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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 -
Malaria Journal Nov 2016The Greater Mekong Subregion is aiming to achieve regional malaria elimination by 2030. Though a shift in malaria parasite species predominance by Plasmodium vivax has...
BACKGROUND
The Greater Mekong Subregion is aiming to achieve regional malaria elimination by 2030. Though a shift in malaria parasite species predominance by Plasmodium vivax has been recently documented, the transmission of the two minor Plasmodium species, Plasmodium malariae and Plasmodium ovale spp., is poorly characterized in the region. This study aims to determine the prevalence of these minor species in the China-Myanmar border area and their genetic diversity.
METHODS
Epidemiology study was conducted during passive case detection in hospitals and clinics in Myanmar and four counties in China along the China-Myanmar border. Cross-sectional surveys were conducted in villages and camps for internally displaced persons to determine the prevalence of malaria infections. Malaria infections were diagnosed initially by microscopy and later in the laboratory using nested PCR for the SSU rRNA genes. Plasmodium malariae and P. ovale infections were confirmed by sequencing the PCR products. The P. ovale subtypes were determined by sequencing the Pocytb, Pocox1 and Pog3p genes. Parasite populations were evaluated by PCR amplification and sequencing of the MSP-1 genes. Antifolate sensitivity was assessed by sequencing the dhfr-ts and dhps genes from the P. malariae and P. ovale isolates.
RESULTS
Analysis of 2701 blood samples collected from the China-Myanmar border by nested PCR targeting the parasite SSU rRNA genes identified 561 malaria cases, including 161 Plasmodium falciparum, 327 P. vivax, 66 P. falciparum/P. vivax mixed infections, 4 P. malariae and 3 P. ovale spp. P. vivax and P. falciparum accounted for >60 and ~30% of all malaria cases, respectively. In comparison, the prevalence of P. malariae and P. ovale spp. was very low and only made up ~1% of all PCR-positive cases. Nevertheless, these two species were often misidentified as P. vivax infections or completely missed by microscopy even among symptomatic patients. Phylogenetic analysis of the SSU rRNA, Pocytb, Pocox1 and Pog3p genes confirmed that the three P. ovale spp. isolates belonged to the subtype P. ovale curtisi. Low-level genetic diversity was detected in the MSP-1, dhfr and dhps genes of these minor parasite species, potentially stemming from the low prevalence of these parasites preventing their mixing. Whereas most of the dhfr and dhps positions equivalent to those conferring antifolate resistance in P. falciparum and P. vivax were wild type, a new mutation S113C corresponding to the S108 position in pfdhfr was identified in two P. ovale curtisi isolates.
CONCLUSIONS
The four human malaria parasite species all occurred sympatrically at the China-Myanmar border. While P. vivax has become the predominant species, the two minor parasite species also occurred at very low prevalence but were often misidentified or missed by conventional microscopy. These minor parasite species displayed low levels of polymorphisms in the msp-1, dhfr and dhps genes.
Topics: Adult; Child; China; Cluster Analysis; Cross-Sectional Studies; DNA, Protozoan; DNA, Ribosomal; Drug Resistance; Female; Genetic Variation; Humans; Malaria; Male; Microscopy; Myanmar; Phylogeny; Plasmodium falciparum; Plasmodium malariae; Plasmodium ovale; Plasmodium vivax; Polymerase Chain Reaction; Prevalence; Protozoan Proteins; RNA, Ribosomal, 18S; Sequence Analysis, DNA; Young Adult
PubMed: 27846879
DOI: 10.1186/s12936-016-1605-y -
Nature Communications Oct 2023Reports suggest non-falciparum species are an underappreciated cause of malaria in sub-Saharan Africa but their epidemiology is ill-defined, particularly in highly...
Reports suggest non-falciparum species are an underappreciated cause of malaria in sub-Saharan Africa but their epidemiology is ill-defined, particularly in highly malaria-endemic regions. We estimated incidence and prevalence of PCR-confirmed non-falciparum and Plasmodium falciparum malaria infections within a longitudinal study conducted in Kinshasa, Democratic Republic of Congo (DRC) between 2015-2017. Children and adults were sampled at biannual household surveys and routine clinic visits. Among 9,089 samples from 1,565 participants, incidences of P. malariae, P. ovale spp., and P. falciparum infections by 1-year were 7.8% (95% CI: 6.4%-9.1%), 4.8% (95% CI: 3.7%-5.9%) and 57.5% (95% CI: 54.4%-60.5%), respectively. Non-falciparum prevalences were higher in school-age children, rural and peri-urban sites, and P. falciparum co-infections. P. falciparum remains the primary driver of malaria in the DRC, though non-falciparum species also pose an infection risk. As P. falciparum interventions gain traction in high-burden settings, continued surveillance and improved understanding of non-falciparum infections are warranted.
Topics: Child; Adult; Humans; Plasmodium ovale; Plasmodium malariae; Democratic Republic of the Congo; Longitudinal Studies; Malaria, Falciparum; Malaria; Prevalence; Plasmodium falciparum
PubMed: 37857597
DOI: 10.1038/s41467-023-42190-w -
Tropical Medicine and Health 2017Human infection caused by non-human primate malarial parasites, such as and , occurs naturally in Southeast Asian countries, including Vietnam. Members of the species... (Review)
Review
Human infection caused by non-human primate malarial parasites, such as and , occurs naturally in Southeast Asian countries, including Vietnam. Members of the species complex are known to be important vectors of human malarial parasites in the forested areas of southern and central Vietnam, including those in Khanh Phu commune and Khanh Hoa Province. Recent molecular epidemiological studies in Vietnam have reported cases of co-infection with , , , and in . The commonly found macaques in the forest in the forested areas are suspected to be bitten by the same population that bites humans. A recent epidemiological study identified six species of malarial parasites in sporozoite-infected using polymerase chain reaction, of which was the most common, followed by , , , , and . Based on a gametocyte analysis, the same allelic gametocyte types were observed in both humans and mosquitoes at similar frequencies. These observations suggest that people who stay overnight in the forests are frequently infected with both human and non-human primate malarial parasites, leading to the emergence of novel zoonotic malaria. Moreover, it is suggested that mosquito vector populations should be controlled and monitored closely.
PubMed: 29046610
DOI: 10.1186/s41182-017-0065-6 -
MedRxiv : the Preprint Server For... Apr 2023Increasing reports suggest that non-falciparum species are an underappreciated cause of malaria in sub-Saharan Africa, but their epidemiology is not well-defined. This...
BACKGROUND
Increasing reports suggest that non-falciparum species are an underappreciated cause of malaria in sub-Saharan Africa, but their epidemiology is not well-defined. This is particularly true in regions of high endemicity such as the Democratic Republic of Congo (DRC), where 12% of the world's malaria cases and 13% of deaths occur.
METHODS AND FINDINGS
The cumulative incidence and prevalence of and spp. infection detected by real-time PCR were estimated among children and adults within a longitudinal study conducted in seven rural, peri-urban, and urban sites from 2015-2017 in Kinshasa Province, DRC. Participants were sampled at biannual household survey visits (asymptomatic) and during routine health facility visits (symptomatic). Participant-level characteristics associated with non-falciparum infections were estimated for single- and mixed-species infections. Among 9,089 samples collected from 1,565 participants over a 3-year period, the incidence of and spp. infection was 11% (95% CI: 9%-12%) and 7% (95% CI: 5%-8%) by one year, respectively, compared to a 67% (95% CI: 64%-70%) one-year cumulative incidence of infection. Incidence continued to rise in the second year of follow-up, reaching 26% and 15% in school-age children (5-14yo) for and spp., respectively. Prevalence of spp., and infections during household visits were 3% (95% CI: 3%-4%), 1% (95% CI: 1%-2%), and 35% (95% CI: 33%-36%), respectively. Non-falciparum malaria was more prevalent in rural and peri-urban vs. urban sites, in school-age children, and among those with P. falciparum co-infection. A crude association was detected between and any anemia in the symptomatic clinic population, although this association did not hold when stratified by anemia severity. No crude associations were detected between non-falciparum infection and fever prevalence.
CONCLUSIONS
remains the primary driver of malaria morbidity and mortality in the DRC. However, non-falciparum species also pose an infection risk across sites of varying urbanicity and malaria endemicity within Kinshasa, DRC, particularly among children under 15 years of age. As interventions gain traction in high-burden settings like the DRC, continued surveillance and improved understanding of non-falciparum infections are warranted.
PubMed: 37790376
DOI: 10.1101/2023.04.20.23288826 -
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 -
Malaria Journal Jul 2020There have been an increasing number of imported cases of malaria in Hubei Province in recent years. In particular, the number of cases of Plasmodium ovale spp. and...
BACKGROUND
There have been an increasing number of imported cases of malaria in Hubei Province in recent years. In particular, the number of cases of Plasmodium ovale spp. and Plasmodium malariae significantly increased, which resulted in increased risks during the malaria elimination phase. The purpose of this study was to acquire a better understanding of the epidemiological characteristics of P. ovale spp. and P. malariae imported to Hubei Province, China, so as to improve case management.
METHODS
Data on all malaria cases from January 2014 to December 2018 in Hubei Province were extracted from the China national diseases surveillance information system (CNDSIS). This descriptive study was conducted to analyse the prevalence trends, latency periods, interval from onset of illness to diagnosis, and misdiagnosis of cases of P. ovale spp. and P. malariae malaria.
RESULTS
During this period, 634 imported malaria cases were reported, of which 87 P. ovale spp. (61 P. ovale curtisi and 26 P. ovale wallikeri) and 18 P. malariae cases were confirmed. The latency periods of P. ovale spp., P. malariae, Plasmodium vivax, and Plasmodium falciparum differed significantly, whereas those of P. ovale curtisi and P. ovale wallikeri were no significant difference. The proportion of correct diagnosis of P. ovale spp. and P. malariae malaria cases were 48.3% and 44.4%, respectively, in the hospital or lower-level Centers for Disease Control and Prevention (CDC). In the Provincial Reference Laboratory, the sensitivity of microscopy and rapid diagnostic tests was 94.3% and 70.1%, respectively, for detecting P. ovale spp., and 88.9% and 38.9%, respectively, for detecting P. malariae. Overall, 97.7% (85/87) of P. ovale spp. cases and 94.4% (17/18) of P. malariae cases originated from Africa.
CONCLUSION
The increase in the number of imported P. ovale spp. and P. malariae cases, long latency periods, and misdiagnosis pose a challenge to this region. Therefore, more attention should be paid to surveillance of imported cases of P. ovale spp. and P. malariae infection to reduce the burden of public health and potential risk of malaria.
Topics: China; Communicable Diseases, Imported; Diagnostic Errors; Latent Infection; Malaria; Plasmodium malariae; Plasmodium ovale; Prevalence
PubMed: 32698906
DOI: 10.1186/s12936-020-03337-y -
Nature Feb 2017Elucidation of the evolutionary history and interrelatedness of Plasmodium species that infect humans has been hampered by a lack of genetic information for three...
Elucidation of the evolutionary history and interrelatedness of Plasmodium species that infect humans has been hampered by a lack of genetic information for three human-infective species: P. malariae and two P. ovale species (P. o. curtisi and P. o. wallikeri). These species are prevalent across most regions in which malaria is endemic and are often undetectable by light microscopy, rendering their study in human populations difficult. The exact evolutionary relationship of these species to the other human-infective species has been contested. Using a new reference genome for P. malariae and a manually curated draft P. o. curtisi genome, we are now able to accurately place these species within the Plasmodium phylogeny. Sequencing of a P. malariae relative that infects chimpanzees reveals similar signatures of selection in the P. malariae lineage to another Plasmodium lineage shown to be capable of colonization of both human and chimpanzee hosts. Molecular dating suggests that these host adaptations occurred over similar evolutionary timescales. In addition to the core genome that is conserved between species, differences in gene content can be linked to their specific biology. The genome suggests that P. malariae expresses a family of heterodimeric proteins on its surface that have structural similarities to a protein crucial for invasion of red blood cells. The data presented here provide insight into the evolution of the Plasmodium genus as a whole.
Topics: Animals; Erythrocytes; Evolution, Molecular; Female; Genome; Genomics; Humans; Malaria; Pan troglodytes; Phylogeny; Plasmodium malariae; Plasmodium ovale
PubMed: 28117441
DOI: 10.1038/nature21038 -
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 -
Zoonoses (Burlington, Mass.) 2021Malaria is a deadly disease that affects the health of hundreds of millions of people annually. There are five parasite species that can naturally infect humans,...
Malaria is a deadly disease that affects the health of hundreds of millions of people annually. There are five parasite species that can naturally infect humans, including and . Some of the parasites can also infect various non-human primates. Parasites mainly infecting monkeys such as (in fact was considered as a parasite of monkeys for years) can also be transmitted to human hosts. Recently, many new species were discovered in African apes, and it is possible that some of the parasites can be transmitted to humans in the future. Here, we searched PubMed and the internet via Google and selected articles concerning zoonotic transmission and evolution of selected malaria parasite species. We reviewed the current advances in the relevant topics emphasizing on transmissions of malaria parasites between humans and non-human primates. We also briefly discuss the transmissions of some avian malaria parasites between wild birds and domestic fowls. Zoonotic malaria transmissions are widespread, which poses a threat to public health. More studies on parasite species identification in non-human primates, transmission, and evolution are needed to reduce or prevent transmission of malaria parasites from non-human primates to humans.
PubMed: 35282332
DOI: 10.15212/zoonoses-2021-0015