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The impact of delayed treatment of uncomplicated P. falciparum malaria on progression to severe malaria: A systematic review and a pooled multicentre individual-patient meta-analysis.
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Delay in receiving treatment for uncomplicated malaria (UM) is often
reported to increase the risk of developing severe malaria (SM),
but access to treatment remains low in most high-burden areas.
Understanding the contribution of treatment delay on progression
to severe disease is critical to determine how quickly patients
need to receive treatment and to quantify the impact of widely
implemented treatment interventions, such as 'test-and-treat'
policies administered by community health workers (CHWs). We
conducted a pooled individual-participant meta-analysis to
estimate the association between treatment delay and presenting
with SM. - Label: METHODS AND FINDINGS NlmCategory: RESULTS
content: "A search using Ovid MEDLINE and Embase was initially
conducted to identify studies on severe Plasmodium falciparum
malaria that included information on treatment delay, such as
fever duration (inception to 22nd September 2017). Studies
identified included 5 case-control and 8 other observational
clinical studies of SM and UM cases. Risk of bias was assessed
using the Newcastle-Ottawa scale, and all studies were ranked as
'Good', scoring \xE2\x89\xA57/10. Individual-patient data (IPD)
were pooled from 13 studies of 3,989 (94.1% aged <15 years)
SM patients and 5,780 (79.6% aged <15 years) UM cases in
Benin, Malaysia, Mozambique, Tanzania, The Gambia, Uganda,
Yemen, and Zambia. Definitions of SM were standardised across
studies to compare treatment delay in patients with UM and
different SM phenotypes using age-adjusted mixed-effects
regression. The odds of any SM phenotype were significantly
higher in children with longer delays between initial symptoms
and arrival at the health facility (odds ratio [OR] = 1.33, 95%
CI: 1.07-1.64 for a delay of >24 hours versus \xE2\x89\xA424
hours; p = 0.009). Reported illness duration was a strong
predictor of presenting with severe malarial anaemia (SMA) in
children, with an OR of 2.79 (95% CI:1.92-4.06; p < 0.001)
for a delay of 2-3 days and 5.46 (95% CI: 3.49-8.53; p <
0.001) for a delay of >7 days, compared with receiving
treatment within 24 hours from symptom onset. We estimate that
42.8% of childhood SMA cases and 48.5% of adult SMA cases in the
study areas would have been averted if all individuals were able
to access treatment within the first day of symptom onset, if
the association is fully causal. In studies specifically
recording onset of nonsevere symptoms, long treatment delay was
moderately associated with other SM phenotypes (OR [95% CI]
>3 to \xE2\x89\xA44 days versus \xE2\x89\xA424 hours:
cerebral malaria [CM] = 2.42 [1.24-4.72], p = 0.01; respiratory
distress syndrome [RDS] = 4.09 [1.70-9.82], p = 0.002). In
addition to unmeasured confounding, which is commonly present in
observational studies, a key limitation is that many severe
cases and deaths occur outside healthcare facilities in endemic
countries, where the effect of delayed or no treatment is
difficult to quantify." - Label: CONCLUSIONS NlmCategory:
CONCLUSIONS content: Our results quantify the relationship
between rapid access to treatment and reduced risk of severe
disease, which was particularly strong for SMA. There was some
evidence to suggest that progression to other severe phenotypes
may also be prevented by prompt treatment, though the
association was not as strong, which may be explained by
potential selection bias, sample size issues, or a difference in
underlying pathology. These findings may help assess the impact
of interventions that improve access to treatment.
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MOUSA, Andria, AL-TAIAR, Abdullah, ANSTEY, Nicholas m., BADAUT, Cyril, BARBER, Bridget e., BASSAT ORELLANA, Quique, CHALLENGER, Joseph d., CUNNINGTON, Aubrey j., DATTA, Dibdyadyuti, DRAKELEY, Chris, GHANI, Azra c., GORDEUK, Victor r., GRIGG, Matthew j., HUGO, Pierre, JOHN, Chandy c., MAYOR APARICIO, Alfredo gabriel, MIGOT-NABIAS, Florence, OPOKA, Robert o., PASVOL, Geoffrey, REES, Claire, REYBURN, Hugh, RILEY, Eleanor m., SHAH, Binal n., SITOE, Antonio, SUTHERLAND, Colin j., THUMA, Philip e., UNGER, Stefan a., VIWAMI, Firmine, WALTHER, Michael, WHITTY, Christopher j. m., WILLIAM, Timothy, OKELL, Lucy c.. The impact of delayed treatment of uncomplicated P. falciparum malaria on progression to severe malaria: A systematic review and a pooled multicentre individual-patient meta-analysis.. _PLOS Medicine _. 2020. Vol. 17. [consulta: 23 de gener de 2026]. ISSN: 1549-1676. [Disponible a: https://hdl.handle.net/2445/185154]