Reduction in total leukocytes in malaria patients compared to febrile controls: A systematic review and meta-analysis

Kotepui, Manas; Kotepui, Kwuntida Uthaisar; Milanez, Giovanni De Jesus; Masangkay, Frederick Ramirez

doi:10.1371/journal.pone.0233913

Cited by 13 publications

(6 citation statements)

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“…Nevertheless, the meta-analysis of those two studies 47 , 48 demonstrated a higher leukocyte count in P. ovale curtisi infection than in P. ovale wallikeri infection. A previous study reported a reduction in total leukocyte counts during malaria infection 66 . In the present study, although the results demonstrated the difference in the mean leukocyte counts between P. ovale curtisi and P. ovale wallikeri malaria, the interpretation could not be made because only a small number of cases were investigated, or the difference suggested that P. ovale curtisi infection induces a higher immune response in patients than P. ovale wallikeri infection.…”

Section: Discussionmentioning

confidence: 85%

Comparison of Plasmodium ovale curtisi and Plasmodium ovale wallikeri infections by a meta-analysis approach

Mahittikorn

Masangkay

Kotepui

et al. 2021

Sci Rep

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Malaria caused by Plasmodium ovale species is considered a neglected tropical disease with limited information about its characteristics. It also remains unclear whether the two distinct species P. ovale curtisi and P. ovale wallikeri exhibit differences in their prevalence, geographic distribution, clinical characteristics, or laboratory parameters. Therefore, this study was conducted to clarify these differences to support global malaria control and eradication programs. Studies reporting the occurrence of P. ovale curtisi and P. ovale wallikeri were explored in databases. Differences in proportion, clinical data, and laboratory parameters between the two species were estimated using a random-effects model and expressed as pooled odds ratios (ORs), mean difference (MD), or standardized MD depending on the types of extracted data. The difference in geographical distribution was visualized by mapping the origin of the two species. A total of 1453 P. ovale cases extracted from 35 studies were included in the meta-analysis. The p-value in the meta-analyses provided evidence favoring a real difference between P. ovale curtisi malaria cases (809/1453, 55.7%) and P. ovale wallikeri malaria cases (644/1453, 44.3%) (p: 0.01, OR 1.61, 95% CI 0.71–3.63, I2: 77%). Subgroup analyses established evidence favoring a real difference between P. ovale curtisi and P. ovale wallikeri malaria cases among the imported cases (p: 0.02, 1135 cases). The p value in the meta-analyses provided evidence favoring a real difference in the mean latency period between P. ovale curtisi (289 cases) and P. ovale wallikeri malaria (266 cases) (p: 0.03, MD: 27.59, 95% CI 1.99–53.2, I2: 94%), total leukocyte count (p < 0.0001, MD: 840, 95% CI 610–1070, I2: 0%, two studies) and platelet count (p < 0.0001, MD: 44,750, 95% CI 2900–60,500, I2: 32%, three studies). Four continents were found to have reports of P. ovale spp., among which Africa had the highest number of reports for both P. ovale spp. in its 37 countries, with a global proportion of 94.46%, and an almost equal distribution of both P. ovale spp., where P. ovale curtisi and P. ovale wallikeri reflected 53.09% and 46.90% of the continent’s proportion, respectively. This is the first systematic review and meta-analysis to demonstrate the differences in the characteristics of the two distinct P. ovale species. Malaria caused by P. ovale curtisi was found in higher proportions among imported cases and had longer latency periods, higher platelet counts, and higher total leukocyte counts than malaria caused by P. ovale wallikeri. Further studies with a larger sample size are required to confirm the differences or similarities between these two species to promote malaria control and effective eradication programs.

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Section: Discussionmentioning

confidence: 85%

Comparison of Plasmodium ovale curtisi and Plasmodium ovale wallikeri infections by a meta-analysis approach

Mahittikorn

Masangkay

Kotepui

et al. 2021

Sci Rep

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“…Thrombocytopenia occurs in approximately 80% of patients infected with either severe or uncomplicated malaria [45]. Lymphopenia and high neutrophil per lymphocyte ratios occur in malaria patients [41], and previous studies have also frequently noted lymphopenia in severe COVID-19 patients [46,47]. Such cases of lymphopenia indicate low T and B cell counts [48][49][50], which may be caused by coronaviruses affecting bone marrow precursors directly, resulting in increased auto-immune response against blood cell precursors [51,52].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

“…Additionally, COVID-19 infected patients have a higher proportion of laboratory alterations than those of co-infected individuals such as CRP, D-dimer, AST, and ALT. Nevertheless, thrombocytopenia, lymphopenia, mild anemia, elevated bilirubin, elevated D-dimer, and elevated ferritin were observed in Plasmodium monoinfected individuals [41][42][43][44]. Therefore, it is not clear whether laboratory parameters could be semi-diagnostic parameters for COVID-19 and Plasmodium co-infected individuals.…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

Prevalence and characteristics of malaria among COVID-19 individuals: A systematic review, meta-analysis, and analysis of case reports

et al. 2021

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Background The world population is currently at a very high risk of Coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). People who live in malaria-endemic areas and get infected by SARS-CoV-2 may be at increased risk of severe COVID-19 or unfavorable disease outcomes if they ignore their malaria status. Therefore, the present study aimed to synthesize, qualitatively and quantitatively, information on the prevalence and characteristics of malaria infection among COVID-19-infected individuals. The findings will help us better understand this particular comorbidity during the COVID-19 pandemic. Methods The systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number: CRD42021247521. We searched for studies reporting on the coinfection of COVID-19 and malaria in PubMed, Web of Science, and Scopus from inception to March 27, 2021 using Medical Subject Headings (MeSH) terms. The study’s methodological quality in the search output was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Tools for cross-sectional study. The pooled prevalence of Plasmodium spp. infection among patients infected with COVID-19 was estimated using the random effect model and then graphically presented as forest plots. The heterogeneity among the included studies was assessed using Cochrane Q and I2 statistics. The characteristics of patients co-infected with COVID-19 and malaria were derived from case reports and series and were formally analyzed using simple statistics. Results Twelve of 1,207 studies reporting the coinfection of COVID-19 and malaria were selected for further analysis. Results of quantitative synthesis show that the pooled prevalence of Plasmodium spp. infection (364 cases) among COVID–19 individuals (1,126 cases) is 11%, with a high degree of heterogeneity (95% CI: 4%–18%, I2: 97.07%, 5 studies). Most of the coinfections were reported in Nigeria (336 cases), India (27 cases), and the Democratic Republic of Congo (1 case). Results of qualitative synthesis indicate that patients with coinfection are typically symptomatic at presentation with mild or moderate parasitemia. An analysis of case reports and series indicates that co-infected individuals often display thrombocytopenia, lymphopenia, and elevated bilirubin levels. Among four patients (30%) who required treatment with intravenous artesunate, one experienced worsened clinical status after administering the drug. One serious outcome of coinfection involved a pregnant woman who experienced fetal abortion due to the initial misdiagnosis of malaria. Conclusions All individuals in malaria-endemic regions who are febrile or display symptoms of COVID-19 should be evaluated for malaria to avoid serious complications. Further prospective studies are required to investigate the burden and outcomes of COVID-19 in malaria-endemic regions. Prompt management is required to prevent serious outcomes in individuals co-infected with COVID-19 and malaria.

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“…Symptoms on admission in this case series were similar to those previously reported [ 3 , 15 ], being anemia and thrombocytopenia two common laboratory alterations among pregnant women with this co-infection [ 3 ]. It is unclear whether laboratory parameters could help discriminate malaria and COVID-19 co-infection [ 3 ], since some laboratory alterations may be more common in SARS-CoV-2 mono-infected than in co-infected patients and yet other more frequent in malaria mono-infected patients [ 17 – 20 ].…”

Section: Discussionmentioning

confidence: 99%

Plasmodium vivax and SARS-CoV-2 co-infection in Venezuelan pregnant women: a case series

Carrión‐Nessi

Mendoza-Millán

Omaña‐Ávila

et al. 2023

Malar J

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Background Malaria‐endemic areas are not spared from the impact of coronavirus disease 2019 (COVID-19), leading to co-infection scenarios where overlapping symptoms impose serious diagnostic challenges. Current knowledge on Plasmodium spp. and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co‐infection in pregnant women remains limited, especially in Latin America, where Plasmodium vivax infection is highly prevalent. Methods This is a case series of five pregnant women with P. vivax and SARS-CoV-2 co-infection hospitalized in two main malaria referral centers of the Capital District and Bolivar state, Venezuela between March 13, 2020 and December 31, 2021. Results Clinical and laboratory data from five pregnant women with a mean age of 22 years were analyzed; three of them were in the third trimester of pregnancy. Comorbidities included obesity in two cases, hypertension in one, and asthma in one. Three out of five patients had severe to critical COVID-19 disease. Dry cough, fever, chills, and headache were the most frequent symptoms reported. Laboratory analyses showed elevated aspartate/alanine aminotransferase and creatinine levels, thrombocytopenia, and severe anemia as the most relevant abnormalities. The mean period between symptom onset and a positive molecular test for SARS-CoV-2 infection or positive microscopy for Plasmodium spp. was 4.8 ± 2.5 days and 2.8 ± 1.6 days, respectively. The mean hospital stay was 5.4 ± 7 days. Three women recovered and were discharged from the hospital. Two women died, one from cerebral malaria and one from respiratory failure. Three adverse fetal outcomes were registered, two miscarriages and one stillbirth. Conclusion This study documented a predominance of severe/critical COVID-19 disease and a high proportion of adverse maternal–fetal outcomes among pregnant women with malaria and COVID-19 co-infection. More comprehensive prospective cohort studies are warranted to explore the risk factors, management challenges, and clinical outcomes of pregnant women with this co-infection.

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Reduction in total leukocytes in malaria patients compared to febrile controls: A systematic review and meta-analysis

Cited by 13 publications

References 50 publications

Comparison of Plasmodium ovale curtisi and Plasmodium ovale wallikeri infections by a meta-analysis approach

Comparison of Plasmodium ovale curtisi and Plasmodium ovale wallikeri infections by a meta-analysis approach

Prevalence and characteristics of malaria among COVID-19 individuals: A systematic review, meta-analysis, and analysis of case reports

Plasmodium vivax and SARS-CoV-2 co-infection in Venezuelan pregnant women: a case series

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