Survival and Haematological Recovery of Children With Severe Malaria
Survival and Haematological Recovery of Children With Severe Malaria
Background: Severe anaemia requiring emergency blood transfusion is a common complication of malaria in children. To ensure access for urgent blood transfusion, the World Health Organization has developed clear guidelines with haemoglobin thresholds prevent unwarranted transfusion,. Few studies have reported outcome and haematological recovery of children with severe malaria where transfusion practice complies with WHO recommendations.
Methods: A prospective observational study of survivors of severe and complicated malaria transfused in accordance with WHO guidelines. Children were invited for review at one month post-discharge. Non-attendees were traced in the community to ascertain survival.
Results: Outcome was assessed in 213 survivors. Those transfused were younger, had a higher base deficit, mean lactate levels and a higher prevalence of respiratory distress. As expected mean admission haemoglobin (Hb) was significantly lower amongst transfused [5.0 g/dL SD: 1.9] compared to non-transfused children [8.3 g/dL SD: 1.7] (p < 0.001). At discharge mean Hb was similar 6.4 g/dL [SD: 1.5] and 6.8 g/dL [SD: 1.6] respectively (p = 0.08), most children remained moderately to severely anaemic. At one month follow up 166 children (78%) returned, in whom we found no differences in mean Hb between the transfused (10.2 g/dL [SD: 1.7]) and non-transfused (10.0 g/dL [SD: 1.3]) survivors (p = 0.25). The major factors affecting haematological recovery were young age (<24 months) and concomitant malaria parasitaemia; Hb being 8.8 g/dL [SD: 1.5] in parasitaemic individuals compared with 10.5 g/dL [SD: 1.3] in those without (p < 0.001).
Conclusion: This data supports the policy of rational use of blood transfusion, as proposed in the WHO guidelines, for children with anaemia in areas where access to emergency transfusion is not guaranteed. We have provided empirical data indicating that transfusion does not influence superior recovery in haemoglobin concentrations and therefore cannot be justified on this basis alone. This may help resolve the disparity between international policy and current clinical practice. Effective anti-malarial treatment at discharge may prevent reoccurrence of anaemia.
Annually approximately two billion people are exposed to Plasmodium falciparum resulting in over 500 million clinical cases and about one million deaths predominantly in children less than five years living in the sub-Saharan Africa (SSA). Malaria complicated with severe anaemia (Hb<5 g/dL) is an important public health problem in this patient population resulting in major life threatening complications and is a major cause of mortality. Anaemia secondary to malaria accounts for up to 70% of all prescribed transfusions in malaria endemic SSA. Previous studies have revealed that severe anaemia secondary to malaria without any other complications leads to about 1% mortality, however, this rises to 16% when complicated with respiratory distress (severe, symptomatic anaemia) and over 30% when both respiratory distress and coma also present.
For children with severe, symptomatic anaemia, it is now recognized that an urgent blood transfusion is life saving. However, in the many African hospitals blood banking facilities are inadequate and urgent transfusions are often not possible. In these circumstances children have to wait while a replacement donor is found and over 60% of deaths in children with severe malaria anaemia occur before a transfusion can be given. The majority of transfusions are, therefore, received by children with stable, uncomplicated anaemia, for whom the acute benefits of transfusion are unproven, One study in Tanzania reported up to 50% avoidable transfusions. Often, what is is not considered is that the risks of transfusion may outweigh the benefits, since blood transfusions continue to be a major source of preventable HIV infection and other transfusion-transmissible infections. These risks are over and above those due to transfusion reactions and often not detected due to poor haemovigilence. It is, therefore, important to carefully delineate a group of patients who need a blood transfusion.
The World Health Organization (WHO) guidelines, which are largely based on expert opinion and a few previous studies, encourage rational use of blood. These guidelines recommend that transfusion be reserved only for children with absolute haemoglobin (Hb) of ≤ 4 g/dL (profound anaemia) or haemoglobin of 4-5 g/dL plus respiratory distress in malaria endemic areas and a higher cut off of 7 g/dl in areas of low malaria transmission. Adherence to the targeted use of transfusion is hampered by the lack of clinical evidence that this policy is safe in both the short and long term. As a result many children, who do not fulfil criteria for transfusion, continue to receive transfusions in the belief that both short and longer term outcome and haematological recovery is improved.
Whilst there is compelling evidence to support use of blood in children with profound anaemia and severe anaemia with respiratory distress evidence supporting transfusion avoidance in the group with severe anaemia (Hb 4-5 g/dL) without respiratory distress or moderately severe anaemia (Hb < 7 g/dl) with life-threatening complications is less convincing. Further, there are conflicting findings on the effect of transfusion on haemoglobin recovery after discharge, which may help inform a decision on the choice of whether or not to conservatively manage these children. Setting aside considerations of availability and safety, often overlooked are the economic considerations of blood transfusion, with an average cost of 30 US dollars in most localities, rising up to 50 US dollars where voluntary non-remunerated donors are used; most of these costs are recovered from the patients or their families.
We have previously reported in-hospital outcome in children with severe malaria including those with and without symptomatic anaemia. In this current study we report haematological recovery at discharge, one month post-admission and longer term survival in children admitted with severe malarial anaemia complicated by respiratory distress transfused in accordance to WHO guidelines.
Background: Severe anaemia requiring emergency blood transfusion is a common complication of malaria in children. To ensure access for urgent blood transfusion, the World Health Organization has developed clear guidelines with haemoglobin thresholds prevent unwarranted transfusion,. Few studies have reported outcome and haematological recovery of children with severe malaria where transfusion practice complies with WHO recommendations.
Methods: A prospective observational study of survivors of severe and complicated malaria transfused in accordance with WHO guidelines. Children were invited for review at one month post-discharge. Non-attendees were traced in the community to ascertain survival.
Results: Outcome was assessed in 213 survivors. Those transfused were younger, had a higher base deficit, mean lactate levels and a higher prevalence of respiratory distress. As expected mean admission haemoglobin (Hb) was significantly lower amongst transfused [5.0 g/dL SD: 1.9] compared to non-transfused children [8.3 g/dL SD: 1.7] (p < 0.001). At discharge mean Hb was similar 6.4 g/dL [SD: 1.5] and 6.8 g/dL [SD: 1.6] respectively (p = 0.08), most children remained moderately to severely anaemic. At one month follow up 166 children (78%) returned, in whom we found no differences in mean Hb between the transfused (10.2 g/dL [SD: 1.7]) and non-transfused (10.0 g/dL [SD: 1.3]) survivors (p = 0.25). The major factors affecting haematological recovery were young age (<24 months) and concomitant malaria parasitaemia; Hb being 8.8 g/dL [SD: 1.5] in parasitaemic individuals compared with 10.5 g/dL [SD: 1.3] in those without (p < 0.001).
Conclusion: This data supports the policy of rational use of blood transfusion, as proposed in the WHO guidelines, for children with anaemia in areas where access to emergency transfusion is not guaranteed. We have provided empirical data indicating that transfusion does not influence superior recovery in haemoglobin concentrations and therefore cannot be justified on this basis alone. This may help resolve the disparity between international policy and current clinical practice. Effective anti-malarial treatment at discharge may prevent reoccurrence of anaemia.
Annually approximately two billion people are exposed to Plasmodium falciparum resulting in over 500 million clinical cases and about one million deaths predominantly in children less than five years living in the sub-Saharan Africa (SSA). Malaria complicated with severe anaemia (Hb<5 g/dL) is an important public health problem in this patient population resulting in major life threatening complications and is a major cause of mortality. Anaemia secondary to malaria accounts for up to 70% of all prescribed transfusions in malaria endemic SSA. Previous studies have revealed that severe anaemia secondary to malaria without any other complications leads to about 1% mortality, however, this rises to 16% when complicated with respiratory distress (severe, symptomatic anaemia) and over 30% when both respiratory distress and coma also present.
For children with severe, symptomatic anaemia, it is now recognized that an urgent blood transfusion is life saving. However, in the many African hospitals blood banking facilities are inadequate and urgent transfusions are often not possible. In these circumstances children have to wait while a replacement donor is found and over 60% of deaths in children with severe malaria anaemia occur before a transfusion can be given. The majority of transfusions are, therefore, received by children with stable, uncomplicated anaemia, for whom the acute benefits of transfusion are unproven, One study in Tanzania reported up to 50% avoidable transfusions. Often, what is is not considered is that the risks of transfusion may outweigh the benefits, since blood transfusions continue to be a major source of preventable HIV infection and other transfusion-transmissible infections. These risks are over and above those due to transfusion reactions and often not detected due to poor haemovigilence. It is, therefore, important to carefully delineate a group of patients who need a blood transfusion.
The World Health Organization (WHO) guidelines, which are largely based on expert opinion and a few previous studies, encourage rational use of blood. These guidelines recommend that transfusion be reserved only for children with absolute haemoglobin (Hb) of ≤ 4 g/dL (profound anaemia) or haemoglobin of 4-5 g/dL plus respiratory distress in malaria endemic areas and a higher cut off of 7 g/dl in areas of low malaria transmission. Adherence to the targeted use of transfusion is hampered by the lack of clinical evidence that this policy is safe in both the short and long term. As a result many children, who do not fulfil criteria for transfusion, continue to receive transfusions in the belief that both short and longer term outcome and haematological recovery is improved.
Whilst there is compelling evidence to support use of blood in children with profound anaemia and severe anaemia with respiratory distress evidence supporting transfusion avoidance in the group with severe anaemia (Hb 4-5 g/dL) without respiratory distress or moderately severe anaemia (Hb < 7 g/dl) with life-threatening complications is less convincing. Further, there are conflicting findings on the effect of transfusion on haemoglobin recovery after discharge, which may help inform a decision on the choice of whether or not to conservatively manage these children. Setting aside considerations of availability and safety, often overlooked are the economic considerations of blood transfusion, with an average cost of 30 US dollars in most localities, rising up to 50 US dollars where voluntary non-remunerated donors are used; most of these costs are recovered from the patients or their families.
We have previously reported in-hospital outcome in children with severe malaria including those with and without symptomatic anaemia. In this current study we report haematological recovery at discharge, one month post-admission and longer term survival in children admitted with severe malarial anaemia complicated by respiratory distress transfused in accordance to WHO guidelines.
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