RESUMO
BACKGROUND: A stable, well-functioning and integrated national medicines regulatory system is a core component of health systems resilient against infectious disease outbreaks. In many low- and middle-income countries, however, sizable gaps exist in the emergency preparedness framework of national regulatory authorities (NRAs). RegTrain-VaccTrain is a project of Germany Ministry of Health's Global Health Protection Programme that contributes to global efforts aimed at strengthening such regulatory systems by providing technical support and advice to partner NRAs. In this study, we probed the outputs of our capacity-strengthening activities for clinical trials oversight (CTO) to take stock of progress made and examine remaining priorities in order to provide specialized technical assistance in addressing them to improve operational readiness for emergencies. METHOD: Data validated from NRA self-benchmarking results in 2017 and worksheet records of November 2021 were utilized to assess the emergency preparedness capacity for CTO in three VaccTrain partner NRAs (Liberia, Sierra Leone, The Gambia) before and after interventional capacity-strengthening partnership, using specific public health emergency-related (sub-)indicators of the WHO Global Benchmarking Tool. RESULTS: A generally weak and vulnerable structural framework for CTO characterized the emergency preparedness capacity in all three partner NRAs at baseline, thus putting their operational readiness for public health emergencies at risk. VaccTrain's collaborative work was successful at supporting individual NRAs to develop the full spectrum of operational structures (including (draft) regulations, guidelines, and standard operating procedures) required to improve regulatory preparedness. A gap in the formal approval and implementation of developed legal documents in two of three NRAs still remains. Notwithstanding, a robust emergency framework now exists and the NRAs stand better prepared to respond to (future) locally-concerning health emergencies, during which time clinical trials activity was observed to heighten. CONCLUSIONS: These results exemplify a north-south capacity-strengthening partnership model that effectively contributes in developing structures to enhance regulatory oversight and support expeditious product development in response to crises. They further underscore the equally critical role local/national processes play in facilitating the full implementation of developed structures.
Assuntos
Planejamento em Desastres , Saúde Pública , Benchmarking , Emergências , Saúde Global , Humanos , Organização Mundial da SaúdeRESUMO
BACKGROUND: Despite appreciable immunogenicity in malaria-naive populations, many candidate malaria vaccines are considerably less immunogenic in malaria-exposed populations. This could reflect induction of immune regulatory mechanisms involving Human Leukocyte Antigen G (HLA-G), regulatory T (Treg), and regulatory B (Breg) cells. Here, we addressed the question whether there is correlation between these immune regulatory pathways and both plasmablast frequencies and vaccine-specific IgG concentrations. METHODS: Fifty Gabonese adults with lifelong exposure to Plasmodium spp were randomized to receive three doses of either 30 µg or 100 µg GMZ2-CAF01, or 100 µg GMZ2-alum, or control vaccine (rabies vaccine) at 4-week intervals. Only plasma and peripheral blood mononuclear cells isolated from blood samples collected before (D0) and 28 days after the third vaccination (D84) of 35 participants were used to measure sHLA-G levels and anti-GMZ2 IgG concentrations, and to quantify Treg, Breg and plasmablast cells. Vaccine efficacy was assessed using controlled human malaria infection (CHMI) by direct venous inoculation of Plasmodium falciparum sporozoites (PfSPZ Challenge). RESULTS: The sHLA-G concentration increased from D0 to D84 in all GMZ2 vaccinated participants and in the control group, whereas Treg frequencies increased only in those receiving 30 µg or 100 µg GMZ2-CAF01. The sHLA-G level on D84 was associated with a decrease of the anti-GMZ2 IgG concentration, whereas Treg frequencies on D0 or on D84, and Breg frequency on D84 were associated with lower plasmablast frequencies. Importantly, having a D84:D0 ratio of sHLA-G above the median was associated with an increased risk of P. falciparum infection after sporozoites injection. CONCLUSION: Regulatory immune responses are induced following immunization. Stronger sHLA-G and Treg immune responses may suppress vaccine induced immune responses, and the magnitude of the sHLA-G response increased the risk of Plasmodium falciparum infection after CHMI. These findings could have implications for the design and testing of malaria vaccine candidates in semi-immune individuals.
Assuntos
Vacinas Antimaláricas , Malária Falciparum , Adulto , Animais , Anticorpos Antiprotozoários , Antígenos de Protozoários , Humanos , Imunização , Leucócitos Mononucleares , Malária Falciparum/prevenção & controle , Plasmodium falciparum , VacinaçãoRESUMO
BACKGROUND: Although Schistosoma haematobium infection has been reported to be associated with alterations in immune function, in particular immune hyporesponsiveness, there have been only few studies that have used the approach of removing infection by drug treatment to establish this and to understand the underlying molecular mechanisms. METHODS: Schistosoma haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared with uninfected controls. Cellular responses were characterized by cytokine production and flow cytometry, and in a subset of children RNA sequencing (RNA-Seq) transcriptome profiling was performed. RESULTS: Removal of S haematobium infection resulted in increased schistosome-specific cytokine responses that were negatively associated with CD4+CD25+FOXP3+ T-cells and accompanied by increased frequency of effector memory T-cells. Innate responses to Toll like receptor (TLR) ligation decreased with treatment and showed positive association with CD4+CD25+FOXP3+ T-cells. At the transcriptome level, schistosome infection was associated with enrichment in cell adhesion, whereas parasite removal was associated with a more quiescent profile. Further analysis indicated that alteration in cellular energy metabolism was associated with S haematobium infection and that the early growth response genes 2 and 3 (EGR 2 and EGR3), transcription factors that negatively regulate T-cell activation, may play a role in adaptive immune hyporesponsiveness. CONCLUSIONS: Using a longitudinal study design, we found contrasting effects of schistosome infection on innate and adaptive immune responses. Whereas the innate immune system appears more activated, the adaptive immunity is in a hyporesponsive state reflected in alterations in CD4+CD25+FOXP3+ T-cells, cellular metabolism, and transcription factors involved in anergy.
Assuntos
Anti-Helmínticos/uso terapêutico , Citocinas/imunologia , Praziquantel/uso terapêutico , Esquistossomose Urinária/imunologia , Transcriptoma , Imunidade Adaptativa , Animais , Criança , Feminino , Citometria de Fluxo , Gabão/epidemiologia , Humanos , Imunidade Inata , Estudos Longitudinais , Masculino , RNA-Seq , Esquistossomose Urinária/tratamento farmacológicoRESUMO
BACKGROUND: GMZ2 is a recombinant malaria vaccine inducing immune responses against Plasmodium falciparum (Pf) merozoite surface protein-3 and glutamate-rich protein. We used standardized controlled human malaria infection (CHMI) to assess the efficacy of this asexual blood-stage vaccine. METHODS: We vaccinated 50 healthy, adult volunteers with lifelong exposure to Pf 3 times, at 4-week intervals, with 30 or 100 µg GMZ2 formulated in CAF01, a liposome-based adjuvant; 100 µg GMZ2, formulated in Alhydrogel; or a control vaccine (Verorab). Approximately 13 weeks after the last vaccination, 35/50 volunteers underwent CHMI by direct venous inoculation of 3200 Pf sporozoites (Sanaria® PfSPZ Challenge). RESULTS: Adverse events were similarly distributed between GMZ2 and control vaccinees. Baseline-corrected anti-GMZ2 antibody concentrations 4 weeks after the last vaccination were higher in all 3 GMZ2-vaccinated arms, compared to the control group. All GMZ2 formulations induced similar antibody levels. CHMI resulted in 29/34 (85%) volunteers with Pf parasitemia and 15/34 (44%) with malaria (parasitemia and symptoms). The proportion of participants with malaria (2/5 control, 6/10 GMZ2-Alhydrogel, 2/8 30 µg GMZ2-CAF01, and 5/11 100 µg GMZ2-CAF01) and the time it took them to develop malaria were similar in all groups. Baseline, vaccine-specific antibody concentrations were associated with protection against malaria. CONCLUSIONS: GMZ2 is well tolerated and immunogenic in lifelong-Pf-exposed adults from Gabon, with similar antibody responses regardless of formulation. CHMI showed no protective effect of prior vaccination with GMZ2, although baseline, vaccine-specific antibody concentrations were associated with protection. CHMI with the PfSPZ Challenge is a potent new tool to validate asexual, blood-stage malaria vaccines in Africa. CLINICAL TRIALS REGISTRATION: Pan-African Clinical Trials: PACTR201503001038304.
Assuntos
Antígenos de Protozoários/imunologia , Vacinas Antimaláricas/imunologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Vacinação , Adjuvantes Imunológicos , Adolescente , Adulto , Método Duplo-Cego , Humanos , Malária Falciparum/parasitologia , Parasitemia , Esporozoítos , Vacinas Sintéticas/imunologia , Adulto JovemRESUMO
BACKGROUND: Malaria burden remains high in the sub-Saharan region where helminths are prevalent and where children are often infected with both types of parasites. Although the effect of helminths on malaria infection is evident, the impact of these co-infections is not clearly elucidated yet and the scarce findings are conflicting. In this study, we investigated the effect of schistosomiasis, considering soil-transmitted helminths (STH), on prevalence and incidence of Plasmodium falciparum infection. METHODOLOGY: This longitudinal survey was conducted in school-age children living in two rural communities in the vicinity of Lambaréné, Gabon. Thick blood smear light microscopy, urine filtration and the Kato-Katz technique were performed to detect malaria parasites, S. haematobium eggs and, STH eggs, respectively. P. falciparum carriage was assessed at inclusion, and incidence of malaria and time to the first malaria event were recorded in correlation with Schistosoma carriage status. Stratified multivariate analysis using generalized linear model was used to assess the risk of plasmodium infection considering interaction with STH, and survival analysis to assess time to malaria. MAIN FINDINGS: The overall prevalence on subject enrolment was 30%, 23% and 9% for S. haematobium, P. falciparum infections and co-infection with both parasites, respectively. Our results showed that schistosomiasis in children tends to increase the risk of plasmodium infection but a combined effect with Trichuris trichiura or hookworm infection clearly increase the risk (aOR = 3.9 [95%CI: 1.7-9.2]). The incidence of malaria over time was 0.51[95%CI: 0.45-0.57] per person-year and was higher in the Schistosoma-infected group compared to the non-infected group (0.61 vs 0.43, p = 0.02), with a significant delay of time-to first-malaria event only in children aged from 6 to 10-years-old infected with Schistosoma haematobium. CONCLUSIONS: Our results suggest that STH enhance the risk for P. falciparum infection in schistosomiasis-positive children, and when infected, that schistosomiasis enhances susceptibility to developing malaria in young children but not in older children.
Assuntos
Helmintíase/complicações , Malária Falciparum/complicações , Plasmodium falciparum , Schistosoma haematobium , Esquistossomose Urinária/complicações , Albendazol/administração & dosagem , Albendazol/uso terapêutico , Animais , Anti-Helmínticos/uso terapêutico , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/administração & dosagem , Combinação Arteméter e Lumefantrina/uso terapêutico , Criança , Feminino , Gabão/epidemiologia , Helmintíase/tratamento farmacológico , Helmintíase/epidemiologia , Helmintíase/parasitologia , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Masculino , Praziquantel/administração & dosagem , Praziquantel/uso terapêutico , Fatores de Risco , Esquistossomose Urinária/tratamento farmacológico , Esquistossomose Urinária/epidemiologia , Esquistossomose Urinária/parasitologiaRESUMO
Both routine and research tuberculosis (TB) laboratory capacity urgently need to be expanded in large parts of Sub-Saharan Africa. In 2009, the Centre de Recherches Médicales de Lambaréné (CERMEL) took a strategic decision to expand its activities by building TB laboratory capacity to address research questions and to improve routine diagnostic and treatment capacity. Over the past 7 years, a standard laboratory has been developed that is contributing significantly to TB diagnosis, treatment, and control in Gabon; training has also been provided for TB research staff in Central Africa. CERMEL has a cordial relationship with the Gabon National TB Control Programme (PNLT), which has culminated in a successful Global Fund joint application. This endeavour is considered a model for similar developments needed in areas of high TB prevalence and where TB control remains poor to date.
Assuntos
Fortalecimento Institucional , Laboratórios/organização & administração , Laboratórios/provisão & distribuição , Saúde Pública , Tuberculose/prevenção & controle , Tuberculose/terapia , África Subsaariana/epidemiologia , Antituberculosos/uso terapêutico , Recursos em Saúde , Humanos , Ciência de Laboratório Médico/educação , Ciência de Laboratório Médico/organização & administração , Vigilância da População , Prevalência , Tuberculose/epidemiologiaRESUMO
Infections with helminths and Plasmodium spp. overlap in their geographical distribution. It has been postulated that helminth infections may influence malarial transmission by altering Plasmodium falciparum gametocytogenesis. This cross-sectional study assessed the effect of helminth infections on P. falciparum gametocyte carriage and on humoral immune responses to sexual stage antigens in Gabon. Schistosoma haematobium and filarial infections as well as P. falciparum asexual forms and gametocyte carriage were determined. The antibody responses measured were to sexual (Pfs230, Pfs48/45) and asexual P. falciparum antigens (AMA1, MSP1, and GLURP). A total of 287 subjects were included. The prevalence of microscopically detectable P. falciparum asexual parasites was higher in S. haematobium-infected subjects in comparison to their uninfected counterparts (47% versus 26%, P = 0.003), but this was not different when filarial infections were considered. Plasmodium falciparum gametocyte carriage was similar between Schistosoma- or filaria-infected and uninfected subjects. We observed a significant decrease of Pfs48/45 immunoglobulin G titer in S. haematobium-infected subjects (P = 0.037), whereas no difference was seen for Pfs230 antibody titer, nor for antibodies to AMA1, MSP1, or GLURP. Our findings suggest an effect of S. haematobium on antibody responses to some P. falciparum gametocyte antigens that may have consequences for transmission-blocking immunity.
Assuntos
Anticorpos Antiprotozoários/biossíntese , Estágios do Ciclo de Vida/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Schistosoma haematobium/imunologia , Esquistossomose Urinária/imunologia , Adolescente , Animais , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Criança , Coinfecção , Estudos Transversais , Feminino , Gabão/epidemiologia , Expressão Gênica , Humanos , Imunidade Humoral , Estágios do Ciclo de Vida/genética , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Proteína 1 de Superfície de Merozoito/genética , Proteína 1 de Superfície de Merozoito/imunologia , Plasmodium falciparum/genética , Plasmodium falciparum/crescimento & desenvolvimento , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Schistosoma haematobium/genética , Schistosoma haematobium/crescimento & desenvolvimento , Esquistossomose Urinária/epidemiologia , Esquistossomose Urinária/parasitologiaRESUMO
BACKGROUND: Helminths and malaria are among the most prevalent infectious diseases in the world. They both occur in tropical area where they often affect the same populations. There are studies suggesting an effect of helminths on malariometric indices. For example, malaria attacks as well as disease severity has been shown to be influenced by a concurrent chronic helminth infection. However, there are also studies that show no effect of concurrent helminth infections on malarial outcomes. To start addressing this issue, the effect of chronic Schistosoma haematobium infection on both the innate and adaptive immune response of Plasmodium falciparum-infected subjects was assessed in an area endemic for both these infections in Gabon. METHOD: Subjects infected with S. haematobium and or P. falciparum, as well as a control group with neither of these infections, were recruited. For innate immune response, heparinized blood was obtained and cultured for 24 hours with a panel of TLR ligands. For adaptive immune response, PBMC was isolated and stimulated with SEB for 72 hours. Cytokines and chemokines were measured in supernatants using a multiplex beads array immunoassay. Principal Component analysis was used to assess pattern of cytokine and chemokine responses representing the innate and adaptive components of the immune system. RESULTS: Overall it was observed that the presence of P. falciparum infection was marked by an increase in innate and adaptive immune responsiveness while S. haematobium infection was characterized by an increased chemokine profile, with at the same time, lower pro inflammatory markers. When the study subjects were split into single infected and co-infected groups no effect of S. haematobium on the immune response of P. falciparum infected subjects was observed, neither for the innate nor for the adaptive component of the immune response. CONCLUSION: This study provides original information on the cellular immune response of S. haematobium and/or P. falciparum in infected subjects. It rules out an effect of S. haematobium on the cytokine profile of subjects co-infected with P. falciparum.
Assuntos
Imunidade Adaptativa , Coinfecção/imunologia , Citocinas/sangue , Imunidade Inata , Malária Falciparum/imunologia , Esquistossomose Urinária/imunologia , Adolescente , Animais , Quimiocinas/sangue , Criança , Coinfecção/parasitologia , Feminino , Gabão , Humanos , Masculino , Plasmodium falciparum/fisiologia , Schistosoma haematobium/fisiologiaRESUMO
BACKGROUND: Children who have been exposed in utero to maternal filarial infection are immunologically less responsive to filarial antigens, have less pathology, and are more susceptible to acquire infection than offspring of uninfected mothers. Moreover children from filaria infected mothers have been shown to be less responsive to vaccination as a consequence of an impairment of their immune response. However, it is not well known how in utero exposure to parasite antigens affects cellular immune responses. METHODOLOGY: Here, 30 pregnant women were examined for the presence of microfilaria of Loa loa and Mansonella perstans in peripheral blood. At delivery, cord blood mononuclear cells (CBMC) were obtained and the CD4+T cells were phenotyped by expression of the transcription factors Tbet, RORγt, and FOXP3. RESULTS: No significant difference was observed between newborns from infected versus uninfected mothers in the frequencies of total CD4+T cells and CD4+T cells subsets including CD4+Tbet+, CD4+RORγt+ T and CD4+CD25hiFOXP3+ T cells. However, there was a negative association between CD4+CD25hiFOXP3+T cells and CD4+Tbet+ as well as CD4+RORγt+ T cells in the infected group only (B = -0.242, P = 0.002; B = -0.178, P = 0.013 respectively). CONCLUSION: Our results suggest that filarial infection during pregnancy leads to an expansion of functionally active regulatory T cells that keep TH1 and TH17 in check.
Assuntos
Linfócitos T CD4-Positivos/metabolismo , Sangue Fetal/citologia , Fatores de Transcrição Forkhead/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Microfilárias/isolamento & purificação , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Proteínas com Domínio T/metabolismo , Adulto , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Feminino , Humanos , Recém-Nascido , Loa/crescimento & desenvolvimento , Loa/fisiologia , Mansonella/crescimento & desenvolvimento , Mansonella/fisiologia , Mães , Gravidez , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th1/citologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/citologia , Células Th17/imunologia , Células Th17/metabolismoRESUMO
BACKGROUND: Malaria and helminth co infection are common in tropical and subtropical areas where they affect the life of millions of people. While both helminth and malaria parasites have immunomodulatory activities, little is known about the consequence of co-infections on malaria antigen specific immune responses. METHOD/DESIGN: This study will be conducted in two rural areas of the Moyen Ogooué province in Gabon, endemic for both Plasmodium falciparum and Schistosoma haematobium infections. Participants, 5 to 50 years old, will be enrolled and grouped according to their infection status. S. haematobium and malaria parasites will be detected, demographic and clinical data will be recorded and blood will be collected for hematological as well as for immunological assays. The level of antibody specific to Plasmodium falciparum blood stage and gametocyte antigens will be measured using ELISA. PBMC will be isolated for phenotyping of different T cell subsets ex vivo by flow cytometry and for culture and cytokine response assessment. DISCUSSION: We will provide a comprehensive picture of the interaction between schistosomes and malaria parasites which co-localize in peripheral blood. We will test the hypothesis that schistosome infection has an impact on specific humoral as well as on cellular immune responses to malaria antigens.
RESUMO
Although differences in immunological responses between populations have been found in terms of vaccine efficacy, immune responses to infections and prevalence of chronic inflammatory diseases, the mechanisms responsible for these differences are not well understood. Therefore, innate cytokine responses mediated by various classes of pattern-recognition receptors including Toll-like receptors (TLR), C-type lectin receptors (CLRs) and nucleotide-binding oligomerisation domain-like receptors (NLRs) were compared between Dutch (European), semi-urban and rural Gabonese (African) children. Whole blood was stimulated for 24 hours and the pro-inflammatory tumor necrosis factor (TNF) and the anti-inflammatory/regulatory interleukin-10 (IL-10) cytokines in culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Gabonese children had a lower pro-inflammatory response to poly(I:C) (TLR3 ligand), but a higher pro-inflammatory response to FSL-1 (TLR2/6 ligand), Pam3 (TLR2/1 ligand) and LPS (TLR4 ligand) compared to Dutch children. Anti-inflammatory responses to Pam3 were also higher in Gabonese children. Non-TLR ligands did not induce substantial cytokine production on their own. Interaction between various TLR and non-TLR receptors was further assessed, but no differences were found between the three populations. In conclusion, using a field applicable assay, significant differences were observed in cytokine responses between European and African children to TLR ligands, but not to non-TLR ligands.
Assuntos
População Negra , Imunidade Inata/imunologia , Imunidade Inata/fisiologia , Interleucina-10/imunologia , Interleucina-6/imunologia , População Branca , Adolescente , Criança , Feminino , Gabão , Humanos , Masculino , Países Baixos , Receptores Toll-Like/agonistas , Receptores Toll-Like/imunologiaRESUMO
Urogenital schistosomiaisis is a serious public health problem in sub-Saharan Africa. In this study, we have updated an established real-time polymerase chain reaction (PCR) routinely used in our laboratory. Schistosoma genus-specific real-time PCR was performed on DNA isolated from 85 urine samples and pellets obtained after centrifugation without and after frozen storage. The results revealed that concentration by centrifugation of the urine samples and freezing of the samples before extracting DNA improves the sensitivity of the PCR.
Assuntos
DNA de Helmintos/urina , Reação em Cadeia da Polimerase em Tempo Real/métodos , Schistosoma haematobium/isolamento & purificação , Esquistossomose Urinária/diagnóstico , Adolescente , Adulto , Animais , Criança , Feminino , Congelamento , Humanos , Masculino , Contagem de Ovos de Parasitas , Schistosoma haematobium/genética , Esquistossomose Urinária/parasitologia , Sensibilidade e Especificidade , Especificidade da Espécie , Adulto JovemRESUMO
In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.).
Assuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Ascaríase/tratamento farmacológico , Infecções por Uncinaria/tratamento farmacológico , Tricuríase/tratamento farmacológico , Adolescente , Albendazol/administração & dosagem , Ancylostomatoidea/efeitos dos fármacos , Ancylostomatoidea/patogenicidade , Animais , Anti-Helmínticos/administração & dosagem , Ascaris lumbricoides/efeitos dos fármacos , Ascaris lumbricoides/patogenicidade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Trichuris/efeitos dos fármacos , Trichuris/patogenicidadeRESUMO
BACKGROUND: GMZ2 is a hybrid protein consisting of the N-terminal region of the glutamate-rich protein fused in frame to the C-terminal region of merozoite surface protein 3 (MSP3). GMZ2 formulated in Al(OH)3 has been tested in 3 published phase 1 clinical trials. The GMZ2/alum formulation showed good safety, tolerability, and immunogenicity, but whether antibodies elicited by vaccination are functional is not known. METHODS: Serum samples prior to vaccination and 4 weeks after the last vaccination from the 3 clinical trials were used to perform a comparative assessment of biological activity against Plasmodium falciparum. RESULTS: We showed that the maximum level of immunoglobulin G (IgG) antibodies obtained by GMZ2 vaccination is independent of ethnicity, time under malaria-exposure, and vaccine dose and that GMZ2 elicits high levels of functionally active IgG antibodies. Both, malaria-naive adults and malaria-exposed preschool children elicit vaccine-specific antibodies with broad inhibitory activity against geographically diverse P. falciparum isolates. Peptide-mapping studies of IgG subclass responses identified IgG3 against a peptide derived from MSP3 as the strongest predictor of antibody-dependent cellular inhibition. CONCLUSIONS: These findings suggest that GMZ2 adjuvanted in Al(OH)3 elicits high levels of specific and functional antibodies with the capacity to control parasite multiplication.
Assuntos
Anticorpos Antiprotozoários/sangue , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/imunologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adulto , Hidróxido de Alumínio/administração & dosagem , Pré-Escolar , Humanos , Imunoglobulina G/sangue , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologiaRESUMO
Antibody responses are thought to play an important role in control of Schistosoma infections, yet little is known about the phenotype and function of B cells in human schistosomiasis. We set out to characterize B cell subsets and B cell responses to B cell receptor and Toll-like receptor 9 stimulation in Gabonese schoolchildren with Schistosoma haematobium infection. Frequencies of memory B cell (MBC) subsets were increased, whereas naive B cell frequencies were reduced in the schistosome-infected group. At the functional level, isolated B cells from schistosome-infected children showed higher expression of the activation marker CD23 upon stimulation, but lower proliferation and TNF-α production. Importantly, 6-months after 3 rounds of praziquantel treatment, frequencies of naive B cells were increased, MBC frequencies were decreased and with the exception of TNF-α production, B cell responsiveness was restored to what was seen in uninfected children. These data show that S. haematobium infection leads to significant changes in the B cell compartment, both at the phenotypic and functional level.
Assuntos
Subpopulações de Linfócitos B/imunologia , Schistosoma haematobium/imunologia , Esquistossomose/imunologia , Adolescente , Animais , Anti-Helmínticos/uso terapêutico , Anticorpos Anti-Helmínticos/sangue , Criança , Feminino , Gabão , Humanos , Masculino , Praziquantel/uso terapêutico , Esquistossomose/tratamento farmacológico , Fatores de TempoRESUMO
Little data is available on the epidemiology of Staphylococcus aureus in Africa. In the present study we aim at characterizing the population structure of S. aureus in healthy subjects from a rural and a semi-urban area in Lambaréné, Gabon as well as in hospital staff and inpatients. In total, 500 subjects were screened for S. aureus colonization of the nares, axillae and inguinal region. Overall, 146 (29%) were positive. We found 46 different spa types. The most frequent spa types were t084 (35%) and the agr II was the most prevalent subtype of the accessory gene regulator (56%, n=82). Five isolates (3%) were methicillin resistant S. aureus (MRSA). Carriage rates of S. aureus in Gabon are comparable to developed countries. MRSA is for the first time described and could pose a significant health threat in this region with limited access to microbiological laboratory facilities and to adequate antimicrobial agents.
Assuntos
Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Axila/microbiologia , Proteínas de Bactérias/genética , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Gabão/epidemiologia , Genótipo , Virilha/microbiologia , Pessoal de Saúde , Hospitais , Humanos , Lactente , Masculino , Resistência a Meticilina , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem Molecular , Mucosa Nasal/microbiologia , População Rural , Proteína Estafilocócica A/genética , Staphylococcus aureus/isolamento & purificação , Transativadores/genética , População Urbana , Adulto JovemRESUMO
SUMMARY OBJECTIVES: To evaluate the epidemiologic data of parasitic infections and co-infections in pregnant women in Lambaréné, Gabon. METHODS: In Lambaréné, Gabon--a region of high endemicity for Plasmodium falciparum and helminths--we conducted a longitudinal survey of malaria and helminth infections during pregnancy. RESULTS: Of 388 pregnant women included in the study, 98 (25%) experienced at least one episode of P. falciparum infection (incidence of 2.6 infections per year of pregnancy). One hundred and seventy pregnant women (49%) were infected with intestinal helminths, and 41 (12%) harboured Shistosoma haematobium. In total, 230 (65%) pregnant women carried at least one parasitic infection are 74 (22%) harboured at least two or more parasite species. Ascaris lumbricoides and primiparity were independently associated with Plasmodium infection during pregnancy [odds ratio (95% confidence intervals) 2.4, (1.4-3.8); 2.1, (1.3-3.5), respectively]. CONCLUSION: This study shows a high burden of parasitic infections with substantial degree of parasitic co-infections in pregnant women in a Central African region. This may have implications for immunological studies and operational research involving pregnant women.