Models to predict the intensity of Plasmodium falciparum transmission: applications to the burden of disease in Kenya.

There is an increasing need to provide spatial distribution maps of the clinical burden of Plasmodium falciparum malaria in Africa. Recent evidence suggests that risk groups and the clinical spectrum of severe malaria are related to the intensity of P. falciparum transmission. Climate operates to affect the vectorial capacity of P. falciparum transmission and this is particularly important in the Horn of Africa and parts of East Africa. We have used a fuzzy logic climate suitability model to define areas of Kenya unsuitable for stable transmission. Kenya's unstable transmission areas can be divided into areas where transmission potential is limited by low rainfall or low temperature and, combined, encompass over 8 million people. Among areas of stable transmission we have used empirical data on P. falciparum infection rates among 124 childhood populations in Kenya to develop a climate-based statistical model of transmission intensity. This model correctly identified 75% (95% confidence interval CI 70-85) of 3 endemicity classes (low, < 20%; high, > or = 70%; and intermediate parasite prevalences). The model was applied to meteorological and remote sensed data using a geographical information system to provide estimates of endemicity for all of the 1080 populated fourth level administrative regions in Kenya. National census data for 1989 on the childhood populations within each administrative region were projected to provide 1997 estimates. Endemicity-specific estimates of morbidity and mortality were derived from published and unpublished sources and applied to their corresponding exposed-to-risk childhood populations. This combined transmission, population and disease-risk model suggested that every day in Kenya approximately 72 and 400 children below the age of 5 years either die or develop clinical malaria warranting in-patient care, respectively. Despite several limitations, such an approach goes beyond 'best guesses' to provide informed estimates of the geographical burden of malaria and its fatal consequences in Kenya.     

Ecological transition from natural forest to tea plantations: effect on the dynamics of malaria vectors in the highlands of Cameroon

From October 2002 to September 2003, an entomological survey was carried out in a rural forested fringed village in the highlands of Mount Cameroon region to determine the temporal dynamics of the anopheline population and the intensity of malaria transmission. A total of 2387 Anopheles spp. were collected, with A. funestus predominating (59.9%), followed by A. hancocki (24.4%) and A. gambiae s.l. (15.7%). Considerable differences were observed in the nocturnal biting cycles of parous mosquitoes, with peak activity in the latter part of the night. PCR revealed that all specimens of the A. funestus group were A. funestus s.s. and all specimens from the A. gambiae complex were A. gambiae s.s. of the S molecular form. Plasmodium falciparum sporozoite rates of 17.3% and 8.5% were recorded for A. funestus and A. hancocki, respectively, with an anthropophilic rate of 96.3%. A strong positive correlation (r = 0.996) was found between the human-biting rate and the entomological inoculation rate (EIR). Malaria transmission was very high and perennial, with an estimated annual EIR of 460.1 infective bites per person per year. These results confirm that in high agricultural activity areas, A. funestus can be by far the major malaria vector responsible for malaria transmission.     

Possible Interruption of Malaria Transmission, Highland Kenya, 2007�C2008

Highland areas where malaria transmission is unstable are targets for malaria elimination because transmission decreases to low levels during the dry season. In highland areas of Kipsamoite and Kapsisiywa, Kenya (population ≈7,400 persons), annual household indoor residual spraying with a synthetic pyrethroid was performed starting in 2005, and artemether/lumefantrine was implemented as first-line malaria treatment in October 2006. During April 2007–March 2008, no microscopy-confirmed cases of malaria occurred at the sites. In 4 assessments of asymptomatic persons during May 2007–April 2008, a total of <0.3% of persons were positive for asexual Plasmodium falciparum by microscopy or PCR at any time, and none were positive by PCR at the last 2 sample collections. Our findings show that in such areas, interruption and eventual elimination of malaria transmission may be achievable with widespread annual indoor residual spraying of households and artemisinin combination therapy.     

成都市中华按蚊在疟疾传播中的阈值

目的研究成都市中华按蚊传播疟疾的阈值和潜势,为当地疟疾监测、预警与防治提供科学评价指标。方法选取蚊密度较高的4个村为调查点,其中坝区2个、浅丘1个、深丘1个。于2011-07/09现场调查媒介按蚊的叮人率、经产蚊比例、人血指数,收集观察期间的平均气温数据。根据基本繁殖率概念计算以媒介按蚊临界叮人率为指标的传播疟疾阈值。结果成都市中华按蚊的人血指数是0.05,实际叮人率为1.20,中华按蚊对恶性疟和间日疟的临界叮人率分别是12.838 4（恶性疟）和10.553 5（间日疟）。结论成都市按蚊的实际叮人率低于其传播疟疾的临界叮人率,由中华按蚊引起的疟疾传播已被阻断。     

Genetic Evidence of Importation of Drug-Resistant Plasmodium falciparum to Guatemala from the Democratic Republic of the Congo

Imported malaria threatens control and elimination efforts in countries that have low rates of transmission. In 2010, an outbreak of Plasmodium falciparum malaria was reported among United Nations peacekeeping soldiers from Guatemala who had recently returned from the Democratic Republic of the Congo (DRC). Epidemiologic evidence suggested that the soldiers were infected in the DRC, but local transmission could not be ruled out in all cases. We used population genetic analyses of neutral microsatellites to determine the outbreak source. Genetic relatedness was compared among parasites found in samples from the soldiers and parasite populations collected in the DRC and Guatemala; parasites identified in the soldiers were more closely related to those from the DRC. A phylogenetic clustering analysis confirms this identification with >99.9% confidence. Thus, results support the hypothesis that the soldiers likely imported malaria from the DRC. This study demonstrates the utility of molecular genotyping in outbreak investigations.     

Spleen rates in children: an old and new surveillance tool for malaria elimination initiatives in island settings

Spleen rates (SR) have been traditionally used to estimate the burden of malaria transmission. Results are presented from 51 surveys, which measured SR and parasite rates (PR) in 29,962 individuals in the archipelago of Vanuatu. Indices for spleen size computed with multivariate statistical tools outperformed the WHO average spleen index and showed that spleen sizes in a population can track shifts in malaria transmission. In general, a positive linear relationship between Plasmodium spp. PR and SR was found for the archipelago. In the context of malaria elimination and for the specific setting of this study we found that spleen examination is a useful tool in post-malaria elimination surveillance. Finally, results highlight the value of measuring spleen sizes to rapidly assess the impact of intervention packages aimed at malaria elimination or control.     

Use of generalized linear mixed models in the spatial analysis of small-area malaria incidence rates in Kwazulu Natal, South Africa.

Spatial statistical analysis of 1994-1995 small-area malaria incidence rates in the population of the northernmost districts of KwaZulu Natal, South Africa, was undertaken to identify factors that might explain very strong heterogeneity in the rates. In this paper, the authors describe a method of adjusting the regression analysis results for strong spatial correlation in the rates by using generalized linear mixed models and variograms. The results of the spatially adjusted, multiple regression analysis showed that malaria incidence was significantly positively associated with higher winter rainfall and a higher average maximum temperature and was significantly negatively associated with increasing distance from water bodies. The statistical model was used to produce a map of predicted malaria incidence in the area, taking into account local variation from the model prediction if this variation was supported by the data. The predictor variables showed that even small differences in climate can have very marked effects on the intensity of malaria transmission, even in areas subject to malaria control for many years. The results of this study have important implications for malaria control programs in the area.     

Epidemiology of malaria transmission in forest and plain ecotype villages in Sundargarh District, Orissa, India

A study of the epidemiology of malaria transmission was undertaken in 13 tribal villages located in forest and plain areas of Sundargarh District of Orissa state, India, from January 2001 to December 2003. In forest areas, intense transmission of malaria is attributed to the highly anthropophagic vector Anopheles fluviatilis sibling species S and is complemented by A. culicifacies sibling species C. In plain areas, A. culicifacies sibling species C is responsible for malaria transmission. The entomological inoculation rate in the forest and plain areas was 0.311 and 0.014 infective bites/person/night, respectively, during 2003. Malaria transmission is perennial both in forest and plain areas but is markedly low in the plain area compared with the forest area. Plasmodium falciparum accounted for 85.0% of the total malaria cases during the study period. In forest and plain areas, the number of P. falciparum cases per 1000 population per year was 284.1 and 31.2, respectively, whereas the parasite rate was 14.0% and 1.7%, respectively. In forest areas, clinical malaria occurs more frequently in children aged 0-5 years and declines gradually with increasing age. The study showed that villages in forest and plain areas separated by short geographical distances have distinct epidemiology of malaria transmission.     

Intensity of malaria transmission,antimalarial-drug use and resistance in Uganda: what is the relationship between these three factors?

We studied (in 1998 and 1999) some factors that may be linked to the spread of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) resistance in 7 discrete communities in Uganda. Exposure to malaria infection was measured by parasitological surveys in children aged 1-9 years, drug use by community surveys and drug resistance by in-vivo tests on children aged 6-59 months with clinical malaria. CQ use was inversely related to parasite prevalence (r = -0.85, P = 0.01). CQ and SP treatment failure rates varied significantly according to parasite prevalence (P = 0.001 and 0.04 respectively). The highest CQ (42.4%, 43.8%) and SP (12.5%, 14.8%) treatment failure rates were observed in sites characterized by high parasite prevalence. Using areas with medium parasite prevalence as reference, the relative risk (RR) for CQ treatment failure was 3.2 (95% CI 1.6-6.4) in high parasite prevalence sites and 3.1 (95% CI 1.2-7.7) in low parasite prevalence sites. The RR for SP treatment failure was also higher in sites with high parasite prevalence but low in those with low parasite prevalence. According to our findings, drug resistance seems to spread faster in higher transmission areas, regardless of drug pressure. In low transmission areas, drug pressure seems to be the critical factor. A decrease in transmission coupled with rational use of drugs may delay the spread of resistance.     

Genetic structure of Plasmodium falciparum and elimination of malaria, Comoros archipelago

The efficacy of malaria control and elimination on islands may depend on the intensity of new parasite inflow. On the Comoros archipelago, where falciparum malaria remains a major public health problem because of spread of drug resistance and insufficient malaria control, recent interventions for malaria elimination were planned on Moheli, 1 of 4 islands in the Comoros archipelago. To assess the relevance of such a local strategy, we performed a population genetics analysis by using multilocus microsatellite and resistance genotyping of Plasmodium falciparum sampled from each island of the archipelago. We found a contrasted population genetic structure explained by geographic isolation, human migration, malaria transmission, and drug selective pressure. Our findings suggest that malaria elimination interventions should be implemented simultaneously on the entire archipelago rather than restricted to 1 island and demonstrate the necessity for specific chemoresistance surveillance on each of the 4 Comorian islands.     

Recent research on impregnated mosquito nets

The present status of impregnated mosquito nets and other impregnated materials is discussed. Research projects which have produced most of the publications on this subject were conducted in areas in Africa with relatively high endemicity of malaria. In these areas, usage of impregnated mosquito nets caused substantial reductions in the sporozoite inoculation rates and some reduction in incidence of malaria attacks. However, there was little or no reduction in parasite rates in the human population. In several countries in Asia and the Pacific, vector control with impregnated mosquito nets has been introduced on a large scale, thus proving its affordability and compatibility with local customs in these countries. Substantial reductions in malaria parasite rates have been obtained in areas with low levels of malaria transmission. In order to develop the vector control method which is most appropriate for each area, much more research is needed on the technical and organizational aspects of vector control with impregnated mosquito nets. Examples are given of data already available as well as an indication of gaps in knowledge which still exist and will need more attention.     

Spatial patterns of malaria in the Amazon: implications for surveillance and targeted interventions

A measure of local spatial association, G(i)*(d), is applied to test for the presence of malaria clusters in a colonization area in the Brazilian Amazon. Clusters of high and low malaria rates at different moments in time are identified. They suggest unambiguous spatial patterns of transmission, most likely linked to the social and natural habitat. Results imply that a comprehensive identification of the determinants of malaria transmission requires a spatial framework of analysis, and that control strategies must be spatially targeted and guided by a surveillance system that constantly learns the specificities of local transmission and adapts interventions to them.     

Development of a transmission-blocking malaria vaccine: Progress,challenges, and the path forward

New interventions are needed to reduce morbidity and mortality associated with malaria, as well as to accelerate elimination and eventual eradication. Interventions that can break the cycle of parasite transmission, and prevent its reintroduction, will be of particular importance in achieving the eradication goal. In this regard, vaccines that interrupt malaria transmission (VIMT) have been highlighted as an important intervention, including transmission-blocking vaccines that prevent human-to-mosquito transmission by targeting the sexual, sporogonic, or mosquito stages of the parasite (SSM-VIMT). While the significant potential of this vaccine approach has been appreciated for decades, the development and licensure pathways for vaccines that target transmission and the incidence of infection, as opposed to prevention of clinical malaria disease, remain ill-defined. This article describes the progress made in critical areas since 2010, highlights key challenges that remain, and outlines important next steps to maximize the potential for SSM-VIMTs to contribute to the broader malaria elimination and eradication objectives.     

Importance and prevention of malaria in pregnancy

Malaria in pregnancy is one of the most important preventable causes of low birthweight deliveries worldwide. It is also a major cause of severe maternal anaemia contributing to maternal mortality. It is estimated that 40% of the world's pregnant women are exposed to malaria infection during pregnancy. The clinical features of Plasmodium falciparum malaria in pregnancy depend to a large extent on the immune status of the woman, which in turn is determined by her previous exposure to malaria. In pregnant women with little or no pre-existing immunity, such as women from non-endemic areas or travellers to malarious areas, infection is associated with high risks of severe disease with maternal and perinatal mortality. Women are at particular risk of cerebral malaria, hypoglycaemia, pulmonary oedema and severe haemolytic anaemia. Fetal and perinatal loss has been documented to be as high as 60-70% in non-immune women with malaria. Adults who are long-term residents of areas of moderate or high malaria transmission, including large parts of sub-Saharan Africa, usually have a high level of immunity to malaria. Infection is frequently asymptomatic and severe disease is uncommon. During pregnancy this immunity to malaria is altered. Infection is still frequently asymptomatic, so may go unsuspected and undetected, but is associated with placental parasitization. Malaria in pregnancy is a common cause of severe maternal anaemia and low birthweight babies, these complications being more common in primigravidae than multigravidae. Preventative strategies include regular chemoprophylaxis, intermittent preventative treatment with antimalarials and insecticide-treated bednets.     

Coastal urban malaria in Cotonou (Republic of Benin). Entomological study]

A one year entomological was carried out the survey in the coastal town of Cotonou to study the urban transmission of malaria. Three representative areas of Cotonou were chosen. The method adopted concerned night catches on human bait and dissection of A. gambiae s.l. The density of the vector (A. gambiae s.l.) fluctuated with the level of urbanization of the areas the annual aggressivity rates reached 1179 in the town center, 3666 in an the outskirts and 3363 in intermediate areas. Mean sporozoitic index was 1.7% and corresponding annual inoculation rate 46. In center of the town, transmission is seasonal and short, with a very high level. Sporozoitic index is 12% and the corresponding inoculation rate is 1.02. Outside of the town, transmission is seasonal and long: lasting 8 months. Transmission is imperceptible in the middle of the dry season and at the beginning of the long rain season. Malaria transmission into urban areas is generally low but in coastal like zones Cotonou, the intensity may be higher.     

Absence of Asymptomatic Malaria Infection in Endemic Area of Bashagard District,Hormozgan Province,Iran

Background

A successful malaria elimination program calls for enough attention to parasite carriers, especially asymptomatic malaria, as well as the diagnosis and treatment of clinical cases. Asymptomatic malaria is an infection that patients do not show any symptom; thus, these patients play critical role in the concept of an elimination program. The current investigation was conducted to evaluate the presence of these cases in Bashagard District, formerly a high malaria transmission area in Hormozgan Province, Iran.

Methods

Blood samples (n = 500) were collected from symptomless individuals residing in Bashagard to evaluate Plasmodium infection by using microscopic, serological and nested-PCR techniques.

Results

Regarding the microscopic and nested-PCR analysis, no asymptomatic infection was detected among studied individuals. Totally, 1% of the studied population (5 of 500) had anti PvMSP-1₁₉-specific IgG antibody; however, only 0.2% (1 of 500) of the individuals was seropositive to recombinant PfMSP-1₁₉, using ELISA.

Conclusion

This study showed no asymptomatic malaria infection in the studied population; hence malaria elimination is feasible and can be successfully carried out in this region.     

Unstable malaria in Sudan: the influence of the dry season. Clone multiplicity of Plasmodium falciparum infections in individuals exposed to variable levels of disease transmission.

Studies of infection and immunity to malaria often take little account of the fact that the amount of infectious challenge individuals receive is very variable. Classic studies in areas of holoendemic transmission showed that clinical immunity develops quite rapidly during childhood, although the processes through which increasing levels of resistance to infection are acquired are still not understood. However, holoendemic transmission is one end of the spectrum of malaria epidemiology and the development of clinical immunity is also affected by factors such as the infection rate and the local parasite species composition. An exceptionally simple type of malaria transmission occurs during the short, autumnal malaria outbreaks of the Sudanese sahel-savannah belt, where a sparse 200-500 mm of rain falls in 2-3 summer months, Plasmodium falciparum causes > 95% of malaria cases in most areas, and the entomological inoculation rate (EIR) is very low by African standards; thus the population dynamics of malaria parasites are less affected by super-infection. A comparison of certain features of parasite genetic diversity, particularly the average number of parasite clones present in infections in the Sudanese sahel and in malaria study sites with different levels of transmission, is presented. It is proposed that increasing EIRs are associated with progressively smaller increases in the average number of malaria parasite clones per host and the implications of this relationship for studies on malaria infection and immunity are discussed.     

湖南省消除疟疾历程及策略评价

目的 分析湖南省疟疾流行规律与防治历程,总结评估消除疟疾策略及措施。 方法 对湖南省历年疟疾防治疫情数据报表、文件、工作计划、防治策略与措施等资料进行描述性分析和总结,根据国家相关文件的要求,从保障措施、技术措施、防控效果3个方面对消除疟疾工作进行评估。 结果 湖南省曾发生过3次疟疾大流行,1954—1956年、1962—1965年和1971—1973年,发病率分别为87.45/万～156.04/万、39/万～ 58.98/万和44.46/万～69.51/万,通过及时调整防治策略和措施,大多数地区疟疾流行得到了有效控制。在启动消除疟疾行动计划以来,通过不断地落实各项疟疾防治策略和措施,疟疾发病率持续稳定在1/10万以下。2010年湖南省报告最后一例本地感染病例后,已连续多年未报告本地感染病例。至2016年,全省122个县(市、区)和14个市(州)均通过了消除疟疾的县级考核和市级评估,2020年通过国家评估达到消除疟疾的标准。 结论 湖南省经过多年疟疾防治,保持连续11年无本地疟疾病例,达到消除疟疾标准,巩固工作重点是加强输入性病例监测,降低本地再传播风险。     

Insecticide-impregnated bed nets for malaria control: a review of the field trials.

Insecticide-impregnated bed nets act as a physical barrier to repel and kill mosquitos. Community intervention trials suggest that these nets are effective in preventing malaria-related mortality and morbidity--but not malaria infection--in areas of low and moderate transmission; the results from areas of high transmission are not so encouraging. Comparison of the results from these trials and their interpretation are difficult because of variations in the epidemiology of malaria and several methodological flaws. Problems such as defining appropriate health indicators, monitoring bed-net usage, introducing bed nets randomly, selecting adequate controls, performing statistical analysis, and comparing bed nets with other available interventions are considered. Further community intervention trials are needed, paying attention to the methods and to assessment of their impact on malaria.     

Estimation of malaria transmission from humans to mosquitoes in two neighbouring villages in south Cameroon: evaluation and comparison of several indices

Malaria transmission from humans to mosquitoes was assessed in two neighbouring villages in a rural area near Yaoundé, Cameroon during high and low transmission seasons during 1998-2000, using several indices previously evaluated in different areas endemic for malaria but never directly compared. These indices were estimated from human parasitological data and mosquito infection rates and, for each individual, thick blood films were prepared at the same time as experimental infection of laboratory-bred mosquitoes. Among the 685 volunteers examined, the prevalence of Plasmodium falciparum gametocyte carriers was 16%, and 8% of individuals were able to infect mosquitoes. The percentage of mosquitoes that became infected by feeding on the infectious individuals was 21%. Children aged < 10 years contributed to about 75% of the infectious reservoir, although they constituted only 35% of the total population. Differences were found between the transmission seasons and the villages, and varied according to the index examined. Although there were more infectious individuals in one of the two villages, they were less infectious than those in the other village during the high transmission season. Comparative analysis of the transmission indices suggests the existence of functioning transmission-blocking immunity in one of the villages, which until now has been only hypothetically considered to play a role in malaria transmission in a natural setting. The epidemiological value of all the indices used and their accuracy in estimating the human infectious reservoir and its natural or induced variations are discussed.