functional Total Blood Volume (TBVf).
- The 3.8% TBVf threshold was compared against intended blood sample volumes (6-10 mL).
Main Results:
- In 5.3% (best case) to 11.4% (worst case) of children, intended blood sampling exceeded the 3.8% guideline.
- The highest violation rates occurred in infants aged 2-6 months (19.0%) and 6 months-2 years (15.7%) in the worst-case scenario.
- A positive rapid diagnostic test for P. falciparum was associated with a higher risk of guideline violation (p=0.016).
Conclusions:
- Blood sampling for P. falciparum research can easily exceed the 3.8% TBVf safety guideline in endemic settings.
- Ethical committees and researchers must exercise caution and implement appropriate precautions.
- The study highlights the need for revised blood volume guidelines or careful application in vulnerable pediatric populations.
Background:
Plasmodium falciparum infection may cause severe anaemia, particularly in children. When planning a diagnostic study on children suspected of severe malaria in sub-Saharan Africa, it was questioned how much blood could be safely sampled; intended blood volumes (blood cultures and EDTA blood) were 6 mL (children aged <6 years) and 10 mL (6-12 years). A previous review [Bull World Health Organ. 89: 46-53. 2011] recommended not to exceed 3.8 % of total blood volume (TBV). In a simulation exercise using data of children previously enrolled in a study about severe malaria and bacteraemia in Burkina Faso, the impact of this 3.8 % safety guideline was evaluated.
Methods:
For a total of 666 children aged >2 months to <12 years, data of age, weight and haemoglobin value (Hb) were available. For each child, the estimated TBV (TBVe) (mL) was calculated by multiplying the body weight (kg) by the factor 80 (ml/kg). Next, TBVe was corrected for the degree of anaemia to obtain the functional TBV (TBVf). The correction factor consisted of the rate 'Hb of the child divided by the reference Hb'; both the lowest ('best case') and highest ('worst case') reference Hb values were used. Next, the exact volume that a 3.8 % proportion of this TBVf would present was calculated and this volume was compared to the blood volumes that were intended to be sampled.
Results:
When applied to the Burkina Faso cohort, the simulation exercise pointed out that in 5.3 % (best case) and 11.4 % (worst case) of children the blood volume intended to be sampled would exceed the volume as defined by the 3.8 % safety guideline. Highest proportions would be in the age groups 2-6 months (19.0 %; worst scenario) and 6 months-2 years (15.7 %; worst case scenario). A positive rapid diagnostic test for P. falciparum was associated with an increased risk of violating the safety guideline in the worst case scenario (p = 0.016).
Conclusions:
Blood sampling in children for research in P. falciparum endemic settings may easily violate the proposed safety guideline when applied to TBVf. Ethical committees and researchers should be wary of this and take appropriate precautions.
