Plasmodium vivax and mixed infections are associated with severe malaria in children: a prospective cohort study from Papua New Guinea.
Plasmodium vivax and mixed infections are associated with severe malaria in children: a prospective cohort study from Papua New Guinea.
复制标题
DOI：
10.1371/journal.pmed.0050127
复制
发表时间：
2008-06-17
期刊：
影响因子：
15.8
通讯作者：
Müller I
中科院分区：
文献类型：
--
作者：
Genton B;D'Acremont V;Rare L;Baea K;Reeder JC;Alpers MP;Müller I
严重疟疾（SM）通常与恶性疟原虫感染有关。关于间日疟原虫对严重疾病的影响的信息很少。有一些流行病学迹象表明间日疟或混合感染可预防并发症和死亡。在四种细菌共存的地区进行了大规模的发病率监测，使我们能够估计感染一种或几种细菌的患者的SM发病率。这是在疟疾疫苗流行病学和评价项目框架内进行的一项前瞻性队列研究。对8年期间在两个农村卫生机构出现的所有疑似疟疾病例进行了调查，包括病史记录、临床检查和实验室评估。SM的病例定义基于世界卫生组织（WHO）适用于该环境的标准（即与无性血期寄生虫病相关的疟疾临床诊断和近期发作史、昏迷史、呼吸窘迫史或贫血史[血红蛋白< 5 g/dl]）。在17,201例推定疟疾病例中，9,537例（55%）确诊为寄生虫病。其中6.2%（95%可信区间[CI] 5.7% ~ 6.8%）符合SM病例定义，以5岁以下儿童居多。在该年龄组中，恶性疟原虫感染SM的比例为11.7%(10.4% ~ 13.2%)，间日疟原虫感染SM的比例为8.8%(7.1% ~ 10.7%)，恶性疟原虫和间日疟原虫混合感染SM的比例为17.3%（11.7% ~ 24.2%）。间日疟原虫比恶性疟原虫更常出现呼吸窘迫（60%比41%，p = 0.002），但较少出现贫血（19%比41%，p = 0.0001）。间日疟原虫单一感染和混合疟原虫感染与SM有关。没有迹象表明混合感染对SM有保护作用。仅针对恶性疟原虫的干预措施可能不足以消除总体疟疾负担，特别是在恶性疟原虫和间日疟原虫共存的地区消除严重疾病。在巴布亚新几内亚进行的一项研究中，Blaise Genton及其同事表明间日疟原虫与严重疟疾有关。疟疾是一种寄生虫感染，通过受感染的蚊子传播给人类。四种不同的寄生虫引起疟疾——恶性疟原虫、间日疟原虫、卵形疟原虫和疟疾疟原虫。其中，间日疟原虫是最常见和分布最广泛的，而恶性疟原虫造成的死亡人数最多。当被感染的蚊子吸食血液时，所有这些寄生虫都会进入它们的人类宿主。然后它们迁移到肝脏，在那里复制而不会引起任何症状。8到9天后，成熟的寄生虫从肝细胞中释放出来，侵入红细胞。在这里，它们迅速繁殖，然后爆发并感染更多的红细胞。疟疾反复出现的流感样症状是由寄生虫血症（血液中的寄生虫）的周期性增加引起的，应及时用抗疟疾药物治疗，以防止出现可能致命的并发症。特别是感染恶性疟原虫会破坏红细胞，从而导致贫血，并会阻塞为重要器官（包括大脑）供血的毛细血管，从而损害重要器官（包括大脑）。人们普遍认为间日疟很少致命。甚至有一些证据表明，单独感染间日疟原虫（单一感染）或感染其他疟疾寄生虫（混合感染）可预防疟疾并发症。然而，最近有报告称，仅与间日疟原虫感染有关的严重疾病和死亡。这些报告大多没有指出严重疟疾病例中有多大比例是由间日疟原虫感染引起的，但如果间日疟原虫造成了很大比例的疟疾死亡，那么预防这些死亡的努力将需要针对间日疟原虫和恶性疟原虫。因此，在这项研究中，科学家们估计了巴布亚新几内亚感染一种或几种疟原虫的患者中严重疟疾病例的比例，而巴布亚新几内亚是所有四种疟原虫并存的国家。研究人员将在巴布亚新几内亚Wosera街道的两个农村卫生机构就诊的每个人（有疟疾症状但没有任何其他疾病症状的人（假定的疟疾病例））纳入了他们的前瞻性队列研究，为期8年。他们询问了每位病人的症状，做了标准的身体检查，在他们的血液中寻找寄生虫，并测量了他们的血红蛋白水平，以确定他们是否贫血。在17201例推定疟疾病例中，483例患有严重疟疾（定义为寄生虫病加上近期发作、昏迷、呼吸问题或贫血史）。大多数重症疟疾患者年龄在5岁以下，儿童对疟原虫缺乏免疫力。在这一年龄组中，11.7%的恶性疟原虫感染患者、8.8%的间日疟原虫感染患者和17.3%的两种寄生虫感染患者患有严重疟疾。间日疟原虫引起的严重疟疾患者比恶性疟原虫感染的患者更常出现呼吸困难，而在恶性疟原虫引起的严重疟疾患者中，贫血比间日疟原虫引起的严重疟疾患者更常见。这组科学家利用这些结果和每种寄生虫感染数量的数据计算出，在巴布亚新几内亚的这个农村地区，间日疟原虫导致了五分之一的严重疟疾病例，恶性疟原虫导致了四分之三的病例，其余的病例涉及恶性疟原虫和疟原虫的混合。间日疟原虫感染。换句话说，这些发现表明，感染间日疟原虫或恶性疟原虫的五岁以下儿童中，大约十分之一可能发展为严重疟疾。然而，这些发现没有提供证据表明混合感染具有保护作用。由于严重疟疾的诊断没有得到结果数据（死亡或终身残疾）的证实，因此需要进行更多更详细的研究来证实这些结果。然而，这些发现（以及同时发表在《公共科学图书馆·医学》上的一篇相关文章中单独报道的结果）表明，与疟疾相关的疾病中有很大一部分可能是由间日疟原虫感染引起的。因此，在间日疟原虫和恶性疟原虫共存的地区，减少或消除疟疾负担的努力必须以间日疟原虫和恶性疟原虫为目标。请通过本摘要的在线版本http://dx.doi.org/10.1371/journal.pmed.0050127访问这些网站。Stephen Rogerson在plos医学研究翻译中发表的一篇文章进一步讨论了这项研究和一篇有关在巴布亚地区医院就诊的患者的间日疟疾感染的相关论文。印度尼西亚MedlinePlus百科全书有一个关于疟疾的页面（英文和西班牙文）美国疾病控制和预防中心提供关于疟疾的信息（英文和西班牙文）减少疟疾伙伴关系提供的关于全球疟疾控制和巴布亚新几内亚疟疾的信息间日疟疾为疟疾研究界提供关于间日疟原虫相关主题的信息疟疾疫苗倡议还提供了一份关于间日疟原虫的情况介绍Plasmodiumvivax疟疾
Severe malaria (SM) is classically associated with Plasmodium falciparum infection. Little information is available on the contribution of P. vivax to severe disease. There are some epidemiological indications that P. vivax or mixed infections protect against complications and deaths. A large morbidity surveillance conducted in an area where the four species coexist allowed us to estimate rates of SM among patients infected with one or several species. This was a prospective cohort study conducted within the framework of the Malaria Vaccine Epidemiology and Evaluation Project. All presumptive malaria cases presenting at two rural health facilities over an 8-y period were investigated with history taking, clinical examination, and laboratory assessment. Case definition of SM was based on the World Health Organization (WHO) criteria adapted for the setting (i.e., clinical diagnosis of malaria associated with asexual blood stage parasitaemia and recent history of fits, or coma, or respiratory distress, or anaemia [haemoglobin < 5 g/dl]). Out of 17,201 presumptive malaria cases, 9,537 (55%) had a confirmed Plasmodium parasitaemia. Among those, 6.2% (95% confidence interval [CI] 5.7%–6.8%) fulfilled the case definition of SM, most of them in children <5 y. In this age group, the proportion of SM was 11.7% (10.4%–13.2%) for P. falciparum, 8.8% (7.1%–10.7%) for P. vivax, and 17.3% (11.7%–24.2%) for mixed P. falciparum and P. vivax infections. P. vivax SM presented more often with respiratory distress than did P. falciparum (60% versus 41%, p = 0.002), but less often with anaemia (19% versus 41%, p = 0.0001). P. vivax monoinfections as well as mixed Plasmodium infections are associated with SM. There is no indication that mixed infections protected against SM. Interventions targeted toward P. falciparum only might be insufficient to eliminate the overall malaria burden, and especially severe disease, in areas where P. falciparum and P. vivax coexist. In a study carried out in Papua New Guinea, Blaise Genton and colleagues show thatPlasmodium vivax is associated with severe malaria. Malaria is a parasitic infection that is transmitted to people by infected mosquitoes. Four different parasites cause malaria—Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. Of these, P. vivax is the commonest and most widely distributed, whereas P. falciparum causes the most deaths. All these parasites enter their human host when an infected mosquito takes a blood meal. They then migrate to the liver where they replicate without causing any symptoms. Eight to nine days later, mature parasites are released from the liver cells and invade red blood cells. Here, they multiply rapidly before bursting out and infecting more red blood cells. The recurring flu-like symptoms of malaria are caused by this cyclical increase in parasitemia (parasites in the blood) and should be treated promptly with antimalarial drugs to prevent the development of potentially fatal complications. Infections with P. falciparum in particular can cause anemia by destroying the red blood cells and can damage vital organs (including the brain) by blocking the capillaries that supply them with blood. It is generally believed that P. vivax malaria is rarely fatal. There is even some evidence that infection with P. vivax alone (monoinfection) or with other malaria parasites (mixed infection) provides protection against malarial complications. Recently, however, there have been reports of severe disease and deaths associated with infection by P. vivax alone. Most of these reports do not indicate what proportion of severe malaria cases are caused by P. vivax infections, but if P. vivax is responsible for a significant proportion of malarial deaths, efforts to prevent these deaths will need to target P. vivax as well as P. falciparum. In this study, therefore, the researchers estimate the proportion of cases of severe malaria among patients infected with one or several Plasmodium species in Papua New Guinea, a country where all four species coexist. The researchers enrolled everyone attending two rural health facilities in the Wosera subdistrict of Papua New Guinea over an eight-year period with symptoms indicative of malaria but without symptoms of any other disease (presumptive malaria cases) into their prospective cohort study. They asked each patient about their symptoms, did a standard physical examination, looked for parasites in their blood, and measured their hemoglobin levels to see whether they were anemic. Out of 17,201 presumptive malaria cases, 483 had severe malaria (defined as parasitemia plus a recent history of fits, coma, breathing problems, or anemia). Most of the patients with severe malaria were less than five years old—children have little immunity to Plasmodium parasites. In this age group, 11.7% of patients infected with P. falciparum, 8.8% of patients infected with P. vivax, and 17.3% of patients infected with both parasites had severe malaria. Patients with severe malaria caused by P. vivax presented with breathing difficulties more often than those infected with P. falciparum, whereas anemia was more common among patients with severe malaria caused by P. falciparum than by P. vivax. The researchers use these results and data on the numbers of infections with each parasite to calculate that, in this rural region of Papua New Guinea, P. vivax is responsible for one-fifth of severe malaria cases, P. falciparum is responsible for three-quarters of cases, and the rest involve mixed P. falciparum/P. vivax infections. Put another way, these findings suggest that about one in ten children under the age of five years infected with either P. vivax or P. falciparum may develop severe malaria. These findings provide no evidence, however, that mixed infections are protective. Because the diagnosis of severe malaria was not confirmed by outcome data (deaths or permanent disability), additional, more detailed studies are needed to confirm these results. Nevertheless, these findings (and those reported separately in a related article published at the same time in PLoS Medicine) suggest that a significant proportion of the illness associated with malaria may be caused by P. vivax infections. Thus, efforts to reduce or eliminate the malarial burden must target P. vivax as well as P. falciparum in regions where these species coexist. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050127. A PLoSMedicine Research in Translation article by Stephen Rogerson further discusses this study and a related paper on vivax malaria infection in patients attending a regional hospital in Papua, Indonesia The MedlinePlus encyclopedia has a page on malaria (in English and Spanish) The US Centers for Disease Control and Prevention provides information on malaria (in English and Spanish) Information is available from the Roll Back Malaria Partnership on global control of malaria and on malaria in Papua New Guinea Vivaxmalaria provides information for the malaria research community on topics related to Plasmodiumvivax The Malaria Vaccine Initiative also provides a fact sheet on Plasmodiumvivax malaria
登录
查看更多内容
DOI：
10.1086/510756
发表时间：
2007-02-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Anstey NM;Handojo T;Pain MC;Kenangalem E;Tjitra E;Price RN;Maguire GP
通讯作者：
Maguire GP
影响因子：
11.8
作者：
Kochar DK;Saxena V;Singh N;Kochar SK;Kumar SV;Das A
通讯作者：
Das A
DOI：
10.1016/s0035-9203(99)90024-x
发表时间：
1999-05-01
影响因子：
2.2
作者：
Berkley, J;Mwarumba, S;Marsh, K
通讯作者：
Marsh, K
DOI：
10.4269/ajtmh.2002.67.555
发表时间：
2002-12-01
影响因子：
3.3
作者：
Mehlotra, RK;Kasehagen, LJ;Zimmerman, PA
通讯作者：
Zimmerman, PA
DOI：
10.4269/ajtmh.2007.77.947
发表时间：
2007-11-01
影响因子：
3.3
作者：
Marfurt, Jutta;Mueeller, Ivo;Genton, Blaise
通讯作者：
Genton, Blaise