Increased platelet distribution width and reduced IL-2 and IL-12 are associated with thrombocytopenia in Plasmodium vivax malaria

Costa, Allyson Guimarães; Chaves, Yury Oliveira; Teixeira-Carvalho, Andréa; Ramasawmy, Rajendranath; Antonelli, Lis R. V.; Barbosa, Lucas; Balieiro, Antônio Alcirley da Silva; Monteiro, Wuelton Marcelo; Mourão, Maria Paula Gomes; Lacerda, Marcus Vinícius Guimarães; Martins‐Filho, Olindo Assis; Costa, Fábio Trindade Maranhão; Malheiro, Adriana; Nogueira, Paulo Afonso

doi:10.1590/0074-02760200080

Cited by 3 publications

(7 citation statements)

References 28 publications

(66 reference statements)

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“…Finally, 20 studies [ 28 – 47 ] were included for qualitative and quantitative syntheses. These studies included 12 [ 28 – 36 , 44 , 46 , 47 ] that compared IL-1β levels in severe and uncomplicated malaria and 8 [ 37 – 43 , 45 ] that compared IL-1β levels in patients with uncomplicated malaria and healthy controls (Fig. 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Briefly, the included studies were published between 1994 and 2020. The included studies were case–control studies (8/20, 40%) [ 29 , 33 , 36 , 37 , 40 , 43 , 44 , 46 ], cross-sectional studies (6/20, 30%) [ 30 , 31 , 34 , 39 , 41 , 45 ], prospective observational studies (5/20, 25%) [ 28 , 35 , 38 , 42 , 47 ] and a cohort study [ 32 ]. The included studies were conducted in Africa (10/20, 50%) [ 28 , 30 , 31 , 33 , 34 , 36 , 38 , 43 , 44 , 47 ], South America (4/20, 20%) [ 37 , 40 , 41 , 45 ], Asia and Oceania [ 29 , 35 , 46 ], Europe [ 39 , 42 ] and North America [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

“…The included studies were case–control studies (8/20, 40%) [ 29 , 33 , 36 , 37 , 40 , 43 , 44 , 46 ], cross-sectional studies (6/20, 30%) [ 30 , 31 , 34 , 39 , 41 , 45 ], prospective observational studies (5/20, 25%) [ 28 , 35 , 38 , 42 , 47 ] and a cohort study [ 32 ]. The included studies were conducted in Africa (10/20, 50%) [ 28 , 30 , 31 , 33 , 34 , 36 , 38 , 43 , 44 , 47 ], South America (4/20, 20%) [ 37 , 40 , 41 , 45 ], Asia and Oceania [ 29 , 35 , 46 ], Europe [ 39 , 42 ] and North America [ 32 ]. Most of the included studies enrolled patients with P. falciparum (13/20, 65%) [ 28 , 30 – 36 , 38 , 39 , 43 , 44 , 47 ] and children aged between less than 1 and 17 years (11/20, 55%) [ 28 , 30 – 34 , 36 , 38 , 44 , 46 , 47 ].…”

Section: Resultsmentioning

confidence: 99%

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Elevation of serum interleukin-1β levels as a potential indicator for malarial infection and severe malaria: a meta-analysis

Mahittikorn

Kwankaew

Rattaprasert

et al. 2022

Malar J

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Background Interleukin (IL)-1β is a proinflammatory cytokine that has a role in disease-related inflammation, including malaria. However, reports on the effect of IL-1β on malaria severity are inconsistent. Therefore, meta-analyses to compare differences in IL-1β levels between patients with severe malaria, patients with uncomplicated malaria and healthy controls were performed. Methods The PRISMA standards were used to perform a systematic review and meta-analysis. A search of PubMed, Scopus, EMBASE and reference lists was conducted for articles providing data on IL-1β levels between patients with severe malaria, patients with uncomplicated malaria and healthy controls between January 1988 and March 2022, using a combination of search terms. The quality of all studies included in this review was determined using the Strengthening the Reporting of Observational Studies in Epidemiology statement: guidelines for reporting observational studies. The evidence was synthesized quantitatively and qualitatively. The differences in IL-1 levels across participant groups were recounted narratively for qualitative synthesis. For quantitative synthesis, the mean difference in IL-1β levels across groups of participants was calculated using a random effects meta-analysis. The publication bias was assessed using funnel plots, Egger’s test and a contour-enhanced funnel plot. Results A total of 1281 articles were discovered, and the 17 that satisfied the inclusion criteria were included for syntheses. The meta-analysis results using data from 555 cases of severe malaria and 1059 cases of uncomplicated malaria showed that severe malaria had a higher mean of IL-1β levels than uncomplicated malaria (P < 0.01, pooled mean difference: 1.92 pg/mL, 95% confidence interval: 0.60–3.25 pg/mL, I2: 90.41%, 6 studies). The meta-analysis results using data from 542 cases of uncomplicated malaria and 455 healthy controls showed no difference in mean IL-1β levels between the two groups (P = 0.07, pooled mean difference: 1.42 pg/mL, 95% confidence interval: − 0.1–2.94 pg/mL, I2: 98.93%, 6 studies). Conclusion The results from the meta-analysis revealed that IL-1β levels were higher in patients with severe malaria than in patients with uncomplicated malaria; however, IL-1β levels were similar in patients with uncomplicated malaria and healthy controls. Based on the limitations of the number of studies included in the meta-analysis and high levels of heterogeneity, further studies are needed to conclude that differences in IL-1β levels can be useful for monitoring the malaria severity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Elevation of serum interleukin-1β levels as a potential indicator for malarial infection and severe malaria: a meta-analysis

Mahittikorn

Kwankaew

Rattaprasert

et al. 2022

Malar J

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“…The overexpression of TIM3 was associated with a decreased risk of clinical malaria [71]. In a group of patients infected with P. vivax, Costa et al have found thrombocythemia and low levels of IL-2 and IL-12 that correlated with platelet distribution width (PDW) values and concluded that these changes may represent an immune response to thrombocytopenia [72].…”

Section: Has An Anti-inflammatory Effect By Inhibiting Th1 Cell Differentiationmentioning

confidence: 99%

Recent Advances in Understanding the Inflammatory Response in Malaria: A Review of the Dual Role of Cytokines

Popa

2021

Journal of Immunology Research

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Malaria is a serious and, in some unfortunate cases, fatal disease caused by a parasite of the Plasmodium genus. It predominantly occurs in tropical areas where it is transmitted through the bite of an infected Anopheles mosquito. The pathogenesis of malaria is complex and incompletely elucidated. During blood-stage infection, in response to the presence of the parasite, the host’s immune system produces proinflammatory cytokines including IL-6, IL-8, IFN-γ, and TNF, cytokines which play a pivotal role in controlling the growth of the parasite and its elimination. Regulatory cytokines such as transforming growth factor- (TGF-) β and IL-10 maintain the balance between the proinflammatory and anti-inflammatory responses. However, in many cases, cytokines have a double role. On the one hand, they contribute to parasitic clearance, and on the other, they are responsible for pathological changes encountered in malaria. Cytokine-modulating strategies may represent a promising modern approach in disease management. In this review, we discuss the host immune response in malaria, analyzing the latest studies on the roles of pro- and anti-inflammatory cytokines.

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“…Elevated IL-12 levels were suggested to play an essential role against systemic damage induced by malaria parasites [ 27 ]. Decreased IL-12 levels were related to thrombocytopenia in P. vivax malaria [ 28 ]. A previous study showed no difference in IL-12 levels between patients with malaria and non-malaria [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Low Interleukin-12 Levels concerning Severe Malaria: A Systematic Review and Meta-Analysis

Wilairatana

Kwankaew

Kotepui

et al. 2022

IJERPH

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Although many studies have investigated the role of interleukin (IL)-12 cytokine in the pathogenesis of severe malaria, these studies were based on a limited number of participants, possibly affecting their outcomes. We analyzed the difference in IL-12 levels between patients with severe and uncomplicated malaria through a meta-analysis. A systematic review was conducted following the Cochrane Handbook for Systematic Reviews of Interventions and was reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. Systematic literature searches were performed between 20 February and 2 March, 2022 in PubMed, Scopus, and Embase to identify studies reporting IL-12 levels in patients with severe and uncomplicated malaria. The quality of included studies was determined using the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. The pooled mean difference (MD) in IL-12 between patients with severe and uncomplicated malaria was estimated using the DerSimonian–Laird method for the random-effects model. Altogether, 1885 potentially relevant articles were identified, and 10 studies enrolling 654 patients with severe malaria and 626 patients with uncomplicated malaria were included in the meta-analysis. Patients with severe malaria had lower mean IL-12 levels than those with uncomplicated malaria (p = 0.01, MD: −33.62, 95% confidence interval [CI]: −58.79 to −8.45, I2: 99.29%, 10 studies). In conclusion, decreased IL-12 levels might significantly contribute to the development of severe malaria. As most published literature demonstrated the role of IL-12 in animal models, human studies are required to understand the mechanisms involved in low IL-12 levels in patients with severe malaria.

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Increased platelet distribution width and reduced IL-2 and IL-12 are associated with thrombocytopenia in Plasmodium vivax malaria

Cited by 3 publications

References 28 publications

Elevation of serum interleukin-1β levels as a potential indicator for malarial infection and severe malaria: a meta-analysis

Elevation of serum interleukin-1β levels as a potential indicator for malarial infection and severe malaria: a meta-analysis

Recent Advances in Understanding the Inflammatory Response in Malaria: A Review of the Dual Role of Cytokines

Low Interleukin-12 Levels concerning Severe Malaria: A Systematic Review and Meta-Analysis

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