Publications by authors named "Thomas Obadia"

Background: Establishing correlates of protection often requires large cohorts. A rapid and adaptable case-control study design can be used to identify antibody correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in serum and saliva.

Methods: We designed a case-control study to compare antibody levels between cases of SARS-CoV-2 infection within 5 days of symptom onset and uninfected controls.

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Background: While invasive fusariosis and lomentosporiosis are known to be associated with fungemia, overall data on mold-related fungemia are limited, hampering early management. This study aimed to describe the epidemiology of mold-positive blood cultures.

Methods: Epidemiological and clinical data on mold-positive blood cultures from 2012 to 2022 were obtained from the RESSIF database.

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Article Synopsis
  • Mucormycosis, a severe fungal infection highlighted by the WHO, was studied in France from 2012 to 2022, revealing significant trends in epidemiology and mortality factors.
  • Out of 550 cases, key underlying conditions included hematological malignancies (65.1%), with pulmonary infections most common (52.4%) and substantial seasonal variations suggesting more cases in autumn.
  • The study linked the rise in PCR diagnostic methods to improved patient outcomes, highlighting that age, ICU diagnosis, and hematological malignancies increased mortality, while diagnosis after 2015 and surgical interventions decreased it.
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Large transcellular pores elicited by bacterial mono-ADP-ribosyltransferase (mART) exotoxins inhibiting the small RhoA GTPase compromise the endothelial barrier. Recent advances in biophysical modeling point toward membrane tension and bending rigidity as the minimal set of mechanical parameters determining the nucleation and maximal size of transendothelial cell macroaperture (TEM) tunnels induced by bacterial RhoA-targeting mART exotoxins. We report that cellular depletion of caveolin-1, the membrane-embedded building block of caveolae, and depletion of cavin-1, the master regulator of caveolae invaginations, increase the number of TEMs per cell.

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Article Synopsis
  • The Great Mekong Subregion has seen significant reductions in malaria cases, yet certain populations, particularly forest workers and migrants, continue to contribute to ongoing transmission hotspots.
  • The study involved tracking the movements of male forest goers over two 28-day periods by combining GPS data, questionnaires, and health exams to assess their exposure to malaria.
  • Findings indicated that malaria risk was higher in villages with less forest cover, suggesting that proximity to forest does not necessarily increase malaria risk, and that there was a notable discrepancy between GPS tracking and self-reported movement data.
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Article Synopsis
  • - Over the past few decades, malaria cases in Cambodia have decreased significantly, leading to fragmented transmission in remote areas, prompting a study to examine the burden of Plasmodium infections near the forest regions in Mondulkiri.
  • - The study involved 950 participants from 2018 to 2020, where blood samples were tested for Plasmodium infections and a risk analysis was conducted. It found that living in the forest greatly increased the risk of infection, particularly in adult males.
  • - Results indicated that baseline serological status (whether participants tested positive or negative) was a strong predictor of future infections, stressing the need for targeted serological testing to effectively address malaria risks, especially in demographics living outside forest areas.
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The mosquito-borne disease, Yellow fever (YF), has been largely controlled via mass delivery of an effective vaccine and mosquito control interventions. However, there are warning signs that YF is re-emerging in both Sub-Saharan Africa and South America. Imported from Africa in slave ships, YF was responsible for devastating outbreaks in the Caribbean.

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Primaquine for radical cure of malaria poses a potentially life-threatening risk of haemolysis in G6PD-deficient patients. Herein, we review five events of acute haemolytic anaemia following the administration of primaquine in four malaria trials from Indonesia, the Solomon Islands, and Vietnam. Five males aged 9 to 48 years were improperly classified as G6PD-normal by various screening procedures and included as subjects in trials of anti-relapse therapy with daily primaquine.

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Background: malaria is challenging to control and eliminate. Treatment with radical cure drugs fails to target the hidden asymptomatic and hypnozoite reservoirs in populations. SeroTAT, a novel serological test-and-treat intervention using a serological diagnostic to screen hypnozoite carriers for radical cure eligibility and treatment, could accelerate elimination.

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To assess the combined role of anti-viral monoclonal antibodies (mAbs) and vaccines in reducing severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission and mortality in the United States, an agent-based model was developed that accounted for social contacts, movement/travel, disease progression, and viral shedding. The model was calibrated to coronavirus disease 2019 (COVID-19) mortality between October 2020 and April 2021 (aggressive pandemic phase), and projected an extended outlook to estimate mortality during a less aggressive phase (April-August 2021). Simulated scenarios evaluated mAbs for averting infections and deaths in addition to vaccines and aggregated non-pharmaceutical interventions.

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First identified in 1947, Zika virus took roughly 70 years to cause a pandemic unusually associated with virus-induced brain damage in newborns. Zika virus is transmitted by mosquitoes, mainly Aedes aegypti, and secondarily, Aedes albopictus, both colonizing a large strip encompassing tropical and temperate regions. As part of the international project ZIKAlliance initiated in 2016, 50 mosquito populations from six species collected in 12 countries were experimentally infected with different Zika viruses.

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Serological markers are a promising tool for surveillance and targeted interventions for Plasmodium vivax malaria. P. vivax is closely related to the zoonotic parasite P.

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Global Positioning System (GPS) technology is an effective tool for quantifying individuals' mobility patterns and can be used to understand their influence on infectious disease transmission. In Cambodia, mobility measurements have been limited to questionnaires, which are of limited efficacy in rural environments. In this study, we used GPS tracking to measure the daily mobility of Cambodian forest goers, a population at high risk of malaria, and developed a workflow adapted to local constraints to produce an optimal dataset representative of the participants' mobility.

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The mosquito Aedes albopictus is an invasive species first detected in Europe in Albania in 1979, and now established in 28 European countries. Temperature is a limiting factor in mosquito activities and in the transmission of associated arboviruses namely chikungunya (CHIKV) and dengue (DENV). Since 2007, local transmissions of CHIKV and DENV have been reported in mainland Europe, mainly in South Europe.

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Background: Eliminating Plasmodium vivax will require targeting the hidden liver-stage reservoir of hypnozoites. This necessitates new interventions balancing the benefit of reducing vivax transmission against the risk of over-treating some individuals with drugs which may induce haemolysis. By measuring antibodies to a panel of vivax antigens, a strategy of serological-testing-and-treatment (PvSeroTAT) can identify individuals with recent blood-stage infections who are likely to carry hypnozoites and target them for radical cure.

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Background: Understanding epidemiological variables affecting gametocyte carriage and density is essential to design interventions that most effectively reduce malaria human-to-mosquito transmission.

Methodology/principal Findings: Plasmodium falciparum and P. vivax parasites and gametocytes were quantified by qPCR and RT-qPCR assays using the same methodologies in 5 cross-sectional surveys involving 16,493 individuals in Brazil, Thailand, Papua New Guinea, and Solomon Islands.

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Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time.

Methods: We developed a multiplex serological test for measuring antibodies to 5 SARS-CoV-2 antigens and the spike proteins of seasonal coronaviruses. We measured antibody responses in cohorts of hospitalized patients and healthcare workers followed for up to 11 months after symptoms.

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Article Synopsis
  • Plasmodium vivax continues to challenge malaria elimination efforts despite intensified control measures, with tafenoquine offering a promising single-dose treatment alternative, particularly in Brazil where the majority of malaria cases are due to this parasite.
  • A mathematical model based on 2018 malaria case data in Brazil suggests that introducing tafenoquine could significantly improve hypnozoite clearance, potentially increasing the effective radical cure rate from 42% to 62% among clinical cases.
  • The rollout of tafenoquine may lead to a predicted 38% reduction in malaria transmission, potentially averting over 214,000 cases from 2021 to 2025, especially in areas with lower prevalence of certain conditions.
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In the malaria-causing parasite's life cycle, Plasmodium sporozoites must travel from the midgut of a mosquito to the salivary glands before they can infect a mammalian host. However, only a fraction of sporozoites complete the journey. Since salivary gland invasion is required for transmission of sporozoites, insights at the molecular level can contribute to strategies for malaria prevention.

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Background: After a marked reduction in malaria burden in Cambodia over the last decades, case numbers increased again in 2017-2018. In light of the national goal of malaria elimination by 2025, remaining pockets of high risk need to be well defined and strategies well-tailored to identify and target the persisting burden cost-effectively. This study presents species-specific prevalence estimates and risk stratification for a remote area in Cambodia.

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Historically endemic to Sub-Saharan Africa and South America, yellow fever is absent from the Asia-Pacific region. Yellow fever virus (YFV) is mainly transmitted by the anthropophilic Aedes mosquitoes whose distribution encompasses a large belt of tropical and sub tropical regions. Increasing exchanges between Africa and Asia have caused imported YFV incidents in non-endemic areas, which are threatening Asia with a new viral emergence.

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, the most widely distributed human malaria parasite, causes severe clinical syndromes despite low peripheral blood parasitemia. This conundrum is further complicated as cytoadherence in the microvasculature is still a matter of investigations. Previous reports in , another parasite species shown to infect humans, demonstrated that variant genes involved in cytoadherence were dependent on the spleen for their expression.

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Article Synopsis
  • There is a significant gap in identifying individuals with silent liver-stage parasites called hypnozoites in the context of Plasmodium vivax elimination efforts.
  • The study created a panel of serological markers to help identify those with recent P. vivax infections who are likely carrying hypnozoites, relying on measurements of IgG antibody responses to numerous P. vivax proteins.
  • Validation of these markers showed that they can accurately classify recent infections with about 80% sensitivity and specificity, and a model suggests that implementing serological testing could significantly lower P. vivax prevalence by 59-69%.
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Background: The genome of Candida albicans displays significant polymorphism. Point mutations in genes involved in resistance to antifungals may either confer phenotypic resistance or be devoid of phenotypic consequences.

Objectives: To catalogue polymorphisms in azole and echinocandin resistance genes occurring in susceptible strains in order to rapidly pinpoint relevant mutations in resistant strains.

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