Plasmodium falciparum pfhrp2 and pfhrp3 Gene Deletions and Relatedness to Other Global Isolates,Djibouti, 2019–2020

Deletions of pfhrp2 and paralogue pfhrp3 (pfhrp2/3) genes threaten Plasmodium falciparum diagnosis by rapid diagnostic test. We examined 1,002 samples from suspected malaria patients in Djibouti City, Djibouti, to investigate pfhrp2/3 deletions. We performed assays for Plasmodium antigen carriage, pfhrp2/3 genotyping, and sequencing for 7 neutral microsatellites to assess relatedness. By PCR assay, 311 (31.0%) samples tested positive for P. falciparum infection, and 296 (95.2%) were successfully genotyped; 37 (12.5%) samples were pfhrp2+/pfhrp3+, 51 (17.2%) were pfhrp2+/pfhrp3–, 5 (1.7%) were pfhrp2–/pfhrp3+, and 203 (68.6%) were pfhrp2–/pfhrp3–. Histidine-rich protein 2/3 antigen concentrations were reduced with corresponding gene deletions. Djibouti P. falciparum is closely related to Ethiopia and Eritrea parasites (pairwise G_ST 0.68 [Ethiopia] and 0.77 [Eritrea]). P. falciparum with deletions in pfhrp2/3 genes were highly prevalent in Djibouti City in 2019–2020; they appear to have arisen de novo within the Horn of Africa and have not been imported.     

柴胡桂枝干姜汤方证辨析

柴胡桂枝干姜汤方出自《伤寒论》＂,伤寒五六日,已发汗而复下之,胸胁满微结,小便不利,渴而不呕,但头汗出,往来寒热,心烦者,此为未解也,柴胡桂枝汤主之＂;方证定位于少阳病兼证,属经腑同病兼津伤阳损证,原文对太阴虚寒症状未作明示,但结合后世医家补充及临床验案,太阴虚寒为必有兼证。刘渡舟定位于胆火内郁兼太阴脾寒更贴近临床实际。方证应无表证,邪已传入少阳,水饮内停并非其兼证。因柴胡黄芩用量与小柴胡汤相同,故归于柴胡剂已达成共识,争论焦点在栝楼根、牡蛎及桂枝干姜的作用,详辨结构,乃小柴胡汤理中汤、栝楼牡蛎散合方之意。多数医者认同该方证病机为少阳枢机不利、胆火内郁,兼津伤阳损,广泛应用于消化系统疾病。刘渡舟主张使用本方,论病机为胆热脾寒,抓主证须重视口苦便溏;断病在少阳,以口苦为准,便溏之证是判断太阴病主要依据,对临床使用影响很大,多按此原则使用,疗效确切,极大地扩大了此方的使用范围。     

肺结核合并恶性疟疾的临床特点与治疗分析

本文就38例肺结核合并恶性疟疾患者有关两病临床症状的异同点、内在联系及诊断和治疗问题提出了一些易于接受的见解,并指出加强疟疾防治、减少算发仍然是疟疾流行区面临的艰巨任务。     

儿童重症疟疾156例临床分析

目的探讨儿童重症疟疾的临床特征,提高早期诊断和治疗水平。方法对2005年6月—2006年5月在尼日尔马拉迪省中心医院儿科住院的156例<5岁重症疟疾患儿的临床表现、实验室检查及临床转归进行回顾性分析。结果重度贫血(45.51%)、高乳酸血症(23.72%)、脑型疟疾(23.08%)、血小板减少(21.15%)、低血糖(21.15%)、高原虫血症(12.18%)、呼吸窘迫(11.54%)是本组患儿的特征性临床表现。2岁以下患儿重度贫血的发生率显著高于2～5岁患儿,差异有统计学意义(P<0.05);而脑型疟疾的发生率2～5岁患儿显著高于2岁以下患儿,差异有统计学意义(P<0.05)。156例患儿中恶性疟的发病人数占显著优势,为113例(72.44%),三日疟25例(16.02%),卵形疟16例(10.26%),间日疟2例(1.28%)。死亡28例(17.95%)。脑型疟疾、惊厥、低血糖、高乳酸血症是患儿死亡的独立高危因素(P<0.05)。结论尼日尔地区儿童重症疟疾主要为恶性疟,重度贫血和脑型疟疾常见,并与患儿年龄相关。脑型疟疾、惊厥、低血糖、高乳酸血症是患儿死亡的独立高危因素。     

Asymptomatic Malaria in Households and Neighbors of Laboratory Confirmed Cases in Raya Kobo District,Northeast Ethiopia

BackgroundMalaria is the leading vector-borne parasitic disease that is causing high morbidity and mortality worldwide. So far huge efforts to control and eliminate malaria are hindered by the occurrence of asymptomatic carriers that are a potential source of infection. Yet, there is a scarcity of data nationally and in the current study area as well. Therefore, this study was aimed to assess the prevalence of asymptomatic malaria in Northeast Ethiopia.MethodsA community-based cross-sectional study was conducted in 2019 involving a total of 270 study participants recruited via purposive non-probability sampling technique. A structured questionnaire was used to collect data on sociodemographic characteristics, individual and household factors related to asymptomatic malaria. Data were entered in Epi Data 3.1 version and analyzed by using SPSS version 20, and p< 0.05 was considered statistically significant.ResultsThe overall prevalence of asymptomatic malaria was 7.0%, with 3.0%, 5.2%, and 12.0%, respectively by Rapid diagnostic tests (RDT), Microscopy and Polymerase chain reaction (PCR). The majority of infections (73.7%) were identified from index households. Previous malaria history (AOR: 4.030, 95% CI: 1.021–15.903), living with index cases (AOR: 3.880, 95% CI: 1.275–11.806) and family size > 6 members (AOR: 4.820, 95% CI: 1.260–18.437) were significant predictors of asymptomatic malaria.ConclusionReactive case detection had identified considerably higher asymptomatic malaria cases in the community. Therefore, active case investigation should be established in the community by tracking the symptomatic cases at the health facilities.     

黔桂灭疟联防区疟疾防治措施及其效果评价

目的 了解联防区疟疾流行状况和发展态势,为防治工作提供依据.方法 对发热病人、流动人口和疫区重点人群进行采血镜检,治疗随访疟疾病人,在病灶点使用菊酯类杀虫剂喷洒或浸帐灭蚊.结果 2004年联防区发现疟疾病例共424例,较2003年下降了21.98%.但有5个县(市)疟疾发病率回升,幅度为21.05%～481.82%.当地病例占多数,问日疟为优势虫种,病例呈高度分散存在.结论 抗疟措施适合实际,效果明显,多数县(市)疟情稳定,个别县(市)疫情有波动.     

Genetic markers of resistance to pyrimethamine and sulfonamides in Plasmodium falciparum parasites compared with the resistance patterns in isolates of Escherichia coli from the same children in Guinea-Bissau

The antifolate drugs sulphadoxine and pyrimethamine are used for treatment of chloroquine-resistant Plasmodium falciparum in Africa. Resistance to pyrimethamine has been associated with point mutations in the dhfr-gene and resistance to sulphadoxine with mutations in the dhps-gene. There is concern that the use of the antifolates trimethoprim and sulphamethoxazole for treatment of other infectious diseases will result in the selection of malaria parasites with mutations in these genes. In Guinea-Bissau, where sulfonamide and trimethoprim-containing drugs have been used extensively, we decided to assess the prevalence of mutations in the dhfr-and dhps-gene in P. falciparum isolated from children suffering from acute malaria and to assess the resistance patterns to trimethoprim/sulphamethoxazole in Escherichia coli isolated from the same patients. A thick film and a blood sample for polymerase chain reaction (PCR) were obtained from 100 children attending the Bandim Health Centre in Bissau with symptoms compatible with malaria. Furthermore, a stool sample was collected from the same children and cultured for E. coli. Of the cultured E. coli, 67% were resistant both to sulfonamides and trimethoprim, 4% to sulfonamides alone, 3% to trimethoprim alone while 26% were fully sensitive to both drugs. PCR was successfully performed in 97 blood samples. Of these, 41% had triple mutations at the dhfr-gene (at codons 51, 59 and 108), and 15% had triple mutations plus mutation at codon 437 in the dhps-gene. Only 45% harboured the wild-type dhfr-gene. Thus both bacterial resistance and mutations in the parasitic genes were common, but not linked in the individual child. As sulphadoxine-pyrimethamine has only been used as a second line treatment for chloroquine resistant malaria in Guinea-Bissau for a few years, it is worrying to find a high prevalence of mutations in the parasitic genes coding for resistance to these drugs. Therefore, restricting the use of sulphadoxine-pyrimethamine for the treatment of chloroquine resistant malaria might not be sufficient to prevent the development of resistance in the parasites as long as antifolate drugs are used extensively.     

Expression of the Plasmodium berghei ookinete protein Pbs21 in a baculovirus-insect cell system produces an efficient transmission blocking immunogen

A surface protein of Plasmodium berghei ookinetes, Pbs21, was expressed in a baculovirus-insect cell system in cell culture and in Heliothis virescens larvae. Groups of BALB/c mice received two intraperitoneal inoculations of either i) Tris-buffer or homogenized H. virescens larvae infected with wild-type baculovirus; ii) enriched, homogenized ookinetes, or Hi) homogenizedH. virescens larvae expressing recombinant Pbs21 (rPbs21). All animals immunized with ookinetes or with rPbs21 had high litres of antibodies (IgG isotype) that bound to native Pbs21. The large majority of antibodies in immune sera of both groups recognized the antigen under non-reducing but not under reducing conditions. The predominant IgG-sub-classes in mice immunized with ookinetes was IgGl and in mice immunized with rPbs21, the subclasses were IgGl and IgG2a. Immunization with rPbs21 reduced the infec-tivity of P. berghei to mosquitoes by 91% compared to a 99% reduction following immunization with ookinetes. This preliminary data indicate that rPbs21 expressed in this eukaryotic system induces a transmission-blocking immunity which is more effective than that achieved using rPbsll expressed in Escherichia coli (Matsuoka et al. 1994).     

Do insecticide-treated curtains reduce all-cause child mortality in Burkina Faso?

To evaluate whether insecticide-treated netting (ITN) reduces child mortality in different epidemiological settings, 4 large, randomized, controlled trials were conducted in Africa. Here we report the findings from the trial in Burkina Faso, in an area of hyperendemic and markedly seasonal malaria transmission. The trial involved 158 villages, with a total population of some 90,000, grouped into 16 geographical clusters. Ascertainment of mortality among children aged 6–59 months began in early 1993. In June/July 1994, 8 of the clusters, randomly selected, received permethrin-treated curtains. Follow-up of children and ascertainment of mortality continued until May 1996. A 15% reduction in all-cause mortality among children aged 6–59 months was observed over the 2-year period following the installation of the curtains (95% c.i. – 4% to 30%). In the first year, post-intervention mortality was substantially lower in the clusters receiving curtains compared with the control clusters (rate ratio = 0.74; 95% c.i. 0.57, 0.95) but in the second year, there was no difference between mortality in the two groups (rate ratio = 0.99). The overall two-year impact of the intervention is consistent with the impacts observed in other trials which have demonstrated reductions in child mortality of from 17% to 33%. However, the year-by-year analysis raises some concerns about the long-term effect of ITN. Further follow-up of this population is warranted.