Prolonged parasite clearance in a Chinese splenectomized patient with falciparum malaria imported from Nigeria

Background:The spleen plays a pivotal role in the rapid clearance of parasitized red blood cells in patients with falciparum malaria after artemisinin treatment.Prolonged parasite clearance can be found in patients who have had a splenectomy,or those with hemoglobin abnormalities and/or reduced immunity,which are all distinguishable from artemisinin resistance.This paper reports on a case of prolonged parasite clearance in a Chinese splenectomized patient with falciparum malaria imported from Nigeria.Case presentation:A 35-year-old Chinese male suffered 2 days of febrile illness after returning to Zhumadian city of Henan province from Nigeria on October 1,2014.The main symptoms were febrile,including the highest axillary temperature of 40℃,headache,and chills.A peripheral blood smear showed parasitemia(53913 asexual parasites/μl)of Plasmodium falciparum.The patient had not used any chemoprophylaxis against malaria in Nigeria when he worked there as a construction worker between 2009 and 2014.The patient had three episodes of malaria in Nigeria and had a splenectomy due to a traffic accident 8 years ago from the time he was admitted to hospital.The patient was orally administrated a total of 320 mg/2.56 g dihydroartemisinin-piperaquine for 2 days and intravenously administrated a total of 3000 mg artesunate for 18 days.The axillary temperature of the patient ranged between 37.0 and 37.7℃ from Day 0 to Day 3,and blood microscopy revealed falciparum malaria parasitemia(26674 asexual parasites/μl)on Day 3.The patient was afebrile on Day 4,falciparum malaria parasitemia was continuously present and then gradually decreased on the next days,and was negative on Day 21.The patient was cured and left hospital on Day 24 after no plasmodium falciparum was found in the blood on Day 21 to Day 23.No mutation was found in the K13 propeller gene when compared with the PF3D7_1343700 K13 propeller gene reference sequence.Conclusions:This is the first reported case in China of prolonged parasite clearance in a splenectomized patient with imported falciparum malaria.Artemisinin resistance should be distinguished when prolonged parasite clearance is found in a malaria patient who has had splenectomy.

Parasite reduction ratio one day after initiation of artemisinin-based combination therapies and its relationship with parasite clearance time in acutely malarious children

Background:In acute falciparum malaria,asexual parasite reduction ratio two days post-treatment initiation(PRRD2)≥10000 per cycle has been used as a measure of the rapid clearance of parasitaemia and efficacy of artemisinin derivatives.However,there is little evaluation of alternative measures;for example,parasite reduction ratio one day after treatment initiation(PRRD1)and its relationship with parasite clearance time(PCT)or PRRD2.This study evaluated the use of PRRD1 as a measure of responsiveness to antimalarial drugs.Methods:In acutely malarious children treated with artesunate-amodiaquine(AA),artemether-lumefantrine(AL)or dihydroartemisinin-piperaquine(DHP),the relationships between PRRD1 or PRRD2 and PCT,and between PRRD1 and PRRD2 were evaluated using linear regression.Agreement between estimates of PCT using PRRD1 and PRRD2 linear regression equations was evaluated using the Bland-Altman analysis.Predictors of PRRD1>5000 per half cycle and PRRD2≥10000 per cycle were evaluated using stepwise multiple logistic regression models.Using the linear regression equation of the relationship between PRRD1 and PCT previously generated in half of the DHP-treated children during the early study phase,PCT estimates were compared in a prospective blinded manner with PCTs determined by microscopy during the later study phase in the remaining half.Results:In 919 malarious children,PRRD1 was significantly higher in DHP-and AA-treated compared with AL-treated children(P<0.0001).PRRD1 or PRRD2 values correlated significantly negatively with PCT values(P<0.0001 for each)and significantly positively with each other(P<0.0001).PCT estimates from linear regression equations for PRRD1 and PRRD2 showed insignificant bias on the Bland-Altman plot(P=0.7)indicating the estimates can be used interchangeably.At presentation,age>15months,parasitaemia>10000/μl and DHP treatment independently predicted PRRD1>5000 per half cycle,while age>30months,haematocrit≥31%,body temperature>37.4°C,parasitaemia>100000/μl,PRRD1 value>1000 and no gametocytaemia independently predicted PRRD2≥10000 per cycle.Using the linear regression equation generated during the early phase in 166 DHP-treated children,PCT estimates and PCTs determined by microscopy in the 155 children in the later phase were similar in the same patients.Conclusions:PRRD1 and estimates of PCT using PRRD1 linear regression equation of PRRD1 and PCT can be used in therapeutic efficacy studies.Trial registration:Pan African Clinical Trial Registration PACTR201709002064150,1 March 2017,http://www.pactr.org.

Di-PEGylated insulin:A long-acting insulin conjugate with superior safety in reducing hypoglycemic events

Although the discovery of insulin 100 years ago revolutionized the treatment of diabetes,its therapeutic potential is compromised by its short half-life and narrow therapeutic index.Current long-acting insulin analogs,such as insulin-polymer conjugates,are mainly used to improve pharmacokinetics by reducing renal clearance.However,these conjugates are synthesized without sacrificing the bioactivity of insulin,thus retaining the narrow therapeutic index of native insulin,and exceeding the efficacious dose still leads to hypoglycemia.Here,we report a kind of di-PEGylated insulin that can simultaneously reduce renal clearance and receptor-mediated clearance.By impairing the binding affinity to the receptor and the activation of the receptor,di-PEGylated insulin not only further prolongs the half-life of insulin compared to classical mono-PEGylated insulin but most importantly,increases its maximum tolerated dose 10-fold.The target of long-term glycemic management in vivo has been achieved through improved pharmacokinetics and a high dose.This work represents an essential step towards long-acting insulin medication with superior safety in reducing hypoglycemic events.

1例来自孟加拉国的青蒿素耐药恶性疟病例分析

收集并分析了联合国驻刚果(金)稳定特派团中国二级医院于2021年2月20日收治的1例来自孟加拉国的青蒿素耐药恶性疟病例的临床资料和实验室检查,讨论了青蒿素耐药目前的现状及相关治疗,为救治青蒿素耐药恶性疟提供思路。该患者主因“高热伴腹痛,呕吐3 d”入院。自诉曾3次得过“疟疾”并痊愈。入院前曾在乌维拉一级医院接受过蒿甲醚治疗(具体不详)。查血涂片及疟疾快速诊断试验诊断为恶性疟,血中疟原虫密度计数43008/μL。血小板数40×10^(9)/L,谷丙转氨酶174 U/L,谷草转氨酶292 U/L,总胆红素38.2μmol/L。予以青蒿琥酯注射治疗2 d后,患者仍有发热,但呕吐症状减轻。2月23日使用口服复方双氢青蒿素片治疗,效果不佳,考虑青蒿素耐药可能。2月25日开始使用奎宁联合多西环素的7 d治疗,随后患者体温恢复正常。复查血中疟原虫清除,肝肾功能正常,患者于3月4日办理出院。28 d随访无复发。