Bone marrow suppression and severe anaemia associated with persistent Plasmodium falciparum infection in African children with microscopically undetectable parasitaemia

BACKGROUND: Severe anaemia can develop in the aftermath of Plasmodium falciparum malaria because of protracted bone marrow suppression, possibly due to residual subpatent parasites. MATERIALS AND METHODS: Blood was collected from patients with recent malaria and negative malaria microscopy. Detection of the Plasmodium antigens, lactate dehydrogenase (Optimal(®)), aldolase and histidine rich protein 2 (Now malaria(®)) were used to differentiate between patients with (1) no malaria, (2) recent cleared malaria, (3) persistent P. falciparum infection. Red cell distribution width (RDW), plasma levels of soluble transferrin receptor (sTfR) and erythropoietin (EPO) were measured as markers of erythropoiesis. Interleukin (IL) 10 and tumour necrosis factor (TNF)α were used as inflammation markers. RESULTS: EPO was correlated with haemoglobin, irrespective of malaria (R = -0.36, P < 0.001). Persistent P. falciparum infection, but not recent malaria without residual parasites, was associated with bone marrow suppression i.e., low RDW (P < 0.001 vs. P = 0.56) and sTfR (P = 0.02 vs. P = 0.36). TNF-α and IL-10 levels were not associated with bone marrow suppression. CONCLUSION: In the treatment of malaria, complete eradication of parasites may prevent subsequent development of anaemia. Severely anaemic children may benefit from antimalarial treatment if antigen tests are positive, even when no parasites can be demonstrated by microscopy

Retinopathy in severe malaria in Ghanaian children - overlap between fundus changes in cerebral and non-cerebral malaria

<p>Abstract</p> <p>Background</p> <p>In malaria-endemic areas, reliably establishing parasitaemia for diagnosis of malaria can be difficult. A retinopathy with some features unique to severe malaria with a predictive value on prognosis, has been described. Detection of this retinopathy could be a useful diagnostic tool. This study was designed to determine the diagnostic usefulness of retinopathy on ophthalmoscopy in severe malaria syndromes: Cerebral malaria (CM) and non-cerebral severe malaria (non-CM), i.e. malaria with respiratory distress (RD) and malaria with severe anaemia (SA), in Ghanaian children. Secondly, to determine any association between retinopathy and the occurrence of convulsions in patients with CM.</p> <p>Methods and subjects</p> <p>A cross-sectional study of consecutive patients on admission with severe malaria who were assessed for retinal signs, at the Department of Child Health, Korle-Bu Teaching Hospital, Accra, from July to August 2002 was done. All children had dilated-fundus examination by direct and indirect ophthalmoscopy.</p> <p>Results</p> <p>Fifty-eight children aged between six months and nine years were recruited. Twenty six(45%) had CM, 22 with convulsion; 26(45%) had SA and six(10%) had RD.</p> <p>Any retinopathy was seen in: CM 19(73%), SA 14(54%), RD 3(50.0%), CM with convulsion 15(68%) and CM without convulsion 4(100%). Comparison between CM versus non-CM groups showed a significant risk relationship between retinal whitening and CM(OR = 11.0, CI = 2.2- 56.1, p = 0.001). There was no significant association with papilloedema(OR = 0.9, CI = 0.3 - 3.0, p = 0.9), macular whitening(OR = 1.6, CI = 0.5 - 4.8, p = 0.4), macular haemorrhage(OR = 0.28, CI = 0.03 - 2.7 p = 0.2), retinal haemorrhage(OR = 1.9, CI = 0.6 - 5.6, p = 0.3), vessel abnormality(OR = 1.9, CI = 0.6 - 6.1, p = 0.3) and cotton wool spots(OR not calculated, p = 0.08).</p> <p>Tortuous and engorged retinal veins, not previously described as a feature of CM, was the most common vascular abnormality(15/58 = 26%) and was detected even in the absence of papilloedema.</p> <p>Conclusion</p> <p>Retinal whitening, a sign suggestive of retinal ischaemia, was significantly more common in CM than in non-CM syndromes. However, the high prevalence of any retinopathy in the latter suggests that the brain and the retina may be suffering from ischaemia in both CM and non-CM.</p

Amodiaquine-artesunate vs artemether-lumefantrine for uncomplicated malaria in Ghanaian children: a randomized efficacy and safety trial with one year follow-up

BACKGROUND: Artesunate-amodiaquine (AS+AQ) and artemether-lumefantrine (AM-L) are efficacious artemisinin combination therapy (ACT) regimens that have been widely adopted in sub-Saharan Africa. However, there is little information on the efficacy of these regimens on subsequent episodes beyond 28 days, or on the safety of repeated treatments. METHODS: Children aged six months to 14 years with uncomplicated malaria were randomly assigned to treatment with AS+AQ (n = 116), or AM-L (n = 111). Recruited subjects were followed-up, initially for 28 days, and then monthly for up to one year. All subsequent attacks of uncomplicated malaria after 28 days were treated with the same regimen as at randomization. Investigations aimed at determining efficacy and side effects were conducted. RESULTS: Adequate clinical and parasitological response in subjects with evaluable end-points were, 97.1% (100/103) and 98.2% (107/109) on day 14, and 94.2% (97/103) and 95.3% (102/107) on day 28 in the AM-L and AS+AQ groups, respectively. Similar results were obtained after PCR correction. The incidence of malaria attacks in the year following recruitment was similar between the two treatment groups (p = 0.93). There was a high incidence of potentially AQ-resistant parasites in the study area. The incidence of adverse events, such as pruritus, fatigue and neutropaenia were similar in the two treatment groups. No patient showed signs of hearing impairment, and no abnormal neurological signs were observed during one year of follow-up. Other adverse events were mild in intensity and overlapped with known malaria symptomatology. No adverse event exacerbation was observed in any of the subjects who received multiple treatment courses with these ACT regimens during one year follow-up. CONCLUSION: AS+AQ and AM-L were efficacious for treatment of children with uncomplicated malaria in Ghana and drug-related adverse events were rare in treated subjects during one year of follow-up. The high prevalence of potentially AQ resistant parasites raises questions about the utility of AQ as a partner drug for ACT in Ghana. The efficacy of AS+AQ in Ghana requires, therefore, continuous monitoring and evaluation. TRIAL REGISTRATION: NCT 0040614