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1.
Immunity ; 56(5): 900-902, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37163989

RESUMO

Monocytes can differentiate into tissue-resident pleural macrophages, but the mechanisms underlying this process are not yet fully understood. In this issue of Immunity, Finlay et al.1 show that Th2 cytokines promote this differentiation in resistant mice infected with Litomosoides sigmodontis.


Assuntos
Filariose , Filarioidea , Animais , Camundongos , Macrófagos , Linfócitos , Citocinas , Camundongos Endogâmicos BALB C
2.
Immunity ; 56(5): 1064-1081.e10, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-36948193

RESUMO

The recent revolution in tissue-resident macrophage biology has resulted largely from murine studies performed in C57BL/6 mice. Here, using both C57BL/6 and BALB/c mice, we analyze immune cells in the pleural cavity. Unlike C57BL/6 mice, naive tissue-resident large-cavity macrophages (LCMs) of BALB/c mice failed to fully implement the tissue-residency program. Following infection with a pleural-dwelling nematode, these pre-existing differences were accentuated with LCM expansion occurring in C57BL/6, but not in BALB/c mice. While infection drove monocyte recruitment in both strains, only in C57BL/6 mice were monocytes able to efficiently integrate into the resident pool. Monocyte-to-macrophage conversion required both T cells and interleukin-4 receptor alpha (IL-4Rα) signaling. The transition to tissue residency altered macrophage function, and GATA6+ tissue-resident macrophages were required for host resistance to nematode infection. Therefore, during tissue nematode infection, T helper 2 (Th2) cells control the differentiation pathway of resident macrophages, which determines infection outcome.


Assuntos
Filariose , Filarioidea , Infecções por Nematoides , Camundongos , Animais , Filarioidea/fisiologia , Células Th2 , Monócitos , Cavidade Pleural , Camundongos Endogâmicos C57BL , Macrófagos/fisiologia , Diferenciação Celular , Camundongos Endogâmicos BALB C
3.
PLoS Pathog ; 20(3): e1012071, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38457461

RESUMO

BACKGROUND: Eosinophilia is a hallmark of helminth infections and eosinophils are essential in the protective immune responses against helminths. Nevertheless, the distinct role of eosinophils during parasitic filarial infection, allergy and autoimmune disease-driven pathology is still not sufficiently understood. In this study, we established a mouse model for microfilariae-induced eosinophilic lung disease (ELD), a manifestation caused by eosinophil hyper-responsiveness within the lung. METHODS: Wild-type (WT) BALB/c mice were sensitized with dead microfilariae (MF) of the rodent filarial nematode Litomosoides sigmodontis three times at weekly intervals and subsequently challenged with viable MF to induce ELD. The resulting immune response was compared to non-sensitized WT mice as well as sensitized eosinophil-deficient dblGATA mice using flow cytometry, lung histology and ELISA. Additionally, the impact of IL-33 signaling on ELD development was investigated using the IL-33 antagonist HpARI2. RESULTS: ELD-induced WT mice displayed an increased type 2 immune response in the lung with increased frequencies of eosinophils, alternatively activated macrophages and group 2 innate lymphoid cells, as well as higher peripheral blood IgE, IL-5 and IL-33 levels in comparison to mice challenged only with viable MF or PBS. ELD mice had an increased MF retention in lung tissue, which was in line with an enhanced MF clearance from peripheral blood. Using eosinophil-deficient dblGATA mice, we demonstrate that eosinophils are essentially involved in driving the type 2 immune response and retention of MF in the lung of ELD mice. Furthermore, we demonstrate that IL-33 drives eosinophil activation in vitro and inhibition of IL-33 signaling during ELD induction reduces pulmonary type 2 immune responses, eosinophil activation and alleviates lung lacunarity. In conclusion, we demonstrate that IL-33 signaling is essentially involved in MF-induced ELD development. SUMMARY: Our study demonstrates that repeated sensitization of BALB/c mice with L. sigmodontis MF induces pulmonary eosinophilia in an IL-33-dependent manner. The newly established model recapitulates the characteristic features known to occur during eosinophilic lung diseases (ELD) such as human tropical pulmonary eosinophilia (TPE), which includes the retention of microfilariae in the lung tissue and induction of pulmonary eosinophilia and type 2 immune responses. Our study provides compelling evidence that IL-33 drives eosinophil activation during ELD and that blocking IL-33 signaling using HpARI2 reduces eosinophil activation, eosinophil accumulation in the lung tissue, suppresses type 2 immune responses and mitigates the development of structural damage to the lung. Consequently, IL-33 is a potential therapeutic target to reduce eosinophil-mediated pulmonary pathology.


Assuntos
Asma , Filariose , Filarioidea , Eosinofilia Pulmonar , Humanos , Animais , Camundongos , Microfilárias , Imunidade Inata , Filariose/parasitologia , Interleucina-33 , Linfócitos/patologia , Filarioidea/fisiologia , Eosinófilos , Camundongos Endogâmicos BALB C
4.
Immunity ; 44(4): 795-806, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-27067058

RESUMO

Eosinophils are now recognized as multifunctional leukocytes that provide critical homeostatic signals to maintain other immune cells and aid tissue repair. Paradoxically, eosinophils also express an armory of granule-localized toxins and hydrolases believed to contribute to pathology in inflammatory disease. How eosinophils deliver their supporting functions while avoiding self-inflicted injury is poorly understood. We have demonstrated that cystatin F (CF) is a critical survival factor for eosinophils. Eosinophils from CF null mice had reduced lifespan, reduced granularity, and disturbed granule morphology. In vitro, cysteine protease inhibitors restored granularity, demonstrating that control of cysteine protease activity by CF is critical for normal eosinophil development. CF null mice showed reduced pulmonary pathology in a model of allergic lung inflammation but also reduced ability to combat infection by the nematode Brugia malayi. These data identify CF as a "cytoprotectant" that promotes eosinophil survival and function by ensuring granule integrity. VIDEO ABSTRACT.


Assuntos
Brugia Malayi/imunologia , Sobrevivência Celular/imunologia , Cistatinas/genética , Cistatinas/imunologia , Grânulos Citoplasmáticos/metabolismo , Eosinófilos/imunologia , Filariose/imunologia , Animais , Sobrevivência Celular/genética , Células Cultivadas , Cisteína Proteases/metabolismo , Filariose/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina/imunologia
5.
Proc Natl Acad Sci U S A ; 119(15): e2120003119, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35377795

RESUMO

Lymphatic filariasis is a vector-borne neglected tropical disease prioritized for global elimination. The filarial nematodes that cause the disease host a symbiotic bacterium, Wolbachia, which has been targeted using antibiotics, leading to cessation of parasite embryogenesis, waning of circulating larvae (microfilariae [mf]), and gradual cure of adult infection. One of the benefits of the anti-Wolbachia mode of action is that it avoids the rapid killing of mf, which can drive inflammatory adverse events. However, mf depleted of Wolbachia persist for several months in circulation, and thus patients treated with antibiotics are assumed to remain at risk for transmitting infections. Here, we show that Wolbachia-depleted mf rapidly lose the capacity to develop in the mosquito vector through a defect in exsheathment and inability to migrate through the gut wall. Transcriptomic and Western blotting analyses demonstrate that chitinase, an enzyme essential for mf exsheathment, is down-regulated in Wolbachia-depleted mf and correlates with their inability to exsheath and escape the mosquito midgut. Supplementation of in vitro cultures of Wolbachia-depleted mf with chitinase enzymes restores their ability to exsheath to a similar level to that observed in untreated mf. Our findings elucidate a mechanism of rapid transmission-blocking activity of filariasis after depletion of Wolbachia and adds to the broad range of biological processes of filarial nematodes that are dependent on Wolbachia symbiosis.


Assuntos
Antibacterianos , Quitinases , Filariose Linfática , Microfilárias , Wolbachia , Animais , Antibacterianos/farmacologia , Quitinases/genética , Filariose Linfática/transmissão , Humanos , Microfilárias/enzimologia , Microfilárias/crescimento & desenvolvimento , Microfilárias/microbiologia , Mosquitos Vetores/parasitologia , Wolbachia/efeitos dos fármacos , Wolbachia/genética
6.
Clin Infect Dis ; 78(Supplement_2): S117-S125, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662702

RESUMO

BACKGROUND: Lymphatic filariasis (LF) is a debilitating, poverty-promoting, neglected tropical disease (NTD) targeted for worldwide elimination as a public health problem (EPHP) by 2030. Evaluating progress towards this target for national programmes is challenging, due to differences in disease transmission and interventions at the subnational level. Mathematical models can help address these challenges by capturing spatial heterogeneities and evaluating progress towards LF elimination and how different interventions could be leveraged to achieve elimination by 2030. METHODS: Here we used a novel approach to combine historical geo-spatial disease prevalence maps of LF in Ethiopia with 3 contemporary disease transmission models to project trends in infection under different intervention scenarios at subnational level. RESULTS: Our findings show that local context, particularly the coverage of interventions, is an important determinant for the success of control and elimination programmes. Furthermore, although current strategies seem sufficient to achieve LF elimination by 2030, some areas may benefit from the implementation of alternative strategies, such as using enhanced coverage or increased frequency, to accelerate progress towards the 2030 targets. CONCLUSIONS: The combination of geospatial disease prevalence maps of LF with transmission models and intervention histories enables the projection of trends in infection at the subnational level under different control scenarios in Ethiopia. This approach, which adapts transmission models to local settings, may be useful to inform the design of optimal interventions at the subnational level in other LF endemic regions.


Assuntos
Erradicação de Doenças , Filariose Linfática , Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Filariose Linfática/transmissão , Etiópia/epidemiologia , Humanos , Prevalência , Modelos Teóricos , Política de Saúde
7.
Clin Infect Dis ; 78(Supplement_2): S131-S137, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662696

RESUMO

Mass drug administration (MDA) of antifilarial drugs is the main strategy for the elimination of lymphatic filariasis (LF). Recent clinical trials indicated that the triple-drug therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) is much more effective against LF than the widely used two-drug combinations (albendazole plus either ivermectin or diethylcarbamazine). For IDA-based MDA, the stop-MDA decision is made based on microfilariae (mf) prevalence in adults. In this study, we assess how the probability of eventually reaching elimination of transmission depends on the critical threshold used in transmission assessment surveys (TAS-es) to define whether transmission was successfully suppressed and triple-drug MDA can be stopped. This analysis focuses on treatment-naive Indian settings. We do this for a range of epidemiological and programmatic contexts, using the established LYMFASIM model for transmission and control of LF. Based on our simulations, a single TAS, one year after the last MDA round, provides limited predictive value of having achieved suppressed transmission, while a higher MDA coverage increases elimination probability, thus leading to a higher predictive value. Every additional TAS, conditional on previous TAS-es being passed with the same threshold, further improves the predictive value for low values of stop-MDA thresholds. An mf prevalence threshold of 0.5% corresponding to TAS-3 results in ≥95% predictive value even when the MDA coverage is relatively low.


Assuntos
Albendazol , Dietilcarbamazina , Quimioterapia Combinada , Filariose Linfática , Filaricidas , Ivermectina , Administração Massiva de Medicamentos , Microfilárias , Filariose Linfática/tratamento farmacológico , Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Humanos , Albendazol/uso terapêutico , Albendazol/administração & dosagem , Filaricidas/uso terapêutico , Dietilcarbamazina/uso terapêutico , Dietilcarbamazina/administração & dosagem , Ivermectina/uso terapêutico , Ivermectina/administração & dosagem , Animais , Índia/epidemiologia , Microfilárias/efeitos dos fármacos , Adulto , Prevalência
8.
Clin Infect Dis ; 78(Supplement_2): S160-S168, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662697

RESUMO

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) aims to reduce and maintain infection levels through mass drug administration (MDA), but there is evidence of ongoing transmission after MDA in areas where Culex mosquitoes are the main transmission vector, suggesting that a more stringent criterion is required for MDA decision making in these settings. METHODS: We use a transmission model to investigate how a lower prevalence threshold (<1% antigenemia [Ag] prevalence compared with <2% Ag prevalence) for MDA decision making would affect the probability of local elimination, health outcomes, the number of MDA rounds, including restarts, and program costs associated with MDA and surveys across different scenarios. To determine the cost-effectiveness of switching to a lower threshold, we simulated 65% and 80% MDA coverage of the total population for different willingness to pay per disability-adjusted life-year averted for India ($446.07), Tanzania ($389.83), and Haiti ($219.84). RESULTS: Our results suggest that with a lower Ag threshold, there is a small proportion of simulations where extra rounds are required to reach the target, but this also reduces the need to restart MDA later in the program. For 80% coverage, the lower threshold is cost-effective across all baseline prevalences for India, Tanzania, and Haiti. For 65% MDA coverage, the lower threshold is not cost-effective due to additional MDA rounds, although it increases the probability of local elimination. Valuing the benefits of elimination to align with the GPELF goals, we find that a willingness to pay per capita government expenditure of approximately $1000-$4000 for 1% increase in the probability of local elimination would be required to make a lower threshold cost-effective. CONCLUSIONS: Lower Ag thresholds for stopping MDAs generally mean a higher probability of local elimination, reducing long-term costs and health impacts. However, they may also lead to an increased number of MDA rounds required to reach the lower threshold and, therefore, increased short-term costs. Collectively, our analyses highlight that lower target Ag thresholds have the potential to assist programs in achieving lymphatic filariasis goals.


Assuntos
Análise Custo-Benefício , Filariose Linfática , Administração Massiva de Medicamentos , Filariose Linfática/prevenção & controle , Filariose Linfática/epidemiologia , Filariose Linfática/economia , Humanos , Administração Massiva de Medicamentos/economia , Haiti/epidemiologia , Tanzânia/epidemiologia , Prevalência , Índia/epidemiologia , Animais , Erradicação de Doenças/economia , Erradicação de Doenças/métodos , Filaricidas/uso terapêutico , Filaricidas/administração & dosagem , Filaricidas/economia , Antígenos de Helmintos/sangue , Culex
9.
Clin Infect Dis ; 78(Supplement_2): S108-S116, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662704

RESUMO

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2030. Although mass treatments have led to huge reductions in LF prevalence, some countries or regions may find it difficult to achieve elimination by 2030 owing to various factors, including local differences in transmission. Subnational projections of intervention impact are a useful tool in understanding these dynamics, but correctly characterizing their uncertainty is challenging. METHODS: We developed a computationally feasible framework for providing subnational projections for LF across 44 sub-Saharan African countries using ensemble models, guided by historical control data, to allow assessment of the role of subnational heterogeneities in global goal achievement. Projected scenarios include ongoing annual treatment from 2018 to 2030, enhanced coverage, and biannual treatment. RESULTS: Our projections suggest that progress is likely to continue well. However, highly endemic locations currently deploying strategies with the lower World Health Organization recommended coverage (65%) and frequency (annual) are expected to have slow decreases in prevalence. Increasing intervention frequency or coverage can accelerate progress by up to 5 or 6 years, respectively. CONCLUSIONS: While projections based on baseline data have limitations, our methodological advancements provide assessments of potential bottlenecks for the global goals for LF arising from subnational heterogeneities. In particular, areas with high baseline prevalence may face challenges in achieving the 2030 goals, extending the "tail" of interventions. Enhancing intervention frequency and/or coverage will accelerate progress. Our approach facilitates preimplementation assessments of the impact of local interventions and is applicable to other regions and neglected tropical diseases.


Assuntos
Filariose Linfática , Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Humanos , África Subsaariana/epidemiologia , Prevalência , Erradicação de Doenças/métodos , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/prevenção & controle , Filaricidas/uso terapêutico
10.
Clin Infect Dis ; 78(Supplement_2): S93-S100, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662701

RESUMO

BACKGROUND: Mass drug administration (MDA) is the cornerstone for the elimination of lymphatic filariasis (LF). The proportion of the population that is never treated (NT) is a crucial determinant of whether this goal is achieved within reasonable time frames. METHODS: Using 2 individual-based stochastic LF transmission models, we assess the maximum permissible level of NT for which the 1% microfilaremia (mf) prevalence threshold can be achieved (with 90% probability) within 10 years under different scenarios of annual MDA coverage, drug combination and transmission setting. RESULTS: For Anopheles-transmission settings, we find that treating 80% of the eligible population annually with ivermectin + albendazole (IA) can achieve the 1% mf prevalence threshold within 10 years of annual treatment when baseline mf prevalence is 10%, as long as NT <10%. Higher proportions of NT are acceptable when more efficacious treatment regimens are used. For Culex-transmission settings with a low (5%) baseline mf prevalence and diethylcarbamazine + albendazole (DA) or ivermectin + diethylcarbamazine + albendazole (IDA) treatment, elimination can be reached if treatment coverage among eligibles is 80% or higher. For 10% baseline mf prevalence, the target can be achieved when the annual coverage is 80% and NT ≤15%. Higher infection prevalence or levels of NT would make achieving the target more difficult. CONCLUSIONS: The proportion of people never treated in MDA programmes for LF can strongly influence the achievement of elimination and the impact of NT is greater in high transmission areas. This study provides a starting point for further development of criteria for the evaluation of NT.


Assuntos
Albendazol , Filariose Linfática , Filaricidas , Ivermectina , Administração Massiva de Medicamentos , Filariose Linfática/tratamento farmacológico , Filariose Linfática/prevenção & controle , Filariose Linfática/epidemiologia , Filariose Linfática/transmissão , Humanos , Animais , Filaricidas/uso terapêutico , Filaricidas/administração & dosagem , Albendazol/administração & dosagem , Albendazol/uso terapêutico , Ivermectina/administração & dosagem , Ivermectina/uso terapêutico , Prevalência , Anopheles/parasitologia , Erradicação de Doenças/métodos , Wuchereria bancrofti/efeitos dos fármacos , Dietilcarbamazina/administração & dosagem , Dietilcarbamazina/uso terapêutico , Quimioterapia Combinada
11.
Emerg Infect Dis ; 30(7): 1398-1401, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38916574

RESUMO

We describe a recent case of lymphatic filariasis in Colombia caused by Wuchereria bancrofti nematodes. Our study combines clinical-epidemiologic findings with phylogenetic data. Resurgence of lymphatic filariasis may be linked to increasing urbanization trends and migration from previously endemic regions. Fieldwork can be a beneficial tool for screening and containing transmission.


Assuntos
Filariose Linfática , Wuchereria bancrofti , Filariose Linfática/epidemiologia , Colômbia/epidemiologia , Wuchereria bancrofti/genética , Humanos , Animais , Filogenia , Masculino , Adulto , Feminino , Pessoa de Meia-Idade
12.
PLoS Pathog ; 18(4): e1010399, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35390105

RESUMO

Lymphatic filariasis (LF) is a chronic debilitating neglected tropical disease (NTD) caused by mosquito-transmitted nematodes that afflicts over 60 million people. Control of LF relies on routine mass drug administration with antiparasitics that clear circulating larval parasites but are ineffective against adults. The development of effective adulticides is hampered by a poor understanding of the processes and tissues driving parasite survival in the host. The adult filariae head region contains essential tissues that control parasite feeding, sensory, secretory, and reproductive behaviors, which express promising molecular substrates for the development of antifilarial drugs, vaccines, and diagnostics. We have adapted spatial transcriptomic approaches to map gene expression patterns across these prioritized but historically intractable head tissues. Spatial and tissue-resolved data reveal distinct biases in the origins of known drug targets and secreted antigens. These data were used to identify potential new drug and vaccine targets, including putative hidden antigens expressed in the alimentary canal, and to spatially associate receptor subunits belonging to druggable families. Spatial transcriptomic approaches provide a powerful resource to aid gene function inference and seed antiparasitic discovery pipelines across helminths of relevance to human and animal health.


Assuntos
Anti-Infecciosos , Brugia Malayi , Filariose Linfática , Parasitos , Vacinas , Animais , Anti-Infecciosos/farmacologia , Antiparasitários/farmacologia , Brugia Malayi/genética , Humanos , Parasitos/genética , Transcriptoma
13.
BMC Microbiol ; 24(1): 28, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245715

RESUMO

BACKGROUND: Filarial worms are important vector-borne pathogens of a large range of animal hosts, including humans, and are responsible for numerous debilitating neglected tropical diseases such as, lymphatic filariasis caused by Wuchereria bancrofti and Brugia spp., as well as loiasis caused by Loa loa. Moreover, some emerging or difficult-to-eliminate filarioid pathogens are zoonotic using animals like canines as reservoir hosts, for example Dirofilaria sp. 'hongkongensis'. Diagnosis of filariasis through commonly available methods, like microscopy, can be challenging as microfilaremia may wane below the limit of detection. In contrast, conventional PCR methods are more sensitive and specific but may show limited ability to detect coinfections as well as emerging and/or novel pathogens. Use of deep-sequencing technologies obviate these challenges, providing sensitive detection of entire parasite communities, whilst also being better suited for the characterisation of rare or novel pathogens. Therefore, we developed a novel long-read metabarcoding assay for deep-sequencing the filarial nematode cytochrome c oxidase subunit I gene on Oxford Nanopore Technologies' (ONT) MinION™ sequencer. We assessed the overall performance of our assay using kappa statistics to compare it to commonly used diagnostic methods for filarial worm detection, such as conventional PCR (cPCR) with Sanger sequencing and the microscopy-based modified Knott's test (MKT). RESULTS: We confirmed our metabarcoding assay can characterise filarial parasites from a diverse range of genera, including, Breinlia, Brugia, Cercopithifilaria, Dipetalonema, Dirofilaria, Onchocerca, Setaria, Stephanofilaria and Wuchereria. We demonstrated proof-of-concept for this assay by using blood samples from Sri Lankan dogs, whereby we identified infections with the filarioids Acanthocheilonema reconditum, Brugia sp. Sri Lanka genotype and zoonotic Dirofilaria sp. 'hongkongensis'. When compared to traditionally used diagnostics, such as the MKT and cPCR with Sanger sequencing, we identified an additional filarioid species and over 15% more mono- and coinfections. CONCLUSIONS: Our developed metabarcoding assay may show broad applicability for the metabarcoding and diagnosis of the full spectrum of filarioids from a wide range of animal hosts, including mammals and vectors, whilst the utilisation of ONT' small and portable MinION™ means that such methods could be deployed for field use.


Assuntos
Coinfecção , Filariose , Filarioidea , Humanos , Animais , Cães , Filarioidea/genética , Filariose/diagnóstico , Filariose/veterinária , Filariose/parasitologia , Brugia/genética , Wuchereria bancrofti/genética , Mamíferos
14.
Microvasc Res ; 152: 104642, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38070864

RESUMO

Filariasis is a chronic disease where parasitic worms survive in human hosts even for decades and lead to complications like lymphedema and elephantiasis. Despite the persistent existence of filarial parasites in human hosts, fatal and thrombotic complications are not known, unlike other parasitic diseases like malaria. This suggests that filarial parasites might be affecting the host's platelet functions. This study was conducted to examine platelet functions in confirmed filariasis patients and healthy controls. Results showed that filariasis patients had larger platelets, inhibited aggregation, and slower speed of aggregation, compared to controls. However, in vivo markers of platelet activation and degranulation (beta thromboglobulin and soluble P-selectin) were not affected. Observations suggested that there is increased platelet turnover, cellular apoptosis and inhibited platelet functions in filariasis patients compared to controls. Platelet function inhibition was not associated with the duration of disease, lymphedema-affected organs, or gender of patients. This study confirms that filarial parasites modulate platelet functions in human hosts.


Assuntos
Filariose Linfática , Linfedema , Humanos , Filariose Linfática/diagnóstico , Filariose Linfática/parasitologia , Doença Crônica
15.
Bull World Health Organ ; 102(3): 204-215, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38420575

RESUMO

Objective: To explore the impact of mosquito collection methods, sampling intensity and target genus on molecular xenomonitoring detection of parasites causing lymphatic filariasis. Methods: We systematically searched five databases for studies that used two or more collection strategies for sampling wild mosquitoes, and employed molecular methods to assess the molecular xenomonitoring prevalence of parasites responsible for lymphatic filariasis. We performed generic inverse variance meta-analyses and explored sources of heterogeneity using subgroup analyses. We assessed methodological quality and certainty of evidence. Findings: We identified 25 eligible studies, with 172 083 mosquitoes analysed. We observed significantly higher molecular xenomonitoring prevalence with collection methods that target bloodfed mosquitoes compared to methods that target unfed mosquitoes (prevalence ratio: 3.53; 95% confidence interval, CI: 1.52-8.24), but no significant difference compared with gravid collection methods (prevalence ratio: 1.54; 95% CI: 0.46-5.16). Regarding genus, we observed significantly higher molecular xenomonitoring prevalence for anopheline mosquitoes compared to culicine mosquitoes in areas where Anopheles species are the primary vector (prevalence ratio: 6.91; 95% CI: 1.73-27.52). One study provided evidence that reducing the number of sampling sites did not significantly affect molecular xenomonitoring prevalence. Evidence of differences in molecular xenomonitoring prevalence between sampling strategies was considered to be of low certainty, due partly to inherent limitations of observational studies that were not explicitly designed for these comparisons. Conclusion: The choice of sampling strategy can significantly affect molecular xenomonitoring results. Further research is needed to inform the optimum strategy in light of logistical constraints and epidemiological contexts.


Assuntos
Filariose Linfática , Mosquitos Vetores , Animais , Filariose Linfática/epidemiologia , Humanos , Culicidae , Prevalência , Anopheles , Manejo de Espécimes/métodos
16.
J Theor Biol ; 585: 111796, 2024 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-38522665

RESUMO

Lymphatic filariasis (LF) has been targeted for elimination as a public health concern by 2030 with a goal to keep the prevalence of LF infections under the 1% threshold. While mass drug administration (MDA) is a primary strategy recommended by WHO, the use of insecticide treated nets (ITN) plays a crucial role as an alternative strategy when MDA cannot be used. In this paper, we use imitation dynamics to incorporate human behavior and voluntary use of ITN into the compartmental epidemiological model of LF transmission. We find the equilibrium states of the dynamics and the ITN usage as it depends on epidemiological parameters and the cost of ITNs. We investigate the conditions under which the voluntary use of ITNs can keep the LF prevalence under the 1% threshold. We found that when the cost of using the ITNs is about 105 smaller than the perceived cost of LF, then the voluntary use of ITNs will eliminate LF as a public health concern. Furthermore, when the ITNs are given away for free, our model predicts that over 80% of the population will use them which would eliminate LF completely in regions where Anopheles are the primary vectors.


Assuntos
Filariose Linfática , Mosquiteiros Tratados com Inseticida , Inseticidas , Animais , Humanos , Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Mosquitos Vetores , Administração Massiva de Medicamentos , Controle de Mosquitos
17.
BMC Infect Dis ; 24(1): 462, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698313

RESUMO

BACKGROUND: Neglected tropical diseases (NTDs) such as leprosy, lymphatic filariasis (LF), schistosomiasis and onchocerciasis are endemic in several African countries. These diseases can lead to severe pain and permanent disability, which can negatively affect the economic productivity of the affected person(s), and hence resulting into low economic performance at the macrolevel. Nonetheless, empirical evidence of the effects of these NTDs on economic performance at the macrolevel is sparse. This study therefore investigates the effects of the above-mentioned NTDs on economic performance at the macrolevel in Africa. METHODS: The study employs a panel design with data comprising 24 to 45 African countries depending on the NTD in question, over the period, 2002 to 2019. Gross domestic product (GDP) is used as the proxy for economic performance (Dependent variable) and the prevalence of the above-mentioned NTDs are used as the main independent variables. The random effects (RE), fixed effects (FE) and the instrumental variable fixed effects (IVFE) panel data regressions are used as estimation techniques. RESULTS: We find that, an increase in the prevalence of the selected NTDs is associated with a fall in economic performance in the selected African countries, irrespective of the estimation technique used. Specifically, using the IVFE regression estimates, we find that a percentage increase in the prevalence of leprosy, LF, schistosomiasis and onchocerciasis is associated with a reduction in economic performance by 0.43%, 0.24%, 0.28% and 0.36% respectively, at either 1% or 5% level of significance. CONCLUSION: The findings highlight the need to increase attention and bolster integrated efforts or measures towards tackling these diseases in order to curb their deleterious effects on economic performance. Such measures can include effective mass drug administration (MDA), enhancing access to basic drinking water and sanitation among others.


Assuntos
Doenças Negligenciadas , Medicina Tropical , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/economia , Humanos , África/epidemiologia , Medicina Tropical/economia , Esquistossomose/epidemiologia , Esquistossomose/economia , Hanseníase/epidemiologia , Hanseníase/economia , Prevalência , Oncocercose/epidemiologia , Oncocercose/economia , Produto Interno Bruto , Filariose Linfática/epidemiologia , Filariose Linfática/economia
18.
BMC Infect Dis ; 24(1): 714, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39033158

RESUMO

BACKGROUND: Loiasis is one of the significant filarial diseases for people living in West and Central Africa with wide endemic area but is not seen in China. As economy booms and international traveling increase, China faces more and more imported parasitic diseases that are not endemic locally. Loiasis is one of the parasitic diseases that enter China by travelers infected in Africa. The better understanding of the clinical and laboratory features of loa loa infection will facilitate the diagnosis and treatment of loiasis in China. METHODS: The study targeted travelers who were infected with L. loa in endemic Africa regions and returned to Beijing between 2014 and 2023. Epidemiological, clinical, and biological data as well as treatment of these patients were collected. RESULTS: Total 21 cases were identified as L. loa infection based on their typical clinical manifestations and parasite finding. All cases had a history of travel to Africa for more than 6 months, most of them are the construction workers dispatched to West Africa with outdoor activities. Calabar swelling (n = 19; 90.5%) and pruritus (n = 11; 52.4%) were among the most common clinical symptoms followed by muscle pain (n = 7; 33.3%) and skin rash (n = 2; 9.5%). The adult worms were observed in the eyelid or subconjunctiva (n = 2; 9.5%) and subcutaneous tissues (n = 2; 9.5%). Although all patients presented with a high eosinophil count (> 0.52 × 109/L), only two cases displayed microfilariae in fresh venous blood and positive for filarial antigen. A cut section of adult worm was observed through biopsy on a skin nodule surrounded by lymphocytes, plasma cells and eosinophils. All subjects were positive in PCR targeting L. loa ITS-1. The constructed phylogenetic tree based on the amplified ITS-1 sequences identified their genetical relation to the L. Loa from Africa. All patients treated with albendazole and diethylcarbamazine were recovered without relapse. CONCLUSION: This study provides useful information and guideline for physicians and researchers in non-endemic countries to diagnose and treat loiasis and L. loa infections acquired from endemic regions.


Assuntos
Loa , Loíase , Humanos , Loíase/epidemiologia , Loíase/tratamento farmacológico , Loíase/diagnóstico , Loíase/parasitologia , Masculino , Adulto , Feminino , Animais , Pessoa de Meia-Idade , Pequim/epidemiologia , Loa/isolamento & purificação , Viagem , Adulto Jovem , Doenças Transmissíveis Importadas/epidemiologia , Doenças Transmissíveis Importadas/parasitologia , Doenças Transmissíveis Importadas/diagnóstico , África/epidemiologia
19.
Mol Biol Rep ; 51(1): 291, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329553

RESUMO

BACKGROUND: Transmission Assessment Survey (TAS) is the WHO recommended method used for decision-making to stop or continue the MDA in lymphatic filariasis (LF) elimination programme. The WHO has also recommended Molecular Xenomonitoring (MX) of LF infection in vectors as an adjunct tool in settings under post-MDA or validation period. Screening of non-vectors by MX in post-MDA / validation settings could be useful to prevent a resurgence of LF infection, as there might be low abundance of vectors, especially in some seasons. In this study, we investigated the presence of LF infection in non-vectors in an area endemic for LF and has undergone many rounds of annual MDA with two drugs (Diethylcarbamazine and Albendazole, DA) and two rounds of triple drug regimens (Ivermectin + DA). METHODS AND RESULTS: Mosquitoes were collected from selected villages of Yadgir district in Karnataka state, India, during 2019. A total of 680 female mosquitoes were collected, identified morphologically by species and separated as pools. The female mosquitoes belonging to 3 species viz., Anopheles subpictus, Culex gelidus and Culex quinquefaciatus were separated, pooled, and the DNA extracted using less expensive method and followed by LDR based real-time PCR assay for detecting Wuchereria bancrofti infection in vector as well as non-vector mosquitoes. One pool out of 6 pools of An. subpictus, 2 pools out of 6 pools of Cx. gelidus, and 4 pools out of 8 pools of Cx. quinquefaciatus were found to be positive for W. bancrofti infection by RT-PCR. The infection rate in vectors and non-vectors was found to be 1.8% (95% CI: 0.5-4.2%) and 0.9% (95% CI: 0.2-2.3%), respectively. CONCLUSIONS: Our study showed that non-vectors also harbour W. bancrofti, thus opening an opportunity of using these mosquitoes as surrogate vectors for assessing risk of transmission to humans in LF endemic and post MDA areas.


Assuntos
Anopheles , Filariose Linfática , Feminino , Humanos , Animais , Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Wuchereria bancrofti/genética , Índia , Mosquitos Vetores , Anopheles/genética , DNA
20.
Mol Biol Rep ; 51(1): 932, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39180621

RESUMO

BACKGROUND: Ocular setariasis is an ectopic infection caused by a parasite under the genus Setaria. Adult worms belong to the Setariidae family and typically reside in the peritoneal cavity of ungulates. However, immature forms of these species may aberrantly migrate to the eyes of cattle, buffalo, goats, horses and several other hosts, leading to corneal opacity and blindness. Here, we have distinguished the Setaria digitata collected from both equine and buffalo hosts based on the morphology, molecular profiling of mitochondrial cytochrome c oxidase subunit 1 (Cox1), cytochrome c oxidase subunit 3 (Cox3) and, Nicotinamide Adenine Dinucleotide dehydrogenase subunit 1 (NAD1) genes. METHODS AND RESULTS: A single filarial worm was collected from the eye of one equine and one bovine host. These worms were then processed for morphological examination and DNA isolation. Cox1, Cox3 and NAD1 genes were amplified using specific primers and subjected to custom sequencing. The sequences were then used for multiple sequence alignment, assessment of entropy, similarity and haplotype diversity analysis. Key morphological features confirmed the worms collected were male and female Setaria digitata from equine and buffalo hosts, respectively. Cox1, Cox3 and NAD1 gene sequence analysis showed a close association of S.digitata Indian isolates with its counterparts from Sri Lanka and China isolates. CONCLUSION: The phylogram of bovine S. digitata sequences shows a close relationship to other equine S. digitata sequences, indicating the need for further in-depth studies on the prevalence of infection across various host species and intermediate hosts. Although the sequence results suggest that S. digitata is likely the causative agent of ocular setariasis in India, additional samples are needed to confirm this conclusion. Comprehensive analysis of the transcriptome and proteome of S. digitata from both bovine and equine hosts is necessary to explore variations in host-parasite interactions. These findings will aid in future parasite identification, investigations into vector prevalence in India, and the development of control measures against ocular setariasis.


Assuntos
Genes Mitocondriais , Variação Genética , Filogenia , Setaria (Nematoide) , Setaríase , Animais , Cavalos/parasitologia , Bovinos , Índia , Setaria (Nematoide)/genética , Genes Mitocondriais/genética , Setaríase/genética , Setaríase/parasitologia , Complexo IV da Cadeia de Transporte de Elétrons/genética , Feminino , Masculino , Doenças dos Cavalos/parasitologia , Doenças dos Cavalos/genética , Búfalos/parasitologia , Búfalos/genética , Doenças dos Bovinos/parasitologia , Doenças dos Bovinos/genética
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