Hawadak et al. Parasites Vectors (2021) 14:297 https://doi.org/10.1186/s13071-021-04797-0 Parasites & Vectors REVIEW Open Access Global trend of Plasmodium malariae and Plasmodium ovale spp. malaria infections in the last two decades (2000–2020): a systematic review and meta-analysis Joseph Hawadak1†, Rodrigue Roman Dongang Nana1,2† and Vineeta Singh1* Abstract Background: Recent studies indicate that the prevalence of non-falciparum malaria, including Plasmodium malariae and Plasmodium ovale spp., is increasing, with some complications in infected individuals. The aim of this review is to provide a better understanding of the malaria prevalence and disease burden due to P. malariae and P. ovale spp. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Joanna Briggs Institute prevalence study assessment tool were used to select and evaluate the studies, respectively. Six databases: PubMed, WHOLIS, Wiley Library, ScienceDirect, Web of Science and Google Scholar were used to screen articles published during the period January 2000–December 2020. The pooled prevalence estimates for P. malariae and P. ovale spp. were analysed using a random-efects model and the possible sources of heterogeneity were evalu- ated through subgroup analysis and meta-regression. Results: Out of the 3297 studies screened, only 113 studies were included; among which 51.33% were from the African Region. The P. malariae and P. ovale spp. pooled prevalence were 2.01% (95% CI 1.31–2.85%) and 0.77% (95% CI 0.50–1.10%) respectively, with the highest prevalence in the African Region. P. malariae was equally distributed among adults (2.13%), children (2.90%) and pregnant women (2.77%) (p 0.862), whereas P. ovale spp. was more prevalent in pregnant women (2.90%) than in children 15 years (0.97%) and= in patients > 15 years old (0.39%) (p 0.021). In this review, data analysis revealed that P. malariae≤ and P. ovale spp. have decreased in the last 20 years, but= not signifcantly, and these species were more commonly present with other Plasmodium species as co-infections. No diference in prevalence between symptomatic and asymptomatic patients was observed for either P. malariae or P. ovale spp. Conclusion: Our analysis suggests that knowledge of the worldwide burden of P. malariae and P. ovale spp. is very important for malaria elimination programmes and a particular focus towards improved tools for monitoring trans- mission for these non-falciparum species should be stressed upon to deal with increased infections in the future. Keywords: Malaria infections, Plasmodium malariae, Plasmodium ovale spp., Prevalence, Meta-analysis Background Malaria is an infectious disease caused by parasites of *Correspondence: [email protected] †Joseph Hawadak and Rodrigue Roman Dongang Nana contributed the genus Plasmodium and transmitted by infected equally to this work Anopheles female mosquitoes in tropical and subtropical 1 ICMR-National Institute of Malaria Research, Dwarka, Sector 8, countries. Tis disease is a major public health problem New-Delhi 110077, India Full list of author information is available at the end of the article globally, with 229 million estimated cases in 2019, mostly © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Hawadak et al. Parasites Vectors (2021) 14:297 Page 2 of 14 in African and South-East Asia regions [1]. Several inter- “epidemiology” OR “proportion” OR “frequency”) AND national programmes have been launched to reduce and/ (“PCR” OR “molecular”)] (Additional fle 2). In addition, or eradicate malaria worldwide, and considerable pro- a manual Google search and fltering of the reference lists gress has been made over the past two decades, resulting of included studies were performed to access additional in a decrease in the global incidence of malaria from 363 articles. Te search included articles in both English and to 225 cases per 1000 population during the years 2000 French languages published between January 2000 and to 2019 [1]. Unfortunately, recent reports of the emer- December 2020. gence of artemisinin resistance in South-East Asia in the Greater Mekong Subregion adds another challenge hin- Selection of studies and data extraction dering the eforts of malaria control programmes [2–4]. All epidemiological studies that reported the prevalence Among all human Plasmodium spp., P. falciparum and of P. malariae and P. ovale spp. using molecular tech- P. vivax receive particular scientifc research interest, as niques as a species identifcation method were consid- they are responsible for the majority of malaria infections ered in this review. Only research articles published in and disease severity in human patients, whereas P. ovale peer-reviewed journals were included, and studies with spp. and P. malariae remain neglected tropical diseases no clear epidemiological data on Plasmodium spp. were due to their low prevalence and still lower disease sever- excluded from the review. All articles were imported ity as compared to falciparum malaria [3, 5, 6]. Te clini- into Zotero bibliographic reference management soft- cal features due to P. malariae and P. ovale spp. are thus ware, and duplicate fles were deleted. A data extraction poorly known, as very few reported studies are available form with the name of the frst author, year of publica- compared to other human Plasmodium spp. [7]. P. ovale tion, period of data collection, geographical location spp. are recognized to generally induce weak parasitae- (continent and country), target group (subject and sub- mia in the infected host, are very often responsible for ject status), type of study, sample size, sampling tech- relapses and sometimes have also been identifed in cer- nique, diagnostic method, target gene and a positive tain renal complications [8]. In recent years, a steady rise result for each human Plasmodium species was prepared in malaria infection cases associated with P. ovale spp. in a Microsoft Excel spreadsheet. Te data fles extracted and P. malariae has been observed in many parts of sub- independently by the frst two authors were systemati- Saharan Africa and South America, with their prevalence cally evaluated for any inconsistencies, and any further being around 10% and 20%, respectively, in both sympto- discrepancies were resolved after discussion with the matic and asymptomatic malaria infections, causing con- team supervisor. cern for elimination programmes [9–14]. Tis increase in prevalence underscores the need for attention towards Evaluation of criteria for inclusion of studies them, and therefore knowledge about their demographic Te quality and risk of bias in included studies were distribution and associated morbidity is essential for assessed using an adapted version of the Joanna Briggs understanding their epidemiology. In this review article, Institute (JBI) prevalence study assessment tool [16]. we have focused on estimating the disease burden and Te evaluation criteria were based on eight parameters: the epidemiological aspects of malaria infections caused (i) appropriate sample frame, (ii) appropriate sampling by P. malariae and P. ovale spp., highlighting the need for technique, (iii) adequate sample size, (iv) description of increased attention towards these species for successful the study subject and settings in detail, (v) sufcient data malaria elimination programmes. analysis, (vi) use of validated methods for the conditions identifed, (vii) valid measurement of the condition for all Methods participants and (viii) use of appropriate statistical analy- Search strategy sis. For each evaluation item, a score of 1 was awarded if Te Preferred Reporting Items for Systematic Reviews found in the article; zero was given if not, and no score if and Meta-Analyses (PRISMA) guidelines were used the evaluation tool was unclear or not applicable to the to select studies for this review [15], and six databases study. Studies that received a score ≥ 5 were considered (PubMed, WHOLIS, Wiley Library, ScienceDirect, Web acceptable for fnal inclusion in the study (Additional of Science and Google Scholar) were explored to access fle 3: Table S1). articles (Additional fle 1). Although the search strategy difers slightly from one database to another, a systematic Data analysis computerized strategy was adopted using MeSH terms Data analysis was performed with Metaprop command and in combination with Boolean operators: [“malaria” [17] in Stata 16.1 software (StataCorp LLC, USA). Te OR “Plasmodium” AND (“malariae” OR “ovale” OR combined prevalence and 95% confdence intervals “curtisi” OR “wallikeri”) AND (“prevalence” OR (CIs) were computed using a random-efects model Hawadak et al. Parasites Vectors (2021) 14:297 Page 3 of 14 with Freeman-Tukey double arcsine transformation and Characteristics of the included studies restricted maximum likelihood method for stabilization Of the 113 studies included in our review, more than half and estimating the covariance. Heterogeneity between (51.33%; n = 58) were published within the last 5 years, studies was assessed using I2, whose values of 25%, 50% but no study was published in the year 2003 (Fig.