N-acetylcysteine in severe falciparum malaria in Thailand

One hundred and eight patients with severe falciparum malaria underwent a placebo controlled trial with the antioxidant, N-acetylcysteine (NAC), as an adjunctive therapy along with standard intravenous artesunate therapy. Three NAC dosage regimens were used: an intravenous loading dose of 140 mg/kg followed by 70 mg/kg every four hours intravenously for up to 18 doses (Group 1); a single intravenous loading dose followed by oral NAC in the same amount as for Group 1 (Group 2); a regimen identical to Group 1 except that oral NAC was administered after the first 24 hours (Group 3). Fifty-four patients received placebo plus artesunate. Two critically ill patients died in Group 1. No patient sustained an adverse reaction to the NAC other than vomiting, and the deaths were attributed to severe disease with multiple organ involvement. The excellent results with NAC, the lack of adverse effects, and the rationale for NAC benefit supports the need for a large, double blind trial of NAC as an adjunctive therapy for severe malaria.     

Fatal invasive aspergillosis complicating severe Plasmodium falciparum malaria.

We report the first 2 cases of fatal invasive aspergillosis complicating severe malaria. In 2 nonimmune European adults without underlying disease, death was directly ascribable to invasive aspergillosis. We believe that transient malaria-induced immunosuppression allowed massive growth and overwhelming dissemination of preexisting Aspergillus colonization.     

Acute renal failure in patients with severe falciparum malaria.

Since 1988 in this referral center for severe cases of malaria for South Vietnam, a specialist team has managed malaria-associated renal failure (MARF) with peritoneal dialysis, and the mortality rate of MARF has fallen from 75% (78 of 104) to 26% (27 of 104) (P < .0002). Sixty-four patients with MARF (of whom 12 died) were compared to 66 patients with severe malaria whose serum creatinine levels remained < 250 mumol/L (six died). MARF had the clinical and biochemical features of acute tubular necrosis and was significantly associated with liver dysfunction (P < .05). A fatal outcome was associated significantly with anuria, a short history of illness, multisystem involvement, and high parasitemia. Most patients died from complications related to renal failure. Recovery of renal function was unrelated to parasitemia or hemoglobinuria; the median (range) time until urine output exceeded 20 mL/(kg.d) was 4 (0-19) days, and the time (mean +/- SD) for serum creatinine level to return to normal was 17 +/- 6 days. MARF can be managed effectively by prompt and careful peritoneal dialysis, but more effective dialysis or diafiltration might reduce the mortality rate further.     

Developmental impairments following severe falciparum malaria in children

OBJECTIVE: Neurological deficits are reported in children after cerebral malaria (CM) but little is known about the prevalence and characteristics of persisting neurocognitive consequences. The prevalence of developmental impairments following other complications of falciparum malaria, such as multiple, prolonged or focal seizures, is not known. Thus, our objective was to investigate the long-term developmental outcome of CM and malaria with complicated seizures (M/S). METHODS: We followed up a cohort of children previously exposed to CM or M/S and children unexposed to either condition. All children between 6 and 9 years of age, exposed to CM, and an equal number of children exposed to M/S were identified from databases of hospital admissions from 1991 to 1998. The unexposed group was randomly selected from a census database. The children's performance was measured using assessments of cognition, motor, speech and language, hearing and vision. A parental questionnaire was used to identify children with epilepsy. RESULTS: CM group scores were significantly lower than unexposed group scores on the assessments of higher level language (adjusted mean difference -1.63, 95% CI: -2.99 to -0.27), vocabulary (-0.02, 95% CI: -0.04 to -0.01), pragmatics (OR 2.81, 95% CI: 1.04-7.6) and non-verbal functioning (-0.33, 95% CI: -0.61 to -0.06). The areas of significantly reduced functioning for the M/S group were concentrated on phonology (OR 2.74, 95% CI: 1.26-5.95), pragmatics (OR 3.23, 95% CI: 1.2-8.71) and behaviour (OR 1.8, 95% CI: 1.0-3.23). The performance of the active epilepsy group was significantly poorer than that of the group without epilepsy on the tests of comprehension, syntax, pragmatics, word finding, memory, attention, behaviour and motor skills. CONCLUSIONS: CM and M/S are associated with developmental impairments. If these impairments persist, this may have implications for least 250,000 children in Sub-Saharan Africa each year. Active epilepsy significantly increases the risk of cognitive and behavioural problems in children with a history of severe malaria.     

重症恶性脑型疟疾的细胞粘附机制

疟疾约占世界感染性疾病的 2 .3% ,仅次于急性肺炎球菌呼吸道感染 (3.5 % )和结核病 (2 .8% ) ,是世界上第 3位重要的感染性疾病。每年约有 15 0～ 2 70万患者死于疟疾 ,主要在非洲 ,其中大多是婴儿和 5岁以下儿童。在感染人的 4种疟原虫中 ,恶性疟原虫(Plasmodium falciparum,P.f)危害最严重 ,可引起多个重要脏器功能障碍 ,发生重症疟疾 ,病死率高达15 %～ 30 %。其中重症脑型疟疾死亡率最高 ,其病理基础是感染疟原虫的红细胞 (IRBC)在脑深部血管床内滞留 (sequestration) ,造成代谢、机能紊乱而出现多种临床表现。其病理机制有“沉积 (…     

Pulmonary edema in severe falciparum malaria. Hemodynamic study and clinicophysiologic correlation

This study was performed to extend the knowledge of the pathogenesis of PE in severe falciparum malaria. Sequential hemodynamic studies were conducted in 13 patients with severe falciparum malaria. Seven patients developed PE, while the other six patients had NPE. Two patients died, one in each group. Hemodynamic changes were found in both groups, including an initial reduction in SVR and PVR, along with an increased CI and variable values (normal and increased) of PCWP. All abnormalities persisted for at least two days; changes in PVR lasted especially longer (throughout five days). The initial hemodynamic changes cannot predict the development of PE; however, heavy parasitemia of more than 60 percent and severe hypoalbuminemia were found to be more common in PE than NPE. Of three patients with PE who had normal PCWP, one died, with postmortem findings of increased pulmonary capillary permeability. The increased PCWP which was found in the other four cases of PE was proven to be volume overload without evidence of CHF. It was concluded that the pathophysiologic changes in severe falciparum malaria were systemic and pulmonary vasodilation. The abnormal pulmonary vascular change was found to be the cause of PE. Volume overload and hypoalbuminemia could aggravate further pulmonary capillary leakage in these cases.     

Automated erythrocytapheresis in the treatment of severe falciparum malaria

Removal of parasitized erythrocytes is generally considered to be of value as adjunctive therapy in severe falciparum malaria with high parasitaemia. This is commonly achieved by exchange transfusion. We describe three cases of severe falciparum malaria treated by automated erythrocytapheresis (red cell exchange) in addition to quinine and conventional supportive therapy. Erythrocytapheresis consists of removal of the red-cell fraction by apheresis. Plasma, leukocyte and platelet fractions are returned to the patient. In all cases, dramatic reduction in parasitaemia was achieved within 2 h with subsequent complete clinical recovery. Erythrocytapheresis has significant advantages over exchange transfusion in terms of speed, efficiency, haemodynamic stability and retention of plasma components such as clotting factors and may thus represent an improvement in adjunctive therapy for severe malaria.     

Severe falciparum malaria: survival without exchange transfusion

A case of severe falciparum malaria with trophozoites in 71% of the patients' erythrocytes is described. The patient was treated with high dose quinine and made an uneventful recovery. Exchange transfusion was not performed.     

输入性重症脑型恶性疟1例报告

患者，男性，34岁，农民，汉源县三郊乡永河村人，因寒战、发热7d。昏迷12h于2006年5月5日入院。7d前患者无明显诱因下出现寒战、发热（39．5℃）（为不规则发热，4～5h后热退，无出汗）伴头昏、呕吐、乏力、腹胀、纳差，在当地诊所治疗无好转，12h前出现昏迷，四肢强直，口吐泡沫，送入本院。     

Fluid management of severe falciparum malaria in African children

Most African children with severe malaria who die do so on the day of admission as a result of the complications of falciparum malaria. We highlight the value of a rapid structured triage assessment to look for emergency signs that will prioritize initial management and implementation of basic life support. This can be delivered with few resources and by non-specialist medical personnel. Reduction in case fatality can only come through the wider appreciation of the need for and application of supportive therapies to treat the life-threatening complications. Hypovolaemia has emerged as a common feature of children presenting with severe malaria complicated by acidosis. Early recognition and prompt treatment may lead to improvements in outcome. We discuss the new evidence supporting the role of hypovolaemia in severe malaria and potential treatment options whilst awaiting the results of clinical trials.     

Immunoglobulin therapy for severe thrombocytopenia complicating falciparum malaria

A 12-year-old Saudi boy with falciparum malaria developed profound thrombocytopenia with associated significant bleeding. Immunoglobulin was used to treat this case.