Plasmodium Falciparum In Children Research Articles

Asymptomatic carriage of Plasmodium falciparum in children living in a hyperendemic area occurs independently of IgG responses but is associated with a balanced inflammatory cytokine ratio

BackgroundAsymptomatic carriage of infected red blood cells (iRBCs) can be prevalent in communities regardless of transmission patterns and can occur with infection of different Plasmodium species. Clinical immunity dampens the inflammatory responses leading to disease symptoms in malaria. The aim of this study was to define the immunological correlates of asymptomatic carriage of Plasmodium falciparum in a highly exposed population.Methods142 asymptomatic Plasmodium-infected individuals greater than 2 years of age without fever (body temperature <37.5 ℃) were followed weekly for 10 weeks before being treated with artemisinin-based combination therapy (ACT). Plasma levels of 38 cytokines were measured at baseline by Luminex and the quantity and growth inhibitory activities of circulating parasite-reactive antibodies measured. The Plasmodium antigen tested included P. falciparum merozoite extract (ME) and schizont extract (SE), and the recombinant proteins erythrocyte binding antigen 175 (EBA-175) and merozoite surface protein 1 (MSP-119).ResultsMedian levels of IgG against P. falciparum EBA-175 and MSP-119 at baseline were significantly higher in those older than 20 years of age compared with the younger age group and appeared to correlate with better parasite control. Amongst all participants there were no discernible changes in IgG levels over time. Parasite density was higher in the younger age group and associated with IL-10, TNF and MCP-1 levels. A balanced IL-10:TNF ratio was associated with asymptomatic malaria regardless of age, and balanced ratios of IL-10/TNF and IL-10/IFN-γ were the only significant correlate of maintenance of asymptomatic malaria over the course of the study in individuals 20 years of age and younger.ConclusionThe above findings indicate that asymptomatic carriage of P. falciparum in children living in a hyperendemic area occurs independently of IgG but is associated with a balanced inflammatory cytokine ratio.

The Need for Novel Asexual Blood-Stage Malaria Vaccine Candidates for Plasmodium falciparum.

Extensive control efforts have significantly reduced malaria cases and deaths over the past two decades, but in recent years, coupled with the COVID-19 pandemic, success has stalled. The WHO has urged the implementation of a number of interventions, including vaccines. The modestly effective RTS,S/AS01 pre-erythrocytic vaccine has been recommended by the WHO for use in sub-Saharan Africa against Plasmodium falciparum in children residing in moderate to high malaria transmission regions. A second pre-erythrocytic vaccine, R21/Matrix-M, was also recommended by the WHO on 3 October 2023. However, the paucity and limitations of pre-erythrocytic vaccines highlight the need for asexual blood-stage malaria vaccines that prevent disease caused by blood-stage parasites. Few asexual blood-stage vaccine candidates have reached phase 2 clinical development, and the challenges in terms of their efficacy include antigen polymorphisms and low immunogenicity in humans. This review summarizes the history and progress of asexual blood-stage malaria vaccine development, highlighting the need for novel candidate vaccine antigens/molecules.

Codetection of Plasmodium falciparum in Children Hospitalized With Dengue Fever in the Dominican Republic.

Cases of malaria and dengue in the Dominican Republic both spiked in 2019, but their rates of codetection are poorly characterized, especially in children. We performed a prospective, observational study in January to December 2019 at the Hospital Infantil Robert Reid Cabral, in the Dominican Republic, enrolling hospitalized children with a clinical suspicion of dengue fever. Participants with a positive plasma dengue IgM antibodies were included in this study. Clinical and hospital data were abstracted, and dried blood spot samples were collected from participants and tested with quantitative polymerase chain reaction to detect the presence of Plasmodium falciparum DNA. A total of 429 children with serological evidence of acute dengue were included in this study, of whom 1.4% (n = 6/429) had codetection of dengue and malaria. There were no significant differences in fever duration or presence of vomiting, abdominal pain and rash between both groups. Children with dengue and malaria codetection were numerically more often admitted to the pediatric intensive care unit, despite no differences found in overall clinical severity. The codetection of malaria and dengue in children was overall uncommon in our Dominican Republic cohort despite the rise in cases in 2019 but may be associated with a more severe hospital course. Further epidemiological and cohort studies to characterize the risk of both pathogens as case numbers fluctuate will be important to better understand the dynamics of coinfections.

A Review of Malaria in Pediatric

Introduction: As a tropical disease, malaria, which causes one death per minutes globally, is still common in both tropical and subtropical regions around the world. From millions of reported cases, one million cases would end in death each year. Data collection: Different databases and search engine, including PubMed and Google Scholar, were investigated to collect required data for the completion of the present review article by two participations authors. The following keywords were used for search in these databases Malaria in Children, Plasmodium Falciparum in Children, Malaria in Paediatrics, and Plasmodium Falciparum in Paediatrics. Results: 47 study in English was included. Children under five years old make the majority of death reports; i.e. 90% of the whole death statistics. Although malaria is mostly common in sub-Saharan Africa, it still occurs in other tropical and subtropical countries. In other regions, malaria is the result of both immigration and travel; regardless of the sources of the disease, it can be potentially severe and, sometimes, fatal. Conclusions: It would be important to become familiar with the clinical presentation of malaria among pedestrians and find approaches to prompt diagnosis, appropriate treatment and sufficient prevention methods against malaria among pedestrians.

Species of plasmodium (P. Falciparum and P. Vivax) involved in children with malaria: An experience from a tertiary childcare hospital.

Objective: To find out different species of plasmodium (P. falciparum and P. vivax) involved in children with malaria at a tertiary childcare hospital. Study Design: Descriptive, Cross-sectional study. Setting: Department of Paediatric Medicine, The Children’s Hospital and Institute of Child Health, Multan. Period: October 2019 to March 2020. Material &amp; Methods: A total of 281 cases of either gender, aged 1 to 12 years and patients with malaria were enrolled. A special template was designed to record study information. Venous blood as five ml sample was drawn and dispatched to institutional laboratory for ICT malaria, complete blood count and giemsa stain smear and observed under light microscope. Data analysis was performed employing SPSS version 24.0. Results: Out of a total of 281 cases, 177 (63.0%) were male ande 104 (37.0%) female. Mean age of study participants was 4.29±2.48 years. A total of 135 (48.0%) children belonged to rural areas and 197 (70.1%) had monthly family income &lt; 25000 rupees. Mean duration of illness was 4.21 ± 2.12 days. Previous history of use of anti-malarial drugs was noted in 62 (22.1%) of our study cases. Plasmodium falciparum was observed in 52 (18.5%) cases and plasmodium vivax in 229 (81.5%). Conclusion: Plasmodium vivax is predominantly more prevalent in our population as compared with plasmodium falciparum in children with malaria. Plasmodium falciparum and plasmodium vivax were significantly linked with age and disease duration. Malaria was noted to be more prevalent among poor families living in slum areas having inadequate sanitation facilities.

Population structure and diversity of Plasmodium falciparum in children with asymptomatic malaria living in different ecological zones of Ghana

BackgroundGenetic diversity in Plasmodium falciparum populations can be used to describe the resilience and spatial distribution of the parasite in the midst of intensified intervention efforts. This study used microsatellite analysis to evaluate the genetic diversity and population dynamics of P. falciparum parasites circulating in three ecological zones of Ghana.MethodsA total of 1168 afebrile children aged between 3 to 13 years were recruited from five (5) Primary schools in 3 different ecological zones (Sahel (Tamale and Kumbungu), Forest (Konongo) and Coastal (Ada and Dodowa)) of Ghana. Asymptomatic malaria parasite carriage was determined using microscopy and PCR, whilst fragment analysis of 6 microsatellite loci was used to determine the diversity and population structure of P. falciparum parasites.ResultsOut of the 1168 samples examined, 16.1 and 39.5% tested positive for P. falciparum by microscopy and nested PCR respectively. The genetic diversity of parasites in the 3 ecological zones was generally high, with an average heterozygosity (He) of 0.804, 0.787 and 0.608 the rainy (peak) season for the Sahel, Forest and Coastal zones respectively. The mean He for the dry (off-peak) season were 0.562, 0.693 and 0.610 for the Sahel, Forest and Coastal zones respectively. Parasites from the Forest zone were more closely related to those from the Sahel than from the Coastal zone, despite the Coastal zone being closer in physical distance to the Forest zone. The fixation indexes among study sites ranged from 0.049 to 0.112 during the rainy season and 0.112 to 0.348 during the dry season.ConclusionA large asymptomatic parasite reservoir was found in the school children during both rainy and dry seasons, especially those in the Forest and Sahel savannah zones where parasites were also found to be related compared to those from the Coastal zone. Further studies are recommended to understand why despite the roll out of several malaria interventions in Ghana, high transmission still persist.

Asymptomatic Plasmodium falciparum malaria prevalence among adolescents and adults in Malawi, 2015\u20132016

Malaria remains a significant cause of morbidity and mortality in Malawi, with an estimated 18–19% prevalence of Plasmodium falciparum in children 2–10 years in 2015–2016. While children report the highest rates of clinical disease, adults are thought to be an important reservoir to sustained transmission due to persistent asymptomatic infection. The 2015–2016 Malawi Demographic and Health Survey was a nationally representative household survey which collected dried blood spots from 15,125 asymptomatic individuals ages 15–54 between October 2015 and February 2016. We performed quantitative polymerase chain reaction on 7,393 samples, detecting an overall P. falciparum prevalence of 31.1% (SE = 1.1). Most infections (55.6%) had parasitemias ≤ 10 parasites/µL. While 66.2% of individuals lived in a household that owned a bed net, only 36.6% reported sleeping under a long-lasting insecticide-treated net (LLIN) the previous night. Protective factors included urbanicity, greater wealth, higher education, and lower environmental temperatures. Living in a household with a bed net (prevalence difference 0.02, 95% CI − 0.02 to 0.05) and sleeping under an LLIN (0.01; − 0.02 to 0.04) were not protective against infection. Our findings demonstrate a higher parasite prevalence in adults than published estimates among children. Understanding the prevalence and distribution of asymptomatic infection is essential for targeted interventions.

A prospective study of comparison of clinical profile, complication and outcome of plasmodium vivax versus plasmodium falciparum in children

Introduction: Malaria is a life – threatening disease but is curable and preventable. As per data of WHO in 2017, there were an estimated 219 million cases of malaria in 90 countries. As plasmodium Vivax malaria has been considered to have a benign course with less mortality, most of the research is focussed on plasmodium falciparum. But in recent years there are number of studies conducted in India and other countries has highlighted that plasmodium vivax can cause severe and fatal malaria, in paediatric patients. Based on this background we have designed a prospective study to evaluate clinical profile, complication and outcome of plasmodium vivax and compare it with plasmodium falciparum malaria. Materials and Methods: Present study is a prospective study conducted in the department of paediatrics Konaseema institute of medical science Amalapuram Andhra Pradesh during the period from Jan 2015 to October 2018.Data regarding patient age, sex clinical presentation, investigation, complication and outcome are recorded. Lab investigation like haemoglobin, total leukocyte cannot platelet count, bleeding time, clotting time, blood sugar, blood urea, serum creatinine, serum Bilirubin, SGOT and SUPT were some for all these investigation standard laboratory procedure was followed. Result: In present study 60 patient admitted with proven malaria to our hospital were analysed. Severe malaria was present in 4(11.12%) p. vivax infection patients and in 2(8.41) P. falciparum infection patient. 4 patients having bleeding manifestation in vivax group and 2 patient having bleeding manifestation in P. falciparum group. Jaundice was present in 4 p. vivax infection patients and 2 P. falciparum infection patients. 12 (33.33%) P .vivax patients were presented with shock, 8(33.33%) patient in falciparum group presented with shock. Renal failure was present in 4(11.12%) p value patient and 2 (8.4%) patients with P falciparum infection. Cerebral malaria was present in 3(8.33%) p. viva

Semisynthetic Derivative of Artemisia annua-Loaded Transdermal Bioadhesive for the Treatment of Uncomplicated Malaria Caused by Plasmodium falciparum in Children

According to the most recent World Health Organization statistics, malaria infected approximately 219 million people in 2017, with an estimate of 435,000 deaths (World Health Organization, 2018). Communities isolated from cities are the most deprived of access to the necessary hospital facilities. Herein we report the development of a transdermal bioadhesive containing artemether (ART), an alternative, potentially lifesaving, treatment regimen for malaria in low-resource settings. Bioadhesives were prepared from an aqueous blend of hydroxyethylcellulose (4.5% w/w), ART, propoxylated-ethoxylated-cetyl-alcohol, polysorbate 80, propyleneglycol, glycerine, mineral oil, and oleic acid. In this study, the average pore size of bioadhesive 5.5b was 52.6 ± 15.31 μm. Differential scanning calorimetry and thermogravimetric analyses confirm the thermal stability of ART bioadhesives at room temperature. Tensile tests indicated good mechanical properties for bioadhesive 5.5b, when compared to 5.5a, where 5.5b showed elastic modulus 0.19 MPa, elongation at break 204%, tensile stress 0.31 MPa, tensile strength at break 0.23 MPa. Bioadhesion assays suggested that formulations containing surfactants had higher detachment forces. Permeation studies demonstrated that the best outcome was achieved with a bioadhesive containing 25 mg ART (5.5b) that after 24 h released 6971 ± 125 μg, which represents approximately 28% of drug permeation. Data reported presents a promising candidate for a new antimalarial transdermal formulation.

Declining Malaria Transmission Differentially Impacts the Maintenance of Humoral Immunity to Plasmodium falciparum in Children.

We investigated the poorly understood impact of declining malaria transmission on maintenance of antibodies to Plasmodium falciparum merozoite antigens and infected erythrocytes (IEs), including functional immunity. In a 3-year longitudinal cohort of 300 Kenyan children, antibodies to different AMA1 and MSP2 alleles of merozoites, IE surface antigens, and antibody functional activities were quantified. Over a period in which malaria transmission declined markedly, AMA1 and MSP2 antibodies decreased substantially; estimated half-lives of antibody duration were 0.8 year and 1-3 years, respectively. However, 69%-74% of children maintained their seropositivity to AMA1 alleles and 42%-52% to MSP2 alleles. Levels and prevalence of antimerozoite antibodies were consistently associated with increasing age and concurrent parasitemia. Antibodies promoting opsonic phagocytosis of merozoites declined rapidly (half-life, 0.15 years). In contrast, complement-fixing antibodies to merozoites did not decline and antibodies to IE surface antigens expressing virulent phenotypes were much better maintained (half-life, 4-10 years). A decline in malaria transmission is associated with reduction in naturally acquired immunity. However, loss of immunity is not universal; some key functional responses and antibodies to IEs were better maintained and these may continue to provide some protection. Findings have implications for malaria surveillance and control measures and informing vaccine development.

Persistence of chloroquine-resistant haplotypes of Plasmodium falciparum in children with uncomplicated Malaria in Lagos, Nigeria, four years after change of chloroquine as first-line antimalarial medicine.

BackgroundIn Nigeria, despite the change in National malaria drug policy to artemisinin combination therapy (ACT) in 2005 due to widespread chloroquine resistance, chloroquine (CQ) is still widely used in the treatment of malaria because it is cheap, affordable and accessible. The use of ACT for the management of uncomplicated malaria is currently being promoted. The employment of genetic markers to track circulating chloroquine-resistant parasites are useful in elucidating likely poor efficacy of chloroquine, especially in settings where it is not recommended for the treatment of uncomplicated falciparum malaria. This study determined the prevalence of pfcrt haplotypes and point mutations in pfmdr1 genes four years after the change in antimalarial treatment policy from CQ to the ACTs in Lagos, a commercial city in South-West, Nigeria.MethodsThis was a cross sectional study on uncomplicated malaria in children less than 12 years that presented with fever and other symptoms suggestive of malaria. Parasite DNA was extracted from 119 patients out of 251 children who were positive for Plasmodium falciparum by microscopy and amplified. The occurrence of haplotypes was investigated in pfcrt gene using probe-based qPCR and single nucleotide polymorphisms in pfmdr1 gene using nested PCR.ResultsOne hundred and nine (109) of the 119 children with P falciparum infection (91.6%) harbourd parasites with the mutant pfcrt haplotype (CVIET). Out of this, 4.2% comprised a mixture of genotypes encoding CVMNK and CVIET, while 4.2% had the wild type (CVMNK). Furthermore, the frequency of point mutations in pfmdr1 was 62.2% and 69.0% for codons Y86 and F184 respectively. There were no mutations at codons 1034, 1042 and 1246 of the Pfmdr1 genes.ConclusionThe high frequency of the CQ-resistant haplotypes (CVIET) and mutations in Pfmdr1 associated with CQ resistance in P. falciparum among these children suggest that CQ-resistant parasites are still in circulation. Continuous use of chloroquine may continue to increase the level of mutations in pfcrt and pfmdr1genes. There is need to strengthen current case management efforts at promoting ACT use as well as urgently restricting access to chloroquine by the National drug regulatory agency, National Agency for Food Drug Administration and Control (NAFDAC).Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2069472010142303

Changing patterns of health in communities impacted by a bioenergy project in northern Sierra Leone.

Large private sector investments in low- and middle-income countries are often critically evaluated with regards to their environmental, social, human rights, and health impacts. A health impact assessment, including a baseline health survey, was commissioned by the Addax Bioenergy Sierra Leone project in 2010. As part of the monitoring, a follow-up survey was conducted three years later. A set of health indicators was assessed at six impacted and two control sites. Most of these indices improved, particularly at the impacted sites. The prevalences of stunting, wasting, and Plasmodium falciparum in children under five years of age decreased significantly at impacted sites (all p < 0.05) and non-significantly at control sites. Anemia in children and in women of reproductive age (15–49 years) decreased significantly at impacted and control sites (p < 0.05 and p < 0.001, respectively). Health facility-based deliveries increased significantly at the impacted sites (p < 0.05). The prevalences of helminth infections in children aged 10–15 years remained approximately at the same levels, although focal increases at the impacted sites were noted. Access to improved sanitation decreased significantly (p < 0.05) at control and non-significantly at impacted sites. Water quality remained poor without significant changes. The epidemiologic monitoring of a bioenergy project provides a useful contribution for evidence-based decision-making.

Relationship between alpha+-thalassaemia and glutathione-S-transferases polymorphisms in children with severe malaria in Tanzania.

Alpha+-thalassaemia is well known for conferring partial protection to severe malaria. On the other, Glutathione-S-transferase (GST) polymorphism has recently been associated to severe malaria in children. A retrospective cross sectional study was carried out to determine the relationship between genotypic polymorphisms of alpha+-thalassaemia and glutathione-S-transferase in children with severe malaria. A total of 148 DNA samples from children aged between 3 and 15 years with mild and severe malaria were retrieved and determined by polymerase chain reaction. Children with Glutathione-S-transferase-pil (GSTP1)-polymorphism were observed to have three fold risk (OR = 2.9; 95% CI =1.3- 6.1; P = 0.006) of developing severe malaria compared to mild malaria in Mnyuzi in Korogwe District, north-eastern, Tanzania. In the presence of Glutathione-S-transferase-pil polymorphism, children were found to have 3% decreased protective effect of alpha+-thalassaemia polymorphisms (homozygotes and heterozygotes) against severe malaria although this was not statistically significant [OR = 0.81 (95% CI = 0.5-1.5; P = 0.5) to OR =0.78(95% CI = 0.4-1.5; P = 0.44)]. We conclude that Glutathione-S-transferase-pil polymorphism increases risk of developing severe malaria due to Plasmodium falciparum in children. The observed inverse relationship between GSTP1 polymorphisms and alpha-thalassaemia to children with severe malaria need further investigation.

Evidence for both innate and acquired mechanisms of protection from Plasmodium falciparum in children with sickle cell trait

AbstractSickle cell trait (HbAS) is known to be protective against Plasmodium falciparum malaria, but it is unclear when during the course of infection this protection occurs and whether protection is innate or acquired. To address these questions, a cohort of 601 children 1-10 years of age were enrolled in Kampala, Uganda, and followed for 18 months for symptomatic malaria and asymptomatic parasitemia. Genotyping was used to detect and follow individual parasite clones longitudinally within subjects. Children with HbAS were protected against the establishment of parasitemia, as assessed by the molecular force of infection at older but not younger ages (at 2 years of age: incidence rate ratio [IRR] = 1.16; 95% confidence interval [95% CI], 0.62-2.19; P = .6; at 9 years of age: IRR = 0.50; 95% CI, 0.28-0.87; P = .01), suggesting an acquired mechanism of protection. Once parasitemic, children with HbAS were less likely to progress to symptomatic malaria, with protection again being the most pronounced at older ages (at 2 years of age: relative risk [RR] = 0.92; 95% CI, 0.77-1.10; P = .3; at 9 years of age: RR = 0.68; 95% CI, 0.51-0.91; P = .008). Conversely, the youngest children were best protected against high parasite density (at 2 years of age: relative density = 0.24; 95% CI, 0.10-0.54; P = .001; at 9 years of age: relative density = 0.59; 95% CI, 0.30-1.19; P = .14), suggesting an innate mechanism of protection against this end point.

Impact of sickle-cell trait on humoral immunity against Plasmodium falciparum in children living in malaria endemic areas of Mali (45.10)

Abstract Previous studies have shown that children with sickle-cell trait (heterozygosity for normal hemoglobin A and sickle hemoglobin S, genotype AS) are resistant to P. falciparum malaria when compared with AA children. Passive transfer studies have established the importance of antibodies against blood-stage parasites. However, the impact of sickle-cell trait on immunity against parasite antigens has not been extensively studied. In a longitudinal study in rural Mali, we followed 73 AS and 126 AA children for an entire 6-month transmission season. Before the transmission season, antibody titers were measured against 4 parasite blood-stage antigens (AMA1, MSP1, EBA175 and MSP2). AS children experienced significantly fewer malaria episodes than AA children. Because there is a significant effect of age on antibody titers, we stratified children in 3 age groups (3-5, 6-8 and 9-11 years). Compared to AA children aged 9-11 years, AS children showed significantly lower antibody titers to all 4 antigens. For the 6-8 years group, AS children showed significantly lower antibody titers to EBA175 and MSP2. No differences were observed between AA and AS children 3-5 years old for any antigen. These data suggest that the antibody titers against these major blood-stage antigens before transmission season are not involved in reducing the incidence of malaria in AS children. The functional activity of antibodies (i.e., in vitro parasite growth-inhibitory activity) will be also presented.

Parascreen as an Alternative Diagnostic Tool for Falciparum Malaria

Malaria is a parasitic disease with high morbidity and mortality. Rapid immunochromatographic are emerging to detect specific antigens of human plasmodia. Objective To determine the sensitivity and specificity of Parascreen for the detection of Plasmodium falciparum in children. Methods A diagnostic test study was performed in Mandailing Natal District, Penyabungan, North Sumatera. Subjects were public health center and hospital patients with symptoms of fever, pallor, headache, and diarrhea. Blood specimens were obtained for Parascreen testing. Microscopy of Giemsa-stained blood samples served as the gold standard. Results One hundred and four subjects were studied. The sensitiv-

Building small dams can decrease malaria: A comparative study from Sundargarh District, Orissa, India

The adverse health effect of environmental changes brought about with the construction of large and small dams has often been reported. Here, we present results of a 5-year (2001–2005) study documenting the positive effect of such developmental projects in reducing malaria in an area where malaria transmission is mainly due to the highly efficient anthropophagic vector Anopheles fluviatilis with some contribution from Anopheles culicifacies. The former breeds exclusively in the slow-flowing streams and the latter breeds in a variety of habitats. The study was conducted in San Dulakudar village and comparisons were made with two control villages situated near the stream with similar topography and malaria transmission pattern. Epidemiological data was collected through longitudinal weekly surveillance and cross-sectional surveys in all the study villages. The mean annual malaria incidence rates due to Plasmodium falciparum in children of 1–5 years age group during 2001 before construction of dam was 1304.3 and 785.7 cases/1000 population in dam site village and control villages, respectively. However, after construction of dam, there was gradual reduction in the malaria cases in dam site village and during 2005 the incidence was significantly reduced to 181.8 ( P < 0.01) whereas it was increased to 1000 in control villages without any significant change in comparison to baseline year ( P > 0.05). A significant reduction in malaria incidence and parasite rate was also recorded in all the age groups in dam site village without registering any significant change in control villages. The construction of a small dam in the study village altered the water flow above and below the dam thereby making it unfavourable for the breeding of A. fluviatilis which in turn brought about significant impact on malaria transmission.

Evaluation of antibody response to Plasmodium falciparum in children according to exposure of Anopheles gambiae s.l or Anopheles funestus vectors

BackgroundIn sub-Saharan areas, malaria transmission was mainly ensured by Anopheles. gambiae s.l. and Anopheles. funestus vectors. The immune response status to Plasmodium falciparum was evaluated in children living in two villages where malaria transmission was ensured by dissimilar species of Anopheles vectors (An. funestus vs An. gambiae s.l.).MethodsA multi-disciplinary study was performed in villages located in Northern Senegal. Two villages were selected: Mboula village where transmission is strictly ensured by An. gambiae s.l. and Gankette Balla village which is exposed to several Anopheles species but where An. funestus is the only infected vector found. In each village, a cohort of 150 children aged from one to nine years was followed during one year and IgG response directed to schizont extract was determined by ELISA.ResultsSimilar results of specific IgG responses according to age and P. falciparum infection were observed in both villages. Specific IgG response increased progressively from one-year to 5-year old children and then stayed high in children from five to nine years old. The children with P. falciparum infection had higher specific antibody responses compared to negative infection children, suggesting a strong relationship between production of specific antibodies and malaria transmission, rather than protective immunity. In contrast, higher variation of antibody levels according to malaria transmission periods were found in Mboula compared to Gankette Balla. In Mboula, the peak of malaria transmission was followed by a considerable increase in antibody levels, whereas low and constant anti-malaria IgG response was observed throughout the year in Gankette Balla.ConclusionThis study shows that the development of anti-malaria antibody response was profoundly different according to areas where malaria exposure is dependent with different Anopheles species. These results are discussed according to i) the use of immunological tool for the evaluation of malaria transmission and ii) the influence of Anopheles vectors species on the regulation of antibody responses to P. falciparum.

Assessment of the therapeutic efficacy of a paediatric formulation of artemether-lumefantrine (Coartesiane®) for the treatment of uncomplicated Plasmodium falciparum in children in Zambia

BackgroundSentinel site surveillance of antimalarials by in-vivo therapeutic efficacy studies in Zambia is one of the key activities ear-marked for monitoring and evaluation. The studies are conducted annually in order to provide timely and reliable information on the status of the recommended regimens for malaria case management. The findings of the therapeutic efficacy of an artemisinin-based combination therapy of pediatric artemether-lumefantrine (Coartesiane®) are reported.MethodThe design is a simple, one-arm, prospective evaluation of the clinical and parasitological response to directly observed treatment for uncomplicated malaria. The study was conducted in sentinel sites using the WHO standardized protocol for the assessment of therapeutic efficacy of antimalarial drugs (WHO 2000) in children under five years of age, weighing less than 10 Kg. The study was conducted at two clinics, one in Chongwe (Lusaka Province) and Chipata (Eastern Province). The 28-day follow-up period was used coupled with PCR genotyping for MSP1 and MSP2 in order to differentiate recrudescence from re-infections for parasites that appeared after Day 14.Results91/111 children enrolled in the study, were successfully followed up. Artemether-lumefantrine (Coartesiane®) was found to produce significant gametocyte reduction. The Adequate Clinical and Parasitological Response (ACPR) was found to be 100% (95% CI 96.0;100).ConclusionCoartesiane® was effective in treating uncomplicated malaria in Zambian children weighing less than 10 kg, an age group normally excluded from taking the tablet formulation of artemether-lumefantrine (Coartem®).

INFLUENCE OF CHEMOTHERAPY ON THE PLASMODIUM GAMETOCYTE SEX RATIO OF MICE AND HUMANS

Plasmodium species, the etiologic agents of malaria, are obligatory sexual organisms. Gametocytes, the precursors of gametes, are responsible for parasite transmission from human to mosquito. The sex ratio of gametocytes has been shown to have consequences for the success of this shift from vertebrate host to insect vector. We attempted to document the effect of chemotherapy on the sex ratio of two different Plasmodium species: Plasmodium falciparum in children from endemic area with uncomplicated malaria treated with chloroquine (CQ) or sulfadoxine-pyrimethamine (SP), and P. vinckei petteri in mice treated with CQ or untreated. The studies involved 53 patients without gametocytes at day 0 (13 CQ and 40 SP) followed for 14 days, and 15 mice (10 CQ and 5 controls) followed for five days. During the course of infection, a positive correlation was observed between the time of the length of infection and the proportion of male gametocytes in both Plasmodium species. No effects of treatment (CQ versus SP for P. falciparum or CQ versus controls for P. vinckei petteri) on the gametocyte sex ratio were found for either Plasmodium species. This indicates that parasites do not respond to chemotherapy by altering their sex allocation strategy, even though, in the case of P. falciparum, they apparently increase their overall investment in sexual stages. This suggests that malaria parasite species respond to different environmental cues for their sex differentiation and sex determination.