Malaria Chemoprevention in the Postdischarge Management of Severe Anemia

Kwambai, Titus K.; Dhabangi, Aggrey; Idro, Richard; Opoka, Robert O.; Watson, Victoria; Kariuki, Simon; Kuya, Nickline; Onyango, Eric D; Otieno, Kephas; Samuels, Aaron M.; Desai, Meghna; Hensbroek, Michaël Boele van; Wang, Duolao; John, Chandy C.; Robberstad, Bjarne; Phiri, Kamija S.; Kuile, Feiko O. ter

doi:10.1056/nejmoa2002820

Cited by 45 publications

(87 citation statements)

References 36 publications

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“…This showed that this group of at-risk children could be protected for a period of 3 months by providing them with two, monthly courses of treatment with artemether-lumefantrine (AL) after their discharge from hospital [ 29 ]. These findings have been confirmed recently in a large, placebo-controlled trial conducted in highly malarious areas in nine hospitals in Uganda and western Kenya [ 30 ]. In this trial, three months of post-discharge malaria chemoprevention (PMC) with monthly DHA-PQ in children who had been admitted to hospital with severe anaemia resulted in a 70% reduction in a combination of mortality or hospital readmission during the first three months after discharge from the hospital.…”

Section: Additional Opportunities For Combining Pre-erythrocytic Vaccination With Chemopreventionsupporting

confidence: 58%

“…In this trial, three months of post-discharge malaria chemoprevention (PMC) with monthly DHA-PQ in children who had been admitted to hospital with severe anaemia resulted in a 70% reduction in a combination of mortality or hospital readmission during the first three months after discharge from the hospital. However, this protective effect was not sustained, and children remained at high risk of dying or requiring readmissions after the protective level of piperaquine levels had waned so that by six months after discharge, the overall reduction in mortality and hospital readmission had fallen to 35% [ 30 ].…”

Section: Additional Opportunities For Combining Pre-erythrocytic Vaccination With Chemopreventionmentioning

confidence: 99%

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Combining malaria vaccination with chemoprevention: a promising new approach to malaria control

Greenwood

Cairns

Chaponda

et al. 2021

Malar J

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Malaria control has stalled in a number of African countries and novel approaches to malaria control are needed for these areas. The encouraging results of a recent trial conducted in young children in Burkina Faso and Mali in which a combination of the RTS,S/AS01E malaria vaccine and seasonal malaria chemoprevention led to a substantial reduction in clinical cases of malaria, severe malaria, and malaria deaths compared with the administration of either intervention given alone suggests that there may be other epidemiological/clinical situations in which a combination of malaria vaccination and chemoprevention could be beneficial. Some of these potential opportunities are considered in this paper. These include combining vaccination with intermittent preventive treatment of malaria in infants, with intermittent preventive treatment of malaria in pregnancy (through vaccination of women of child-bearing age before or during pregnancy), or with post-discharge malaria chemoprevention in the management of children recently admitted to hospital with severe anaemia. Other potential uses of the combination are prevention of malaria in children at particular risk from the adverse effects of clinical malaria, such as those with sickle cell disease, and during the final stages of a malaria elimination programme when vaccination could be combined with repeated rounds of mass drug administration. The combination of a pre-erythrocytic stage malaria vaccine with an effective chemopreventive regimen could make a valuable contribution to malaria control and elimination in a variety of clinical or epidemiological situations, and the potential of this approach to malaria control needs to be explored.

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Section: Additional Opportunities For Combining Pre-erythrocytic Vaccination With Chemopreventionsupporting

confidence: 58%

Section: Additional Opportunities For Combining Pre-erythrocytic Vaccination With Chemopreventionmentioning

confidence: 99%

Combining malaria vaccination with chemoprevention: a promising new approach to malaria control

Greenwood

Cairns

Chaponda

et al. 2021

Malar J

Self Cite

View full text Add to dashboard Cite

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“…AKI is associated with increased post-discharge mortality in severe malaria 14 and increased readmission or mortality in both pediatric and adult AKI survivors in high-income settings. [121][122][123][124][125][126] Children with severe malaria are at increased risk of readmission following discharge, [127][128][129][130] but the relationship between AKI and readmission in children with severe malaria has not been investigated. A recent study has implicated hemoglobinuria or blackwater fever with post-discharge morbidity and mortality.…”

Section: Impact Of Aki On Short-term and Long-term Outcomes Survival Length Of Hospital Stay And Risk Of Readmission Or Deathmentioning

confidence: 99%

Malaria-Associated Acute Kidney Injury in African Children: Prevalence, Pathophysiology, Impact, and Management Challenges

Batte¹,

Berrens²,

Murphy³

et al. 2021

IJNRD

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Acute kidney injury (AKI) is emerging as a complication of increasing clinical importance associated with substantial morbidity and mortality in African children with severe malaria. Using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to define AKI, an estimated 24-59% of African children with severe malaria have AKI with most AKI community-acquired. AKI is a risk factor for mortality in pediatric severe malaria with a stepwise increase in mortality across AKI stages. AKI is also a risk factor for postdischarge mortality and is associated with increased long-term risk of neurocognitive impairment and behavioral problems in survivors. Following injury, the kidney undergoes a process of recovery and repair. AKI is an established risk factor for chronic kidney disease and hypertension in survivors and is associated with an increased risk of chronic kidney disease in severe malaria survivors. The magnitude of the risk and contribution of malaria-associated AKI to chronic kidney disease in malaria-endemic areas remains undetermined. Pathways associated with AKI pathogenesis in the context of pediatric severe malaria are not well understood, but there is emerging evidence that immune activation, endothelial dysfunction, and hemolysis-mediated oxidative stress all directly contribute to kidney injury. In this review, we outline the KDIGO bundle of care and highlight how this could be applied in the context of severe malaria to improve kidney perfusion, reduce AKI progression, and improve survival. With increased recognition that AKI in severe malaria is associated with substantial post-discharge morbidity and long-term risk of chronic kidney disease, there is a need to increase AKI recognition through enhanced access to creatinine-based and nextgeneration biomarker diagnostics. Long-term studies to assess severe malaria-associated AKI's impact on long-term health in malaria-endemic areas are urgently needed.

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“…Furthermore, in TRACT, although few children had severe malnutrition (n = 75), nutritional status was not a risk factor for readmission. A multicentre placebo-controlled trial of 3 days of dihydroartemisinin-piperaquine (DHA-PPQ) malaria chemoprevention administered at 2, 6, and 10 weeks post discharge to children admitted with severe anaemia and were followed for 180 days [39]. DHA-PPQ reduced readmissions by 70% (but not deaths) in the 3-14 weeks following discharge (i.e.…”

Section: Discussionmentioning

confidence: 99%

Incidence and predictors of hospital readmission in children presenting with severe anaemia in Uganda and Malawi: a secondary analysis of TRACT trial data

et al. 2021

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Background Severe anaemia (haemoglobin < 6 g/dL) is a leading cause of recurrent hospitalisation in African children. We investigated predictors of readmission in children hospitalised with severe anaemia in the TRACT trial (ISRCTN84086586) in order to identify potential future interventions. Methods Secondary analyses of the trial examined 3894 children from Uganda and Malawi surviving a hospital episode of severe anaemia. Predictors of all-cause readmission within 180 days of discharge were identified using multivariable regression with death as a competing risk. Groups of children with similar characteristics were identified using hierarchical clustering. Results Of the 3894 survivors 682 (18%) were readmitted; 403 (10%) had ≥2 re-admissions over 180 days. Three main causes of readmission were identified: severe anaemia (n = 456), malaria (n = 252) and haemoglobinuria/dark urine syndrome (n = 165). Overall, factors increasing risk of readmission included HIV-infection (hazard ratio 2.48 (95% CI 1.63–3.78), p < 0.001); ≥2 hospital admissions in the preceding 12 months (1.44(1.19–1.74), p < 0.001); history of transfusion (1.48(1.13–1.93), p = 0.005); and missing ≥1 trial medication dose (proxy for care quality) (1.43 (1.21–1.69), p < 0.001). Children with uncomplicated severe anaemia (Hb 4-6 g/dL and no severity features), who never received a transfusion (per trial protocol) during the initial admission had a substantially lower risk of readmission (0.67(0.47–0.96), p = 0.04). Malaria (among children with no prior history of transfusion) (0.60(0.47–0.76), p < 0.001); younger-age (1.07 (1.03–1.10) per 1 year younger, p < 0.001) and known sickle cell disease (0.62(0.46–0.82), p = 0.001) also decreased risk of readmission. For anaemia re-admissions, gross splenomegaly and enlarged spleen increased risk by 1.73(1.23–2.44) and 1.46(1.18–1.82) respectively compared to no splenomegaly. Clustering identified four groups of children with readmission rates from 14 to 20%. The cluster with the highest readmission rate was characterised by very low haemoglobin (mean 3.6 g/dL). Sickle Cell Disease (SCD) predominated in two clusters associated with chronic repeated admissions or severe, acute presentations in largely undiagnosed SCD. The final cluster had high rates of malaria (78%), severity signs and very low platelet count, consistent with acute severe malaria. Conclusions Younger age, HIV infection and history of previous hospital admissions predicted increased risk of readmission. However, no obvious clinical factors for intervention were identified. As missing medication doses was highly predictive, attention to care related factors may be important. Trial registration ISRCTN ISRCTN84086586.

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Malaria Chemoprevention in the Postdischarge Management of Severe Anemia

Cited by 45 publications

References 36 publications

Combining malaria vaccination with chemoprevention: a promising new approach to malaria control

Combining malaria vaccination with chemoprevention: a promising new approach to malaria control

Malaria-Associated Acute Kidney Injury in African Children: Prevalence, Pathophysiology, Impact, and Management Challenges

Incidence and predictors of hospital readmission in children presenting with severe anaemia in Uganda and Malawi: a secondary analysis of TRACT trial data

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