RESUMO
BACKGROUND: The existing metrics of malaria transmission are limited in sensitivity under low transmission intensity. Robust surveillance systems are needed as interventions to monitor reduced transmission and prevention of rapid reintroduction. Serological tools based on antibody responses to parasite and vector antigens are potential tools for transmission measurements. The current study sought to evaluate antibody responses to Anopheles gambiae salivary gland peptide (gSG6- P1), as a biomarker of human exposure to Anopheles bites, in different transmission settings and seasons. The comparison between anti-MSP-1(19) IgG immune responders and non-responders allowed exploring the robustness of the gSG6-P1 peptide as a surveillance tool in an area of decreasing malaria transmission. METHODS: Total IgG levels to gSG6-P1 were measured in an age-stratified cohort (< 5, 5-14 and ≥ 15 years) in a total of 1,366 participants from three localities in western Kenya [Kisii (hypoendemic), Kakamega (mesoendemic), and Kombewa (hyperendemic)] including 607 sera that were additionally tested for MSP-1(19) specific responses during a low and a high malaria transmission seasons. Antibody prevalence and levels were compared between localities with different transmission intensities. Regression analysis was performed to examine the association between gSG6-P1 and MSP-1(19) seroprevalence and parasite prevalence. RESULT: Seroprevalence of gSG6-P1 in the uphill population was 36% while it was 50% valley bottom (χ(2) = 13.2, df = 1, p < 0.001). Median gSG6-P1 antibody levels in the Valley bottom were twice as high as that observed in the uphill population [4.50 vs. 2.05, p < 0.001] and showed seasonal variation. The odds of gSG6-P1 seropositives having MSP-1(19) antibodies were almost three times higher than the odds of seronegatives (OR = 2.87, 95% CI [1.977, 4.176]). The observed parasite prevalence for Kisii, Kakamega and Kombewa were 4%, 19.7% and 44.6% whilst the equivalent gSG6-P1 seroprevalence were 28%, 34% and 54%, respectively. CONCLUSION: The seroprevalence of IgG to gSG6-P1 was sensitive and robust in distinguishing between hypo, meso and hyper transmission settings and seasonal fluctuations.
Assuntos
Anopheles/imunologia , Proteínas de Insetos/imunologia , Malária Falciparum/imunologia , Malária Falciparum/transmissão , Proteínas e Peptídeos Salivares/imunologia , Animais , Anopheles/parasitologia , Anticorpos Antiprotozoários/sangue , Estudos de Coortes , Estudos Transversais , Monitoramento Epidemiológico , Interações Hospedeiro-Parasita/imunologia , Humanos , Imunoglobulina G/sangue , Insetos Vetores/imunologia , Insetos Vetores/parasitologia , Quênia/epidemiologia , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Proteína 1 de Superfície de Merozoito/imunologia , Plasmodium falciparum/imunologia , Estações do Ano , Estudos SoroepidemiológicosRESUMO
OBJECTIVES: To determine the malaria prevalence by microscopy, antigen detection and nucleic acid detection in a defined subpopulation in a Plasmodium falciparum-endemic region during the peak transmission season. METHODS: Blood specimens were collected in a cross-sectional study involving children aged 5-10 years (n = 195) presenting with acute fever to two clinics in Western Kenya. All specimens underwent microscopy, HRP2 and aldolase antigen detection by enzyme immunoassay (EIA), parasite-specific DNA and total nucleic acid (RNA and DNA) by real-time PCR (qPCR) and reverse-transcriptase PCR (qRT-PCR). RESULTS: Microscopy detected 65/195 cases of malaria infection [95% confidence interval (CI) 52-78]. HRP2 and aldolase EIA had similar sensitivity levels detecting antigen in 65/195 (95% CI, 52-78) and 57/195 (95% CI, 45-70) cases. Discordants in antigen detection vs. microscopy occurred at <470 parasites/µl and <4900 parasites/µl for HRP2 and aldolase, respectively. Detection of total nucleic acid allowed a 3 log lower limit of detection than just DNA detection by real-time PCR in vitro. In clinical specimens, 114/195 (95% CI, 100-127) were qPCR positive (DNA), and 187/195 (95% CI, 179-191) were qRT-PCR positive (DNA plus RNA). CONCLUSIONS: The prevalence of submicroscopic malaria infection was significantly higher when detecting total nucleic acid than just DNA in this outpatient population during the high transmission season. Defining standards for submicroscopic infection will be important for control programmes, diagnostics development efforts and molecular epidemiology studies.
Assuntos
Antígenos de Protozoários/isolamento & purificação , DNA de Protozoário/isolamento & purificação , Doenças Endêmicas , Malária Falciparum/diagnóstico , Malária Falciparum/epidemiologia , Técnicas de Amplificação de Ácido Nucleico , Contagem de Ovos de Parasitas , Plasmodium falciparum/isolamento & purificação , Proteínas de Protozoários/isolamento & purificação , Criança , Pré-Escolar , Estudos Transversais , Feminino , Frutose-Bifosfato Aldolase/imunologia , Humanos , Técnicas Imunoenzimáticas , Quênia/epidemiologia , Malária Falciparum/transmissão , Masculino , Microscopia , Plasmodium falciparum/genética , Plasmodium falciparum/imunologia , Prevalência , RNA de Protozoário/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Data on pathogen prevalence is crucial for informing exposure and disease risk. We evaluated serological evidence of tick-borne encephalitis (TBE), West Nile (WN), Hepatitis E virus (HEV), Crimean-Congo Hemorrhagic Fever (CCHF), Yersiniosis, Lyme Disease (LD), and brucellosis in 1033 patients presenting with acute febrile illness at 9 health care facilities from diverse ecological zones of Kenya: arid and semiarid (Garissa District Hospital, Lodwar District Hospital, Marigat District Hospital, Gilgil District Hospital), Lake Victoria basin (Kisumu District Hospital, Alupe District Hospital, Kombewa Sub-County Hospital), Kisii highland (Kisii District Hospital), and coastal (Malindi District Hospital). Epidemiological information of the patients such as geography, age, gender, and keeping animals were analyzed as potential risk factors. Of the 1033 samples, 619 (59.9%) were seropositive to at least one pathogen by IgM (current exposure), IgG/IgM (recent exposure), and IgG (past exposure). Collective seroprevalence for current, recent, and past to the pathogens was 9.4%, 5.1%, and 21.1% for LD; 3.6%, 0.5%, and 12.4% for WN; 0.9%, 0.5%, and 16.9% for HEV; 5.8%, 1.3%, and 3.9% for brucellosis; 5.7%, 0.2%, and 2.3% for yersiniosis; 1.7%, 0%, and 6.2% for TBE; and 0.4%, 0%, and 1.9% for CCHF. Brucellosis risk was higher in patients recruited at Garissa District Hospital (odds ratio [OR] = 3.41), HEV (OR = 2.45) and CCHF (OR = 5.46) in Lodwar District Hospital, LD in Alupe District Hospital (OR = 5.73), Kombewa Sub-district hospital (OR = 8.17), and Malindi District hospital (OR = 3.3). Exposure to LD was highest in the younger age group, whereas yersiniosis did not vary with age. Age was a significant risk for WN, brucellosis, CCHF, TBE, and HEV and in those aged >14 years there was an increased risk to WN (OR = 2.30, p < 0.0001), brucellosis (OR = 1.84, p = 0.005), CCHF (OR = 4.35, p = 0.001), TBE (OR = 2.78, p < 0.0001), and HEV (OR = 1.94, p = 0.0001). We conclude that LD is pervasive and constitutes a significant health burden to the study population, whereas yersiniosis and CCHF are not significant threats. Going forward, community-based studies will be needed to capture the true seroprevalence rates and the associated risk factors.
Assuntos
Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Viroses/epidemiologia , Viroses/virologia , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Brucelose/epidemiologia , Criança , Pré-Escolar , Encefalite Transmitida por Carrapatos/epidemiologia , Feminino , Febre Hemorrágica da Crimeia/epidemiologia , Hepatite E/epidemiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Quênia/epidemiologia , Doença de Lyme/epidemiologia , Masculino , Estudos Soroepidemiológicos , Febre do Nilo Ocidental/epidemiologia , Yersiniose/epidemiologia , Adulto JovemRESUMO
We conducted a phase 1 trial of candidate malaria vaccine RTS,S/AS02A in western Kenya to determine its safety and immunogenicity in healthy adults in an area hyperendemic for malaria. Twenty adults were enrolled and received RTS,S/AS02A (50 microg of RTS,S in 0.5 mL of AS02A) by intramuscular injection on a 0-, 28-, and 178-day schedule. All 60 scheduled immunizations were given, and 18 of 20 volunteers completed the last study visit on day 210. The vaccine was safe and well-tolerated. There were no vaccine-related severe adverse events. The most common solicited adverse events associated with immunization were injection site pain and headache. The geometric mean concentration of antibodies to circumsporozoite protein was 1.9 microg/mL at baseline and it increased 2-4 weeks after each dose to 16, 17.8, and 36.6 microg/mL, respectively. These safety and immunogenicity data from adults in hyperendemic Kenya are comparable to data reported earlier from two trials in west African adults in hypo-endemic and meso-endemic areas of The Gambia. We conclude that in this small study, RTS,S/AS02A is safe and similarly immunogenic in malaria-exposed African adults of different ethnicity in different transmission settings.
Assuntos
Doenças Endêmicas , Vacinas Antimaláricas/imunologia , Malária/prevenção & controle , Proteínas de Protozoários/imunologia , Vacinas de DNA/imunologia , Adolescente , Adulto , Animais , Anticorpos Antiprotozoários/sangue , Anticorpos Antivirais/sangue , Formação de Anticorpos/imunologia , Combinação de Medicamentos , Epitopos de Linfócito T/imunologia , Feminino , Antígenos de Superfície da Hepatite B/imunologia , Humanos , Quênia/epidemiologia , Lipídeo A/análogos & derivados , Lipídeo A/imunologia , Malária/epidemiologia , Vacinas Antimaláricas/efeitos adversos , Vacinas Antimaláricas/normas , Masculino , Saponinas/imunologia , Fatores de Tempo , Vacinas de DNA/efeitos adversos , Vacinas de DNA/normasRESUMO
OBJECTIVE: The antigen, falciparum malaria protein 1 (FMP1), represents the 42-kDa C-terminal fragment of merozoite surface protein-1 (MSP-1) of the 3D7 clone of P. falciparum. Formulated with AS02 (a proprietary Adjuvant System), it constitutes the FMP1/AS02 candidate malaria vaccine. We evaluated this vaccine's safety, immunogenicity, and efficacy in African children. METHODS: A randomised, double-blind, Phase IIb, comparator-controlled trial.The trial was conducted in 13 field stations of one mile radii within Kombewa Division, Nyanza Province, Western Kenya, an area of holoendemic transmission of P. falciparum. We enrolled 400 children aged 12-47 months in general good health.Children were randomised in a 1ratio1 fashion to receive either FMP1/AS02 (50 microg) or Rabipur(R) rabies vaccine. Vaccinations were administered on a 0, 1, and 2 month schedule. The primary study endpoint was time to first clinical episode of P. falciparum malaria (temperature >/=37.5 degrees C with asexual parasitaemia of >/=50,000 parasites/microL of blood) occurring between 14 days and six months after a third dose. Case detection was both active and passive. Safety and immunogenicity were evaluated for eight months after first immunisations; vaccine efficacy (VE) was measured over a six-month period following third vaccinations. RESULTS: 374 of 400 children received all three doses and completed six months of follow-up. FMP1/AS02 had a good safety profile and was well-tolerated but more reactogenic than the comparator. Geometric mean anti-MSP-1(42) antibody concentrations increased from1.3 microg/mL to 27.3 microg/mL in the FMP1/AS02 recipients, but were unchanged in controls. 97 children in the FMP1/AS02 group and 98 controls had a primary endpoint episode. Overall VE was 5.1% (95% CI: -26% to +28%; p-value = 0.7). CONCLUSIONS: FMP1/AS02 is not a promising candidate for further development as a monovalent malaria vaccine. Future MSP-1(42) vaccine development should focus on other formulations and antigen constructs. TRIAL REGISTRATION: Clinicaltrials.gov NCT00223990.
Assuntos
Complexo Antígeno-Anticorpo/sangue , Vacinas Antimaláricas/administração & dosagem , Proteína 1 de Superfície de Merozoito/uso terapêutico , Animais , Criança , Pré-Escolar , Método Duplo-Cego , Humanos , Lactente , Quênia , Malária Falciparum/prevenção & controle , Proteína 1 de Superfície de Merozoito/imunologia , Plasmodium falciparum/imunologia , Vacina Antirrábica , Falha de Tratamento , Resultado do TratamentoRESUMO
We report the first trial of candidate malaria vaccine antigen FMP1, a 42kDa fragment from the C-terminus of merozoite surface protein-1 (MSP-1) from the 3D7 strain of Plasmodium falciparum, in an endemic area. Forty adult male and female residents of western Kenya were enrolled to receive 3 doses of either FMP1/AS02A or Imovax rabies vaccine by intra-deltoid injection on a 0, 1, 2 month schedule. Thirty-seven volunteers received all three immunizations and 38 completed the 12-month evaluation period. Slightly more recipients of the FMP1/AS02A vaccine experienced any instance of pain at 24 h post-immunization than in the Imovax group (95% versus 65%), but otherwise the two vaccines were equally safe and well-tolerated. Baseline antibody levels were high in both groups and were boosted in the FMP1/AS02A group. Longitudinal models revealed a highly significant difference between groups for both the average post-baseline antibody responses to MSP-1(42) (F1,335=13.16; P<0.001) and the Day 90 responses to MSP-1(42) (F1,335=16.69; P<0.001). The FMP1/AS02A vaccine is safe and immunogenic in adults and should progress to safety testing in children at greatest risk of malaria.