Ultrasonographic assessment of splenic volume at presentation and after anti-malarial therapy in children with malarial anaemia

Background: Splenic enlargement is a component of the host response to malaria and may also influence the genesis and progression of malarial anaemia. Few cross-sectional and no longitudinal studies have assessed the relationship between splenic volume measured ultrasonographically and haemoglobin concentrations in children with malaria. Methods: Fifteen Papua New Guinean children with severe malarial anaemia (SMA; haemoglobin <50 g/L) and ten with moderate malarial anaemia (MMA; 51-99 g/L) were recruited. The SMA patients were given intramuscular artemether followed by oral artemisinin combination therapy (ACT), and were transfused one unit of packed cells 0.3-4.0 days post-admission. The MMA patients were treated with ACT. Splenic enlargement (Hackett's grade, subcostal distance and ultrasonographically determined volume) and haemoglobin concentrations were measured on days 0, 1, 2, 3, 7, 14, 28, and 42. Results: Associations between Hackett's grade, subcostal distance and splenic volume were modest (r(s) = 0.90). Mean splenic volume had fallen by approximately 50 % at day 14 in children with MMA ( P = 0.30). There was no change in haemoglobin in the MMA group during follow-up but a rise in the SMA group to day 7 ( P <= 0.05 vs days 0, 1, 2, and 3) which paralleled the packed cell volume transfused. Conclusions: Clinical assessment of splenomegaly is imprecise compared with ultrasonography. Serial splenic volumes and haemoglobin concentrations suggest that the spleen does not influence post-treatment haemoglobin, including after transfusion

Features and Prognosis of Severe Malaria Caused by Plasmodium falciparum, Plasmodium vivax and Mixed Plasmodium Species in Papua New Guinean Children

BACKGROUND: Mortality from severe pediatric falciparum malaria appears low in Oceania but Plasmodium vivax is increasingly recognized as a cause of complications and death. The features and prognosis of mixed Plasmodium species infections are poorly characterized. Detailed prospective studies that include accurate malaria diagnosis and detection of co-morbidities are lacking. METHODS AND FINDINGS: We followed 340 Papua New Guinean (PNG) children with PCR-confirmed severe malaria (77.1% P. falciparum, 7.9% P. vivax, 14.7% P. falciparum/vivax) hospitalized over a 3-year period. Bacterial cultures were performed to identify co-incident sepsis. Clinical management was under national guidelines. Of 262 children with severe falciparum malaria, 30.9%, 24.8% and 23.2% had impaired consciousness, severe anemia, and metabolic acidosis/hyperlactatemia, respectively. Two (0.8%) presented with hypoglycemia, seven (2.7%) were discharged with neurologic impairment, and one child died (0.4%). The 27 severe vivax malaria cases presented with similar phenotypic features to the falciparum malaria cases but respiratory distress was five times more common (P=0.001); one child died (3.7%). The 50 children with P. falciparum/vivax infections shared phenotypic features of mono-species infections, but were more likely to present in deep coma and had the highest mortality (8.0%; P=0.003 vs falciparum malaria). Overall, bacterial cultures were positive in only two non-fatal cases. 83.6% of the children had alpha-thalassemia trait and seven with coma/impaired consciousness had South Asian ovalocytosis (SAO). CONCLUSIONS: The low mortality from severe falciparum malaria in PNG children may reflect protective genetic factors other than alpha-thalassemia trait/SAO, good nutrition, and/or infrequent co-incident sepsis. Severe vivax malaria had similar features but severe P. falciparum/vivax infections were associated with the most severe phenotype and worst prognosis

Artemisinin-Naphthoquine versus Artemether-Lumefantrine for Uncomplicated Malaria in Papua New Guinean Children: An Open-Label Randomized Trial

© 2014 Laman et al. Artemisinin combination therapies (ACTs) with broad efficacy are needed where multiple Plasmodium species are transmitted, especially in children, who bear the brunt of infection in endemic areas. In Papua New Guinea (PNG), artemether-lumefantrine is the first-line treatment for uncomplicated malaria, but it has limited efficacy against P. vivax. Artemisinin-naphthoquine should have greater activity in vivax malaria because the elimination of naphthoquine is slower than that of lumefantrine. In this study, the efficacy, tolerability, and safety of these ACTs were assessed in PNG children aged 0.5–5 y.An open-label, randomized, parallel-group trial of artemether-lumefantrine (six doses over 3 d) and artemisinin-naphthoquine (three daily doses) was conducted between 28 March 2011 and 22 April 2013. Parasitologic outcomes were assessed without knowledge of treatment allocation. Primary endpoints were the 42-d P. falciparum PCR-corrected adequate clinical and parasitologic response (ACPR) and the P. vivax PCR-uncorrected 42-d ACPR. Non-inferiority and superiority designs were used for falciparum and vivax malaria, respectively. Because the artemisinin-naphthoquine regimen involved three doses rather than the manufacturer-specified single dose, the first 188 children underwent detailed safety monitoring. Of 2,542 febrile children screened, 267 were randomized, and 186 with falciparum and 47 with vivax malaria completed the 42-d follow-up. Both ACTs were safe and well tolerated. P. falciparum ACPRs were 97.8% and 100.0% in artemether-lumefantrine and artemisinin-naphthoquine-treated patients, respectively (difference 2.2% [95% CI -3.0% to 8.4%] versus -5.0% non-inferiority margin, p?=?0.24), and P. vivax ACPRs were 30.0% and 100.0%, respectively (difference 70.0% [95% CI 40.9%–87.2%], p&lt;0.001). Limitations included the exclusion of 11% of randomized patients with sub-threshold parasitemias on confirmatory microscopy and direct observation of only morning artemether-lumefantrine dosing.Artemisinin-naphthoquine is non-inferior to artemether-lumefantrine in PNG children with falciparum malaria but has greater efficacy against vivax malaria, findings with implications in similar geo-epidemiologic settings within and beyond Oceania.Australian New Zealand Clinical Trials Registry ACTRN12610000913077.Please see later in the article for the Editors' Summary

Odds ratios from logistic regression of imputed datasets.

<p>Multiple imputation (MI) averages and 95% confidence intervals (CI) are given, together with partial attributable risks and boot strap 95% CI.</p

Clinical, laboratory and genetic features of children with severe anemia by <i>Plasmodium falciparum</i> infection status.

<p>Data are percentages or median and [inter-quartile range].</p

Consort diagram describing the recruitment process of children with severe anemia.

<p>Consort diagram describing the recruitment process of children with severe anemia.</p

Summary of logistic regression model for severe anemia.

<p>Summary of logistic regression model for severe anemia.</p

Demographic and anthropometric characteristics of severely anemic children and healthy non-anemic controls.

<p>Data are percentages or median and [inter-quartile range].</p

Biochemical, hematologic and genetic characteristics of severely anemic children and non-anemic controls.

<p>Data are percentages or median and [inter-quartile range].</p