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Malaria Journal Jul 2020Severe complications among patients with Plasmodium malariae infection are rare. This is the first systematic review and meta-analysis demonstrating the global... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Severe complications among patients with Plasmodium malariae infection are rare. This is the first systematic review and meta-analysis demonstrating the global prevalence and mortality of severe P. malariae infection in humans.
METHODS
The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All research articles published on the severity and mortality of P. malariae infection cases in humans were retrieved from three public databases: PubMed, Scopus, and ISI Web of Science. The pooled prevalence estimate and 95% confidence interval (CI) of complications in patients with P. malariae malaria was analysed using the random-effects model provided in Stata software. The pooled odds ratio (OR) and 95% CI of severe malaria for P. malariae infection and Plasmodium falciparum infection were analysed using Review Manager software.
RESULTS
Six studies were used to estimate the pooled prevalence of severe P. malariae malaria. Out of 10,520 patients infected with P. malariae, the pooled prevalence estimate of severe P. malariae infection was 3% (95% CI 2-5%), with high heterogeneity (I: 90.7%). Severe anaemia (3.32%), pulmonary complications (0.46%), and renal impairments (0.24%) were the most common severe complications found in patients with P. malariae infection. The pooled proportion of severe anaemia for P. malariae infection and P. falciparum infection was comparable among the four included studies (OR: 0.74, 95% CI 0.22-2.45, I = 98%). The pooled proportion of pulmonary complications was comparable between patients with P. malariae infection and those with P. falciparum infection among the four included studies (OR: 1.44; 95% CI 0.17-12.31, I: 92%). For renal complications, the funnel plot showed that the pooled proportion of renal complications for P. malariae infection and P. falciparum infection was comparable among the four included studies (OR: 0.94, 95% CI 0.18-4.93, I: 91%). The mortality rate of patients with P. malariae infection was 0.17% (18/10,502 cases).
CONCLUSIONS
This systematic review demonstrated that approximately two percent of patients with P. malariae infection developed severe complications, with a low mortality rate. Severe anaemia, pulmonary involvement, and renal impairment were the most common complications found in patients with P. malariae infection. Although a low prevalence and low mortality of P. malariae infection have been reported, patients with P. malariae infection need to be investigated for severe anaemia and, if present, treated aggressively to prevent anaemia-related death.
Topics: Humans; Malaria; Plasmodium malariae; Prevalence
PubMed: 32736635
DOI: 10.1186/s12936-020-03344-z -
Frontiers in Genetics 2022Many standard-textbook population-genetic results apply to a wide range of species. Sometimes, however, population-genetic models and principles need to be tailored to a...
Many standard-textbook population-genetic results apply to a wide range of species. Sometimes, however, population-genetic models and principles need to be tailored to a particular species. This is particularly true for malaria, which next to tuberculosis and HIV/AIDS ranks among the economically most relevant infectious diseases. Importantly, malaria is not one disease-five human-pathogenic species of exist. is not only the most severe form of human malaria, but it also causes the majority of infections. The second most relevant species, , is already considered a neglected disease in several endemic areas. All human-pathogenic species have distinct characteristics that are not only crucial for control and eradication efforts, but also for the population-genetics of the disease. This is particularly true in the context of selection. Namely, fitness is determined by so-called fitness components, which are determined by the parasites live-history, which differs between malaria species. The presence of hypnozoites, i.e., dormant liver-stage parasites, which can cause disease relapses, is a distinct feature of and sp. In inactivated blood-stage parasites can cause a recrudescence years after the infection was clinically cured. To properly describe population-genetic processes, such as the spread of anti-malarial drug resistance, these features must be accounted for appropriately. Here, we introduce and extend a population-genetic framework for the evolutionary dynamics of malaria, which applies to all human-pathogenic malaria species. The model focuses on, but is not limited to, the spread of drug resistance. The framework elucidates how the presence of dormant liver stage or inactivated blood stage parasites that act like seed banks delay evolutionary processes. It is shown that, contrary to standard population-genetic theory, the process of selection and recombination cannot be decoupled in malaria. Furthermore, we discuss the connection between haplotype frequencies, haplotype prevalence, transmission dynamics, and relapses or recrudescence in malaria.
PubMed: 36406132
DOI: 10.3389/fgene.2022.1030463 -
Malaria Journal May 2022During the twentieth century, there was an explosion in understanding of the malaria parasites infecting humans and wild primates. This was built on three main data... (Review)
Review
During the twentieth century, there was an explosion in understanding of the malaria parasites infecting humans and wild primates. This was built on three main data sources: from detailed descriptive morphology, from observational histories of induced infections in captive primates, syphilis patients, prison inmates and volunteers, and from clinical and epidemiological studies in the field. All three were wholly dependent on parasitological information from blood-film microscopy, and The Primate Malarias" by Coatney and colleagues (1971) provides an overview of this knowledge available at that time. Here, 50 years on, a perspective from the third decade of the twenty-first century is presented on two pairs of primate malaria parasite species. Included is a near-exhaustive summary of the recent and current geographical distribution for each of these four species, and of the underlying molecular and genomic evidence for each. The important role of host transitions in the radiation of Plasmodium spp. is discussed, as are any implications for the desired elimination of all malaria species in human populations. Two important questions are posed, requiring further work on these often ignored taxa. Is Plasmodium brasilianum, circulating among wild simian hosts in the Americas, a distinct species from Plasmodium malariae? Can new insights into the genomic differences between Plasmodium ovale curtisi and Plasmodium ovale wallikeri be linked to any important differences in parasite morphology, cell biology or clinical and epidemiological features?
Topics: Animals; Genomics; Humans; Malaria; Parasites; Plasmodium malariae; Plasmodium ovale; Primates
PubMed: 35505317
DOI: 10.1186/s12936-022-04151-4 -
The American Journal of Tropical... May 2021In 2016, we reported the presence of Plasmodium vivax in Botswana through active case detection. A real-time PCR was used during a similar study in 10 districts to...
In 2016, we reported the presence of Plasmodium vivax in Botswana through active case detection. A real-time PCR was used during a similar study in 10 districts to assess changes in the P. vivax prevalence. We assessed 1,614 children (2-13 years of age) for hemoglobin (Hb; g/dL) and Plasmodium parasites. The median age of all participants was 5.0 years (25th percentile, 3 years; 75th percentile, 8 years). The median Hb (g/dL) level was 12.1, but 18.3% of the participants had anemia (Hb < 11.0 g/dL); these participants were clustered in the younger than 5 years age group in all districts (P < 0.001). The risk of anemia decreased with age 5 years or older (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.197-0.34; P < 0.001). The prevalence rates of Plasmodium parasites were as follows: P. vivax, 12.7%; P. falciparum, 12.7%; P. malariae, 0.74%; and P. ovale (P. ovale curtisi), 0.68%. Mixed infection rates were as follows: P. falciparum and P. vivax, 2.35%; P. falciparum and P. ovale curtisi, 0.56%; P. vivax and P. malariae, 0.06%; and P. falciparum and P. malariae, 0.68%. The infections were largely asymptomatic (99.6%). Using logistic regression, the risk of infection with P. vivax was highest in Kweneng East (OR, 6.2; 95% CI, 2.9-13.1), followed by South East (OR, 5.6; 95% CI, 2.5-12.3) and Ngami (OR, 5.1; 95% CI, 2.2-12.0). Compared to the risk of infection for children younger than 5 years, the risk of infection decreased for children 5 years or older in regions with high rates of P. vivax and P. falciparum infections. P. vivax and P. falciparum have expanded within the asymptomatic population in Botswana; therefore, careful attention is required for their elimination.
Topics: Adolescent; Asymptomatic Infections; Botswana; Child; Child, Preschool; DNA, Protozoan; Humans; Malaria, Falciparum; Malaria, Vivax; Odds Ratio; Plasmodium falciparum; Plasmodium vivax; Prevalence; Real-Time Polymerase Chain Reaction
PubMed: 33939635
DOI: 10.4269/ajtmh.21-0083 -
Tropical Parasitology 2020Malaria, a mosquito-transmitted parasitic disease, has been targeted for elimination in many parts of the world. For many years, and have been known to cause malaria... (Review)
Review
Malaria, a mosquito-transmitted parasitic disease, has been targeted for elimination in many parts of the world. For many years, and have been known to cause malaria in humans. Now, is considered to be an important cause of malaria, especially in Southeast Asia. The emergence of zoonotic implication is a challenge in the elimination efforts of malaria in Southeast Asia. is known to cause severe complicated malaria in humans. parasite is transmitted between humans and wild macaque through mosquito vectors. It appears that the malaria disease severity and host immune evasion depend on antigenic variation exhibited at the surface of the infected erythrocyte. is sensitive to antimalarial drug artemisinin. Identification of vector species, their biting behavior, timely correct diagnosis, and treatment are important steps in disease management and control. There is a need to identify and implement effective intervention measures to cut the chain of transmissions from animals to humans. The zoonotic malaria definitely poses a significant challenge in elimination and subsequent eradication of all types of malaria from this globe.
PubMed: 32775284
DOI: 10.4103/tp.TP_17_18 -
Journal of Tropical Medicine 2022Worldwide, transmission of emerging and reemerging malaria infections poses a significant threat to human health in the Sub-Saharan Africa, one that can quickly... (Review)
Review
Worldwide, transmission of emerging and reemerging malaria infections poses a significant threat to human health in the Sub-Saharan Africa, one that can quickly overwhelm public health resources. While the disease burden of malaria in the Sub-Saharan Africa appears to be on a gradual decline, it is characterized by spatial and temporal variability occasioning a sorry state for the Global South Countries. New evidence on long-term complications of malaria heightens our awareness of its public health impact. Given the likelihood of misdiagnosis, and the unknown levels of malaria transmission across different landscapes, many missed opportunities for prevention occur. Africa's population growth, unplanned urbanization, habitat destruction, and trans-border travel are contributing to a rise in the calamitous epidemiology of malaria. Despite empirical statistics demonstrating a downward trend in the malaria disease burden attributable to the scale-up of multiple control strategies, including new diagnostic technologies, malaria remains a global threat to human health in Sub-Sahara Africa. Malaria is a severe public health threat globally, despite several advancements and innovations in its control. Six species of the genus including and are known to infect humans. However, greatest disease burden and fatalities are caused by . Globally, about 3 billion individuals are at risk of contracting malaria disease every year, with over 400,000 fatalities reported in the Sub-Saharan Africa. World Health Organization (WHO) 2018 malaria report indicated that approximately 405,000 mortalities and 228 million cases were reported worldwide, with Africa carrying the highest disease burden. Over the last decade, there has been a significant decline in malaria deaths and infections, which may be related to the availability of effective diagnostic techniques. However, in certain areas, the rate of decline has slowed or even reversed the gains made so far. Accurate diagnosis, adequate treatment, and management of the disease are critical WHO-set goals of eliminating malaria by 2030. Microscopy, rapid diagnostic tests (RDTs), nucleic acid amplification tests (NAATs), and biosensors are all currently accessible diagnostic methods. These technologies have substantial flaws and triumphs that could stymie or accelerate malaria eradication efforts. The cost, ease, accessibility, and availability of skilled persons all influence the use of these technologies. These variables have a direct and indirect ramification on the entire management portfolio of patients. Despite the overall decline in the malaria disease burden driven partly by new diagnostic technologies, a sobering pattern marked by limited number of studies and spatial as well as temporal heterogeneity remains a concern. This review summarizes the principle, performance, gaps, accomplishments, and applicability of numerous malaria diagnostic techniques and their potential role in reducing the malaria disease burden in Sub-Saharan Africa.
PubMed: 35360189
DOI: 10.1155/2022/7324281 -
Genome Medicine Nov 2023Malaria continues to be a major threat to global public health. Whole genome sequencing (WGS) of the underlying Plasmodium parasites has provided insights into the...
BACKGROUND
Malaria continues to be a major threat to global public health. Whole genome sequencing (WGS) of the underlying Plasmodium parasites has provided insights into the genomic epidemiology of malaria. Genome sequencing is rapidly gaining traction as a diagnostic and surveillance tool for clinical settings, where the profiling of co-infections, identification of imported malaria parasites, and detection of drug resistance are crucial for infection control and disease elimination. To support this informatically, we have developed the Malaria-Profiler tool, which rapidly (within minutes) predicts Plasmodium species, geographical source, and resistance to antimalarial drugs directly from WGS data.
RESULTS
The online and command line versions of Malaria-Profiler detect ~ 250 markers from genome sequences covering Plasmodium speciation, likely geographical source, and resistance to chloroquine, sulfadoxine-pyrimethamine (SP), and other anti-malarial drugs for P. falciparum, but also providing mutations for orthologous resistance genes in other species. The predictive performance of the mutation library was assessed using 9321 clinical isolates with WGS and geographical data, with most being single-species infections (P. falciparum 7152/7462, P. vivax 1502/1661, P. knowlesi 143/151, P. malariae 18/18, P. ovale ssp. 5/5), but co-infections were identified (456/9321; 4.8%). The accuracy of the predicted geographical profiles was high to both continental (96.1%) and regional levels (94.6%). For P. falciparum, markers were identified for resistance to chloroquine (49.2%; regional range: 24.5% to 100%), sulfadoxine (83.3%; 35.4- 90.5%), pyrimethamine (85.4%; 80.0-100%) and combined SP (77.4%). Markers associated with the partial resistance of artemisinin were found in WGS from isolates sourced from Southeast Asia (30.6%).
CONCLUSIONS
Malaria-Profiler is a user-friendly tool that can rapidly and accurately predict the geographical regional source and anti-malarial drug resistance profiles across large numbers of samples with WGS data. The software is flexible with modifiable bioinformatic pipelines. For example, it is possible to select the sequencing platform, display specific variants, and customise the format of outputs. With the increasing application of next-generation sequencing platforms on Plasmodium DNA, Malaria-Profiler has the potential to be integrated into point-of-care and surveillance settings, thereby assisting malaria control. Malaria-Profiler is available online (bioinformatics.lshtm.ac.uk/malaria-profiler) and as standalone software ( https://github.com/jodyphelan/malaria-profiler ).
Topics: Humans; Animals; Antimalarials; Parasites; Coinfection; Malaria; Plasmodium; Malaria, Falciparum; Chloroquine; Malaria, Vivax; Drug Resistance; Plasmodium falciparum
PubMed: 37950308
DOI: 10.1186/s13073-023-01247-7 -
The American Journal of Tropical... Dec 2020Although continues to be the main target for malaria elimination, other species persist in Africa. Their clinical diagnosis is uncommon, whereas rapid diagnostic tests...
Although continues to be the main target for malaria elimination, other species persist in Africa. Their clinical diagnosis is uncommon, whereas rapid diagnostic tests (RDTs), the most widely used malaria diagnostic tools, are only able to distinguish between and non- species, the latter as "pan-species." Blood samples from health facilities were collected in southern Nigeria (Lagos and Calabar) in 2017 (October-December) and Calabar only in 2018 (October-November), and analyzed by several methods, namely, microscopy, quantitative real-time PCR (qPCR), and peptide serology targeting candidate antigens ( apical membrane antigen, . lactose dehydrogenase, and . circumsporozoite surface protein). Both microscopy and qPCR diagnostic approaches detected comparable proportions (∼80%) of all RDT-positive samples infected with the dominant malaria parasite. However, higher proportions of non- species were detected by qPCR than microscopy, 10% against 3% infections for and 3% against 0% for , respectively. No infection was detected. Infection rates for varied between age-groups, with the highest rates in individuals aged > 5 years. -specific seroprevalence rates fluctuated in those aged < 10 years but generally reached the peak around 20 years of age for all peptides. The heterogeneity and rates of these non-falciparum species call for increased specific diagnosis and targeting by elimination strategies.
Topics: Adolescent; Antigens, Protozoan; Child; Child, Preschool; Diagnostic Tests, Routine; Female; Humans; Infant; Malaria; Male; Microscopy; Nigeria; Plasmodium; Plasmodium malariae; Plasmodium ovale; Plasmodium vivax; Protozoan Proteins; Real-Time Polymerase Chain Reaction; Seroepidemiologic Studies; Surveys and Questionnaires
PubMed: 33124531
DOI: 10.4269/ajtmh.20-0593 -
The Lancet. Microbe Aug 2022High-quality evidence for the therapeutic efficacy and effectiveness of antimalarials for infections caused by Plasmodium malariae, Plasmodium ovale spp, and...
Effectiveness of pyronaridine-artesunate against Plasmodium malariae, Plasmodium ovale spp, and mixed-Plasmodium infections: a post-hoc analysis of the CANTAM-Pyramax trial.
BACKGROUND
High-quality evidence for the therapeutic efficacy and effectiveness of antimalarials for infections caused by Plasmodium malariae, Plasmodium ovale spp, and mixed-Plasmodium infections is scarce. In this study, we aimed to analyse the efficacy of pyronaridine-artesunate for the treatment of non-falciparum and mixed-species Plasmodium infections from a large phase 3b/4 clinical trial in central Africa.
METHODS
This post-hoc analysis was done in a random subset of samples from two sites (in the Democratic Republic of the Congo and in Gabon) of the CANTAM-Pyramax trial assessing pyronaridine-artesunate therapy. We randomly selected paired dried blood spot samples from day 0 and day 28 (or unforeseen visit) and analysed them by quantitative PCR for mixed Plasmodium infections or non-falciparum mono-infections. Day 28 (or unforeseen visit) samples positive for non-falciparum malaria were re-assessed by microscopy to identify microscopic versus submicroscopic infections. Analyses were done on two sample sets: a per-protocol set and an intention-to-treat set.
FINDINGS
Among 1502 randomly selected samples, 192 (12·8%) showed mixed-Plasmodium infections or non-falciparum mono-infections. We did not detect P vivax in the samples. For both the per-protocol and intention-to-treat sets, the overall day 28 cure rates for P malariae, P ovale curtisi, and P ovale wallikeri were 96·3% or higher (95% CIs from 81·0-99·9 to 95·7-100). Cure rates were consistently high in P malariae (99·2%, 95·7-100) and P ovale spp (97·9%, 88·7-99·9, for P ovale curtisi and 96·3%, 81·0-99·9, for P ovale wallikeri) infections.
INTERPRETATION
This post-hoc analysis provides important evidence supporting the high efficacy of pyronaridine-artesunate against mono-infections with P malariae, P ovale curtisi, or P ovale wallikeri and mixed-Plasmodium infections in a real-world setting.
FUNDING
Medicines for Malaria Venture.
Topics: Artesunate; Drug Combinations; Humans; Malaria; Naphthyridines; Plasmodium malariae; Plasmodium ovale
PubMed: 35654079
DOI: 10.1016/S2666-5247(22)00092-1 -
Comparative Medicine Jun 2024Malaria is a parasitic disease caused by protozoan species of the genus and transmitted by female mosquitos of the genus and other Culicidae. Most of the parasites of...
Malaria is a parasitic disease caused by protozoan species of the genus and transmitted by female mosquitos of the genus and other Culicidae. Most of the parasites of the genus are highly species specific with more than 200 species described affecting different species of mammals, birds, and reptiles. species strictly affecting humans are , , , and More recently, and other nonhuman primate plasmodia were found to naturally infect humans. Currently, malaria occurs mostly in poor tropical and subtropical areas of the world, and in many of these countries it is the leading cause of illness and death. For more than 100 y, animal models, have played a major role in our understanding of malaria biology. Avian species were the first to be used as models to study human malaria. Malaria parasite biology and immunity were first studied using mainly and . Rodent malarias, particularly and , have been used extensively as models to study malaria in mammals. Several species of from nonhuman primates have been used as surrogate models to study human malaria immunology, pathogenesis, candidate vaccines, and treatments. , , and are important models for studying malaria produced by and , while is used as a model for studying severe malaria. Other nonhuman primate malarias used in research are , , , , and . Very few nonhuman primate species can develop an infection with human malarias. Macaques in general are resistant to infection with , , , and . Only apes and a few species of New World monkeys can support infection with human malarias. Herein we review the most common, and some less common, avian, reptile, and mammal plasmodia species used as models to study human malaria.
PubMed: 38902006
DOI: 10.30802/AALAS-CM-24-000019