Publications by authors named "Thomas Nutman"

The role of innate receptors in initiating the early inflammatory response to helminth larval stages in affected tissues during their life cycle within the host remains poorly understood. Given its pivotal role in detecting microbial elements and eliciting immune responses, exploring the NOD1 receptor could offer crucial insights into immune responses to parasitic infections. By using the larval ascariasis model, the acute model for early Ascaris sp.

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Background And Objectives: Subarachnoid neurocysticercosis (SANCC) is the most severe form of CNS infection and accounts for the majority of neurocysticercosis-associated mortality. Inflammation is important in the treatment of SANCC because overactivity can lead to serious complications, but excessive suppression may be counterproductive toward parasite eradication. A relative abundance of CSF IL-10 to IL-12 has been associated with increased treatment duration for patients with SANCC, suggesting that IL-10 plays an important role in this disease process.

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Introduction: Live microfilariae (mf) and mf-derived extracellular vesicles (EVs) have been shown to modulate human antigen presenting cell (APC) function, most notably by suppressing the induction of IL-12 (and other pro-inflammatory cytokines) following activation with LPS and interferon-y.

Methods: To explore further how EVs alter human APC function, we studied the effect of mf and EVs on human elutriated monocyte-derived dendritic cells (DC) following exposure to Mf, mf-derived excretory/secretory (E/S) products, E/S depleted of EVs through ultracentrifugation and purified EVs.  After demonstrating that the measurable responses induced by live mf could be recapitulated by EVs and EV-containing E/S, we next performed RNAseq analysis of human DC following exposure to live mf, EVs, E/S, or EV-depleted E/S.

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  • A study examines why high-mobility individuals in Mali have never received preventive chemotherapy during mass drug administration (MDA) for neglected tropical diseases, highlighting the need for high treatment coverage to eliminate these illnesses as public health issues.
  • Researchers conducted qualitative interviews and focus groups with displaced persons, nomads, and economic migrants to gather insights on their experiences and challenges related to MDA.
  • Key reasons for not receiving treatment included geographic mobility, lack of awareness, negative rumors, fear of side effects, and logistical challenges, leading to recommendations for community involvement and flexible intervention strategies to improve access.
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  • The study identifies the need for a more effective diagnostic tool for onchocerciasis, focusing on creating sensitive and specific assays to improve surveillance and monitoring efforts for the disease.
  • The researchers developed qPCR assays based on NGS data, targeting specific DNA sequences from the parasites O. volvulus (Ov) and O. ochengi (Oo), with promising results showing high sensitivity and specificity in identifying infections.
  • The new assays, especially Ov16R, demonstrated superior detection capabilities and are adaptable to user-friendly formats for field use, enhancing the potential for effective disease management.*
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Humans can be infected with anthroponotic ( and ) and with zoonotic (, , , and ) hookworms from dogs. Anthroponotic species are usually thought not to infect dogs. We used the internal transcribed spacer-1 (ITS1) gene in a quantitative PCR to detect anthroponotic and zoonotic hookworm species in fecal samples from 54 children and 79 dogs living in an indigenous community in tropical Northwestern Ecuador.

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  • - Lymphedema (LE), a serious condition resulting from lymphatic filariasis, is primarily treated through limb hygiene and local care, with a study exploring doxycycline's potential benefits.
  • - A multicenter trial in Mali tested doxycycline (200 mg/day) against a placebo for 6 weeks in patients with LE stages 1-3, measuring the disease's progression over 24 months.
  • - Results showed no significant difference in LE progression between the doxycycline and placebo groups, but both experienced reduced acute adenolymphangitis attacks; doxycycline was well tolerated but not more effective than hygiene alone.
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Background: Nodding syndrome is a poorly understood neurological disorder that predominantly occurs in Africa. We hypothesised that nodding syndrome is a neuroinflammatory disorder, induced by antibodies to Onchocerca volvulus or its Wolbachia symbiont, cross-reacting with host neuronal proteins (HNPs), and that doxycycline can be used as treatment.

Methods: In this randomised, double-blind, placebo-controlled, phase 2 trial, we recruited participants from districts affected by nodding syndrome in northern Uganda.

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To unravel the heterogeneity and molecular signature of effector memory Th2 cells (Tem2), we analyzed 23 individuals' PBMCs of filaria-infected (Filaria+) and 24 healthy volunteers (Filaria-), with or without coincident house dust mite (HDM) allergic sensitization. Flow cytometry revealed 3 CD4+ Tem subsets - CCR4+CCR6+CRTH2- Tem17, CCR4+CCR6-CRTH2+ Tem2, and CCR6+CCR4+CRTH2+ Tem17.2 - markedly enriched in Filaria+ individuals.

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  • The study explores how the helminth Strongyloides stercoralis (Ss) might influence complement system activation in people with type 2 diabetes (T2D), suggesting a protective effect against disease progression.
  • Researchers compared complement protein levels in individuals with T2D who had Ss infections versus those without, finding that Ss-infected individuals had lower complement levels and regulatory proteins.
  • After treating Ss-infected individuals with anthelmintics, some complement levels improved, indicating that helminth infections could play a role in reducing inflammation related to diabetes.
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Zoonotic human infections with Ancylostoma ceylanicum have recently been reported in the Americas. We used archived human stool samples to study the geographic distribution of human infections with A. ceylanicum and anthropophilic hookworms in different geoclimatic regions (coastal, Andean, and Amazon) of Ecuador.

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Background: Multisystem inflammatory syndrome (MIS) in children is considered to be a post-infectious complication of COVID-19. T-cell responses in children with this condition have not been well-studied.

Methods: We aimed to study the immune responses in children with MIS in comparison to children with acute COVID-19 and children with other infections.

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Background: Onchocerca volvulus is a filarial parasite that is a major cause of dermatitis and blindness in endemic regions primarily in sub-Saharan Africa. Widespread efforts to control the disease caused by O. volvulus infection (onchocerciasis) began in 1974 and in recent years, following successful elimination of transmission in much of the Americas, the focus of efforts in Africa has moved from control to the more challenging goal of elimination of transmission in all endemic countries.

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Background: Onchocerciasis control activities in Mali began in 1975 with vector larviciding carried out by the Onchocerciasis Control Programme (OCP), followed by the distribution of ivermectin from 1998 until the closure of the OCP in 2002. At that time, epidemiological evaluations, using skin snip microscopy and O-150 pool screening PCR in black flies, indicated that the disease had been largely controlled as a public health problem. Ivermectin distribution was nevertheless continued after 2002 in 34 of the 75 health districts in Mali as these were known to still be meso- or hyper-endemic for onchocerciasis.

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Background: The immunologic mechanisms underlying pulmonary type 2 inflammation, including the dynamics of eosinophil recruitment to the lungs, still need to be elucidated.

Objective: We sought to investigate how IL-13-producing T2 effector cells trigger eosinophil migration in house dust mite (HDM)-driven allergic pulmonary inflammation.

Methods: Multiparameter and molecular profiling of murine lungs with HDM-induced allergy was investigated in the absence of IL-13 signaling by using IL-13Rα1-deficient mice and separately through adoptive transfer of CD4 T cells from IL-5-deficient mice into TCRα mice before allergic inflammation.

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  • The text refers to a correction made to a previously published article in a scientific journal.
  • The correction is specifically linked to the article with DOI (Digital Object Identifier) 10.1371/journal.pntd.0010682.
  • Such corrections are typically made to address errors or inaccuracies in the original publication.
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Neurocysticercosis prevalence estimates often are based on serosurveys. However, assessments of Taenia solium seropositivity durability in patients with various neurocysticercosis types are lacking. We optimized a triplex serologic ELISA by using synthetic GP50, T24H, and Ts18var3 antigens for T.

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Mass drug administration programs targeting filarial infections depend on diagnostic tools that are sensitive and specific. The coendemicity of Loa loa with other filarial species often hampers the control programs. LL2634 was identified as the most promising target among several highly repeated targets, with sensitivity between 500 ag and 1 fg of genomic DNA.

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Background: The control of onchocerciasis currently relies on annual distribution of single dose ivermectin. Because ivermectin has minimal effects on the adult parasite, mass drug administration (MDA) campaigns against onchocerciasis require at least 15 years of annual uninterrupted ivermectin distribution. Mathematical models have predicted that short-term disruption of MDA (as was seen during COVID-19) could impacted the microfilaridermia prevalence depending on the pre-control endemicity and the histories of treatment, requiring corrective measures (such as biannual MDA) to mitigate the effect on onchocerciasis elimination.

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Importance: Multisystem inflammatory syndrome in children (MIS-C) is a severe and unrestrained inflammatory response with multiorgan involvement, which occurs within a few weeks following the resolution of acute SARS-CoV-2 infection. The complement system is a vital part of the innate immune system and plays a role in COVID-19 pathogenesis.

Objective: To examine and compare the levels of complement components and regulators along with complement activation products in the different clinical spectrum of children with SARS-CoV-2 and a control group.

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  • * Current serological tests are not fully effective due to cross-reactive antibodies and lingering antibodies from past infections, highlighting the need for improved diagnostic methods.
  • * Recent research has identified specific glycan antigens from the nematodes that stimulate distinct IgG responses, showing potential for more accurate diagnostics by analyzing IgG responses in infected individuals.
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Introduction: Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in many diseases.

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Background And Objective: Nodding syndrome (NS) is a unique childhood-onset epileptic disorder that occurs predominantly in several regions of sub-Saharan Africa. The disease has been associated with -induced immune responses and possible cross-reactivity with host proteins. The aim of this study was to compare structural changes in the brain on MRI between NS and other forms of onchocerciasis-associated epilepsies (OAEs) and to relate structural changes to the Ov-induced immune responses and level of disability.

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