2019年江苏省疟疾疫情分析

目的　分析2019年江苏省疟疾疫情,为制订防止疟疾输入再传播监测策略和措施提供科学依据。方法　收集2019年江苏省疟疾病例报告信息、流行病学个案调查、疫点调查与处置结案报告等疟疾疫情资料,并采用描述性方法进行分析。结果　2019年江苏省累计报告疟疾病例244例,均为实验室确诊的境外感染输入性病例,其中间日疟4例、恶性疟206例、三日疟12例、卵形疟22例;11例发展为重症病例,1例死亡。全省13个设区市报告病例数居前5位的依次为南京、南通、连云港、泰州、常州,报告的疟疾病例数占全省报告病例总数的59.84%。2019年报告的244例疟疾病例中,2例感染地为大洋洲巴布亚新几内亚、1例为亚洲巴基斯坦,其他241例均为非洲的27个国家或地区,其中输入来源较多的国家为安哥拉、刚果民主共和国、尼日利亚、赤道几内亚和科特迪瓦。244例疟疾病例中,在发病当天和发病后1～3 d就诊分别有77例（31.55%）和146例（59.84%）,首次就诊和就诊后1～3 d确诊分别有149例（61.06%）和77例（31.55%）,从就诊到确诊平均时间为（0.80 ± 1.59）d,较2018年的（1.34 ± 2.59）d显著缩短（U = 2.53,P < 0.05）。结论　江苏省应继续加强输入性疟疾监测和管理,提高输入性疟疾诊断能力和危重疟疾病例救治能力,以巩固消除疟疾成果。     

脑型疟小鼠小胶质细胞的活化特征分析

目的利用血脑屏障分隔小胶质细胞与外周巨噬细胞,探讨小胶质细胞在实验型脑型疟(experimental cerebral malaria,ECM)发生中的活化特征。方法利用依文思兰渗出法确定ECM小鼠血脑屏障开放时间,在不同感染时间点,采用流式细胞技术和间接免疫荧光法检测小胶质细胞的活化特征,采用实时荧光定量PCR技术检测炎症和活化因子的变化。结果ECM小鼠血脑屏障显著开放始于感染后第6 d。感染后第5 d,脑内促炎因子、巨噬细胞活化相关因子的转录水平以及CD11b⁺、CD45⁺细胞的占比和数目均显著上调。CD11b⁺细胞可根据CD45表达量分群,其中CD45^high亚群占比在感染后第5 d下调而第7 d上调。结论小胶质细胞参与ECM小鼠脑内炎症反应,且其活化与CD45表达量相关,CD11b⁺CD45^high可作为活化小胶质细胞的标志物。     

Plasmodium vivax resistance to chloroquine in Dawei, southern Myanmar

Objective  To assess the efficacy of chloroquine in the treatment of Plasmodium vivax malaria in in Dawei District, southern Myanmar.
Methods  Enrolled patients at Sonsinphya clinic >6 months of age were assessed clinically and parasitologically every week for 28 days. To differentiate new infections from recrudescence, we genotyped pre- and post-treatment parasitaemia. Blood chloroquine was measured to confirm resistant strains.
Results  Between December 2002 and April 2003, 2661 patients were screened, of whom 252 were included and 235 analysed. Thirty-four per cent (95% CI: 28.1–40.6) of patients had recurrent parasitaemia and were considered treatment failures. 59.4% of these recurrences were with a different parasite strain. Two (0.8%) patients with recurrences on day 14 had chloroquine concentrations above the threshold of 100 ng/ml and were considered infected with chloroquine resistant parasites. 21% of failures occurred during the first 3 weeks of follow-up: early recurrence and median levels of blood chloroquine comparable to those of controls suggested P. vivax resistance.
Conclusions  Plasmodium vivax resistance to chloroquine seems to be emerging in Dawei, near the Thai-Burmese border. While chloroquine remains the first-line drug for P. vivax infections in this area of Myanmar, regular monitoring is needed to detect further development of parasite resistance.     

输入性间日疟2例

湖北省五峰县是以间日疟为主的低疟区,通过综合防治,1990年初已基本消灭疟疾.此后末冉发现本地新感染病例,偶有未经正规治疗而复发病例,其症状轻微、不典型.2007年7月,发现2例从海南省打工返乡的间日疟输入性病例,报告如下.     

Differential antibody recognition of FC27-like Plasmodium falciparum merozoite surface protein MSP2 antigens which lack 12 amino acid repeats

Three alleles of the FC27-type allelic family of the MSP2 gene of the malaria parasite Plasmodium falciparum have been sequenced from parasites from the field (The Gambia and Tanzania). These alleles lack the 12 amino acid repeat units which are usual in this family of MSP2 alleles. We have investigated the recognition by sera from an endemic area (The Gambia) of three recombinant MSP2 proteins that have 5, 1 and no copies of this repeat region. Antibody recognition of these recombinant proteins varied according to the number of repeats present. High titre antibody levels were seen with most sera using the recombinant protein with 5 × 12-mer repeats, whereas only low responses were measured using proteins containing 1 or no 12-mer repeats. Several sera entirely failed to recognise the protein which lacked 12-mer repeats. The data suggest that variation in the number of tandem repeat sequences could allow the parasite to avoid high avidity antibody binding and this may allow escape from immune recognition.     

Evidence for a neutrophil-mediated protective response in malaria

Zymosan-activated and non-activated human polymorphonuclear neutrophils (PMN) were added to in-vitro cultures of the human malaria parasite Plasmodium falciparum in microtitre wells. Microscopic counting of parasites in Giemsa-stained smears showed that at a PMN:RBC ratio of 1:150, the same as occurs in human malaria, parasites in wells with zymosan-activated neutrophils were suppressed 65%. Determination of parasite nucleic acid synthesis by 3H-hypoxanthine incorporation showed that in wells with PMN:RBC ratio of 1:150 parasite viability was only 22% of control. Various oxygen scavengers were tested for ability to reverse the effects of activated neutrophils on parasite development. Superoxide dismutase (20 mg/ml) and catalase (50 mg/ml) had no effect; tryptophan protected the parasites to a moderate degree while histidine alleviated suppression of parasite development to the greatest extent. This suggests that singlet oxygen is the most effective neutrophil product in killing or suppressing the growth of parasites. We also observed that non-activated neutrophils were activated by parasites and/or their products resulting in killing of newly-released parasites.     

Impact of a double dose of sulphadoxine-pyrimethamine to reduce prevalence of pregnancy malaria in southern Mozambique

Malarial infection during pregnancy increases the risks of severe sequelae for the pregnant woman and the risk of delivering a low birthweight baby. The aim of this intervention study was to reduce significantly the prevalence of malaria parasitaemia in adolescent parturients in Matola and Boane in Mozambique. The study was focused upon the most malaria-vulnerable group, adolescent nulliparous and primiparous women. After completing the usual antenatal clinic and giving informed consent, 600 pregnant women were randomly chosen in a double blind manner to one of two regimens comparing the prevailing routine (placebo) for malaria prevention with a two dose regimen of sulphadoxine-pyrimethamine (SP). The first dose was given at enrollment with a second dose at the beginning of the third trimester. At delivery maternal and placental malaria parasitaemia as well as birthweight and gestational duration were analysed. At booking the prevalence of malaria parasitaemia was 35.3% in the placebo group and 30.6% in the SP group. At the second dose, the prevalence of malaria parasitaemia in the placebo group and SP group was 19.7% and 8.7%, respectively. This implies a relative risk (RR) of 2.24 with 95% CI (1.34, 3.75). The corresponding figures at delivery were 13.6% and 6.3% with an RR of 2.22 (1.07, 4.60) and in placenta 13.3% and 2.4% with an RR of 4.87 (1.58, 15.0). Newborns with malaria within 7 days were significantly more frequent in the placebo group, 6.4% and 0.7% respectively, with an RR of 6.55 (1.20, 35.7). Almost all (approximately 98%) of the women studied had Plasmodium falciparum, the remainder had P. malariae and P. ovale. The mean birthweight in the SP group was 3077 g and in the placebo group 2926 g. The estimated mean difference between the two groups was 151 g with 95% CI (51, 252). The mean placental weight in the placebo group was 596 and 645 g in the SP group, implying a difference of 49 g with a 95% CI (11, 88). The mean gestational duration was 6.1 days longer in the SP group, 95% CI (1.5, 10.6). In the placebo group there were two cases of urticaria and one case of nausea; in the SP group there was one case of vomiting. No newborn showed any sign of serious SP side-effect. Two doses of SP were enough to significantly reduce the prevalence of peripheral and placental malaria parasitaemia among young nulliparous and primiparous pregnant women in Matola and Boane.     

Household burden of malaria in South Africa and Mozambique: is there a catastrophic impact?

Objectives  To evaluate treatment-seeking behaviour, financial impact and time lost due to malaria events, in southern Mozambique and eastern South Africa.
Methods  In-depth household surveys (828 in Mozambique and 827 in South Africa) were analysed. An asset index was calculated using principal component analysis to allow comparison across socio-economic groups. Direct costs of seeking care and the time lost due to malaria were determined. The extent of catastrophic payments was assessed using as thresholds the traditional 10% of household income and 40% of non-food income, as recently recommended by WHO.
Results  Poverty was highly prevalent: 70% of the South African and 95% of Mozambican households studied lived on less than $1 per capita per day. Around 97% of those with recent malaria sought healthcare, mainly in public facilities. Out-of-pocket household expenditure per malaria episode averaged $2.30 in South Africa and $6.50 in Mozambique. Analysis at the individual household level found that 32–34% of households in Mozambique, compared with 9–13% of households in South Africa, incurred catastrophic payments for malaria episodes. Results based on mean values underestimated the prevalence of catastrophic payments. Days off work/school were higher in Mozambique.
Conclusions  The high rate of health seeking in public health facilities seems unusual in the African context, which bodes well for high coverage with artemisinin-based combinations, even if only deployed within the public sector. However, despite no or modest charges for public sector primary healthcare, households frequently incur catastrophic expenditure on a single malaria episode.     

The roles of the glycosylphosphatidylinositol anchor on the production and immunogenicity of recombinant ookinete surface antigen Pbs21 of Plasmodium berghei when prepared in a baculovirus expression system

Malarial ookinetes express an immunodominant surface protein (P28) that is a priority candidate for the development of transmission-blocking vaccines. The full length P28 gene from Plasmodium berghei [Pbs21(1-213)] and a deletion construct [Pbs21(1-188)] encoding a protein that lacks the 25 C-terminal amino acids, including the glycosylphosphatidylinositol (GPI) anchor signal, were expressed in insect cells using baculovirus vectors. Pbs21(1-213) protein is strongly hydrophobic, found in the cytoplasm and on the surface of Spodoptera Sf21 cells, and in the culture medium. Pbs21(1-188) protein was largely found in the aqueous phase of the medium and in the cytoplasm of Sf21 cells, but was not detected on the cell surface. The presence of 25 C-terminal amino acids is therefore critical to the attachment of recombinant Pbs21 to the parasite plasma membrane. Mice were immunized subcutaneously or intramuscularly with affinity purified recombinant Pbs21(1-213), Pbs21(1-188) or native Pbs21 proteins. Following two immunizations, native Pbs21 induces higher titres when administered by either route, than the recombinant protein bearing an insect GPI anchor, which in turn is markedly more immunogenic than the recombinant polypeptide lacking a GPI anchor. When specific anti Pbs21 antibody titres exceeded 1 mg/ml all three antigens were capable of inducing transmission blockade > or = 90%, below 1 mg/ml blockade did not correlate with antibody concentration.     

Socially marketed insecticide-treated nets improve malaria and anaemia in pregnancy in southern Tanzania

OBJECTIVES: To study the uptake of socially marketed insecticide-treated nets (ITNs) and their impact on malaria and anaemia in pregnancy; and to report on a discount voucher system which aimed to increase coverage in pregnancy. METHODS: A 12-month cross-sectional study of women in the second or third trimester of pregnancy. ITN use and other factors were assessed by questionnaire and a blood sample taken for malaria parasitaemia and anaemia. 'Non-users' of ITNs included both women not using any net and women using untreated nets. RESULTS: Fifty three per cent of pregnant women used ITNs. Women aged 15-19, primigravidae, unmarried women, and those with no access to cash had the lowest ITN use. Fewer ITN users were positive for malaria than ITN non-users (25 vs. 33%: P=0.06), and the protective efficacy (PE) for parasitaemia was 23% (CI 2-41). Multiparous ITN users had a twofold decrease in parasite density compared with multiparous non-ITN users (625 parasites/microl vs. 1173 parasited/microl: P=0.01). Fewer ITN users were anaemic (Hb < 11 g/dl) than ITN non-users (72 vs. 82%: P=0.01). ITNs had a PE of 12% (CI 2-21) against mild anaemia and a PE of 38% (CI 4-60) against severe anaemia (Hb < 8 g/dl). There was a trend in the prevalence of severe, mild and no anaemia, and of high density, low density and no malaria infection by ITN status. Recently treated nets were most effective at preventing malaria and anaemia (prevalence of mild anaemia was 68% compared with 82% for those without nets (P=0.002); prevalence of malaria was 22% compared with 33% for those without nets (P=0.02). Knowledge and reported use of the discount voucher system were low. Further qualitative research is ongoing. CONCLUSIONS: A modest impact of ITNs on pregnancy malaria and anaemia was shown in our high malaria transmission setting. The development of ITN programmes for malaria control should include pregnant women as a specific target group.