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1.
Sci Transl Med ; 12(544)2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434846

RESUMO

For some diseases, successful vaccines have been developed using a nonpathogenic counterpart of the causative microorganism of choice. The nonpathogenicity of the rodent Plasmodium berghei (Pb) parasite in humans prompted us to evaluate its potential as a platform for vaccination against human infection by Plasmodium falciparum (Pf), a causative agent of malaria. We hypothesized that the genetic insertion of a leading protein target for clinical development of a malaria vaccine, Pf circumsporozoite protein (CSP), in its natural pre-erythrocytic environment, would enhance Pb's capacity to induce protective immunity against Pf infection. Hence, we recently generated a transgenic Pb sporozoite immunization platform expressing PfCSP (PbVac), and we now report the clinical evaluation of its biological activity against controlled human malaria infection (CHMI). This first-in-human trial shows that PbVac is safe and well tolerated, when administered by a total of ~300 PbVac-infected mosquitoes per volunteer. Although protective efficacy evaluated by CHMI showed no sterile protection at the tested dose, significant delays in patency (2.2 days, P = 0.03) and decreased parasite density were observed after immunization, corresponding to an estimated 95% reduction in Pf liver parasite burden (confidence interval, 56 to 99%; P = 0.010). PbVac elicits dose-dependent cross-species cellular immune responses and functional PfCSP-dependent antibody responses that efficiently block Pf sporozoite invasion of liver cells in vitro. This study demonstrates that PbVac immunization elicits a marked biological effect, inhibiting a subsequent infection by the human Pf parasite, and establishes the clinical validation of a new paradigm in malaria vaccination.

3.
J Infect Dis ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32173745

RESUMO

BACKGROUND: The World Health Organization recommends monitoring Onchocerca volvulus Ov16 serology in children aged <10 years for stopping mass ivermectin administration. Transmission models can help to identify the most informative age groups for serological monitoring and investigate the discriminatory power of serology-based elimination thresholds. Model predictions depend on assumed age-exposure patterns and transmission efficiency at low infection levels. METHODS: The individual-based transmission model, EPIONCHO-IBM, was used to assess (1) the most informative age groups for serological monitoring using receiver operating characteristic curves for different elimination thresholds under various age-dependent exposure assumptions, including those of ONCHOSIM (another widely used model), and (2) the influence of within-human density-dependent parasite establishment (included in EPIONCHO-IBM but not ONCHOSIM) on positive predictive values for different serological thresholds. RESULTS: When assuming EPIONCHO-IBM exposure patterns, children aged <10 years are the most informative for seromonitoring; when assuming ONCHOSIM exposure patterns, 5-14 year olds are the most informative (as published elsewhere). Omitting density-dependent parasite establishment results in more lenient seroprevalence thresholds, even for higher baseline infection prevalence and shorter treatment durations. CONCLUSIONS: Selecting appropriate seromonitoring age groups depends critically on age-dependent exposure patterns. The role of density dependence on elimination thresholds largely explains differing EPIONCHO-IBM and ONCHOSIM elimination predictions.

4.
PLoS Med ; 17(3): e1003042, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32142509

RESUMO

BACKGROUND: In the generalised epidemics of sub-Saharan Africa (SSA), human immunodeficiency virus (HIV) prevalence shows patterns of clustered micro-epidemics. We mapped and characterised these high-prevalence areas for young adults (15-29 years of age), as a proxy for areas with high levels of transmission, for 7 countries in Eastern and Southern Africa: Kenya, Malawi, Mozambique, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS AND FINDINGS: We used geolocated survey data from the most recent United States Agency for International Development (USAID) demographic and health surveys (DHSs) and AIDS indicator surveys (AISs) (collected between 2008-2009 and 2015-2016), which included about 113,000 adults-of which there were about 53,000 young adults (27,000 women, 28,000 men)-from over 3,500 sample locations. First, ordinary kriging was applied to predict HIV prevalence at unmeasured locations. Second, we explored to what extent behavioural, socioeconomic, and environmental factors explain HIV prevalence at the individual- and sample-location level, by developing a series of multilevel multivariable logistic regression models and geospatially visualising unexplained model heterogeneity. National-level HIV prevalence for young adults ranged from 2.2% in Tanzania to 7.7% in Mozambique. However, at the subnational level, we found areas with prevalence among young adults as high as 11% or 15% alternating with areas with prevalence between 0% and 2%, suggesting the existence of areas with high levels of transmission Overall, 15.6% of heterogeneity could be explained by an interplay of known behavioural, socioeconomic, and environmental factors. Maps of the interpolated random effect estimates show that environmental variables, representing indicators of economic activity, were most powerful in explaining high-prevalence areas. Main study limitations were the inability to infer causality due to the cross-sectional nature of the surveys and the likely under-sampling of key populations in the surveys. CONCLUSIONS: We found that, among young adults, micro-epidemics of relatively high HIV prevalence alternate with areas of very low prevalence, clearly illustrating the existence of areas with high levels of transmission. These areas are partially characterised by high economic activity, relatively high socioeconomic status, and risky sexual behaviour. Localised HIV prevention interventions specifically tailored to the populations at risk will be essential to curb transmission. More fine-scale geospatial mapping of key populations,-such as sex workers and migrant populations-could help us further understand the drivers of these areas with high levels of transmission and help us determine how they fuel the generalised epidemics in SSA.

6.
J Infect Dis ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829425

RESUMO

Starting and stopping preventive chemotherapy (PC) for soil-transmitted helminthiasis is typically based on the prevalence of infection as measured by Kato-Katz (KK) fecal smears. Kato-Katz-based egg counts can vary highly over repeated stool samples and smears. Consequentially, the sensitivity of KK-based surveys depends on the number of stool samples per person and the number of smears per sample. Given finite resources, collecting multiple samples and/or smears means screening fewer individuals, thereby lowering the statistical precision of prevalence estimates. Using population-level data from various epidemiological settings, we assessed the performance of different sampling schemes executed within the confines of the same budget. We recommend the use of single-slide KK for determining prevalence of moderate-to-heavy intensity infection and policy decisions for starting and continuing PC; more sensitive sampling schemes may be required for policy decisions involving stopping PC. Our findings highlight that guidelines should include specific guidance on sampling schemes.

7.
J Infect Dis ; 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31841593

RESUMO

BACKGROUND: Control of visceral leishmaniasis (VL) on the Indian subcontinent relies on prompt detection and treatment of symptomatic cases. Detection efforts influence the observed VL incidence and how well it reflects the underlying true incidence. As control targets are defined in terms of observed cases, there is an urgent need to understand how changes in detection delay and population coverage of improved detection affect VL control. METHODS: Using a mathematical model for transmission and control of VL, we predict the impact of reduced detection delays and/or increased population coverage of the detection programs on observed and true VL incidence and mortality. RESULTS: Improved case detection, either by higher coverage or reduced detection delay, causes an initial rise in observed VL incidence before a reduction. Relaxation of improved detection may lead to an apparent temporary (1 year) reduction in VL incidence, but comes with a high risk of resurging infection levels. Duration of symptoms in detected cases shows an unequivocal association with detection effort. CONCLUSIONS: VL incidence on its own is not a reliable indicator of the performance of case detection programs. Duration of symptoms in detected cases can be used as an additional marker of the performance of case detection programs.

8.
J Infect Dis ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31853554

RESUMO

The low prevalence levels associated with lymphatic filariasis elimination pose a challenge for effective disease surveillance. As more countries achieve the World Health Organization criteria for halting mass treatment and move on to surveillance, there is increasing reliance on the utility of transmission assessment surveys (TAS) to measure success. However, the long-term disease outcomes after passing TAS are largely untested. Using 3 well-established mathematical models, we show that low-level prevalence can be maintained for a long period after halting mass treatment and that true elimination (0% prevalence) is usually slow to achieve. The risk of resurgence after achieving current targets is low and is hard to predict using just current prevalence. Although resurgence is often quick (<5 years), it can still occur outside of the currently recommended postintervention surveillance period of 4-6 years. Our results highlight the need for ongoing and enhanced postintervention monitoring, beyond the scope of TAS, to ensure sustained success.

9.
PLoS Negl Trop Dis ; 13(8): e0007115, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398203

RESUMO

BACKGROUND: Ghana started its national programme to eliminate lymphatic filariasis (LF) in 2000, with mass drug administration (MDA) with ivermectin and albendazole as main strategy. We review the progress towards elimination that was made by 2016 for all endemic districts of Ghana and analyze microfilaria (mf) prevalence from sentinel and spot-check sites in endemic districts. METHODS: We reviewed district level data on the history of MDA and outcomes of transmission assessment surveys (TAS). We further collated and analyzed mf prevalence data from sentinel and spot-check sites. RESULTS: MDA was initiated in 2001-2006 in all 98 endemic districts; by the end of 2016, 81 had stopped MDA after passing TAS and after an average of 11 rounds of treatment (range 8-14 rounds). The median reported coverage for the communities was 77-80%. Mf prevalence survey data were available for 430 communities from 78/98 endemic districts. Baseline mf prevalence data were available for 53 communities, with an average mf prevalence of 8.7% (0-45.7%). Repeated measurements were available for 78 communities, showing a steep decrease in mean mf prevalence in the first few years of MDA, followed by a gradual further decline. In the 2013 and 2014 surveys, 7 and 10 communities respectively were identified with mf prevalence still above 1% (maximum 5.6%). Fifteen of the communities above threshold are all within districts where MDA was still ongoing by 2016. CONCLUSIONS: The MDA programme of the Ghana Health Services has reduced mf prevalence in sentinel sites below the 1% threshold in 81/98 endemic districts in Ghana, yet 15 communities within 13 districts (MDA ongoing by 2016) had higher prevalence than this threshold during the surveys in 2013 and 2014. These districts may need to intensify interventions to achieve the WHO 2020 target.


Assuntos
Erradicação de Doenças/métodos , Filariose Linfática/tratamento farmacológico , Filariose Linfática/epidemiologia , Albendazol/uso terapêutico , Animais , Criança , Pré-Escolar , Filariose Linfática/diagnóstico , Filariose Linfática/prevenção & controle , Doenças Endêmicas , Feminino , Gana/epidemiologia , Pesquisa sobre Serviços de Saúde , Humanos , Ivermectina/uso terapêutico , Masculino , Administração Massiva de Medicamentos/métodos , Microfilárias/patogenicidade , Prevalência , Inquéritos e Questionários , Organização Mundial da Saúde
10.
Health Aff (Millwood) ; 38(7): 1173-1181, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31260360

RESUMO

Health systems in sub-Saharan Africa are facing an ongoing HIV epidemic and increasing burden of noncommunicable disease. With the focus shifting to the development of comprehensive primary health care and chronic disease treatment, multidisease modeling is integral to estimating future health care needs. We extended an established agent-based model of HIV transmission to include hypertension in two rural settings: KwaZulu-Natal, South Africa, and western Kenya. We estimated that from 2018 to 2028 hypertension prevalence would increase from 40 percent to 46 percent in KwaZulu-Natal and from 29 percent to 35 percent in western Kenya, while HIV prevalence is stabilizing and predicted to decrease. As the health system burden in sub-Saharan Africa is changing, innovative chronic disease treatment and the broadening of successful programs, such as integrated HIV and noncommunicable disease care, are necessary to reach universal health care coverage.

11.
Trends Parasitol ; 35(8): 590-592, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31266711

RESUMO

Post-kala-azar dermal leishmaniasis (PKDL) is a parasitic skin infection which can occur after visceral leishmaniasis (VL). Recent xenodiagnosis studies (Mondal et al., Clin. Infect. Dis., 2018) have uncovered the infectiousness of PKDL. When including this in a transmission model, PKDL cases appear as an important reservoir of infection, likely frustrating the VL elimination efforts on the Indian subcontinent.

12.
PLoS Negl Trop Dis ; 13(6): e0007514, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31242194

RESUMO

BACKGROUND: The current World Health Organization (WHO) target for the three major soil-transmitted helminth (STH) infections is to reduce prevalence of moderate-to-heavy infections to below 1% by 2020. In terms of monitoring and evaluation (M&E), the current WHO guidelines for control of STHs recommend evaluation of infection levels in school-age children (SAC) after five to six years of preventive chemotherapy (PC), using the standard Kato-Katz faecal smear. Here, we assess the predictive performance of various sampling designs for the evaluation of the morbidity target. METHODOLOGY/PRINCIPAL FINDINGS: Using two mathematical models for STH transmission and control, we simulate how the number of villages and SAC sampled affect the ability of survey results in sentinel villages to predict the achievement of the morbidity target in PC implementation units (e.g. districts). As PC is stopped when the prevalence of infection in SAC in sentinel villages is less than 1%, we estimate the positive predictive value (PPV) of this indicator for meeting the morbidity target in the whole district. The PPV varies by species and PC strategy, and it is generally higher in areas with lower pre-control prevalence. Sampling a fixed number of SAC spread out over 10 instead of 5 sentinel villages may increase the PPV by up to 20 percentage points. If every SAC in a village is tested, a higher number of villages may increase the PPV by up to 80 percentage points. Increasing the proportion of SAC tested per village does not result in a relevant increase of PPV. CONCLUSIONS/SIGNIFICANCE: Although the WHO guidelines provide a combined strategy to control the three STH species, the efficacy of PC strategies clearly differs by species. There is added value in considering more villages within implementation units for M&E of morbidity targets, the extent varying by STH species. A better understanding of pre- and post-control local STH prevalence levels is essential for an adequate M&E strategy including the definition of morbidity targets at the appropriate geographical scale.


Assuntos
Anti-Helmínticos/uso terapêutico , Quimioprevenção/métodos , Controle de Doenças Transmissíveis/métodos , Transmissão de Doença Infecciosa/prevenção & controle , Pesquisa sobre Serviços de Saúde/métodos , Helmintíase/diagnóstico , Helmintíase/prevenção & controle , Adolescente , Criança , Pré-Escolar , Feminino , Helmintíase/epidemiologia , Humanos , Masculino
13.
J Infect Dis ; 220(6): 1044-1048, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31077279

RESUMO

Four healthy volunteers were infected with 50 Necator americanus infective larvae (L3) in a controlled human hookworm infection trial and followed for 52 weeks. The kinetics of fecal egg counts in volunteers was assessed with Bayesian multilevel analysis, which revealed an increase between weeks 7 and 13, followed by an egg density plateau of about 1000 eggs/g of feces. Variation in egg counts was minimal between same-day measurements but varied considerably between days, particularly during the plateau phase. These analyses pave the way for the controlled human hookworm model to accelerate drug and vaccine efficacy studies.

14.
Am J Epidemiol ; 188(9): 1723-1732, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31062838

RESUMO

The World Health Organization currently recommends assessing elimination of onchocerciasis by testing whether Ov16 antibody prevalence in children aged 0-9 years is below 0.1%. However, the certainty of evidence for this recommendation is considered to be low. We used the established ONCHOSIM model to investigate the predictive value of different Ov16-antibody prevalence thresholds in various age groups for elimination of onchocerciasis in a variety of endemic settings and for various mass drug administration scenarios. According to our simulations, the predictive value of Ov16 antibody prevalence for elimination depends highly on the precontrol epidemiologic situation, history of mass drug administration, the age group that is sampled, and the chosen Ov16-antibody prevalence threshold. The Ov16 antibody prevalence in children aged 5-14 years performs best in predicting elimination. Appropriate threshold values for this age group start at 2.0% for very highly endemic areas; for lower-endemic areas, even higher threshold values are safe to use. Guidelines can be improved by sampling school-aged children, which also is operationally more feasible than targeting children under age 10 years. The use of higher threshold values allows sampling of substantially fewer children. Further improvement can be achieved by taking a differentiated sampling approach based on precontrol endemicity.

16.
AIDS ; 33(1): 123-131, 2019 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-30475261

RESUMO

BACKGROUND: HIV took off rapidly in Zimbabwe during the 1980s. Yet, between 1998 and 2003, as the economy faltered, HIV prevalence declined abruptly and without clear explanation. METHODS: We reviewed epidemiological, behavioural, and economic data over three decades to understand changes in economic conditions, migrant labour and sex work that may account for observed fluctuations in Zimbabwe's HIV epidemic. Potential biases related to changing epidemic paradigms and data sources were examined. RESULTS: Early studies describe rural poverty, male migrant labour and sex work as conditions facilitating HIV/sexually transmitted infection (STI) transmission. By the mid-1990s, as Zimbabwe's epidemic became more generalized, research focus shifted to general population household surveys. Yet, less than half as many men than women were found at home during surveys in the 1990s, increasing to 80% during the years of economic decline. Other studies suggest that male demand for sex work fell abruptly as migrant workers were laid off, picking up again when the economy rebounded after 2009. Numbers of clients reported by sex workers, and their STI rates, followed similar patterns reaching a nadir in the early 2000s. Studies from 2009 describe a return to more active sex work, linked to increasing client demand, as well as a revitalized programme reaching sex workers. CONCLUSION: The importance of the downturn in migrant labour and resultant changes in sex work may be underestimated as drivers of Zimbabwe's rapid HIV incidence and prevalence declines. Household surveys underrepresent populations at the highest risk of HIV/STI acquisition and transmission, and these biases vary with changing economic conditions.


Assuntos
Transmissão de Doença Infecciosa , Economia , Emigração e Imigração/estatística & dados numéricos , Epidemias , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Trabalho Sexual , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem , Zimbábue/epidemiologia
17.
PLoS Negl Trop Dis ; 12(12): e0006888, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30521529

RESUMO

BACKGROUND: Despite the overall decrease in visceral leishmaniasis (VL) incidence on the Indian subcontinent, there remain spatiotemporal clusters or 'hotspots' of new cases. The characteristics of these hotspots, underlying transmission dynamics, and their importance for shaping control strategies are not yet fully understood and are investigated in this study for a VL endemic area of ~100,000 inhabitants in Bihar, India between 2007-2015. METHODOLOGY/PRINCIPAL FINDINGS: VL incidence (cases/10,000/year) dropped from 12.3 in 2007 to 0.9 in 2015, which is just below the World Health Organizations' threshold for elimination as a public health problem. Clustering of VL was assessed between subvillages (hamlets), using multiple geospatial and (spatio)temporal autocorrelation and hotspot analyses. One to three hotspots were identified each year, often persisting for 1-5 successive years with a modal radius of ~500m. The relative risk of having VL was 5-86 times higher for inhabitants of hotspots, compared to those living outside hotspots. Hotspots harbour significantly more households from the two lowest asset quintiles (as proxy for socio-economic status). Overall, children and young adelescents (5-14 years) have the highest risk for VL, but within hotspots and at the start of outbreaks, older age groups (35+ years) show a comparable high risk. CONCLUSIONS/SIGNIFICANCE: This study demonstrates significant spatiotemporal heterogeneity in VL incidence at subdistrict level. The association between poverty and hotspots confirms that VL is a disease of 'the poorest of the poor' and age patterns suggest a potential role of waning immunity as underlying driver of hotspots. The recommended insecticide spraying radius of 500m around detected VL cases corresponds to the modal hotspot radius found in this study. Additional data on immunity and asymptomatic infection, and the development of spatiotemporally explicit transmission models that simulate hotspot dynamics and predict the impact of interventions at the smaller geographical scale will be crucial tools in sustaining elimination.


Assuntos
Imunidade , Leishmaniose Visceral/epidemiologia , Adolescente , Adulto , Animais , Infecções Assintomáticas , Criança , Pré-Escolar , Análise por Conglomerados , Humanos , Incidência , Índia/epidemiologia , Lactente , Inseticidas/administração & dosagem , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/prevenção & controle , Leishmaniose Visceral/transmissão , Pessoa de Meia-Idade , Modelos Estatísticos , Pobreza , Saúde Pública , Risco , Análise Espaço-Temporal , Adulto Jovem
18.
PLoS Negl Trop Dis ; 12(12): e0006758, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30522129

RESUMO

BACKGROUND: Regular preventive chemotherapy (PCT) targeting high-risk populations is an effective way to control STH in the short term, but sustainable long-term STH control is expected to require improved access to water, sanitation, and hygiene (WASH). However, experimental studies have not been able to conclusively demonstrate the benefit of WASH in preventing STH (re-)infections. We investigated the impact of WASH on STH infections during and after PCT using mathematical modelling. METHODS AND FINDINGS: We use the individual-based transmission model WORMSIM to predict the short and long-term impact of WASH on STH transmission in contexts with and without PCT. We distinguish two WASH modalities: sanitation, which reduces individuals' contributions to environmental contamination; and hygiene, which reduces individuals' exposure to infection. We simulate the impact of varying levels of uptake and effectiveness of each WASH modality, as well as their combined impact. Clearly, sanitation and hygiene interventions have little observable short-term impact on STH infections levels in the context of PCT. However, in the long term, both are pivotal to sustain control or eliminate infection levels after scaling down or stopping PCT. The impact of hygiene is determined more by the effectiveness of the intervention than its overall uptake, whereas the impact of sanitation depends more directly on the product of uptake and the effectiveness. INTERPRETATION: The impact of WASH interventions on STH transmission highly depends on the worm species, WASH modality, and uptake and effectiveness of the intervention. Also, the impact of WASH is difficult to measure in the context of ongoing PCT programmes. Still, we show a clear added benefit of WASH to sustain the gains made by PCT in the long term, such that PCT may be scaled down or even stopped altogether. To safely stop or scale down PCT, policy for WASH and PCT should be integrated.


Assuntos
Helmintíase/prevenção & controle , Helmintos/fisiologia , Higiene , Saneamento , Solo/parasitologia , Água/parasitologia , Animais , Feminino , Helmintíase/transmissão , Humanos , Masculino , Modelos Teóricos
19.
Int J Behav Nutr Phys Act ; 15(1): 107, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30382862

RESUMO

BACKGROUND: Income inequalities in sports participation are shaped by a system in which individuals and the environment interact. We developed an agent-based model (ABM) that could represent this system and used it to provide a proof-of-concept of its potential to explore the impact of individual and environmental interventions on reducing inequalities in sports participation. METHODS: Our ABM simulates sports participation of individuals in the Dutch city of Eindhoven. In the model, sports participation is determined by an individual's tendency to start sports (at a fitness center, sports club or self-organized), which is influenced by attributes of individuals (i.e. age, sex, income), sports facilities (i.e. price, accessibility) and the social environment (i.e. social cohesion, social influence). Sports facilities can adapt to changes in the demand by closures or startups, which in turn influence the tendency of individuals to participate in sport. We explored the impact of five interventions scenarios. RESULTS: Explorative results show that providing health education, increasing the availability of sports facilities, lowering prices of facilities and improving safety levels can increase sports participation and modestly reduce absolute income inequalities in sports participation. The largest gain can be attained through health education, if the effect and reach is sufficiently large. Environmental interventions alone have a modest impact. Marked effects are only achieved after five to 10 years. CONCLUSIONS: ABMs have much potential to test the population-level effects of various interventions in the context of a system. Our study highlights the challenges of ABM development and reveals gaps in empirical data. With further refinements, our model could aid in understanding and finding optimal pathways to reduce income inequalities in sports participation.


Assuntos
Comportamentos Relacionados com a Saúde , Características de Residência/estatística & dados numéricos , Meio Social , Fatores Socioeconômicos , Esportes/economia , Esportes/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Feminino , Academias de Ginástica , Educação em Saúde , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Países Baixos , Fatores Sexuais , Adulto Jovem
20.
PLoS Negl Trop Dis ; 12(10): e0006624, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30296264

RESUMO

BACKGROUND: Stable low pre-control prevalences of helminth infection are not uncommon in field settings, yet it is poorly understood how such low levels can be sustained, thereby challenging efforts to model them. Disentangling possible facilitating mechanisms is important, since these may differently affect intervention impact. Here we explore the role of assortative (i.e. non-homogenous) mixing and exposure heterogeneity in helminth transmission, using onchocerciasis as an example. METHODOLOGY/PRINCIPAL FINDINGS: We extended the established individual-based model ONCHOSIM to allow for assortative mixing, assuming that individuals who are relatively more exposed to fly bites are more connected to each other than other individuals in the population as a result of differential exposure to a sub-population of blackflies. We used the model to investigate how transmission stability, equilibrium microfilarial (mf) prevalence and intensity, and impact of mass drug administration depend on the assumed degree of assortative mixing and exposure heterogeneity, for a typical rural population of about 400 individuals. The model clearly demonstrated that with homogeneous mixing and moderate levels of exposure heterogeneity, onchocerciasis could not be sustained below 35% mf prevalence. In contrast, assortative mixing stabilised onchocerciasis prevalence at levels as low as 8% mf prevalence. Increasing levels of assortative mixing significantly reduced the probability of interrupting transmission, given the same duration and coverage of mass drug administration. CONCLUSIONS/SIGNIFICANCE: Assortative mixing patterns are an important factor to explain stable low prevalence situations and are highly relevant for prospects of elimination. Their effect on the pre-control distribution of mf intensities in human populations is only detectable in settings with mf prevalences <30%, where high skin mf density in mf-positive people may be an indication of assortative mixing. Local spatial variation in larval infection intensity in the blackfly intermediate host may also be an indicator of assortative mixing.


Assuntos
Transmissão de Doença Infecciosa , Modelos Estatísticos , Oncocercose/transmissão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Exposição Ambiental , Feminino , Humanos , Masculino , Administração Massiva de Medicamentos , Pessoa de Meia-Idade , Modelos Biológicos , Oncocercose/tratamento farmacológico , Prevalência , População Rural , Simuliidae/crescimento & desenvolvimento , Adulto Jovem
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