Cases Of Severe Falciparum Malaria Research Articles

Challenging Experience with Severe Complicated Malaria in the City of Dhaka

Malaria is a vector-borne febrile illness that requires an association of three factors- parasite, vector, andhost- to continue its life cycle. The physical and cultural environments, as rainfall, humidity, and temperaturepermitted Bangladesh to be a malaria-endemic area, where Plasmodium falciparum is the dominantparasite and accounts for 93% of the malaria cases in the country. Due to the high degree of severity of thedisease and about 15% of total annual deaths in Bangladesh, in the year of 1961, Malaria EradicationProgram (MEP) was introduced. NMEP caused a significant reduction in total malaria incidences, severityand deaths. Still 33.6% of the total population in Bangladesh is at risk of malaria and the majority of casesare reported in 13 endemic areas of 64 districts in the country. Above all, resurgence of malaria andtreatment resistant cases have become a burning issue to think about in recent years. Here, we presenttwo severe falciparum malaria cases that challenged us with the complicated nature of the disease inDhaka city, which is not listed as a malaria endemic zone of Bangladesh. J MEDICINE 2022; 23: 87-95

Imported Malaria: A <i>Plasmodium falciparum</i> Malaria Case in Turkey with Rarely Seen Blood Stages of Infection

Malaria is an important public health problem, with about 219 million cases, which account for 435 thousand deaths of children in Africa in 2017. The infection is transmitted by female anopheles mosquito, including Plasmodium species pathogen for human. In Turkey, no domestic cases have been reported; however, according to Annual Health Statistics, 214 imported cases were reported in 2017. Although P. vivax exactly was reported in previous years, imported Plasmodium falciparum (P. falciparum) cases have increased in the last few years. Herein, we report a case of a 41-year-old male patient who returned two weeks ago from a one-week African journey. A limited number of different blood stages of the parasite (mature trophozoite, young and mature schizont) have been seen in the examination of the peripheral smear; however, the gametocyte stage was not seen. In the present case, detecting mature stages beside the early forms at the peripheral smear could not eliminate the probability of P. falciparum. To confirm the diagnosis and regulate the treatment protocol, molecular methods were employed to differentiate the potential mixture of infection. In this case study, we propose how to approach an uncertain case of severe falciparum malaria or mixture of malaria infection combined with another Plasmodium species, as a result of limited number of different blood stages of the infection at the peripheral smear.

STUDY OF ADRENAL INSUFFICIENCY IN SEVERE FALCIPARUM MALARIA WITH SHOCK KEY WORDS: Falciparum Malaria, Shock, Adrenal

Malaria remains a serious health problem in South East Asian Region (SEAR) with nearly 290 million people are estimated to be at high risk.India accounts for 77% of the regional total malarial cases.Most of deaths in malaria are due to severe falciparum malaria. Odisha is a unique state in the eastern region of India, which contributes 4% of the population and counting up to >40% of total falciparum malaria cases of India. Malaria is one of the most important public health disease in Odisha. In spite of such an important disease, there are many areas on severe falciparum malarias where research work is scanty. One among of them is detection of relative adrenal insufficiency in severe falciparum malaria. As there is limited work about the relative adrenal insufficiency in severe falciparum malaria with shock and its relation to mortality. This study has been undertaken with the following aims and objectives, firstly detection of relative adrenal insufficiency in severe falciparum malaria with shock and secondly to establish the relation of mortality with or without adrenal insufficiency in severe falciparum malaria.The present study has established that relative adrenal insufficiency is an important cause contributing to shock and increased mortality. Thus addition of corticosteroid saves life and must be used in the relative adrenal insufficiency. However the firm diagnosis of relative adrenal insufficiency depends upon estimation of basal serum cortisol level & post ACTH serum cortisol level. As corticosteroid reduces the mortality rate, it should be empirically used in critically ill severe falciparum malaria cases with shock.

Analysis of 11 imported severe malaria cases in Jiangsu

Objective This paper analyzed 11 cases of severe malaria in Jiangsu Province, summarized the causes of severe malaria, evaluated the effect of diagnosis and treatment, and provided scientific basis for formulating feasible treatment measures of severe malaria. Methods The case information, epidemiological investigation reports and inpatient medical records of 11 severe malaria cases in Jiangsu Province in 2019 were collected from the Infectious Disease Report Information Management System and Parasitic Disease Prevention and Control Information Management System. The onset time, clinical manifestations, diagnosis process and treatment of severe malaria cases were summarized and analyzed. Results Totally 11 cases of severe malaria, including 10 cases of falciparum malaria, and 1 case of ovale malaria, were all imported cases from abroad. The shortest time of living abroad was 22 days, and the longest was 1 070 days. Four cases had malaria while abroad. All of the 10 severe cases of falciparum malaria developed within one month after they returned to China, and three of them became ill on the day they returned home. One severe case of Plasmodium ovale began onset 134 days after returning home. The average time from onset to treatment was 2.5 days, and the average interval time from visit to diagnosis was 1.81 days. There were 3 cases of coma or shock, 3 cases of severe anemia, 4 cases of acute renal failure, and 1 case of acute respiratory distress syndrome. 1 case of Plasmodium ovale had severe anemia due to spontaneous rupture of spleen. Except one case of ovale malaria was treated with dihydroartemisinin piperaquine tablets plus primaquine tablets, the other 10 severe falciparum malaria cases were treated with artesunate injection for antimalarial treatment, and all of them were cured and discharged from hospital after receiving antimalarial treatment. 11 cases of severe cases, the shortest length of stay was 9 days, the longest was 40 days, with an average of 22.64 days; the minimum hospitalization cost was 9 270 yuan, the maximum was 177 174 yuan, with an average of 81 520.76 yuan. Conclusion It is necessary to strengthen multi department cooperation to improve patients’ awareness of timely treatment, strengthen the professional knowledge and professional training of medical staff, find and treat imported malaria cases as soon as possible, so as to prevent severe malaria caused by delayed diagnosis. 摘要:目的 对江苏省11例输入性重症疟疾病例进行分析,总结重症疟疾的成因、评价诊治效果,为制定切实可行 的重症疟疾救治措施提供科学依据。 方法 收集2019年江苏省11例重症疟疾病例传染病报告信息管理系统和寄生 虫病防治信息管理系统的个案信息、流行病学调查报告以及住院病历,对重症疟疾病例的发病时间、临床表现、诊断过 程、治疗情况进行汇总分析。 结果 11例重症疟疾病例中恶性疟10例、卵形疟1例,均为境外输入性病例,在境外生活 时间最短22 d最长1 070 d在国外期间有4例曾患过疟疾。10例恶性疟重症病例均在回国后一个月内发病,其中有 3例在回国当天就发病。1例卵形疟重症病例在回国后134 d才开始发病。11例重症疟疾病例发病至就诊平均时间为 2.5 d,就诊至确诊平均时间为1.81 d。重症表现为昏迷或休克3例、重度贫血3例、急性肾功能衰竭4例、急性呼吸窘迫 综合征1例。1例卵形疟由于出现自发性脾破裂引起重度贫血。除1例卵形疟病例给予双氢青蒿素哌喹片加服伯氨喹 片治疗外,其余10例恶性疟重症病例均采用青蒿琥酯注射抗疟治疗,接受抗疟治疗后均痊愈出院。11例重症病例,住 院天数最短9 d最长40 d平均22.64 d;住院费用最少9 270元,最多177 174元,平均81 520.76元。 结论 应加强多部 门合作,提高患者及时就诊意识;加强医务人员疟疾专业知识和业务的培训,尽早发现输入性疟疾病例并及时治疗,防 止因延误诊断造成的重症疟疾。

Electrocardiographic abnormalities with quinine and artesunate combinations in comparison to quinine or artesunate alone in severe falciparum malaria

Background: In Multi drug resistant falciparum malaria anti-malarial combinations are frequently used i.e. Quinine and IV Artesunate. Quinine is associated with electrocardiographic disturbances. Artesunate in high dose produce QTC prolongation in animal models, so the electrocardiogram (ECG) is thoroughly studied.Methods: Severe falciparum malaria cases 15 to 60 years were randomly allocated into 3 treatment regimens i.e. Artesunate, Quinine alone and their combination. Electrocardiographic recordings were taken periodically in 3 groups and compared statistically.Results: The mean QTC interval is significantly prolonged in combination treatment group from 0.40+0.02 to 0.49+0.09 (P<0.05) ECG disturbance (44%). QTC prolongation was commonest (i.e. 27%) with electrolyte imbalance could produce life threatening cardiac arrhythmia (Polymorphic VT with Sr K+ 2.9). Artesunate alone was list prone (i.e. only 6%) Quinine though has comparatively more (i.e. 25%) but there is no life-threatening cardiac arrhythmia in artesunate and Quinine.

Diagnosis of imported malaria cases in Henan Province from 2015 to 2019

To analyze the diagnosis of imported malaria cases in Henan Province from 2015 to 2019, so as to provide the evidence for malaria surveillance during the post-elimination stage. The data pertaining to malaria cases in Henan Province from 2015 to 2019 were extracted via the web-based Chinese Information System for Infectious Diseases Control and Prevention and the Parasitic Diseases Information Reporting Management System (PDIRMS) of Chinese Center for Disease Control and Prevention, and the diagnostic methods, diagnostic institutions and diagnostic time of imported malaria cases were analyzed. A total of 952 imported malaria cases were reported in Henan Province during the period from 2015 through 2019, and all cases were laboratory-confirmed. The positive rate of malaria rapid diagnostic tests (RDTs) was 98.61% (779/790), which was significantly greater than that (94.22%, 897/952) of microscopic examinations (χ2 = 22.773, P < 0.05). The proportion of imported malaria cases diagnosed in medical institutions increased from 65.22% (120/184) in 2015 to 81.50% (185/227) in 2019. Among the 238 imported malaria cases diagnosed in centers for disease control and prevention (CDC), 71.01% (169/238) were diagnosed in county-level CDC, and among the 704 cases diagnosed in medical institutions, only 8.38% (59/704) were diagnosed at county-level medical institutions. The median time from onset to definitive diagnosis of malaria was 3 days, and the median duration between onset and initial diagnosis of malaria was 1 day. The duration between initial diagnosis and definitive diagnosis of malaria varied significantly among years (χ2 = 24.956, P < 0.05), and the interquartile range from initial diagnosis to definitive diagnosis reduced from 4 days in 2016 to 2 days in 2019. In addition, the median time from initial diagnosis to definitive diagnosis was significantly longer in severe falciparum malaria cases than in non-severe falciparum malaria cases (2 days vs. 1 day; Z = 7.557, P < 0.05). Medical institutions play a more and more important role in the identification and surveillance of malaria cases; however, the diagnostic capability of malaria remains low in county-level medical institutions. The diagnostic awareness and capability of county-level medical institutions requires to be improved, in order to play their roles as sentinel hospitals in the malaria surveillance during the post-elimination stage.

Impact of Sever Plasmodium falciparum infection on Platelets Parameters among Sudanese children Living in Al-Jazira State

Background: Falciparum malaria remains one of the most global infection among children particularly in communities with poor resources. Falciparum malaria associated with several hematological changes that affect the major blood cell lines such as platelets lead to platelets parameters (platelets count and indices) abnormalities.&#x0D; Objectives: The aim of this study was to evaluate the effects of falciparum malaria on platelets parameters (platelets count and indices) among Sudanese children. In addition to study relationships and correlation between platelets parameters and malaria parasitemia and parasite count.&#x0D; Materials and Methods: A case control study was conducted in Wad Medani Pediatric Hospital in collaboration with Faculty of Medical laboratory Sciences, University of Gezira, Sudan among 100 children with severe falciparum malaria (mean age 8.63 ± 3.40 years; 61% males), 100 children with uncomplicated falciparum malaria (mean age 8.83 ± 4.20 years; 45% males) and 100 children with normal healthy children controls (mean age 10.08 ± 3.58 years; 50% males). Parasitemia and parasite count (%) was determined directly from thick and thin blood films respectively. The platelets parameters (platelets count and indices) measured by using Sysmex XP 300 N automated analyzer, and platelets count was confirmed and assessed using stained thin blood film. SPSS software (V 20.0) and Stat disk software (V 13.0) were used for data analysis.&#x0D; Results: 72 % of severe falciparum malaria (SM) have hyperparasitemia, while 18 % among uncomplicated falciparum malaria (UM). The thrombocytopenia account for 43 % (SM: 30.5 %; UM: 12.5 %), low PCT account for 35.5 % (SM: 27 %; UM: 8.5 %) and high PDW account for 46.5 % (SM: 23.5 %; UM: 23 %) in falciparum malaria cases. The mean PLTs count and PDW were statistically significantly differences between falciparum malaria cases and normal healthy control (P value 0.000 and 0.008 respectively). The mean PLTs count and PCT in severe falciparum malaria cases were lower than uncomplicated falciparum malaria cases (P value 0.005 and 0.000 respectively). The PLTs count and PCT had significant negative correlation within malaria parasitemia (P value 0.000; r -0.286; P value 0.004; r -0.205 respectively) and malaria parasite count (P value 0.000; r -0.450; P value 0.000; r -0.270 respectively).&#x0D; Conclusion: The study concluded that thrombocytopenia, low PCT and high PDW were observed as most platelets parameters changes in falciparum malaria. PLTs count along with PCT to be recommended as hematological diagnostic markers and prognostic tool to assess the disease severity and to improve the management of falciparum malaria among patients.

Imported Malaria at a Referral Hospital in Tokyo from 2005 to 2016: Clinical Experience and Challenges in a Non-Endemic Setting.

.In this study, we reviewed imported malaria cases observed at the National Center for Global Health and Medicine, Tokyo, between 2005 and 2016, to comprehend their demographic and clinical characteristics. Data on 169 cases were used to analyze demographic information; data on 146 cases were used for the analysis of clinical information. The median patients’ age was 34 years, and 79.3% of them were male. The proportion of non-Japanese patients increased and surpassed that of Japanese patients after 2015. In 82.2% of the cases, the region of acquisition was Africa, and Plasmodium falciparum was the dominant species (74.0%) followed by Plasmodium vivax (15.4%). We observed 19 (18.4%, 19/103) severe falciparum malaria cases. Mefloquine was the most commonly used drug for treatment until the early 2010s; atovaquone/proguanil was the most commonly used after its licensure in 2013. Although none of the patients died, four recrudescence episodes after artemether/lumefantrine (A/L) treatment and one relapse episode were observed. Overall, malaria was diagnosed on median day 4 of illness, and, thereon, treatment was initiated without delay. Diagnosis on day 5 or later was significantly associated with severe disease in Japanese cases (odds ratio = 4.1; 95% CI = 1.2–14.3). We observed a dominance of falciparum malaria, an increase in the number of non-Japanese cases, late treatment failure after A/L treatment, a low relapse rate, and an association between delayed malaria diagnosis and higher disease severity. Pretravel care and early diagnosis are necessary to reduce malaria-related mortality and morbidity in settings such as ours.

A Case of Severe Falciparum Malaria Successfully Treated with Rectal Artesunate and Intravenous Quinine in Combination

A Case of Severe Falciparum Malaria Successfully Treated with Rectal Artesunate and Intravenous Quinine in Combination

Epidemic situation and diagnosis and treatment of severe falciparum malaria in Nantong City

To retrospectively analyze the epidemic situation and diagnosis and treatment of severe falciparum malaria in Nantong City, summarize the causes of severe falciparum malaria, and evaluate the effect of diagnosis and treatment, so as to provide the evidence for formulating the practical treatment measures for this disease. All the data of falciparum malaria cases in Nantong City from 2009 to 2016 were collected and analyzed for the onset time, diagnosis process and treatment of the disease. A total of 359 malaria cases, including 289 falciparum malaria cases, were reported in Nantong City from 2009 to 2016, including 26 severe falciparum malaria cases. All the severe falciparum malaria cases were imported from Africa, including 57.70% of cases (15/26) from Angola. All of them were male labor exporting personnel. The incidence of malaria was not obviously seasonal. The average time from onset to definite diagnosis was 5.2 days, and 11 cases were diagnosed 5 days after the onset. All the 26 cases were cured by anti-malaria treatment and symptomatic treatment, and there was no death. Severe falciparum malaria seriously harm the people's health and its clinical manifestations are complicated. Therefore, the training of medical staff and health education in residents, especially in labor exporting personnel, should be further strengthened.

Cases diagnosis of imported malaria in Jiangsu province, 2014-2016

Objective: To understand the situation related to health seeking and diagnosis of imported malaria and to provide practical measures for malaria elimination in Jiangsu province. Methods: Data on imported malaria cases in Jiangsu province was retrieved in CISDCP from 2014 to 2016. Relevant information on health seeking behavior, diagnosis and treatment of the disease was gathered. Results: A total of 1 068 imported cases were reported in Jiangsu province from 2014 to 2016. Except for one malaria case that was caused by blood transfusion, the rest patients were all recognized as 'imported'. Majority of the cases were migrant laborers working in African countries. The accurate rates on the diagnosis of ovale, vivax and quartan malaria and mixed infection were relatively low, as 79.3% (107/135), 29.5% (18/61), 52.9% (18/34) and 0.0% (0/2) at the primary health care settings, respectively. Rate of seeking health care on the same day of onset was more in 2015 than in 2014 and 2016 (χ(2)=18.6, P=0.001). While only 65.4% (699/1 068) of the patients were diagnosed correctly at the primary health care settings. There appeared no statistical difference in the 3-year-study period (χ(2)=5.4, P=0.246). Capacity on 'correct diagnosis' seemed stronger at the CDC than at the hospital levels (χ(2)=13.2, P=0.000; χ(2)=5.4, P=0.020). Totally, 72.7% (32/44) of the severe falciparum malaria cases did not immediately seek for health care when the symptoms started. Conclusions: Migrant workers returning from the high endemic malaria areas seemed to have poor awareness in seeking health care services. Capability on correct diagnosis for malaria at the primary health care settings remained unsatisfactory and staff from these settings needs to receive adequate training.

An Imported Case of Severe Falciparum Malaria with Prolonged Hemolytic Anemia Clinically Mimicking a Coinfection with Babesiosis

While imported falciparum malaria has been increasingly reported in recent years in Korea, clinicians have difficulties in making a clinical diagnosis as well as in having accessibility to effective anti-malarial agents. Here we describe an unusual case of imported falciparum malaria with severe hemolytic anemia lasting over 2 weeks, clinically mimicking a coinfection with babesiosis. A 48-year old Korean man was diagnosed with severe falciparum malaria in France after traveling to the Republic of Benin, West Africa. He received a 1-day course of intravenous artesunate and a 7-day course of Malarone (atovaquone/proguanil) with supportive hemodialysis. Coming back to Korea 5 days after discharge, he was readmitted due to recurrent fever, and further treated with Malarone for 3 days. Both the peripheral blood smears and PCR test were positive for Plasmodium falciparum. However, he had prolonged severe hemolytic anemia (Hb 5.6 g/dl). Therefore, 10 days after the hospitalization, Babesia was considered to be potentially coinfected. A 7-day course of Malarone and azithromycin was empirically started. He became afebrile within 3 days of this babesiosis treatment, and hemolytic anemia profiles began to improve at the completion of the treatment. He has remained stable since his discharge. Unexpectedly, the PCR assays failed to detect DNA of Babesia spp. from blood. In addition, during the retrospective review of the case, the artesunate-induced delayed hemolytic anemia was considered as an alternative cause of the unexplained hemolytic anemia.

MALARIA TREATMENT VS. MALARIA PROPHYLAXIS : A COST COMPARISON.

Aim This research aims to evaluate the cost of using drugs to combat an established infection as compared with drugs used for prophylactic purposes. And this aim was achieved by using the following objective which was: (i) To estimate the cost of using anti-malarial drugs as treatment compared to using them as prophylaxis. Methods The study used 142 subjects (n=142) who had travelled to Liberia for six months to work among the Jordanian Level III Hospital within the United Nations Mission in Liberia (UNMIL). This is a malarious area, so the participants have to take prophylactic medicine, or they will be at risk of acquiring malaria. The prophylactic medicines that have been taken by the participants cost the RMS a particular value (Cost 1), In contrast those who acquired malaria will need treatment and hospitalization and this will incur on the RMS another different set of costs (Cost 2). A questionnaire was distributed among the participants to collect the data needed. In addition, data was collected from the records of the financial offices in the hospitals of Royal Medical Services (RMS) where the malarious patients were treated. Results From the 142 participants, 52.1% used Mefloquine for prophylaxis in comparison with Doxycycline which was used by 29.6% of them, and the rest, 18.3%, used more than one prophylactic method. One case of malaria infection occurred during the study period and it was diagnosed as Severe Falciparum Malaria (SFM). The patient answered that he didn’t use any prophylactic medication, Cost 1 and Cost 2 evaluated and found to be £10189.00 and £1220.00 respectively. Conclusion The study showed much less cost when using these drugs for prophylaxis by 94% per capita comparing with the cost of treating one case of Severe Falciparum Malaria (SFM). Key words Malaria, Imported, Prophylaxis, Antimalarials, Costs.

Severe falciparum malaria with dengue coinfection complicated by rhabdomyolysis and acute kidney injury: an unusual case with myoglobinemia, myoglobinuria but normal serum creatine kinase

BackgroundAcute kidney injury (AKI) is a complication of severe malaria, and rhabdomyolysis with myoglobinuria is an uncommon cause. We report an unusual case of severe falciparum malaria with dengue coinfection complicated by AKI due to myoglobinemia and myoglobinuria while maintaining a normal creatine kinase (CK).Case presentationA 49-year old Indonesian man presented with fever, chills, and rigors with generalized myalgia and was diagnosed with falciparum malaria based on a positive blood smear. This was complicated by rhabdomyolysis with raised serum and urine myoglobin but normal CK. Despite rapid clearance of the parasitemia with intravenous artesunate and aggressive hydration maintaining good urine output, his myoglobinuria and acidosis worsened, progressing to uremia requiring renal replacement therapy. High-flux hemodiafiltration effectively cleared his serum and urine myoglobin with recovery of renal function. Further evaluation revealed evidence of dengue coinfection and past infection with murine typhus.ConclusionIn patients with severe falciparum malaria, the absence of raised CK alone does not exclude a diagnosis of rhabdomyolysis. Raised serum and urine myoglobin levels could lead to AKI and should be monitored. In the event of myoglobin-induced AKI requiring dialysis, clinicians may consider using high-flux hemodiafiltration instead of conventional hemodialysis for more effective myoglobin removal. In Southeast Asia, potential endemic coinfections that can also cause or worsen rhabdomyolysis, such as dengue, rickettsiosis and leptospirosis, should be considered.

Cytoadherence and virulence - the case of Plasmodium knowlesi malaria

BackgroundCytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigens, expressed on the surface of infected erythrocytes, to endothelial receptors including, ICAM-1, VCAM and CD36. In fatal cases of severe falciparum malaria with coma, blood vessels in the brain are characteristically congested with infected erythrocytes. Brain sections from a fatal case of knowlesi malaria, but without coma, were similarly congested with infected erythrocytes. The objective of this study was to determine the binding phenotype of Plasmodium knowlesi infected human erythrocytes to recombinant human ICAM-1, VCAM and CD36.MethodsFive patients with PCR-confirmed P. knowlesi malaria were recruited into the study with consent between April and August 2010. Pre-treatment venous blood was washed and cultured ex vivo to increase the proportion of schizont-infected erythrocytes. Cultured blood was seeded into Petri dishes with triplicate areas coated with ICAM-1, VCAM and CD36. Following incubation at 37°C for one hour the dishes were washed and the number of infected erythrocytes bound/mm2 to PBS control areas and to recombinant human ICAM-1 VCAM and CD36 coated areas were recorded. Each assay was performed in duplicate. Assay performance was monitored with the Plasmodium falciparum clone HB3.ResultsBlood samples were cultured ex vivo for up to 14.5 h (mean 11.3 ± 1.9 h) to increase the relative proportion of mature trophozoite and schizont-infected red blood cells to at least 50% (mean 65.8 ± 17.51%). Three (60%) isolates bound significantly to ICAM-1 and VCAM, one (20%) isolate bound to VCAM and none of the five bound significantly to CD36.ConclusionsPlasmodium knowlesi infected erythrocytes from human subjects bind in a specific but variable manner to the inducible endothelial receptors ICAM-1 and VCAM. Binding to the constitutively-expressed endothelial receptor CD36 was not detected. Further work will be required to define the pathological consequences of these interactions.

A −436C&gt;A Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria

Human genetics and immune responses are considered to critically influence the outcome of malaria infections including life-threatening syndromes caused by Plasmodium falciparum. An important role in immune regulation is assigned to the apoptosis-signaling cell surface receptor CD95 (Fas, APO-1), encoded by the gene FAS. Here, a candidate-gene association study including variant discovery at the FAS gene locus was carried out in a case-control group comprising 1,195 pediatric cases of severe falciparum malaria and 769 unaffected controls from a region highly endemic for malaria in Ghana, West Africa. We found the A allele of c.−436C>A (rs9658676) located in the promoter region of FAS to be significantly associated with protection from severe childhood malaria (odds ratio 0.71, 95% confidence interval 0.58–0.88, pempirical = 0.02) and confirmed this finding in a replication group of 1,412 additional severe malaria cases and 2,659 community controls from the same geographic area. The combined analysis resulted in an odds ratio of 0.71 (95% confidence interval 0.62–0.80, p = 1.8×10−7, n = 6035). The association applied to c.−436AA homozygotes (odds ratio 0.47, 95% confidence interval 0.36–0.60) and to a lesser extent to c.−436AC heterozygotes (odds ratio 0.73, 95% confidence interval 0.63–0.84), and also to all phenotypic subgroups studied, including severe malaria anemia, cerebral malaria, and other malaria complications. Quantitative FACS analyses assessing CD95 surface expression of peripheral blood mononuclear cells of naïve donors showed a significantly higher proportion of CD69+CD95+ cells among persons homozygous for the protective A allele compared to AC heterozygotes and CC homozygotes, indicating a functional role of the associated CD95 variant, possibly in supporting lymphocyte apoptosis.

Automated erythrocytapheresis for severe falciparum malaria

We describe a case of severe falciparum malaria with hyperparasitaemia. Treatment with automated erythrocytapheresis, in conjunction with parenteral artesunate, produced a rapid and sustained fall in parasite burden. Several poor prognostic features were present at admission. Despite the development of a severe headache with abnormal cerebrospinal fluid parameters and transient pulmonary oedema, a complete recovery was observed. Erythrocytapheresis can be considered in selected cases where facilities exist and has theoretical and practical advantages over traditional methods of red cell exchange transfusion. The paucity of systematic or trial evidence convincingly demonstrating a benefit in terms of morbidity or mortality has limited its application. However, the lack of robust trial data should not in itself invalidate considering this therapeutic option in the appropriate context.

Combined Intravenous Treatment with Artesunate and Quinine for Severe Malaria in Italy

Severe imported malaria is an important problem in European countries, where approximately 8,000 cases of Plasmodium falciparum malaria are reported each year. Although the World Health Organization recommends intravenous artesunate (IVA) as the treatment of choice for severe malaria in areas of low transmission, it is rarely used in Europe, because it is not yet available as a drug manufactured under Good Manufacturing Practices. We report a series of eight imported severe falciparum malaria cases treated with IVA combined with intravenous quinine (IVQ). This combined therapy was found to be efficacious, safe, and well-tolerated. The only observed death occurred in a young man who presented 10 days after the onset of symptoms. IVA plus IVQ treatment seems to be an acceptable approach, because the legal risks in using an unlicensed drug for treating a severe malaria case denies the patient the possibility of being treated with the most effective regimen.

A Case of Severe Falciparum Malaria Complicated with DIC

患者は32歳の女性．アフリカから帰国後，発熱・嘔吐・下痢を発症した．輸入感染症を疑い，血液塗沫検査で赤血球内に2つのクロマチン顆粒をもつ輪状体が複数存在し，熱帯熱マラリアと診断した．赤血球感染率7%で重症マラリアとも診断した．集中治療室で，全身管理およびキニーネ静注による治療を行った．播種性血管内凝固症候群（disseminated intravascular coagulation：DIC）も合併し，血小板輸血とアンチトロンビン製剤投与を行った．その後，マラリア感染およびDICは改善した．抗マラリア薬の適正な使用と，DICに対する早期治療が奏効したと考えられた．

Nitrosative stress with HIV dementia causes decreased L-prostaglandin D synthase activity

The prevalence of HIV-associated neurocognitive disorders is increasing as HIV-infected individuals are living longer. The clinical manifestations of the syndrome also continue to evolve under the influence of antiretroviral drugs and comorbidities such as drugs of abuse. However, there are no surrogate markers for the disease, either to identify it de novo or to track its progression, and there is no proven treatment with the exception of antiretroviral drugs. Levels of nitric oxide, nitrate, and 3-nitrotyrosine (3-NT)-modified proteins were measured in the CSF of 46 patients with HIV infection stratified according to their neurocognitive status and history of IV drug use (IVD). The 3-NT-modified proteins were isolated and identified by tandem mass spectrometry, and the functional consequence of 3-NT modification of L-prostaglandin D synthase (L-PGDS), the most abundant protein, was determined. 3-NT-modified proteins were significantly elevated in patients with HIV infection who had progressive neurocognitive decline over the next 6 months and in patients with a history of IVD. Thirteen different proteins with 3-NT modification were identified in the CSF of these patients. L-PGDS was the most abundant. 3-NT modification of this protein resulted in loss of its enzymatic activity. There is increased nitrosative stress in CSF of HIV-infected patients with active dementia and in patients with a history of IV drug use, measurement of which may serve as a surrogate marker for these patients. Nitrosative stress may also have important functional consequences and may impact the pathogenesis of HIV-associated neurocognitive disorders.