Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 79
Filtrar
1.
BMC Infect Dis ; 21(1): 194, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607958

RESUMO

BACKGROUND: Long-lasting insecticidal nets (LLINs) are currently the primary method of malaria control in sub-Saharan Africa and have contributed to a significant reduction in malaria burden over the past 15 years. However, this progress is threatened by the wide-scale selection of insecticide-resistant malaria vectors. It is, therefore, important to accelerate the generation of evidence for new classes of LLINs. METHODS: This protocol presents a three-arm superiority, single-blinded, cluster randomized controlled trial to evaluate the impact of 2 novel dual-active ingredient LLINs on epidemiological and entomological outcomes in Benin, a malaria-endemic area with highly pyrethroid-resistant vector populations. The study arms consist of (i) Royal Guard® LLIN, a net combining a pyrethroid (alpha-cypermethrin) plus an insect growth regulator (pyriproxyfen), which in the adult female is known to disrupt reproduction and egg fertility; (ii) Interceptor G2® LLIN, a net incorporating two adulticides (alpha-cypermethrin and chlorfenapyr) with different modes of action; and (iii) the control arm, Interceptor® LLIN, a pyrethroid (alpha-cypermethrin) only LLIN. In all arms, one net for every 2 people will be distributed to each household. Sixty clusters were identified and randomised 1:1:1 to each study arm. The primary outcome is malaria case incidence measured over 24 months through active case detection in a cohort of 25 children aged 6 months to 10 years, randomly selected from each cluster. Secondary outcomes include 1) malaria infection prevalence (all ages) and prevalence of moderate to severe anaemia in children under 5 years old, measured at 6 and 18 months post-intervention; 2) entomological indices measured every 3 months using human landing catches over 24 months. Insecticide resistance intensity will also be monitored over the study period. DISCUSSION: This study is the second cluster randomised controlled trial to evaluate the efficacy of these next-generation LLINs to control malaria transmitted by insecticide-resistant mosquitoes. The results of this study will form part of the WHO evidence-based review to support potential public health recommendations of these nets and shape malaria control strategies of sub-Saharan Africa for the next decade. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03931473 , registered on 30 April 2019.

2.
PLoS Med ; 17(10): e1003370, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33119589

RESUMO

BACKGROUND: Reactive malaria strategies are predicated on the assumption that individuals infected with malaria are clustered within households or neighbourhoods. Despite the widespread programmatic implementation of reactive strategies, little empirical evidence exists as to whether such strategies are appropriate and, if so, how they should be most effectively implemented. METHODS AND FINDINGS: We collated 2 different datasets to assess clustering of malaria infections within households: (i) demographic health survey (DHS) data, integrating household information and patent malaria infection, recent fever, and recent treatment status in children; and (ii) data from cross-sectional and reactive detection studies containing information on the household and malaria infection status (patent and subpatent) of all-aged individuals. Both datasets were used to assess the odds of infections clustering within index households, where index households were defined based on whether they contained infections detectable through one of 3 programmatic strategies: (a) Reactive Case Detection (RACD) classifed by confirmed clinical cases, (b) Mass Screen and Treat (MSAT) classifed by febrile, symptomatic infections, and (c) Mass Test and Treat (MTAT) classifed by infections detectable using routine diagnostics. Data included 59,050 infections in 208,140 children under 7 years old (median age = 2 years, minimum = 2, maximum = 7) by microscopy/rapid diagnostic test (RDT) from 57 DHSs conducted between November 2006 and December 2018 from 23 African countries. Data representing 11,349 infections across all ages (median age = 22 years, minimum = 0.5, maximum = 100) detected by molecular tools in 132,590 individuals in 43 studies published between April 2006 and May 2019 in 20 African, American, Asian, and Middle Eastern countries were obtained from the published literature. Extensive clustering was observed-overall, there was a 20.40 greater (95% credible interval [CrI] 0.35-20.45; P < 0.001) odds of patent infections (according to the DHS data) and 5.13 greater odds (95% CI 3.85-6.84; P < 0.001) of molecularly detected infections (from the published literature) detected within households in which a programmatically detectable infection resides. The strongest degree of clustering identified by polymerase chain reaction (PCR)/ loop mediated isothermal amplification (LAMP) was observed using the MTAT strategy (odds ratio [OR] = 6.79, 95% CI 4.42-10.43) but was not significantly different when compared to MSAT (OR = 5.2, 95% CI 3.22-8.37; P-difference = 0.883) and RACD (OR = 4.08, 95% CI 2.55-6.53; P-difference = 0.29). Across both datasets, clustering became more prominent when transmission was low. However, limitations to our analysis include not accounting for any malaria control interventions in place, malaria seasonality, or the likely heterogeneity of transmission within study sites. Clustering may thus have been underestimated. CONCLUSIONS: In areas where malaria transmission is peri-domestic, there are programmatic options for identifying households where residual infections are likely to be found. Combining these detection strategies with presumptively treating residents of index households over a sustained time period could contribute to malaria elimination efforts.

3.
Genet Med ; 22(10): 1653-1666, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32665703

RESUMO

PURPOSE: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. METHODS: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. RESULTS: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10-72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10-50). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10-22) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10-12) carriers. The associations in the prospective cohort were similar. CONCLUSION: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.

4.
Eur Urol ; 78(4): 494-497, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32532514

RESUMO

A BRCA2 prostate cancer cluster region (PCCR) was recently proposed (c.7914 to 3') wherein pathogenic variants (PVs) are associated with higher prostate cancer (PCa) risk than PVs elsewhere in the BRCA2 gene. Using a prospective cohort study of 447 male BRCA2 PV carriers recruited in the UK and Ireland from 1998 to 2016, we estimated standardised incidence ratios (SIRs) compared with population incidences and assessed variation in risk by PV location. Carriers of PVs in the PCCR had a PCa SIR of 8.33 (95% confidence interval [CI] 4.46-15.6) and were at a higher risk of PCa than carriers of other BRCA2 PVs (SIR = 3.31, 95% CI 1.97-5.57; hazard ratio = 2.34, 95% CI 1.09-5.03). PCCR PV carriers had an estimated cumulative PCa risk of 44% (95% CI 23-72%) by the age of 75 yr and 78% (95% CI 54-94%) by the age of 85 yr. Our results corroborate the existence of a PCCR in BRCA2 in a prospective cohort. PATIENT SUMMARY: In this report, we investigated whether the risk of prostate cancer for men with a harmful mutation in the BRCA2 gene differs based on where in the gene the mutation is located. We found that men with mutations in one region of BRCA2 had a higher risk of prostate cancer than men with mutations elsewhere in the gene.

6.
Breast Cancer Res ; 22(1): 8, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31948486

RESUMO

BACKGROUND: The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. METHODS: A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. RESULTS: There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. CONCLUSION: We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/epidemiologia , Mutação , Salpingo-Ooforectomia/métodos , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Estudos de Coortes , Feminino , Humanos , Incidência , Agências Internacionais , Menopausa , Pessoa de Meia-Idade , Estudos Prospectivos , Comportamento de Redução do Risco
7.
BMC Med ; 18(1): 9, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31987052

RESUMO

BACKGROUND: In order to improve malaria burden estimates in low transmission settings, more sensitive tools and efficient sampling strategies are required. This study evaluated the use of serological measures from repeated health facility-based cross-sectional surveys to investigate Plasmodium falciparum and Plasmodium vivax transmission dynamics in an area nearing elimination in Indonesia. METHODS: Quarterly surveys were conducted in eight public health facilities in Kulon Progo District, Indonesia, from May 2017 to April 2018. Demographic data were collected from all clinic patients and their companions, with household coordinates collected using participatory mapping methods. In addition to standard microscopy tests, bead-based serological assays were performed on finger-prick bloodspot samples from 9453 people. Seroconversion rates (SCR, i.e. the proportion of people in the population who are expected to seroconvert per year) were estimated by fitting a simple reversible catalytic model to seroprevalence data. Mixed effects logistic regression was used to examine factors associated with malaria exposure, and spatial analysis was performed to identify areas with clustering of high antibody responses. RESULTS: Parasite prevalence by microscopy was extremely low (0.06% (95% confidence interval 0.03-0.14, n = 6) and 0 for P. vivax and P. falciparum, respectively). However, spatial analysis of P. vivax antibody responses identified high-risk areas that were subsequently the site of a P. vivax outbreak in August 2017 (62 cases detected through passive and reactive detection systems). These areas overlapped with P. falciparum high-risk areas and were detected in each survey. General low transmission was confirmed by the SCR estimated from a pool of the four surveys in people aged 15 years old and under (0.020 (95% confidence interval 0.017-0.024) and 0.005 (95% confidence interval 0.003-0.008) for P. vivax and P. falciparum, respectively). The SCR estimates in those over 15 years old were 0.066 (95% confidence interval 0.041-0.105) and 0.032 (95% confidence interval 0.015-0.069) for P. vivax and P. falciparum, respectively. CONCLUSIONS: These findings demonstrate the potential use of health facility-based serological surveillance to better identify and target areas still receptive to malaria in an elimination setting. Further implementation research is needed to enable integration of these methods with existing surveillance systems.


Assuntos
Surtos de Doenças , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Estudos Soroepidemiológicos , Adulto , Análise por Conglomerados , Estudos Transversais , Testes Diagnósticos de Rotina , Feminino , Instalações de Saúde , Humanos , Indonésia/epidemiologia , Modelos Logísticos , Malária/epidemiologia , Masculino , Microscopia , Pessoa de Meia-Idade , Plasmodium falciparum/imunologia , Plasmodium vivax/imunologia , Prevalência , Análise Espacial
8.
Eur Urol ; 77(1): 24-35, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31495749

RESUMO

BACKGROUND: BRCA1 and BRCA2 mutations have been associated with prostate cancer (PCa) risk but a wide range of risk estimates have been reported that are based on retrospective studies. OBJECTIVE: To estimate relative and absolute PCa risks associated with BRCA1/2 mutations and to assess risk modification by age, family history, and mutation location. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study of male BRCA1 (n = 376) and BRCA2 carriers (n = 447) identified in clinical genetics centres in the UK and Ireland (median follow-up 5.9 and 5.3 yr, respectively). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Standardised incidence/mortality ratios (SIRs/SMRs) relative to population incidences or mortality rates, absolute risks, and hazard ratios (HRs) were estimated using cohort and survival analysis methods. RESULTS AND LIMITATIONS: Sixteen BRCA1 and 26 BRCA2 carriers were diagnosed with PCa during follow-up. BRCA2 carriers had an SIR of 4.45 (95% confidence interval [CI] 2.99-6.61) and absolute PCa risk of 27% (95% CI 17-41%) and 60% (95% CI 43-78%) by ages 75 and 85 yr, respectively. For BRCA1 carriers, the overall SIR was 2.35 (95% CI 1.43-3.88); the corresponding SIR at age <65 yr was 3.57 (95% CI 1.68-7.58). However, the BRCA1 SIR varied between 0.74 and 2.83 in sensitivity analyses to assess potential screening effects. PCa risk for BRCA2 carriers increased with family history (HR per affected relative 1.68, 95% CI 0.99-2.85). BRCA2 mutations in the region bounded by positions c.2831 and c.6401 were associated with an SIR of 2.46 (95% CI 1.07-5.64) compared to population incidences, corresponding to lower PCa risk (HR 0.37, 95% CI 0.14-0.96) than for mutations outside the region. BRCA2 carriers had a stronger association with Gleason score ≥7 (SIR 5.07, 95% CI 3.20-8.02) than Gleason score ≤6 PCa (SIR 3.03, 95% CI 1.24-7.44), and a higher risk of death from PCa (SMR 3.85, 95% CI 1.44-10.3). Limitations include potential screening effects for these known mutation carriers; however, the BRCA2 results were robust to multiple sensitivity analyses. CONCLUSIONS: The results substantiate PCa risk patterns indicated by retrospective analyses for BRCA2 carriers, including further evidence of association with aggressive PCa, and give some support for a weaker association in BRCA1 carriers. PATIENT SUMMARY: In this study we followed unaffected men known to carry mutations in the BRCA1 and BRCA2 genes to investigate whether they are at higher risk of developing prostate cancer compared to the general population. We found that carriers of BRCA2 mutations have a high risk of developing prostate cancer, particularly more aggressive prostate cancer, and that this risk varies by family history of prostate cancer and the location of the mutation within the gene.

9.
J Med Genet ; 57(4): 226-236, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31719169

RESUMO

BACKGROUND: Germline TP53 gene pathogenic variants (pv) cause a very high lifetime risk of developing cancer, almost 100% for women and 75% for men. In the UK, annual MRI breast screening is recommended for female TP53 pv carriers. The SIGNIFY study (Magnetic Resonance Imaging screening in Li Fraumeni syndrome: An exploratory whole body MRI) study reported outcomes of whole-body MRI (WB-MRI) in a cohort of 44 TP53 pv carriers and 44 matched population controls. The results supported the use of a baseline WB-MRI screen in all adult TP53 pv carriers. Here we report the acceptability of WB-MRI screening and effects on psychosocial functioning and health-related quality of life in the short and medium terms. METHODS: Psychosocial and other assessments were carried out at study enrolment, immediately before MRI, before and after MRI results, and at 12, 26 and 52 weeks' follow-up. RESULTS: WB-MRI was found to be acceptable with high levels of satisfaction and low levels of psychological morbidity throughout. Although their mean levels of cancer worry were not high, carriers had significantly more cancer worry at most time-points than controls. They also reported significantly more clinically significant intrusive and avoidant thoughts about cancer than controls at all time-points. There were no clinically significant adverse psychosocial outcomes in either carriers with a history of cancer or in those requiring further investigations. CONCLUSION: WB-MRI screening can be implemented in TP53 pv carriers without adverse psychosocial outcomes in the short and medium terms. A previous cancer diagnosis may predict a better psychosocial outcome. Some carriers seriously underestimate their risk of cancer. Carriers of pv should have access to a clinician to help them develop adaptive strategies to cope with cancer-related concerns and respond to clinically significant depression and/or anxiety.

10.
Trends Parasitol ; 35(10): 822-834, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31474558

RESUMO

As data at progressively granular spatial scales become available, the temptation is to target interventions to areas with higher malaria transmission - so-called hotspots - with the aim of reducing transmission in the wider community. This paper reviews literature to determine if hotspots are an intrinsic feature of malaria epidemiology and whether current evidence supports hotspot-targeted interventions. Hotspots are a consistent feature of malaria transmission at all endemicities. The smallest spatial unit capable of supporting transmission is the household, where peri-domestic transmission occurs. Whilst the value of focusing interventions to high-burden areas is evident, there is currently limited evidence that local-scale hotspots fuel transmission. As boundaries are often uncertain, there is no conclusive evidence that hotspot-targeted interventions accelerate malaria elimination.


Assuntos
Malária/epidemiologia , Malária/prevenção & controle , Análise Espacial , Humanos , Malária/transmissão
11.
Eur Urol ; 76(6): 831-842, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31537406

RESUMO

BACKGROUND: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations. OBJECTIVE: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status. DESIGN, SETTING, AND PARTICIPANTS: Men aged 40-69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians. RESULTS AND LIMITATIONS: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65). CONCLUSIONS: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers. PATIENT SUMMARY: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening.

12.
Malar J ; 18(1): 246, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331340

RESUMO

BACKGROUND: Measures of malaria burden using microscopy and rapid diagnostic tests (RDTs) in cross-sectional household surveys may incompletely describe the burden of malaria in low-transmission settings. This study describes the pattern of malaria transmission in Ethiopia using serological antibody estimates derived from a nationwide household survey completed in 2015. METHODS: Dried blood spot (DBS) samples were collected during the Ethiopian Malaria Indicator Survey in 2015 from malarious areas across Ethiopia. Samples were analysed using bead-based multiplex assays for IgG antibodies for six Plasmodium antigens: four human malaria species-specific merozoite surface protein-1 19kD antigens (MSP-1) and Apical Membrane Antigen-1 (AMA-1) for Plasmodium falciparum and Plasmodium vivax. Seroprevalence was estimated by age, elevation and region. The seroconversion rate was estimated using a reversible catalytic model fitted with maximum likelihood methods. RESULTS: Of the 10,278 DBS samples available, 93.6% (9622/10,278) had valid serological results. The mean age of participants was 15.8 years and 53.3% were female. National seroprevalence for antibodies to P. falciparum was 32.1% (95% confidence interval (CI) 29.8-34.4) and 25.0% (95% CI 22.7-27.3) to P. vivax. Estimated seroprevalences for Plasmodium malariae and Plasmodium ovale were 8.6% (95% CI 7.6-9.7) and 3.1% (95% CI 2.5-3.8), respectively. For P. falciparum seroprevalence estimates were significantly higher at lower elevations (< 2000 m) compared to higher (2000-2500 m) (aOR 4.4; p < 0.01). Among regions, P. falciparum seroprevalence ranged from 11.0% (95% CI 8.8-13.7) in Somali to 65.0% (95% CI 58.0-71.4) in Gambela Region and for P. vivax from 4.0% (95% CI 2.6-6.2) in Somali to 36.7% (95% CI 30.0-44.1) in Amhara Region. Models fitted to measure seroconversion rates showed variation nationally and by elevation, region, antigen type, and within species. CONCLUSION: Using multiplex serology assays, this study explored the cumulative malaria burden and regional dynamics of the four human malarias in Ethiopia. High malaria burden was observed in the northwest compared to the east. High transmission in the Gambela and Benishangul-Gumuz Regions and the neglected presence of P. malariae and P. ovale may require programmatic attention. The use of a multiplex assay for antibody detection in low transmission settings has the potential to act as a more sensitive biomarker.


Assuntos
Malária/epidemiologia , Plasmodium/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antiprotozoários , Criança , Pré-Escolar , Etiópia/epidemiologia , Feminino , Humanos , Imunoglobulina G/análise , Lactente , Recém-Nascido , Malária/classificação , Masculino , Pessoa de Meia-Idade , Plasmodium/classificação , Prevalência , Estudos Soroepidemiológicos , Testes Sorológicos , Adulto Jovem
13.
Malar J ; 18(1): 227, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286973

RESUMO

BACKGROUND: Analysis of anti-malarial antibody responses has the potential to improve characterization of the variation in exposure to infection in low transmission settings, where conventional measures, such as entomological estimates and parasitaemia point prevalence become less sensitive and expensive to measure. This study evaluates the use of sero-epidemiological analysis to investigate heterogeneity of transmission in area conducting elimination in Indonesia. METHODS: Filter paper bloodspots and epidemiological data were collected through a community-based cross-sectional study conducted in two sub-districts in Sabang municipality, Aceh province, Indonesia in 2013. Antibody responses to merozoite surface protein 1 (MSP-119) and apical membrane antigen 1 (AMA-1) for Plasmodium falciparum and Plasmodium vivax were measured using indirect enzyme-linked immunosorbent assay (ELISA). Seroconversion rates (SCR) were estimated by fitting a simple reversible catalytic model to seroprevalence data for each antibody. Spatial analysis was performed using a Normal model (SaTScan v.9.4.2) to identify the clustering of higher values of household antibody responses. Multiple logistic regression was used to investigate factors associated with exposure. RESULTS: 1624 samples were collected from 605 households. Seroprevalence to any P. falciparum antigen was higher than to any P. vivax antigen, 6.9% (95% CI 5.8-8.2) vs 2.0% (95% CI 1.4-2.8). SCR estimates suggest that there was a significant change in P. falciparum transmission with no exposure seen in children under 5 years old. Plasmodium falciparum SCR in over 5 years old was 0.008 (95% CI 0.003-0.017) and 0.012 (95% CI 0.005-0.030) in Sukakarya and Sukajaya sub-districts, respectively. Clusters of exposure were detected for both P. falciparum and P. vivax, most of them in Sukajaya sub-district. Higher age, P. vivax seropositivity and use of long-lasting insecticide-treated bed net (LLIN) were associated with higher P. falciparum exposure. CONCLUSION: Analysis of community-based serological data helps describe the level of transmission, heterogeneity and factors associated with malaria transmission in Sabang. This approach could be an important additional tool for malaria monitoring and surveillance in low transmission settings in Indonesia.


Assuntos
Malária Falciparum/epidemiologia , Malária Falciparum/transmissão , Malária Vivax/epidemiologia , Malária Vivax/transmissão , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Indonésia/epidemiologia , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum , Plasmodium vivax/fisiologia , Estudos Soroepidemiológicos , Adulto Jovem
15.
Nat Commun ; 10(1): 1433, 2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30926893

RESUMO

Malaria infections occurring below the limit of detection of standard diagnostics are common in all endemic settings. However, key questions remain surrounding their contribution to sustaining transmission and whether they need to be detected and targeted to achieve malaria elimination. In this study we analyse a range of malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections. Asymptomatically infected individuals have lower parasite densities on average in low transmission settings compared to individuals in higher transmission settings. In cohort studies, subpatent infections are found to be predictive of future periods of patent infection and in membrane feeding studies, individuals infected with subpatent asexual parasite densities are found to be approximately a third as infectious to mosquitoes as individuals with patent (asexual parasite) infection. These results indicate that subpatent infections contribute to the infectious reservoir, may be long lasting, and require more sensitive diagnostics to detect them in lower transmission settings.


Assuntos
Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Parasitos/fisiologia , Plasmodium falciparum/fisiologia , Animais , Células Germinativas/metabolismo , Humanos , Parasitemia/parasitologia , Probabilidade , Fatores de Tempo
16.
Trans R Soc Trop Med Hyg ; 113(3): 152-159, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30496556

RESUMO

BACKGROUND: Malaria transmission in African highland areas can be prone to epidemics, with minor fluctuations in temperature or altitude resulting in highly heterogeneous transmission. In the Kenyan Highlands, where malaria prevalence has been increasing, characterising malaria incidence and identifying risk factors for infection is complicated by asymptomatic infection. METHODS: This all-age cohort study, one element of the Malaria Transmission Consortium, involved monthly follow-up of 3155 residents of the Kisii and Rachuonyo South districts during June 2009-June 2010. Participants were tested for malaria using rapid diagnostic testing at every visit, regardless of symptoms. RESULTS: The incidence of Plasmodium falciparum infection was 0.2 cases per person, although infections were clustered within individuals and over time, with the majority of infections detected in the last month of the cohort study. Overall, incidence was higher in the Rachuonyo district and infections were detected most frequently in 5-10-year-olds. The majority of infections were asymptomatic (58%). Travel away from the study area was a notable risk factor for infection. CONCLUSIONS: Identifying risk factors for malaria infection can help to guide targeting of interventions to populations most likely to be exposed to malaria.


Assuntos
Malária Falciparum/etiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Incidência , Lactente , Quênia/epidemiologia , Malária Falciparum/epidemiologia , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum , Prevalência , Fatores de Risco , Fatores Sexuais , Fatores Socioeconômicos , Adulto Jovem
17.
BJU Int ; 123(2): 284-292, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29802810

RESUMO

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening.


Assuntos
Detecção Precoce de Câncer/psicologia , Genes BRCA1 , Genes BRCA2 , Neoplasias da Próstata/genética , Neoplasias da Próstata/psicologia , Adulto , Ansiedade/etiologia , Estudos de Casos e Controles , Depressão/etiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mutação , Percepção , Neoplasias da Próstata/diagnóstico , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Fatores de Risco , Inquéritos e Questionários
18.
BMC Public Health ; 18(1): 894, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-30021543

RESUMO

BACKGROUND: Access to long-lasting insecticidal nets (LLINs) has increased and malaria has decreased globally, but malaria transmission remains high in parts of sub-Saharan Africa and insecticide resistance threatens current progress. Eave tubes are a new tool for the targeted delivery of insecticides against mosquitoes attempting to enter houses. The primary objective of this trial is to test whether screening plus eave tubes (SET) provides protection against malaria, on top of universal coverage with LLINs in an area of intense pyrethroid resistance. The trial will also assess acceptability and cost-effectiveness of the intervention. METHODS/DESIGN: A two-armed, cluster randomized controlled trial will be conducted to evaluate the effect of SET on clinical malaria incidence in children living in central Côte d'Ivoire. Forty villages will be selected based on population size and the proportion of houses suitable for modification with SET. Using restricted randomization, half the villages will be assigned to the treatment arm (SET + LLINs) and the remainder will be assigned to the control arm (LLINs only). In both arms, LLINs will be distributed and in the treatment arm, householders will be offered SET. Fifty children aged six months to eight years old will be enrolled from randomly selected households in each of the 40 villages. Cohorts will be cleared of malaria parasites at the start of the study and one year after recruitment, and will be monitored for clinical malaria case incidence by active case detection over two years. Mosquito densities will be assessed using CDC light traps and human landing catches and a subset of Anopheles mosquitoes will be examined for parity status and tested for sporozoite infection. Acceptability of SET will be monitored using surveys and focus groups. Cost-effectiveness analysis will measure the incremental cost per case averted and per disability-adjusted life year (DALY) averted of adding SET to LLINs. Economic and financial costs will be estimated from societal and provider perspective using standard economic evaluation methods. DISCUSSION: This study will be the first evaluation of the epidemiological impact of SET. Trial findings will show whether SET is a viable, cost-effective technology for malaria control in Côte d'Ivoire and possibly elsewhere. TRIAL REGISTRATION: ISRCTN18145556 , registered on 01 February 2017 - retrospectively registered.


Assuntos
Mosquiteiros Tratados com Inseticida , Inseticidas , Malária/prevenção & controle , Controle de Mosquitos/métodos , Anemia/prevenção & controle , Animais , Anopheles/parasitologia , Criança , Pré-Escolar , Análise Custo-Benefício , Costa do Marfim/epidemiologia , Transmissão de Doença Infecciosa/prevenção & controle , Doenças Endêmicas/prevenção & controle , Feminino , Humanos , Incidência , Lactente , Malária/epidemiologia , Malária/transmissão , Masculino , Projetos de Pesquisa , Estações do Ano , Inquéritos e Questionários
19.
Int J Health Geogr ; 17(1): 21, 2018 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-29914506

RESUMO

BACKGROUND: Identifying fine-scale spatial patterns of disease is essential for effective disease control and elimination programmes. In low resource areas without formal addresses, novel strategies are needed to locate residences of individuals attending health facilities in order to efficiently map disease patterns. We aimed to assess the use of Android tablet-based applications containing high resolution maps to geolocate individual residences, whilst comparing the functionality, usability and cost of three software packages designed to collect spatial information. RESULTS: Using Open Data Kit GeoODK, we designed and piloted an electronic questionnaire for rolling cross sectional surveys of health facility attendees as part of a malaria elimination campaign in two predominantly rural sites in the Rizal, Palawan, the Philippines and Kulon Progo Regency, Yogyakarta, Indonesia. The majority of health workers were able to use the tablets effectively, including locating participant households on electronic maps. For all households sampled (n = 603), health facility workers were able to retrospectively find the participant household using the Global Positioning System (GPS) coordinates and data collected by tablet computers. Median distance between actual house locations and points collected on the tablet was 116 m (IQR 42-368) in Rizal and 493 m (IQR 258-886) in Kulon Progo Regency. Accuracy varied between health facilities and decreased in less populated areas with fewer prominent landmarks. CONCLUSIONS: Results demonstrate the utility of this approach to develop real-time high-resolution maps of disease in resource-poor environments. This method provides an attractive approach for quickly obtaining spatial information on individuals presenting at health facilities in resource poor areas where formal addresses are unavailable and internet connectivity is limited. Further research is needed on how to integrate these with other health data management systems and implement in a wider operational context.


Assuntos
Computadores de Mão , Sistemas de Informação Geográfica , Mapeamento Geográfico , Recursos em Saúde , Telemedicina/métodos , Sistemas de Informação Geográfica/estatística & dados numéricos , Instalações de Saúde/estatística & dados numéricos , Recursos em Saúde/estatística & dados numéricos , Humanos , Indonésia/epidemiologia , Filipinas/epidemiologia , População Rural/estatística & dados numéricos , Telemedicina/instrumentação , Telemedicina/estatística & dados numéricos
20.
Lancet Infect Dis ; 18(6): 640-649, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29650424

RESUMO

BACKGROUND: Scale-up of insecticide-based interventions has averted more than 500 million malaria cases since 2000. Increasing insecticide resistance could herald a rebound in disease and mortality. We aimed to investigate whether insecticide resistance was associated with loss of effectiveness of long-lasting insecticidal nets and increased malaria disease burden. METHODS: This WHO-coordinated, prospective, observational cohort study was done at 279 clusters (villages or groups of villages in which phenotypic resistance was measurable) in Benin, Cameroon, India, Kenya, and Sudan. Pyrethroid long-lasting insecticidal nets were the principal form of malaria vector control in all study areas; in Sudan this approach was supplemented by indoor residual spraying. Cohorts of children from randomly selected households in each cluster were recruited and followed up by community health workers to measure incidence of clinical malaria and prevalence of infection. Mosquitoes were assessed for susceptibility to pyrethroids using the standard WHO bioassay test. Country-specific results were combined using meta-analysis. FINDINGS: Between June 2, 2012, and Nov 4, 2016, 40 000 children were enrolled and assessed for clinical incidence during 1·4 million follow-up visits. 80 000 mosquitoes were assessed for insecticide resistance. Long-lasting insecticidal net users had lower infection prevalence (adjusted odds ratio [OR] 0·63, 95% CI 0·51-0·78) and disease incidence (adjusted rate ratio [RR] 0·62, 0·41-0·94) than did non-users across a range of resistance levels. We found no evidence of an association between insecticide resistance and infection prevalence (adjusted OR 0·86, 0·70-1·06) or incidence (adjusted RR 0·89, 0·72-1·10). Users of nets, although significantly better protected than non-users, were nevertheless subject to high malaria infection risk (ranging from an average incidence in net users of 0·023, [95% CI 0·016-0·033] per person-year in India, to 0·80 [0·65-0·97] per person year in Kenya; and an average infection prevalence in net users of 0·8% [0·5-1·3] in India to an average infection prevalence of 50·8% [43·4-58·2] in Benin). INTERPRETATION: Irrespective of resistance, populations in malaria endemic areas should continue to use long-lasting insecticidal nets to reduce their risk of infection. As nets provide only partial protection, the development of additional vector control tools should be prioritised to reduce the unacceptably high malaria burden. FUNDING: Bill & Melinda Gates Foundation, UK Medical Research Council, and UK Department for International Development.


Assuntos
Culicidae/efeitos dos fármacos , Mosquiteiros Tratados com Inseticida , Malária/transmissão , Controle de Mosquitos/métodos , Mosquitos Vetores/efeitos dos fármacos , Piretrinas/farmacologia , Adolescente , África ao Sul do Saara/epidemiologia , Animais , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Índia/epidemiologia , Lactente , Resistência a Inseticidas , Internacionalidade , Malária/epidemiologia , Estudos Prospectivos , Organização Mundial da Saúde
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA