我国17例输入性疟疾死亡病例临床特征分析

目的 我国在2021年由WHO认证为无疟疾国家,疟疾已成为一种罕见传染性疾病,防止输入性疟疾再传播和减少因输入性疟疾死亡是中国消除疟疾后面临的主要挑战。本文分析输入性疟疾死亡病例特征,为境外务工的民众和医务工作者提供预防和治疗建议。方法 收集国家重症疟疾救治专家组2016—2020年疟疾死亡病例分析研讨会上报告17例疟疾死亡病例的数据,分析相关临床流行病学资料和病例资料。结果 17例疟疾死亡病例均为非洲输入的恶性疟原虫感染（疟疾脑型）,发病月份无明显规律,其中男性16例,5例合并糖尿病等基础疾病,首诊机构为二级及以下医院10例。排除在救护车上呼吸心脏骤停的死亡病例外,16例初次发病至疟疾确诊的平均时间为6.8 d（中位数5.5 d）,初次发病到服用抗疟药物治疗的平均时间为7.4 d（中位数6 d）,初次发病到病例死亡的平均时间为10.3 d（中位数8.5 d）。排除国外发病和回国时间不明的病例,14例病例均于回国后30 d内发病。结论 死亡病例均为非洲输入的恶性疟原虫感染（疟疾脑型）,患者积极就诊意识薄弱,乡镇级及以下卫生机构诊治能力不足所导致就医延迟是死亡病例发生的主要原因。建议加强境外疟疾流行地区务工人员自我保护意识,提升对疟疾危害的认知。基层医疗机构对来自疟疾高风险地区的归国人员,应关注患者的非洲旅行史,提升诊断疟疾的意识、疟疾诊断和处理能力,遵循抗疟治疗全程、足量的个体化治疗方案。     

Fulminant falciparum malaria

A case of fulminant falciparum malaria with a 35% parasitaemia, shock and subcoma was treated successfully by using parenteral chemotherapy, exchange transfusion, dexamethasone, circulatory support and mechanical ventilation. Pathophysiology and complications of falciparum malaria are discussed. The treatment of severe malaria should aim for a fast reduction in parasitaemia and toxic products. An exchange transfusion can be additive to parenteral chemotherapy. Blocking the over-reacting cell-mediated immune response, aggressive shock treatment, prevention of secondary infections and maintaining normoglycaemia might reduce morbidity and mortality of fulminant falciparum malaria.     

Acute inflammatory demyelinating polyradiculoneuropathy following malaria

Among the neurologic complications of malaria, acute inflammatory demyelinating polyradiculoneuropathy is a rarely reported phenomenon. We describe a patient with acute inflammatory demyelinating polyradiculoneuropathy following malaria in a 26-year-old traveler to an endemic area and review the clinical features of all 23 previously reported patients. Malarial infection should be considered as a potential preceding trigger in patients residing in or travelers returning from malaria-endemic areas presenting with the clinical features of acute inflammatory demyelinating polyradiculoneuropathy in the setting of a recent or ongoing febrile illness.     

贵州省凯里等12个基本消灭疟疾县（市）的监测结果

目的：评价本地区基本消灭疟疾９年来的监测结果。方法：采用传统的疟疾度量调查各项指标。结果：（１）年带虫发病率波动在０．００５６‰至０．０００３３‰间；（２）居民发热病人血检阳性率平均为０．７３，居民普查原虫率平均为０．８２；（３）流动人口发热病人血检阳性率及原虫率分别为４１３．１和７．０６；（４）在９９４个疫点中，活动性疫点占１０．７％。结论：输入病例是疟疾病例的主要来源（９３．４％），仍需继续加强流动人口的管理。     

广西疟疾监测措施研究

目的探讨广西基本消除和消除疟疾地区疟疾监测措施及其效果,为制订疟疾监测方案提供依据。方法采用病原学、血清学和昆虫学同步综合监测方法,对监测点发热病人血检疟原虫;小学生取滤纸血用IFAT测定疟疾抗体水平;半通宵(19:00～22:00)室外人诱捕蚊加早晨(5:00～7:00)50床蚊帐内捕蚊观察叮人率。结果监测点3个乡(镇)平均疟疾发病率和血检疟原虫阳性率2005年分别为0.69/万和0.26%,至2007年均下降为0;小学生年平均疟疾抗体阳性率为0.25%;3年间监测点未发生输入疟疾继发病例。结论早期发现和及时根治传染源是控制疟疾传播的关键措施。     

Polymorphisms in Plasmodium falciparum dhfr and dhps genes and age related in vivo sulfadoxine-pyrimethamine resistance in malaria-infected patients from Nigeria

Mutations in Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes have been used as means to predict treatment failure to sulfadoxine-pyrimethamine (SP) and for monitoring/surveillance of resistance to the drug in many areas where malaria is endemic. However, patients responses to treatment are significantly dependent on factors like host immunity profile of treated patients. In order to investigate the relationship between molecular markers of SP resistance, host immunity and clinical outcome, the association between pre-treatment dhfr and dhps genotypes, age and treatment outcomes was evaluated in 109 children treated with SP for acute uncomplicated malaria in Ibadan, Nigeria. Seventy-three percent of the children were cured with the drug, while 27% failed treatment after 28 days of follow-up. All children infected with parasites harboring less than two dhfr/dhps mutations were cured with SP. The dhfr triple (Asn-108/Ile-51/Arg-59) mutants or the dhps double mutants (Gly-437/Glu-540) were independently associated with SP treatment failure in children aged less than 5 years, but not in older children. The dhfr and dhps quintuple mutant (dhfr triple mutant+dhps double mutant) was the genotype most strongly associated with SP treatment failure (OR=24.72, 95%CI=8.24-74.15) in both younger and older children.     

Splenomegaly, pancytopenia and pregnancy: a case report and review of the literature

We present a 35-year-old previously healthy primigravida who presented at 26^4/7 weeks of gestation with pancytopenia and hepatosplenomegaly. She received 10 transfusions and delivered at 34^4/7 weeks of gestation by cesarean section. Two months later following splenectomy, she was diagnosed with malaria. Physicians should have a high index of suspicion for malaria in the context of splenomegaly and pancytopenia in pregnancy even in the absence of fever.     

Anti-malarial efficacy of pyronaridine and artesunate in combination in vitro and in vivo

Pyronaridine is a Mannich base anti-malarial with demonstrated efficacy against drug resistant Plasmodium falciparum, P. vivax, P. ovale and P. malariae. However, resistance to pyronaridine can develop quickly when it is used alone but can be considerably delayed when it is administered with artesunate in rodent malaria models. The aim of this study was to evaluate the efficacy of pyronaridine in combination with artesunate against P. falciparum in vitro and in rodent malaria models in vivo to support its clinical application. Pyronaridine showed consistently high levels of in vitro activity against a panel of six P. falciparum drug-sensitive and resistant strains (Geometric Mean IC50=2.24 nM, 95% CI=1.20-3.27). In vitro interactions between pyronaridine and artesunate showed a slight antagonistic trend, but in vivo compared to pyronaridine and artesunate administered alone, the 3:1 ratio of the combination, reduced the ED90 of artesunate by approximately 15.6-fold in a pyronaridine-resistant P. berghei line and by approximately 200-fold in an artesunate-resistant line of P. berghei. Complete cure rates were achieved with doses of the combination above or equal to 8 mg/kg per day against P. chabaudi AS. These results indicate that the combination had an enhanced effect over monotherapy and lower daily doses of artesunate could be used to obtain a curative effect. The data suggest that the combination of pyronaridine and artesunate should have potential in areas of multi-drug resistant malaria.     

Association between Fc-gamma receptor IIa (CD32) gene polymorphism and malaria susceptibility: A meta-analysis based on 6928 subjects

BackgroundPrevious studies about the association between the -131R/H polymorphism in the Fc-gamma receptor IIa (FcγRIIa) gene and malaria susceptibility have yielded conflicting results. The aim of this meta-analysis was to clarify more accurately the association of this polymorphism with malaria risk.MethodsA systematic literature search of the associated studies up to August 1, 2013, was conducted using the following electronic databases: PubMed, Embase, Medline, and the China National Knowledge Infrastructure (CNKI). Statistical analyses were performed by STATA12.0 software, with odds ratios (ORs) and their 95% confidence intervals (CIs).ResultsSix eligible studies including 4111 malaria cases and 2817 controls were identified. A pooled analysis of these studies pointed to a significant association between the variant H allele and reduced susceptibility to malaria or possible protection against malaria: H vs. R (OR = 0.691, P_OR = 0.009); HH vs. RR (OR = 0.523, P_OR = 0.013); RH vs. RR (OR = 0.770, P_OR = 0.037); RH + HH vs. RR (OR = 0.664, P_OR = 0.019); and HH vs. RH + RR (OR = 0.649, P_OR = 0.037). In subgroup analysis, similar significant associations were also found in Asia (HH vs. RR: OR = 0.137, P_OR = 0.009; HH vs. RH + RR: OR = 0.267, P_OR = 0.000) and in Africa (RH vs. RR: OR = 0.842, P_OR = 0.002; RH + HH vs. RR: OR = 0.859, P_OR = 0.004).ConclusionsThis meta-analysis suggests that the variant H allele of the FcγRIIa-131R/H polymorphism may be a protective factor against blood-stages of malaria infection, both in Asians and Africans. The finding may aid the development of effective immune protection strategies against malaria that focus on antibody responses and enrich current knowledge of gene polymorphism in the malaria. Further large and well-designed studies are needed to confirm this association.