Severe anaemia associated with Plasmodium falciparum infection in children: consequences for additional blood sampling for research

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 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.status: publishe

Numbers of children with positive microscopy, RDT and IBI.

<p><i>TBF, RDT and IBI results for all children (n = 711), 169 children tested negative on all three items. Areas in Venn-diagram approximately to scale. TBF  =  thick blood film, RDT  =  rapid diagnostic test, IBI  =  invasive bacterial infection, SM  =  severe malaria, UM  =  uncomplicated malaria</i>.</p

Severe malaria and invasive bacterial infections by age group.

<p><i>IBI  =  invasive bacterial infection, m  =  months</i>.</p><p><i>*Including those with IBI co-infection, ^§Including those with malaria co-infection</i>.</p

Clinically significant organisms isolated from blood culture and age-specific frequencies.

<p><i>Data displayed are numbers and percentages of clinically significant bacteria isolated</i>.</p><p><i>m =  months, IQR  =  interquartile range</i>.</p><p>*<i>In one patient 2 pathogens were isolated (E. coli and Leuconostoc)</i>.</p

Demographic, clinical and laboratory characteristics upon admission.

<p><i>Hb  =  hemoglobin IQR  =  interquartile range, *For 670 children data on severe malnutrition known</i>.</p

Antibiotic resistance patterns of <i>Enterobacteriaceae</i>.

<p><i>DCS  =  decreased ciprofloxacin susceptibility, ESBL  =  extended-spectrum beta-lactamase, MDR  =  multidrug resistant, NA  =  non applicable, TMP-SMX  =  trimethoprim-sulfamethoxazole</i>.</p><p><i>*Isolated from CSF</i>.</p