Stopping prereferral rectal artesunate — a grave error

Watson, James A; Warsame, Marian; Peto, Thomas J.; Onyamboko, Marie; Fanello, Caterina; Dondorp, Arjen M.; White, Nicholas J.

doi:10.1136/bmjgh-2022-010006

Cited by 12 publications

(12 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rapid recognition of the disease and early administration of effective treatment are critical determinants of outcome 2,16,17,25,26 . Delays in diagnosis and the administration of artesunate cost lives 1,2 .…”

Section: Discussionmentioning

confidence: 99%

The prognostic and diagnostic value of intraleukocytic malaria pigment in patients with severe falciparum malaria

et al. 2022

Self Cite

View full text Add to dashboard Cite

Severe falciparum malaria is a major cause of death in tropical countries, particularly in African children. Rapid and accurate diagnosis and prognostic assessment are critical to clinical management. In 6027 prospectively studied patients diagnosed with severe malaria we assess the prognostic value of peripheral blood film counts of malaria pigment containing polymorphonuclear leukocytes (PMNs) and monocytes. We combine these results with previously published data and show, in an individual patient data meta-analysis (n = 32,035), that the proportion of pigment containing PMNs is predictive of in-hospital mortality. In African children the proportion of pigment containing PMNs helps distinguish severe malaria from other life-threatening febrile illnesses, and it adds to the prognostic assessment from simple bedside examination, and to the conventional malaria parasite count. Microscopy assessment of pigment containing PMNs is simple and rapid, and should be performed in all patients hospitalised with suspected severe malaria.

show abstract

Section: Discussionmentioning

confidence: 99%

The prognostic and diagnostic value of intraleukocytic malaria pigment in patients with severe falciparum malaria

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Rapid recognition of the disease and early administration of artesunate are important determinants of outcome [1, 15, 16]. Delays in the management of severe malaria cost lives [24, 25]. In hospitals and health centres confirmation of the diagnosis of malaria and recognition of the three major clinical components of severe malaria (coma, acidotic breathing, severe anaemia) can be done immediately.…”

Section: Discussionmentioning

confidence: 99%

“…While prevention is certainly better than cure, the apparently unchanged recent annual death toll of hundreds of thousands of African children cannot continue to be ignored [37]. Access to better diagnosis, assessment and treatment is possible with readily implemented existing tools [24, 25]. Although it is recommended that both thin and thick blood films are taken from patients suspected of having severe malaria, in many centres only a rapid test or a thick blood film is performed [38].…”

Section: Discussionmentioning

confidence: 99%

The prognostic and diagnostic value of intraleukocytic malaria pigment: an individual patient data pooled meta-analysis of 32,000 patients with severe falciparum malaria in Africa and Asia

Srinamon¹,

Watson²,

Silamut³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Severe falciparum malaria is a major cause of death in tropical countries, particularly in African children. Accurate diagnosis and prognostic assessment are critical to clinical management. Methods: The prognostic value of the malaria parasite count, and the proportions of polymorphonuclear leukocytes (PMNs) and monocytes (PMMs) containing malaria pigment in peripheral blood films were assessed in three randomized controlled trials conducted in severe malaria patients; two in Southeast Asia (AQ Vietnam; n=483 and SEAQUAMAT; n=1,330) and one in Africa (AQUAMAT; n=4,211). Following a systematic review of the literature, we incorporated these data into an individual patient data meta-analysis including published data from the Severe Malaria in African children (SMAC) network (n=25,845) and a study from Mali (n=166). Findings: The proportion of pigment containing PMNs on peripheral blood films was strongly positively correlated with prognosis (odds-ratio for in-hospital mortality for a tenfold increase: 2.53 [95% CI: 2.13-3.00], p=10^-26). The meta-analytic odds-ratio estimate for in-hospital death in patients with >5% pigment containing PMNs compared with lower values was 2.67 (95% CI: 2.08-3.42; p=10-14). Particularly in African children, the proportion of pigment containing PMNs added substantially to the prognostic assessment from simple bedside examination, and also to the conventional parasite count. In all analyses, the proportion of pigment containing monocytes had a lower prognostic value. Interpretation: Microscopy assessment of the proportion of pigment containing PMNs in a blood film is simple and rapid, and should be performed in all patients hospitalised with suspected severe malaria. Patients with >5% pigment containing PMNs have more than double the risk of death. Other: Funded by Wellcome. The systematic review was registered prospectively on PROSPERO, number CRD42021284527.

show abstract

“…Mortality reportedly increased after rectal artesunate was deployed, attributed to delays in the referral of severely ill children. However, there are serious concerns over the design of the study, potential major confounders, the accuracy of the diagnosis, and particularly—the causal interpretation of the results [ 101 ]. The CARAMAL study identified important problems with the referral of severely ill children, but it should not be used to evaluate the effectiveness of pre-referral rectal artesunate.…”

Section: The Immediate Management Of Severe Malariamentioning

confidence: 99%

“…Pre-referral rectal artesunate should be given to all children with suspected severe malaria [ 2 , 98 ]. The WHO moratorium [ 99 ] on rectal artesunate will hopefully soon be lifted [ 101 ]. Pre-referral antibiotic formulations should be developed.…”

Section: Implications For the Assessment And Treatment Of Patients Di...mentioning

confidence: 99%

Severe malaria

White

2022

Malar J

View full text Add to dashboard Cite

Severe malaria is a medical emergency. It is a major cause of preventable childhood death in tropical countries. Severe malaria justifies considerable global investment in malaria control and elimination yet, increasingly, international agencies, funders and policy makers are unfamiliar with it, and so it is overlooked. In sub-Saharan Africa, severe malaria is overdiagnosed in clinical practice. Approximately one third of children diagnosed with severe malaria have another condition, usually sepsis, as the cause of their severe illness. But these children have a high mortality, contributing substantially to the number of deaths attributed to ‘severe malaria’. Simple well-established tests, such as examination of the thin blood smear and the full blood count, improve the specificity of diagnosis and provide prognostic information in severe malaria. They should be performed more widely. Early administration of artesunate and broad-spectrum antibiotics to all children with suspected severe malaria would reduce global malaria mortality.

show abstract

Stopping prereferral rectal artesunate — a grave error

Cited by 12 publications

References 15 publications

The prognostic and diagnostic value of intraleukocytic malaria pigment in patients with severe falciparum malaria

The prognostic and diagnostic value of intraleukocytic malaria pigment in patients with severe falciparum malaria

The prognostic and diagnostic value of intraleukocytic malaria pigment: an individual patient data pooled meta-analysis of 32,000 patients with severe falciparum malaria in Africa and Asia

Severe malaria

Contact Info

Product

Resources

About