Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon

BACKGROUND: The development of novel artemisinin-combination therapies suitable for the treatment of pediatric patients suffering from malaria is a research priority. The aim of this study was to investigate a novel fixed-dose pyronaridine-artesunate combination for the treatment of uncomplicated falciparum malaria in Gabonese patients 2-14 years old. METHODS: The study was designed as an open-label dose-escalation study recruiting 60 pediatric patients sequentially in 4 treatment cohorts: study drugs were administered once daily for 3 days, as tablet coformulations (pyronaridine:artesunate ratios of 6:2, 9:3, and 12:4 mg/kg) and as a granule coformulation (pyronaridine:artesunate ratio of 9:3 mg/kg). The primary end points were tolerability, safety, and pharmacokinetics of pyronaridine-artesunate treatment. Efficacy was treated as a secondary outcome measure. RESULTS: The drugs had a good tolerability and safety profile, at all dose levels. Pharmacokinetic analysis revealed a dose-dependent increase in the maximum plasma/blood concentration and the area under the curve, as well as comparable relative bioavailability for the granule coformulation. Polymerase chain reaction-corrected cure rates at day 28 were 100% in per-protocol analysis, at all dose levels. CONCLUSIONS: Pyronaridine-artesunate is a promising novel artemisinin-combination therapy for pediatric patients with uncomplicated Plasmodium falciparum malaria, and the development of both the tablet and the granule coformulations is warranted.     

Family analysis of malaria infection in Dienga,Gabon

Fifty children from 9 families were enrolled in a longitudinal study of 8 months to evaluate individual levels of Plasmodium falciparum density in blood during asymptomatic infections. Individual parasite densities were adjusted for age and date of blood intake. The arithmetic means of these adjusted parasite densities (MAPD) were not influenced by sickle cell trait nor by G6PD enzyme activity. On the contrary, family analysis revealed the presence of similar MAPD values according to the sibships. Moreover, sibships frequently infected with P. malariae exhibited the highest P. falciparum MAPDs. The difference in aggressiveness of malaria vectors between the northern and southern halves of the village did not explain the distribution of MAPD, nor did it explain the differences in mean frequency of P. malariae infection among the sibships. We conclude that the familial characteristic of susceptibility to both P. falciparum and P. malariae infections is more likely influenced by the host's genetic background than by differences in the levels of malaria transmission.     

Differences in presentation of severe malaria in urban and rural Gabon

There are rare comparative studies of the clinical and laboratory features of severe and moderate malaria, including predictors of poor outcome, in rural and urban areas for regions of high malaria transmission. We therefore studied 2,235 children hospitalized for malaria in a rural (Lambaréné) and an urban (Libreville) area in Gabon between January 2001 and December 2002. From children screened, 33% and 48% were hospitalized for malaria in Libreville and Lambaréné, respectively (P < 0.001). Two malaria clinical groups were identified according to the World Health Organization 2000 classification of severe malaria. In both areas, severe malaria was characterized by a high proportion of severe anemia. The case fatality rate was 5-fold lower in Lambaréné than in Libreville (1% versus 5%; P < 0.0001). In both sites, cerebral malaria associated with respiratory distress was the most important predictor of fatal malaria (odds ratio = 10.7, 95% confidence interval = 4.8-23.8 P < 0.0001).     

Complicated malaria and other severe febrile illness in a pediatric ward in Libreville, Gabon

ABSTRACT: BACKGROUND: Although a substantial decline of Plasmodium falciparum infection is observed in Africa following implementation of new control strategies, malaria is still considered as the major cause of febrile illness in hospitalized African children. The present study was designed to assess the management of febrile illness and to determine the proportion of children with febrile illness hospitalized for primary diagnosis of malaria who had confirmed complicated malaria after implementation of new malaria control strategies in Libreville, Gabon. METHODS: Demographic, clinical and biological data from hospitalized children with fever or a history of fever with a primary diagnosis of clinical malaria, aged less than 18 years old, who benefited from hematological measurements and microscopic malaria diagnosis were recorded and analyzed during a prospective and observational study conducted in 2008 in the Centre Hospitalier de Libreville. RESULTS: A total of 418 febrile children were admitted at hospital as malaria cases. Majority of them (79.4%) were aged below five years. After medical examination, 168 were diagnosed and treated as clinical malaria and, among them, only 56.7% (n = 95) had Plasmodium falciparum positive blood smears. Age above five years, pallor, Blantyre Coma Score <=2 and thrombocytopenia were predictive of malaria infection. Respiratory tract infections was the first leading cause of hospitalization (41.1%), followed by malaria (22.7%); co-morbidities were frequent (22%). Less than 5% of suspected bacterial infections were confirmed by culture. Global case fatality rate was 2.1% and 1% for malaria. Almost half (46%) of the children who received antimalarial therapy had negative blood smears. Likewise, antibiotics were frequently prescribed without bacteriological confirmation. CONCLUSIONS: The use of clinical symptoms for the management of children febrile illness is frequent in Gabon. Information, training of health workers and strengthening of diagnosis tools are necessary to improve febrile children care.     

Antibodies against malaria sporozoites in patients with acute uncomplicated malaria and patients with cerebral malaria

Serum samples from 95 patients with acute uncomplicated falciparum malaria (AM) and 95 patients with cerebral malaria (CM) were tested by the indirect immunofluorescent assay (IFA) for IgG and IgM antibodies against Plasmodium falciparum and P. vivax sporozoites. Forty-six (48%) CM patients were positive for antibodies against P. falciparum sporozoites whereas only 23 (24%) were positive for antibodies against P. vivax sporozoites (P less than 0.002). A similar result was obtained in AM patients. However, CM patients had significantly lower mean IgG anti-sporozoite titer for P. falciparum than did AM patients (P less than 0.05), especially when only anti-sporozoite antibody-positive CM and AM patients were compared (P less than 0.0005), suggesting that CM patients had relatively less exposure and were probably less immune to malaria than were AM patients. The persistence of anti-sporozoite antibodies also was investigated in paired sera taken 63 days apart from 108 patients with acute falciparum malaria. There were significant decreases in the mean antibody titers in the follow-up sera during the period of stay in the malaria-free area. It was proposed that determination of anti-sporozoite antibody be made as a substitute for, or in addition to, anti-blood stage antibody for seroepidemiological study of malaria, especially in the monitoring of the success of the malaria control program.     

Plasma and in vitro levels of cytokines during and after a Plasmodium falciparum malaria attack in Gabon

Fifty subjects living in a malaria endemic area were studied at diagnosis of a Plasmodium falciparum attack and 3 weeks later. Absolute numbers of CD3(+), CD4(+) and CD8(+) lymphocytes as well as plasma cytokines and secreted cytokines after in vitro mitogenic stimulation were measured. At enrollment, lymphopenia was observed, lending support to the reallocation hypothesis during the acute phase. A significant elevation of the number of CD8(+) cells was present in the peripheral blood during the recovery phase. During the acute phase, plasma IL-6 levels peaked while in vitro production capacity was high at both phases. Plasma IL-6 concentrations were positively related to blood parasite density at D0, as IL-4 and IFN-gamma, suggesting an early intervention of these cytokines. Plasma IL-2 levels were low at diagnosis although cells retained their ability to produce IL-2, which was found more frequently in plasma after cure. Acquisition of immunity with age was in relation with greater secretion abilities of cells for type 1 and type 2 cytokines during the parasite clearance phase. We conclude to an early implication of type 2 cytokines and IFN-gamma, with particularly high levels of IL-6.     

Therapeutic efficacy of clindamycin in combination with quinine for treating uncomplicated malaria in a village dispensary in Gabon

The efficacy of a 3-day clindamycin-quinine regimen to treat clinical malaria attacks was investigated in 256 children from western Gabon. Treatment was well tolerated by all of the children and its efficacy was higher than 97% by day 20. Thus this 3-day clindamycin-quinine regimen might constitute a potential alternative to chloroquine for treating clinical malarial attacks in children from Gabon.     

我国疟疾漏报现状

传染病是我国疾病监测的重要内容。监测收集到的疫情数据是国家和各省在疾病防治方面确定重点疾病、防治方向、经费投入、人力资源配置的重要依据。为此国家专门设立机构,建立全国从上到下、从省到乡村的信息网络对疫情进行收集汇总、分析、发布和管理。目前除了常规的疫情报告系统外,国家还建立特定的疫情监测哨点对疫情进行收集和分析。这些哨点的信息收集更全面、更细致。前者收集到的一般称为“大疫情”、后者称为“小疫情”。小疫情可以对大疫情进行校正。疟疾是全国疫情管理的病种之一,与其他病种一样存在着漏报问题,专家估计全国疟疾…     

Susceptibility status of malaria vectors to insecticides commonly used for malaria control in Tanzania

Objective The aim of the study was to monitor the insecticide susceptibility status of malaria vectors in 12 sentinel districts of Tanzania. Methods WHO standard methods were used to detect knock‐down and mortality in the wild female Anopheles mosquitoes collected in sentinel districts. The WHO diagnostic doses of 0.05% deltamethrin, 0.05% lambdacyhalothrin, 0.75% permethrin and 4% DDT were used. Results The major malaria vectors in Tanzania, Anopheles gambiae s.l., were susceptible (mortality rate of 98–100%) to permethrin, deltamethrin, lambdacyhalothrin and DDT in most of the surveyed sites. However, some sites recorded marginal susceptibility (mortality rate of 80–97%); Ilala showed resistance to DDT (mortality rate of 65% [95% CI, 54–74]), and Moshi showed resistance to lambdacyhalothrin (mortality rate of 73% [95% CI, 69–76]) and permethrin (mortality rate of 77% [95% CI, 73–80]). Conclusions The sustained susceptibility of malaria vectors to pyrethroid in Tanzania is encouraging for successful malaria control with Insecticide‐treated nets and IRS. However, the emergency of focal points with insecticide resistance is alarming. Continued monitoring is essential to ensure early containment of resistance, particularly in areas that recorded resistance or marginal susceptibility and those with heavy agricultural and public health use of insecticides.     

2018年河南省疟疾疫情及消除疟疾进展

目的了解2018年河南省疟疾疫情及消除疟疾进展,为制定疟疾防控策略提供科学依据。方法收集2018年河南省疟疾疫情资料及病例个案调查资料,采用描述流行病学方法对疟疾疫情及病例诊治情况进行分析。结果 2018年河南省共报告疟疾病例174例,男女性别比33.8∶1,主要集中在30~和40~岁年龄组,职业以农民为主,所有病例均为境外输入性病例,96.55%(168/174)的病例来自于非洲。全省17个地级市有病例报告,其中郑州、洛阳、许昌和濮阳4个市共报告疟疾病例110例,占总病例数的63.22%。从发病到初次就诊及初次就诊到确诊时间中位时间均为1 d,超过7 d就诊6例,占3.45%;超过7 d确诊(延迟确诊)13例,占7.47%。所有病例均在24 h内完成上报,3 d内流行病学个案调查完成率为98.28%(171/174)。截至2018年12月,河南省全部省辖市均已通过市级消除疟疾考核评估。结论 2018年河南省报告的疟疾病例均为境外输入性病例,应加强对非洲和东南亚返乡人员的疟疾监测,及时发现和治疗输入性疟疾病例,防止出现继发病例,确保河南省如期实现消除疟疾目标。     

Post-transfusion malaria in thalassaemia patients

Summary A total of 125 -thalassaemia patients receiving repeated blood transfusions were screened by Giemsa stain, Acridine-orange stain and antigen detection for evidence of malaria infection on each visit. A total of 8 (6.4%) of the patients developed post-transfusion malaria (PMT) as confirmed by tracing the infected blood donors. A high incidence of PTM in thalassaemia patients appears to be due to the use of fresh blood and the high frequency of blood transfusions required by these patients. Antigen detection using monoclonal antibody was found to be more sensitive for diagnosis of PTM and for screening suspected donors than the conventional blood smear examination methods and is therefore recommended for routine blood donor screening to rule out malaria infection.     

Pseudo-borreliosis in patients with malaria

Malaria and relapsing fever are arthropod-borne infections characterized by fever, myalgia, headache, and a tendency to relapse. Both are diagnosed through examination of stained blood films, and both might respond to tetracycline therapy. In at least four published case reports, the presence of malarial microgametes possibly resulted in misdiagnosis of borreliosis in patients with malaria. An additional case is presented, and the mechanism of microgamete production in clinical specimens is discussed.     

百色市疟疾流行现状和消除疟疾可行性探讨

目的 分析百色市2001-2010年疟疾流行现况和趋势,探讨百色市2018年消除疟疾的可行性.方法 收集2001-2010年百色市12个县(区)当地居民发热患者、病灶点居民和流动人口监测资料进行描述和分析.结果 10年间百色市共血检本地发热患者92.44万人次,病灶点居民1.90万人次,外出回归农民工2.69万人次,外来人群5.60万人次,检出疟疾病例297例,三类人群血检阳性率分别为0.005 9％、0、0.705 9％和0.092 6％.本地疟疾病例从2001年的10例下降到2007年的1例,2008-2010年连续3年无本地病例发生.结论 10年来百色市疟疾发病率控制在1/10万以下,按照世界卫生组织消除疟疾的标准,百色市疟疾疫情已进入消除疟疾阶段巩固期,但在黔桂交界、中越边境地区仍有个别本地病例发生,只要加大经费投入和技术措施执行力度,百色市2018年消除疟疾是可以实现的.     

Susceptibility status of malaria vectors to insecticides in India

The use of chemical insecticides for control of malaria vector populations continues to be the mainstay of malaria control strategy in India. Monitoring vector susceptibility to chemical insecticides is an important activity under the National Malaria Eradication Programme to ensure judicious and effective use of chemical Insecticides. 72 entomological zones were established under NMEP in 1977 for undertaking entomological studies in the malaria problematic areas. These zones have been generating insecticide susceptibility data in respect of the various malaria vectors. In this paper the insecticide susceptibility data, in respect of major vectors of malaria as on 1997, is presented.     

Relationship between entomological inoculation rate,Plasmodium falciparum prevalence rate,and incidence of malaria attack in rural Gabon

To assess the relationships between variations of Plasmodium falciparum transmission and those of peripheral parasitaemia prevalence or malaria attack incidence rates in regions with limited fluctuations of transmission, we conducted a follow-up in two Gabonese populations. Entomological surveys were carried out from May 1995 to April 1996 in Dienga, and from May 1998 to April 1999 in Benguia. In Dienga, malaria transmission was seasonal, being not detected during two 3-month periods. Mean entomological inoculation rate (EIR) was 0.28 infective bite/person/night. In Benguia, malaria transmission was perennial with seasonal fluctuations, mean EIR being 0.76 infective bite/person/night. In Dienga, 301 schoolchildren were followed from October 1995 to March 1996. Clinical malaria attack was defined as fever associated with >5000 parasites/microl of blood. P. falciparum prevalence varied from 28 to 42%, and monthly malaria attack incidence from 30 to 169 per thousand. In Benguia, the entire population (122 persons) was followed from November 1998 to April 1999. Prevalence varied from 22 to 50%, and monthly malaria attack incidence from 52 to 179 per thousand. In each area, entomological variations were not related to parasite prevalence, but preceded malaria attack incidence with 1- or 2-month time lag, corresponding to the pre-patency period that differs in the two populations, possibly according to differences in immunity related to parasite transmission.