Point-of-care ultrasound to assess volume status and pulmonary oedema in malaria patients.

PURPOSE: Fluid management is challenging in malaria patients given the risks associated with intravascular fluid depletion and iatrogenic fluid overload leading to pulmonary oedema. Given the limitations of the physical examination in guiding fluid therapy, we evaluated point-of-care ultrasound (POCUS) of the inferior vena cava (IVC) and lungs as a novel tool to assess volume status and detect early oedema in malaria patients. METHODS: To assess the correlation between IVC and lung ultrasound (LUS) indices and clinical signs of hypovolaemia and pulmonary oedema, respectively, concurrent clinical and sonographic examinations were performed in an observational study of 48 malaria patients and 62 healthy participants across age groups in Gabon. RESULTS: IVC collapsibility index (CI) ≥ 50% on enrolment reflecting intravascular fluid depletion was associated with an increased number of clinical signs of hypovolaemia in severe and uncomplicated malaria. With exception of dry mucous membranes, IVC-CI correlated with most clinical signs of hypovolaemia, most notably sunken eyes (r = 0.35, p = 0.0001) and prolonged capillary refill (r = 0.35, p = 0.001). IVC-to-aorta ratio ≤ 0.8 was not associated with any clinical signs of hypovolaemia on enrolment. Among malaria patients, a B-pattern on enrolment reflecting interstitial fluid was associated with dyspnoea (p = 0.0003), crepitations and SpO2 ≤ 94% (both p < 0.0001), but not tachypnoea (p = 0.069). Severe malaria patients had increased IVC-CI (p < 0.0001) and more B-patterns (p = 0.004) on enrolment relative to uncomplicated malaria and controls. CONCLUSION: In malaria patients, POCUS of the IVC and lungs may improve the assessment of volume status and detect early oedema, which could help to manage fluids in these patients.

Monitoring of efficacy, tolerability and safety of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Lambaréné, Gabon: an open-label clinical trial.

BACKGROUND: Malaria remains a major public health problem, affecting mainly low-and middle-income countries. The management of this parasitic disease is challenged by ever increasing drug resistance. This study, investigated the therapeutic efficacy, tolerability and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), used as first-line drugs to treat uncomplicated malaria in Lambaréné, Gabon. METHODS: A non-randomized clinical trial was conducted between October 2017 and March 2018 to assess safety, clinical and parasitological efficacy of fixed-doses of AL and AS-AQ administered to treat uncomplicated Plasmodium falciparum malaria in children aged from 6 months to 12 years. After 50 children were treated with AL, another 50 children received ASAQ. The 2009 World Health Organization protocol for monitoring of the efficacy of anti­malarial drugs was followed. Molecular markers msp1 and msp2 were used to differentiate recrudescence and reinfection. For the investigation of artemisinin resistant markers, gene mutations in Pfk13 were screened. RESULTS: Per-protocol analysis on day 28 showed a PCR corrected cure rate of 97% (95% CI 86-100) and 95% (95% CI 84-99) for AL and AS-AQ, respectively. The most frequent adverse event in both groups was asthenia. No mutations in the kelch-13 gene associated with artemisinin resistance were identified. All participants had completed microscopic parasite clearance by day 3 post-treatment. CONCLUSION: This study showed that AL and AS-AQ remain efficacious, well-tolerated, and are safe to treat uncomplicated malaria in children from Lambaréné. However, a regular monitoring of efficacy and a study of molecular markers of drug resistance to artemisinin in field isolates is essential. Trial registration ANZCTR, ACTRN12616001600437. Registered 18 November, http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12616001600437p&isBasic=True.