Laouenan, C. | bioRxiv Science

bioRxiv2022

Cytokine profiles in adults with imported malaria: insights from the PALUREA cohort study

The increase in worldwide travel is making imported malaria a growing health concern in nonendemic countries. Most data on the pathophysiology of malaria come from endemic areas. Little is known about cytokine profiles during imported malaria. We report cytokine profiles in adults with Plasmodium falciparum malaria included in PALUREA, a prospective cohort study conducted in France between 2006 and 2010. The patients were classified as having uncomplicated malaria (UM) or severe malaria (SM), with this last further categorized as very severe malaria (VSM) or less severe malaria (LSM). At hospital admission, eight blood cytokines were assayed in duplicate using Luminex technology: interleukin (IL)-1, IL-1{beta}, IL-2, IL-4, IL-10, tumor necrosis factor (TNF), interferon (IFN){gamma}, and macrophage migration inhibitory factor (MIF). These assays were repeated on days 1 and 2 in the SM group. Of the 278 patients, 134 had UM and 144 SM. At hospital admission, over half the patients had undetectable levels of IL-1, IL-1 {beta}, IL-2, IL-4, IFN {gamma}, and TNF, while IL-10 and MIF were significantly higher in the SM vs. the UM group. Higher IL-10 was significantly associated with higher parasitemia (R=0.32 [0.16-0.46]; P=0.0001). In the SM group, IL-10 elevation persisting from admission to day 2 was significantly associated with subsequent nosocomial infection. Of eight tested cytokines, only MIF and IL-10 were associated with disease severity in adults with imported P. falciparum malaria. At admission, many patients had undetectable cytokine levels, suggesting that circulating cytokine assays may not be helpful as part of the routine evaluation of adults with imported malaria. Author SummaryPlasmodium falciparum malaria is increasingly common in nonendemic areas. Improved understanding of its pathophysiology might help to decrease mortality. We therefore routinely assayed eight cytokines in 278 adults with imported P. falciparum malaria at hospital admission; in the group with severe malaria (n=144), we repeated the assays on the next two days. The cytokine levels were often undetectable, suggesting that cytokine storm might not be a driving mechanism at the time of clinical presentation. IL-10 and macrophage migration inhibitory factor (MIF) were significantly higher in the group with severe vs. uncomplicated disease. Thus, the roles for these two cytokines in severe malaria, may deserve further investigation. A complicating factor is that greater IL-10 elevation may be a response to a heavy parasite burden and/or may promote parasite replication. IL-10 elevation that persisted over the first 2 days after admission was significantly associated with subsequent nosocomial infections in the group with severe malaria suggesting its possible role in acquired immune suppression syndrome.

immunology↗

bioRxiv2019

Prevalence of chronic chikungunya and associated risks factors in the French West Indies (La Martinique). A prospective cohort study

BackgroundThe chikungunya virus (CHIKV) is a re-emerging alphavirus that can cause chronic rheumatic musculoskeletal disorders, named chronic chikungunya (CHIKC+), which may be long-term incapacitating. A chikungunya outbreak occurred in 2013 in La Martinique. We constituted the first prospective cohort study of CHIKV-infected subjects in the Caribbean to assess the prevalence of CHIKC+ at 12 months and to search for factors present at the acute stage significantly associated with chronicity.\n\nMethodology/Principal findingsA total of 193 patients who tested positive for RT-PCR CHIKV, were submitted to clinical investigations in the acute phase (<21 days), and 3, 6, and 12 months after their inclusion. A total of 167 participants could be classified as either suffering or not from CHIKC+. They were analyzed using logistic regression models. At 12 months, the overall prevalence of CHIKC+ was 52.1% (95%CI: 44.5-59.7). In univariate analysis, age (OR: 1.04; 95% CI: 1.02-1.07; p=0.0003), being male (OR: 0.51; 95%CI: 0.27-0.98; p=0.04), headache (OR: 1.90; 95%CI: 1.02-3.56; p=0.04), vertigo (OR: 2.06; 95%CI: 1.05-4.03; p=0.04), vomiting (OR: 2.51; 95%CI: 1.07-5.87; p = 0.03), urea (OR: 1.33; 95%CI: 1.05-1.70; p=0.02) were associated with CHIKC+. In final multivariate logistic regression models for 167 participants, predictors of CHIKC+ were age (OR 1.06; 95%CI: 1.03-1.08; p<0.0001), male sex (OR: 0.40; 95%CI: 0.19-0.84; p=0.015), vertigo (OR: 2.46; 95%CI: 1.16-5.20; p=0.019), hypotension (OR 4.72; 95% -CI: 1.19-18.79; p=0.028), recoloration time >3 seconds (OR: 3.79; 95%-CI: 1.01-14.25).\n\nConclusionsThis cohort study in La Martinique confirms that CHIKC+ is a frequent complication of acute chikungunya disease. Analysis emphasized the importance of age and female sex for CHIKC occurrence, and pointed out the potential aggravating role of dehydration at the acute phase. Early and adequate hydration could reduce the risk chronic chikungunya disorders.\n\nAuthor SummaryChikungunya is a mosquito-borne virus found in tropical countries that has been re-emerging in the last decade. It has caused major epidemics in recent years, such as in Reunion Island and in Southeast Asia. Nearly 2.5 billion people around the world are at risk of contracting the virus. During the acute phase of the illness, patients experience a flu-like syndrome with fever, headache, myalgia, rash, and severe arthralgia. These symptoms can persist for several months in some patients, and can lead to significant functional disability. During the 2013 epidemic in Martinique, we followed nearly 200 patients who had contracted chikungunya. More than half of the patients had a chronic form of the disease--mainly women over 50 years of age. Our statistical analyses indicate that poor hydration during the acute phase may be a risk factor for developing chronic rheumatism. Therefore, in the context of a chikungunya epidemic, it seems important to encourage patients to drink plenty of fluids as soon as the first symptoms appear.

microbiology↗