RESUMO
Animal-source foods (ASFs) are a food group of interest for interventions aimed at reducing stunting and other inadequate growth measures in early childhood. The aim of this systematic review was to examine the relation between ASF consumption and stunting in children aged 6-60 mo in low- and middle-income countries (LMICs). The secondary aim was to examine the relation between ASF consumption and other indicators of growth and development (length/height, weight, head circumference, and anemia). A search of the peer-reviewed and grey literature published from January 1980 to June 2017 was conducted. Databases searched included CINAHL, Embase, Global Index Medicus, PubMed, and Web of Science. There were 14,783 records and 116 full text articles dual screened; 21 studies were included in the review and were dual evaluated for risk of bias (RoB). The relation between ASF and stunting (length- or height-for-age z-scoreâ2) was examined in randomized-controlled trials [(RCTs), n = 3] and cross-sectional studies (n = 4) only; ASF reduced stunting in 1 RCT and was associated with reduced stunting in 1 cross-sectional study. We did not identify any longitudinal cohorts that examined this relation. The relation between ASF and secondary indicators length/height, weight, head circumference, and anemia were largely nonsignificant across study designs. The intervention/exposure, comparator, outcome measures, methods, and analyses were highly heterogeneous. Although we did not find a consistent relation between ASF consumption and our primary and secondary outcomes, this may have been a function of inconsistencies in study design. Foods in the whole diet, particularly combination dishes, are inherently difficult to assess. To quantitatively assess the relation between ASF and stunting and other indicators of growth and iron status in early childhood, future research should provide consistency in the definition and quantification of the exposure and outcomes allowing for interstudy quantitative comparisons.
Assuntos
Transtornos da Nutrição Infantil/epidemiologia , Dieta/efeitos adversos , Transtornos do Crescimento/epidemiologia , Carne/efeitos adversos , Transtornos da Nutrição Infantil/etiologia , Fenômenos Fisiológicos da Nutrição Infantil , Pré-Escolar , Estudos Transversais , Países em Desenvolvimento , Dieta/métodos , Inquéritos sobre Dietas , Ingestão de Alimentos/fisiologia , Feminino , Transtornos do Crescimento/etiologia , Humanos , Renda , Lactente , Masculino , Carne/análise , Pobreza/estatística & dados numéricosRESUMO
BACKGROUND: Despite considerable global efforts to reduce growth faltering in early childhood, rates of stunting remain high in many regions of the world. Current interventions primarily target nutrition-specific risk factors, but these have proven insufficient. The objective of this study was to synthesize the evidence on the relationship between active tobacco use during pregnancy and growth outcomes in children under five years of age. METHODS: In this systematic review and meta-analysis, six online databases were searched to identify studies published from January 1, 1980, through October 31, 2016, examining the association between active tobacco use during pregnancy and small-for-gestational age (SGA), length/height, and/or head circumference. Ecological studies were not included. A meta-analysis was conducted, and subgroup analyses were carried out to explore the effect of tobacco dosage. RESULTS: Among 13,189 studies identified, 210 were eligible for inclusion in the systematic review, and 124 in the meta-analysis. Active tobacco use during pregnancy was associated with significantly higher rates of SGA (pooled adjusted odds ratio [AORs] = 1.95; 95% confidence interval [CI]: 1.76, 2.16), shorter length (pooled weighted mean difference [WMD] = 0.43; 95% CI: 0.41, 0.44), and smaller head circumference (pooled WMD = 0.27; 95% CI: 0.25, 0.29) at birth. In addition, a dose-response effect was evident for all growth outcomes. CONCLUSION: Tobacco use during pregnancy may represent a major preventable cause of impaired child growth and development.
Assuntos
Deficiências do Desenvolvimento/etiologia , Efeitos Tardios da Exposição Pré-Natal , Uso de Tabaco/efeitos adversos , Pré-Escolar , Feminino , Humanos , Lactente , GravidezRESUMO
The Manhiça Health Research Centre, established in 1996 in a rural area of southern Mozambique, currently follows around 92 000 individuals living in approximately 20 000 enumerated and geo-positioned households. Its main strength is the possibility of linking demographic data and clinical data to promote and conduct biomedical research in priority health areas. Socio-demographic data are updated twice a year and clinical data are collected on a daily basis. The data collected in Manhiça HDSS comprises household and individual characteristics, household socio-economic assets, vital data, migration, individual health history and cause of death, among others. Studies conducted in this HDSS contributed to guide the health authorities and decision-making bodies to define or adjust health policies such as the introduction of Mozambique's expanded programme of immunization with different vaccines (Haemophilus influenzae type b, Pneumococcus) or the development of the concept of Intermittent Preventive Treatment for Infants (IPTi) that led to the World Health Organization recommendation of this method as best practice for the control of malaria among infants. Manhiça's data can be accessed through a formal request to Diana Quelhas (diana.quelhas@manhica.net) accompanied by a proposal that will be analysed by the Manhiça HDSS internal scientific and ethics committees.
Assuntos
Pesquisa Biomédica , Coleta de Dados , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Diarreia/epidemiologia , Disenteria/epidemiologia , Disenteria Bacilar/epidemiologia , Emigração e Imigração , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Programas de Imunização , Malária/epidemiologia , Malária/prevenção & controle , Masculino , Mortalidade , Moçambique/epidemiologia , Pneumonia Bacteriana/epidemiologia , Pneumonia Bacteriana/prevenção & controle , População Rural , Infecções por Salmonella/epidemiologia , Tuberculose/epidemiologia , Tuberculose/terapiaRESUMO
Plasmodium falciparum infected erythrocytes (IE) accumulate in the placenta through the interaction between Duffy-binding like (DBL) domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA) receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antigenicity or CSA-binding affinity, eventually increasing parasitemia and its adverse effects on pregnancy outcomes. A total of 373 DBL2X and 328 DBL3X sequences were obtained from transcripts of 20 placental isolates infecting Mozambican women, resulting in 176 DBL2X and 191 DBL3X unique sequences at the protein level. Sequence alignments were divided in segments containing combinations of correlated polymorphisms and the association of segment sequences with placental parasite density was tested using Bonferroni corrected regression models, taking into consideration the weight of each sequence in the infection. Three DBL2X and three DBL3X segments contained signatures of high parasite density (P<0.003) that were highly prevalent in the parasite population (49-91%). Identified regions included a flexible loop that contributes to DBL3X-CSA interaction and two DBL3X motifs with evidence of positive natural selection. Limited antibody responses against signatures of high parasite density among malaria-exposed pregnant women could not explain the increased placental parasitemia. These results suggest that a higher binding efficiency to CSA rather than reduced antigenicity might provide a biological advantage to parasites with high parasite density signatures in VAR2CSA. Sequences contributing to high parasitemia may be critical for the functional characterization of VAR2CSA and the development of tools against placental malaria.
Assuntos
Antígenos de Protozoários/química , Sulfatos de Condroitina/química , Malária Falciparum/metabolismo , Placenta/parasitologia , Plasmodium falciparum/química , Complicações Parasitárias na Gravidez/metabolismo , Proteínas de Protozoários/química , Adolescente , Sequência de Aminoácidos , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/genética , Antígenos de Protozoários/metabolismo , Sítios de Ligação , Sulfatos de Condroitina/metabolismo , Eritrócitos/metabolismo , Eritrócitos/parasitologia , Feminino , Humanos , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Malária Falciparum/patologia , Simulação de Acoplamento Molecular , Dados de Sequência Molecular , Placenta/imunologia , Placenta/patologia , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , Gravidez , Complicações Parasitárias na Gravidez/imunologia , Complicações Parasitárias na Gravidez/parasitologia , Complicações Parasitárias na Gravidez/patologia , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Transcriptoma , Adulto JovemRESUMO
BACKGROUND: Cytokines and chemokines are key mediators of anti-malarial immunity. We evaluated whether Intermittent Preventive Treatment in infants with Sulfadoxine-Pyrimethamine (IPTi-SP) had an effect on the acquisition of these cellular immune responses in Mozambican children. Multiple cytokines and chemokines were quantified in plasma by luminex, and antigen-specific cytokine production in whole blood was determined by intracellular cytokine staining and flow cytometry, at ages 5, 9, 12 and 24 months. RESULTS: IPTi-SP did not significantly affect the proportion of CD3+ cells producing IFN-γ, IL-4 or IL-10. Overall, plasma cytokine or chemokine concentrations did not differ between treatment groups. Th1 and pro-inflammatory responses were higher than Th2 and anti-inflammatory responses, respectively, and IFN-γ:IL-4 ratios were higher for placebo than for SP recipients. Levels of cytokines and chemokines varied according to age, declining from 5 to 9 months. Plasma concentrations of IL-10, IL-12 and IL-13 were associated with current infection or prior malaria episodes. Higher frequencies of IFN-γ and IL-10 producing CD3+ cells and elevated IL-10, IFN-γ, MCP-1 and IL-13 in plasma were individually associated with increased malaria incidence, at different time points. When all markers were analyzed together, only higher IL-17 at 12 months was associated with lower incidence of malaria up to 24 months. CONCLUSIONS: Our work has confirmed that IPTi-SP does not negatively affect the development of cellular immune response during early childhood. This study has also provided new insights as to how these cytokine responses are acquired upon age and exposure to P. falciparum, as well as their associations with malaria susceptibility. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00209795.
Assuntos
Antimaláricos/uso terapêutico , Quimiocinas/sangue , Espaço Intracelular/metabolismo , Malária Falciparum/tratamento farmacológico , Malária Falciparum/prevenção & controle , Plasmodium falciparum/fisiologia , Pirimetamina/uso terapêutico , Sulfadoxina/uso terapêutico , Antimaláricos/farmacologia , Criança , Combinação de Medicamentos , Citometria de Fluxo , Humanos , Incidência , Lactente , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/parasitologia , Malária Falciparum/sangue , Malária Falciparum/epidemiologia , Moçambique/epidemiologia , Plasmodium falciparum/efeitos dos fármacos , Pirimetamina/farmacologia , Sulfadoxina/farmacologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologiaRESUMO
Cytokines and chemokines are key mediators of anti-malarial immunity. We evaluated whether Intermittent Preventive Treatment in infants with Sulfadoxine-Pyrimethamine (IPTi-SP) had an effect on the acquisition of these cellular immune responses in Mozambican children. Multiple cytokines and chemokines were quantified in plasma by luminex, and antigen-specific cytokine production in whole blood was determined by intracellular cytokine staining and flow cytometry, at ages 5, 9, 12 and 24 months. Results: IPTi-SP did not significantly affect the proportion of CD3+ cells producing IFN-γ, IL-4 or IL-10. Overall, plasma cytokine or chemokine concentrations did not differ between treatment groups. Th1 and pro-inflammatory responses were higher than Th2 and anti-inflammatory responses, respectively, and IFN-γ:IL-4 ratios were higher for placebo than for SP recipients. Levels of cytokines and chemokines varied according to age, declining from 5 to 9 months. Plasma concentrations of IL-10, IL-12 and IL-13 were associated with current infection or prior malaria episodes. Higher frequencies of IFN-γ and IL-10 producing CD3+ cells and elevated IL-10, IFN-γ, MCP-1 and IL-13 in plasma were individually associated with increased malaria incidence, at different time points. When all markers were analyzed together, only higher IL-17 at 12 months was associated with lower incidence of malaria up to 24 months. Conclusions: Our work has confirmed that IPTi-SP does not negatively affect the development of cellular immune response during early childhood. This study has also provided new insights as to how these cytokine responses are acquired upon age and exposure to P. falciparum, as well as their associations with malaria susceptibility.
Assuntos
Humanos , Lactente , Pré-Escolar , Criança , Malária Falciparum/tratamento farmacológico , Quimiocinas/efeitos dos fármacos , Espaço Intracelular/parasitologia , Incidência , Citocinas/efeitos dos fármacos , Malária Falciparum/sangue , Células Th1/imunologia , Antimaláricos/farmacocinéticaRESUMO
Cytokines and chemokines are key mediators of anti-malarial immunity. We evaluated whether Intermittent Preventive Treatment in infants with Sulfadoxine-Pyrimethamine (IPTi-SP) had an effect on the acquisition of these cellular immune responses in Mozambican children. Multiple cytokines and chemokines were quantified in plasma by luminex, and antigen-specific cytokine production in whole blood was determined by intracellular cytokine staining and flow cytometry, at ages 5, 9, 12 and 24 months...
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Malária Falciparum/prevenção & controle , Malária Falciparum/epidemiologia , Antimaláricos/uso terapêutico , Antimaláricos/farmacologiaRESUMO
Plasmodium falciparum blood-stage antigens such as merozoite surface protein 1 (MSP-1), apical membrane antigen 1 (AMA-1), and the 175-kDa erythrocyte binding antigen (EBA-175) are considered important targets of naturally acquired immunity to malaria. However, it is not clear whether antibodies to these antigens are effectors in protection against clinical disease or mere markers of exposure. In the context of a randomized, placebo-controlled trial of intermittent preventive treatment in infants conducted between 2002 and 2004, antibody responses to Plasmodium falciparum blood-stage antigens in a cohort of 302 Mozambican children were evaluated by immunofluorescence antibody test and enzyme-linked immunosorbent assay at 5, 9, 12, and 24 months of age. We found that IgG subclass responses to EBA-175 were differentially associated with the incidence of malaria in the follow-up period. A double amount of cytophilic IgG1 or IgG3 was associated with a significant decrease in the incidence of malaria (incidence rate ratio [IRR] = 0.49, 95% confidence interval [CI] = 0.25 to 0.97, and P = 0.026 and IRR = 0.44, CI = 0.19 to 0.98, and P = 0.037, respectively), while a double amount of noncytophilic IgG4 was significantly correlated with an increased incidence of malaria (IRR = 3.07, CI = 1.08 to 8.78, P = 0.020). No significant associations between antibodies to the 19-kDa fragment of MSP-1 (MSP-1(19)) or AMA-1 and incidence of malaria were found. Age, previous episodes of malaria, present infection, and neighborhood of residence were the main factors influencing levels of antibodies to all merozoite antigens. Deeper understanding of the acquisition of antibodies against vaccine target antigens in early infancy is crucial for the rational development and deployment of malaria control tools in this vulnerable population.
Assuntos
Anticorpos Antiprotozoários/sangue , Imunoglobulina G/imunologia , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Fatores Etários , Anticorpos Antiprotozoários/imunologia , Formação de Anticorpos , Antígenos de Protozoários/imunologia , Pré-Escolar , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Masculino , Proteínas de Membrana/imunologia , Proteína 1 de Superfície de Merozoito/imunologia , Moçambique/epidemiologia , Proteínas de Protozoários/imunologiaRESUMO
BACKGROUND: An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries. METHODS: From March 2009 through January 2011, we enrolled 15,460 children in two age categories--6 to 12 weeks of age and 5 to 17 months of age--for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories. RESULTS: In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64). CONCLUSIONS: The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .).
Assuntos
Vacinas Antimaláricas , Malária Falciparum/prevenção & controle , Plasmodium falciparum , África , Fatores Etários , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Incidência , Lactente , Análise de Intenção de Tratamento , Vacinas Antimaláricas/efeitos adversos , Vacinas Antimaláricas/imunologia , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Masculino , Meningite/epidemiologia , Meningite/etiologia , Carga Parasitária , Plasmodium falciparum/imunologia , Plasmodium falciparum/isolamento & purificação , Convulsões/epidemiologia , Convulsões/etiologia , Resultado do TratamentoRESUMO
This study aimed to evaluate whether intermittent preventive treatment in infants with sulfadoxine-pyrimethamine (IPTi-SP) had an effect on the acquisition of IgG against Plasmodium falciparum variant surface antigens (VSA) and growth-inhibitory antibodies in Manhiça, Mozambique. In addition, we assessed factors affecting the magnitude of these responses and the association between antibody levels and protection against malaria. IgG to VSA expressed by MOZ2, R29 and E8B parasite isolates were measured in plasma samples collected at 5, 9, 12 and 24 months of age by flow cytometry. Growth-inhibitory antibodies in dialyzed plasmas using GFP-D10 parasites were measured by flow cytometry at 12 and 24 months. IPTi-SP did not significantly modify the levels of IgG against VSA nor the growth-inhibitory capacity of antibodies up to 2 years of age. Age but not previous episodes of malaria influenced the magnitude of these responses. In addition, anti-VSA IgG levels were 7% higher in children with current P. falciparum infection and were associated with neighborhood of residence. Children aged 24 months had 10% less parasite growth than those aged 12 months (95% CI 0.88-0.93, P<0.0001). Growth-inhibitory antibodies correlated with levels of IgG against AMA-1, when evaluating the 10% (R(2)=0.444, P=0.049) and 20% (R(2)=0.230, P=0.037) highest inhibitory samples. None of the responses were associated with subsequent risk of malaria. In conclusion, IPTi-SP does not negatively affect the development of antibody responses thought to be major contributors to the acquisition of immunity to malaria in infancy.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Plasmodium falciparum/imunologia , Anticorpos Antiprotozoários , Proteínas de Protozoários/imunologia , Malária Falciparum/imunologia , Proteínas de Membrana/imunologia , Antígenos de Protozoários/imunologia , Antígenos de Superfície/imunologia , Plasmodium falciparum/patogenicidade , Imunoglobulina G/sangue , Anticorpos Antiprotozoários/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/química , Malária Falciparum/prevenção & controle , Malária Falciparum/sangue , Malária Falciparum/epidemiologia , Moçambique , Formação de Anticorpos/efeitos da radiaçãoRESUMO
BACKGROUND: Multiplex cytokine profiling systems are useful tools for investigating correlates of protective immunity. Several Luminex and flow cytometry methods are commercially available but there is limited information on the relative performance of different kits. A series of comparison experiments were carried out to determine the most appropriate method for our subsequent studies. METHODS: Two Luminex methods were compared, the Bio-Rad human 17-plex panel and the Invitrogen (formerly BioSource) human cytokine 10-plex kit, and two flow cytometry methods, the Becton Dickinson Human Th1/Th2 Cytokine Kit (CBA) and the Bender MedSystems Human Th1/Th2 11plex FlowCytomix Multiplex Kit. All kits were tested for the measurement of cytokines in supernatants collected from human leukocytes stimulated with viable Plasmodium falciparum infected red blood cells (iRBC) or P. falciparum schizont lysates. RESULTS: Data indicated that the kits differed in sensitivity and reproducibility depending on the cytokine, and detected different quantities of some cytokines. The Bio-Rad 17-plex kit was able to detect more positive responses than the Invitrogen 10-plex kit. However, only when detecting IL-1, IL-6 or TNF did the two Luminex based methods correlate with one another. In this study, the flow cytometry based techniques were less variable and correlated better with one another. The two flow cytometry based kits showed significant correlation when detecting IFN-γ, IL-2, TNF, IL-10 and IL-6, but overall the BD kit detected more positive responses than the Bender MedSystems kit. CONCLUSIONS: The microsphere suspension array technologies tested differed in reproducibility and the absolute quantity of cytokine detected. Sample volume, the number of cytokines measured, and the time and cost of the assays also differed. These data provide an accurate assessment of the four techniques, which will allow individual researchers to select the tool most suited for their study population.
Assuntos
Técnicas de Laboratório Clínico/métodos , Citocinas/análise , Análise em Microsséries/métodos , Microesferas , Plasmodium falciparum/imunologia , Kit de Reagentes para Diagnóstico , Adulto , Células Cultivadas , Humanos , Leucócitos Mononucleares/imunologia , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
This study aimed to evaluate whether intermittent preventive treatment in infants with sulfadoxine-pyrimethamine (IPTi-SP) had an effect on the acquisition of IgG against Plasmodium falciparum variant surface antigens (VSA) and growth-inhibitory antibodies in Manhiça, Mozambique. In addition, we assessed factors affecting the magnitude of these responses and the association between antibody levels and protection against malaria. IgG to VSA expressed by MOZ2, R29 and E8B parasite isolates were measured in plasma samples collected at 5, 9, 12 and 24 months of age by flow cytometry. Growth-inhibitory antibodies in dialyzed plasmas using GFP-D10 parasites were measured by flow cytometry at 12 and 24 months. IPTi-SP did not significantly modify the levels of IgG against VSA nor the growth-inhibitory capacity of antibodies up to 2 years of age. Age but not previous episodes of malaria influenced the magnitude of these responses. In addition, anti-VSA IgG levels were 7% higher in children with current P. falciparum infection and were associated with neighborhood of residence. Children aged 24 months had 10% less parasite growth than those aged 12 months (95% CI 0.88-0.93, P<0.0001). Growth-inhibitory antibodies correlated with levels of IgG against AMA-1, when evaluating the 10% (R(2)=0.444, P=0.049) and 20% (R(2)=0.230, P=0.037) highest inhibitory samples. None of the responses were associated with subsequent risk of malaria. In conclusion, IPTi-SP does not negatively affect the development of antibody responses thought to be major contributors to the acquisition of immunity to malaria in infancy.
Assuntos
Antígenos de Protozoários/imunologia , Antígenos de Superfície/imunologia , Malária Falciparum/imunologia , Proteínas de Membrana/imunologia , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Pirimetamina/administração & dosagem , Sulfadoxina/administração & dosagem , Fatores Etários , Anticorpos Antiprotozoários/sangue , Formação de Anticorpos/efeitos dos fármacos , Variação Antigênica , Combinação de Medicamentos , Inibidores do Crescimento/sangue , Humanos , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Malária Falciparum/sangue , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Moçambique , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/patogenicidadeRESUMO
We evaluated the impact of intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP), which was given at ages 3, 4, and 9 months through the Expanded Program on Immunization (EPI), on the development of antibody responses to Plasmodium falciparum in Mozambique. Immunoglobulin M (IgM) and IgG subclass antibodies specific to whole asexual parasites and to recombinant MSP-1(19), AMA-1, and EBA-175 were measured at ages 5, 9, 12, and 24 months for 302 children by immunofluorescence antibody tests and by enzyme-linked immunosorbent assays. Antibody responses did not significantly differ between children receiving IPTi with SP and those receiving a placebo at any time point measured, with the exception of the responses of IgG and IgG1 to AMA-1 and/or MSP-1(19), which were significantly higher in the SP-treated group than in the placebo group at ages 5, 9, and/or 24 months. IPTi with SP given through the EPI reduces the frequency of malarial illness while allowing the development of naturally acquired antibody responses to P. falciparum antigens
Assuntos
Humanos , Animais , Pré-Escolar , Criança , Plasmodium falciparum/imunologia , Anticorpos Antiprotozoários/genética , Anticorpos Antiprotozoários/imunologia , Anticorpos Antiprotozoários/sangue , Malária Falciparum/imunologia , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Pirimetamina/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Malária Falciparum/prevenção & controle , MoçambiqueRESUMO
We evaluated the impact of intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP), which was given at ages 3, 4, and 9 months through the Expanded Program on Immunization (EPI), on the development of antibody responses to Plasmodium falciparum in Mozambique. Immunoglobulin M (IgM) and IgG subclass antibodies specific to whole asexual parasites and to recombinant MSP-1(19), AMA-1, and EBA-175 were measured at ages 5, 9, 12, and 24 months for 302 children by immunofluorescence antibody tests and by enzyme-linked immunosorbent assays. Antibody responses did not significantly differ between children receiving IPTi with SP and those receiving a placebo at any time point measured, with the exception of the responses of IgG and IgG1 to AMA-1 and/or MSP-1(19), which were significantly higher in the SP-treated group than in the placebo group at ages 5, 9, and/or 24 months. IPTi with SP given through the EPI reduces the frequency of malarial illness while allowing the development of naturally acquired antibody responses to P. falciparum antigens.
Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Antimaláricos , Malária Falciparum/prevenção & controle , Plasmodium falciparum/imunologia , Pirimetamina , Sulfadoxina , Animais , Antígenos de Protozoários/genética , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Pré-Escolar , Esquema de Medicação , Combinação de Medicamentos , Eritrócitos/parasitologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Malária Falciparum/imunologia , Moçambique , Pirimetamina/administração & dosagem , Pirimetamina/uso terapêutico , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Sulfadoxina/administração & dosagem , Sulfadoxina/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: The candidate malaria vaccine RTS,S/AS02A is a recombinant protein containing part of the circumsporozoite protein (CSP) sequence of Plasmodium falciparum, linked to the hepatitis B surface antigen and formulated in the proprietary adjuvant system AS02A. In a recent trial conducted in children younger than age five in southern Mozambique, the vaccine demonstrated significant and sustained efficacy against both infection and clinical disease. In a follow-up study to the main trial, breakthrough infections identified in the trial were examined to determine whether the distribution of csp sequences was affected by the vaccine and to measure the multiplicity of infecting parasite genotypes. DESIGN: P. falciparum DNA from isolates collected during the trial was used for genotype studies. SETTING: The main trial was carried out in the Manhiça district, Maputo province, Mozambique, between April 2003 and May 2004. PARTICIPANTS: Children from the two cohorts of the main trial provided parasite isolates as follows: children from Cohort 1 who were admitted to hospital with clinical malaria; children from Cohort 1 who were parasite-positive in a cross-sectional survey at study month 8.5; children from Cohort 2 identified as parasite-positive during follow-up by active detection of infection. OUTCOME: Divergence of DNA sequence encoding the CSP T cell-epitope region sequence from that of the vaccine sequence was measured in 521 isolates. The number of distinct P. falciparum genotypes was also determined. RESULTS: We found no evidence that parasite genotypes from children in the RTS,S/AS02A arm were more divergent than those receiving control vaccines. For Cohort 1 (survey at study month 8.5) and Cohort 2, infections in the vaccine group contained significantly fewer genotypes than those in the control group, (p = 0.035, p = 0.006), respectively, for the two cohorts. This was not the case for children in Cohort 1 who were admitted to hospital (p = 0.478). CONCLUSIONS: RTS,S/AS02A did not select for genotypes encoding divergent T cell epitopes in the C-terminal region of CSP in this trial. In both cohorts, there was a modest reduction in the mean number of parasite genotypes harboured by vaccinated children compared with controls, but only among those with asymptomatic infections.
RESUMO
The candidate malaria vaccine RTS,S/AS02A is a recombinant protein containing part of the circumsporozoite protein (CSP) sequence of Plasmodium falciparum, linked to the hepatitis B surface antigen and formulated in the proprietary adjuvant system AS02A. In a recent trial conducted in children younger than age five in southern Mozambique, the vaccine demonstrated significant and sustained efficacy against both infection and clinical disease. In a follow-up study to the main trial, breakthrough infections identified in the trial were examined to determine whether the distribution of csp sequences was affected by the vaccine and to measure the multiplicity of infecting parasite genotypes. Design: P. falciparum DNA from isolates collected during the trial was used for genotype studies. Setting: The main trial was carried out in the Manhiça district, Maputo province, Mozambique, between April 2003 and May 2004. Participants: Children from the two cohorts of the main trial provided parasite isolates as follows: children from Cohort 1 who were admitted to hospital with clinical malaria; children from Cohort 1 who were parasite-positive in a cross-sectional survey at study month 8.5; children from Cohort 2 identified as parasite-positive during follow-up by active detection of infection. Outcome: Divergence of DNA sequence encoding the CSP T cell-epitope region sequence from that of the vaccine sequence was measured in 521 isolates. The number of distinct P. falciparum genotypes was also determined. Results: We found no evidence that parasite genotypes from children in the RTS,S/AS02A arm were more divergent than those receiving control vaccines. For Cohort 1 (survey at study month 8.5) and Cohort 2, infections in the vaccine group contained significantly fewer genotypes than those in the control group, (p = 0.035, p = 0.006), respectively, for the two cohorts. This was not the case for children in Cohort 1 who were admitted to hospital (p = 0.478). Conclusions: RTS,S/AS02A did not select for genotypes encoding divergent T cell epitopes in the C-terminal region of CSP in this trial. In both cohorts, there was a modest reduction in the mean number of parasite genotypes harboured by vaccinated children compared with controls, but only among those with asymptomatic infections.