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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 -
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 -
Parasitology Nov 2023Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously... (Review)
Review
Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously considered a non-human primate (NHP) infecting species, is now a cause of human malaria in Malaysia. The other NHP species, , , , , and cause malaria in primates, which are mainly reported in southeast Asia and South America. The non- NHP species also emerged and were found to cross-transmit from their natural hosts (NHP) – to human hosts in natural settings. Here we have reviewed and collated data from the literature on the NHPs-to-human-transmitting species. It was observed that the natural transmission of these NHP parasites to humans had been reported from 2010 onwards. This study shows that: (1) the majority of the non- NHP mixed species infecting human cases were from Yala province of Thailand; (2) mono/mixed infections with other human-infecting species were prevalent in Malaysia and Thailand and (3) and were found in Central and South America.
Topics: Animals; Humans; Malaria; Plasmodium knowlesi; Primates; Asia, Southeastern; Plasmodium vivax
PubMed: 37929579
DOI: 10.1017/S003118202300077X -
Infectious Diseases of Poverty Aug 2021China has reached important milestones in the elimination of malaria. However, the numbers of imported recurrent cases of Plasmodium vivax and P. ovale are gradually...
BACKGROUND
China has reached important milestones in the elimination of malaria. However, the numbers of imported recurrent cases of Plasmodium vivax and P. ovale are gradually increasing, which increases the risk of malaria re-establishment in locations where Anopheles mosquitoes exist. The aim of this study is to characterize the epidemiological profiles of imported recurrent P. vivax and P. ovale cases, quantifying the recurrence burden and guiding the development of appropriate public health intervention strategies.
METHODS
Individual-level data of imported recurrent P. vivax and P. ovale cases were collected from 2013 to 2020 in China via the Parasitic Diseases Information Reporting Management System. Demographic characteristics, temporal and spatial distributions, and the interval from previous infection to recurrence were analyzed by SAS, ArcGIS and GraphPad Prism software, respectively, to explore the epidemiological profiles of imported recurrent cases.
RESULTS
A total of 307 imported recurrent cases, including 179 P. vivax and 128 P. ovale cases, were recorded. The majority of cases occurred in males (P. vivax 91.1%, P. ovale 93.8%) and migrant workers (P. vivax 43.2%, P. ovale 44.7%). Individuals aged 30-39 years had the highest P. vivax and P. ovale recurrent infection rates, respectively. The number of imported recurrent cases of infection by these two malaria species increased from 2013 to 2018, and P. vivax infection showed well-defined seasonality, with two peaks in February and June, respectively. More than 90% of patients with recurrent cases did not receive radical treatment for previous infection. Most imported recurrent P. vivax cases were reported in Yunnan Province and were imported from Myanmar, Ethiopia, and Pakistan, while most recurrent P. ovale cases were reported in southern China and primarily imported from Cameroon, Ghana, and Nigeria. The intervals from previous malaria infection to recurrence among different continents were significantly different (P = 0.0016) for P. vivax malaria but not for P. ovale malaria (P = 0.2373).
CONCLUSIONS
The large number of imported recurrent cases has been a major challenge in the prevention of malaria re-establishment in China. This study provides evidence to guide the development of appropriate public health intervention strategies for imported recurrent P. vivax and P. ovale cases.
Topics: Animals; Anopheles; China; Humans; Malaria; Male; Plasmodium ovale; Plasmodium vivax
PubMed: 34425898
DOI: 10.1186/s40249-021-00896-3 -
Frontiers in Public Health 2023This study aimed at exploring the epidemiological pattern of imported malaria in China before malaria elimination in 2021, to provide evidence-based data for preventing...
BACKGROUND
This study aimed at exploring the epidemiological pattern of imported malaria in China before malaria elimination in 2021, to provide evidence-based data for preventing malaria re-establishment in China.
METHODS
Nine-year surveillance data on imported malaria in four provincial-level administrative divisions (PLADs) (Anhui, Chongqing, Guangxi, and Zhejiang) between 2011 and 2019 were thoroughly collected and analyzed.
RESULTS
A quite stable trend in imported malaria cases between 2011 and 2019 was observed. In total, 6,064 imported patients were included. was the most frequently reported species (4,575, 75.6%). Cases of malaria were most frequently imported from Western Africa (54.4%). We identified an increasing trend in and a persistence of infections among the cases of malaria imported from Western Africa. Most patients (97.5%) were 20-50 years old. Among imported malaria infections, the main purposes for traveling abroad were labor export (4,914/6,064, 81.0%) and business trips (649, 10.7%). Most patients (2,008/6,064, 33.1%) first visited county-level medical institutions when they sought medical help in China. More patients were diagnosed within 3 days after visiting Centers for Disease Control and Prevention (CDCs) or entry-exit quarantine facilities (EQFs) (1,147/1609, 71.3%) than after visiting medical institutions (2,182/3993, 54.6%).
CONCLUSION
Imported malaria still poses a threat to the malaria-free status of China. County-level institutions are the primary targets in China to improve the sensitivity of the surveillance system and prevent the re-establishment of malaria. Health education should focus on exported labors, especially to Western and Central Africa. Increasing trend in and persistence of infections indicated their underestimations in Western Africa. Efficient diagnostic tools and sensitive monitoring systems are required to identify species in Africa.
Topics: Humans; Young Adult; Adult; Middle Aged; Plasmodium ovale; Plasmodium vivax; Incidence; China; Malaria
PubMed: 37448654
DOI: 10.3389/fpubh.2023.1203095 -
Frontiers in Public Health 2023In 2021, India contributed for ~79% of malaria cases and ~ 83% of deaths in the South East Asia region. Here, we systematically and critically analyzed data... (Review)
Review
INTRODUCTION
In 2021, India contributed for ~79% of malaria cases and ~ 83% of deaths in the South East Asia region. Here, we systematically and critically analyzed data published on malaria in pregnancy (MiP) in India.
METHODS
Epidemiological, clinical, parasitological, preventive and therapeutic aspects of MiP and its consequences on both mother and child were reviewed and critically analyzed. Knowledge gaps and solution ways are also presented and discussed. Several electronic databases including Google scholar, Google, PubMed, Scopus, Wiley Online library, the Malaria in Pregnancy Consortium library, the World Malaria Report, The WHO regional websites, and ClinicalTrials.gov were used to identify articles dealing with MiP in India. The archives of local scientific associations/journals and website of national programs were also consulted.
RESULTS
Malaria in pregnancy is mainly due to () and (), and on rare occasions to spp. and too. The overall prevalence of MiP is ~0.1-57.7% for peripheral malaria and ~ 0-29.3% for placental malaria. Peripheral infection at antenatal care (ANC) visits decreased from ~13% in 1991 to ~7% in 1995-1996 in Madhya Pradesh, while placental infection at delivery unit slightly decreased from ~1.5% in 2006-2007 to ~1% in 2012-2015 in Jharkhand. In contrast, the prevalence of peripheral infection at ANC increased from ~1% in 2006-2007 to ~5% in 2015 in Jharkhand, and from ~0.5% in 1984-1985 to ~1.5% in 2007-2008 in Chhattisgarh. Clinical presentation of MiP is diverse ranging from asymptomatic carriage of parasites to severe malaria, and associated with comorbidities and concurrent infections such as malnutrition, COVID-19, dengue, and cardiovascular disorders. Severe anemia, cerebral malaria, severe thrombocytopenia, and hypoglycemia are commonly seen in severe MiP, and are strongly associated with tragic consequences such as abortion and stillbirth. Congenital malaria is seen at prevalence of ~0-12.9%. Infected babies are generally small-for-gestational age, premature with low birthweight, and suffer mainly from anemia, thrombocytopenia, leucopenia and clinical jaundice. Main challenges and knowledge gaps to MiP control included diagnosis, relapsing malaria, mixed infection treatment, self-medication, low density infections and utility of artemisinin-based combination therapies.
CONCLUSION
All taken together, the findings could be immensely helpful to control MiP in malaria endemic areas.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Abortion, Spontaneous; Anemia; India; Malaria; Malaria, Vivax; Placenta; Thrombocytopenia
PubMed: 37927870
DOI: 10.3389/fpubh.2023.1150466 -
Microbiology Spectrum Jun 2023Malaria treatments resulted in the decline of the deadliest Plasmodium falciparum globally while species, such as , infections have been increasingly detected across...
Malaria treatments resulted in the decline of the deadliest Plasmodium falciparum globally while species, such as , infections have been increasingly detected across sub-Saharan Africa. Currently, no experimental drug sensitivity data are available to guide effective treatment and management of infections, which is necessary for effective malaria elimination. We conducted a prospective study to evaluate epidemiology over 1 year and determined susceptibility of the field isolates to existing and lead advanced discovery antimalarial drugs. We report that while P. falciparum dominated both symptomatic and asymptomatic malaria cases, in mono or co-infections caused 7.16% of symptomatic malaria. Frontline antimalarials artesunate and lumefantrine inhibited as potently as P. falciparum. Chloroquine, which has been withdrawn in Ghana, was also highly inhibitory against both and P. falciparum. In addition, and P. falciparum displayed high susceptibility to quinine, comparable to levels observed with chloroquine. Pyrimethamine, which is a major drug for disease massive prevention, also showed great inhibition of , comparable to effects on P. falciparum. Furthermore, we identified strong inhibition of using GNF179, a close analogue of KAF156 imidazolopiperazines, which is a novel class of antimalarial drugs currently in clinical phase II testing. We further demonstrated that the phosphatidylinositol-4-OH kinase (PI4K)-specific inhibitor, KDU691, is highly inhibitory against and P. falciparum field isolates. Our data indicated that existing and lead advanced discovery antimalarial drugs are suitable for the treatment of infections in Ghana. Current malaria control and elimination tools such as drug treatments are not specifically targeting . can form hypnozoite and cause relapsing malaria. is the third most dominant species in Africa and requires radical cure treatment given that it can form liver dormant forms called hypnozoites that escape all safe treatments. The inappropriate treatment of would sustain its transmission in Africa where the medical need is the greatest. This is a hurdle for successful malaria control and elimination. Here, we provided experiment data that were lacking to guide treatment and disease control policy makers using reference antimalarial drugs. We also provided key experimental data for 2 clinical candidate drugs that can be used for prioritization selection of lead candidate's identification for clinical development.
Topics: Humans; Antimalarials; Plasmodium falciparum; Plasmodium ovale; Ghana; Prospective Studies; Malaria; Malaria, Falciparum; Chloroquine
PubMed: 37093000
DOI: 10.1128/spectrum.04916-22 -
British Journal of Clinical Pharmacology Jun 2022Methaemoglobin results from the oxidation of ferrous to ferric iron in the centre of the haem moiety of haemoglobin. The production of dose-dependent methaemoglobinaemia... (Review)
Review
Methaemoglobin results from the oxidation of ferrous to ferric iron in the centre of the haem moiety of haemoglobin. The production of dose-dependent methaemoglobinaemia by 8-aminoquinoline antimalarial drugs appears to be associated with, but is not directly linked to, therapeutic efficacy against latent Plasmodium vivax and Plasmodium ovale malarias (radical cure). Iatrogenic methaemoglobinaemia may be a useful pharmacodynamic measure in 8-aminoquinoline drug and dose optimization.
Topics: Aminoquinolines; Antimalarials; Humans; Methemoglobinemia; Plasmodium vivax
PubMed: 34997616
DOI: 10.1111/bcp.15219 -
Microbiology Spectrum Oct 2022Since 2010, the human-infecting malaria parasite Plasmodium ovale spp. has been divided into two genetically distinct species, P. ovale wallikeri and P. ovale curtisi....
Since 2010, the human-infecting malaria parasite Plasmodium ovale spp. has been divided into two genetically distinct species, P. ovale wallikeri and P. ovale curtisi. In recent years, application of whole-genome sequencing (WGS) to spp. allowed to get a better understanding of its evolutionary history and discover some specific genetic patterns. Nevertheless, WGS data from spp. are still scarce due to several drawbacks, including a high level of human DNA contamination in blood samples, infections with commonly low parasite density, and the lack of robust culture. Here, we developed two selective whole-genome amplification (sWGA) protocols that were tested on six and five mono-infection clinical samples. Blood leukodepletion by a cellulose-based filtration was used as the gold standard for intraspecies comparative genomics with sWGA. We also demonstrated the importance of genomic DNA preincubation with the endonuclease McrBC to optimize spp. sWGA. We obtained high-quality WGS data with more than 80% of the genome covered by ≥5 reads for each sample and identified more than 5,000 unique single-nucleotide polymorphisms (SNPs) per species. We also identified some amino acid changes in and for which similar mutations in P. falciparum and P. vivax are associated with pyrimethamine or cycloguanil resistance. In conclusion, we developed two sWGA protocols for spp. WGS that will help to design much-needed large-scale spp. population studies. Plasmodium ovale spp. has the ability to cause relapse, defined as recurring asexual parasitemia originating from liver-dormant forms. Whole-genome sequencing (WGS) data are of importance to identify putative molecular markers associated with relapse or other virulence mechanisms. Due to low parasitemia encountered in spp. infections and no culture available, WGS of spp. is challenging. Blood leukodepletion by filtration has been used, but no technique exists yet to increase the quantity of parasite DNA over human DNA when starting from genomic DNA extracted from whole blood. Here, we demonstrated that selective whole-genome amplification (sWGA) is an easy-to-use protocol to obtain high-quality WGS data for both spp. species from unprocessed blood samples. The new method will facilitate spp. population genomic studies.
Topics: Humans; Plasmodium ovale; Parasitemia; Pyrimethamine; Malaria; Recurrence; Amino Acids; Endonucleases
PubMed: 36098524
DOI: 10.1128/spectrum.00726-22 -
Clinical Infectious Diseases : An... Feb 2023The impact of chemoprophylaxis targeting Plasmodium falciparum on Plasmodium vivax and Plasmodium ovale, which may remain quiescent as hypnozoites in the liver, is...
Impact of Chemoprophylaxis on Plasmodium vivax and Plasmodium ovale Infection Among Civilian Travelers: A Nested Case-Control Study With a Counterfactual Approach on 862 Patients.
BACKGROUND
The impact of chemoprophylaxis targeting Plasmodium falciparum on Plasmodium vivax and Plasmodium ovale, which may remain quiescent as hypnozoites in the liver, is debated.
METHODS
We conducted a nested case-control analysis of the outcomes of P. vivax and P. ovale infections in imported malaria cases in France among civilian travelers from 1 January 2006, to 31 December 2017. Using adjusted logistic regression, we assessed the effect of chemoprophylaxis on the incubation period, time from symptoms to diagnosis, management, blood results, symptoms, and hospitalization duration. We analyzed the effect of blood-stage drugs (doxycycline, mefloquine, chloroquine, chloroquine-proguanil) or atovaquone-proguanil on the incubation period. We used a counterfactual approach to ascertain the causal effect of chemoprophylaxis on postinfection characteristics.
RESULTS
Among 247 P. vivax- and 615 P. ovale-infected travelers, 30% and 47%, respectively, used chemoprophylaxis, and 7 (3%) and 8 (1%) were severe cases. Chemoprophylaxis users had a greater risk of presenting symptoms >2 months after returning for both species (P. vivax odds ratio [OR], 2.91 [95% confidence interval {CI}, 1.22-6.95], P = .02; P. ovale OR, 2.28 [95% CI, 1.47-3.53], P < .001). Using drugs only acting on the blood stage was associated with delayed symptom onset after 60 days, while using atovaquone-proguanil was not.
CONCLUSIONS
Civilian travelers infected with P. vivax or P. ovale reporting chemoprophylaxis use, especially of blood-stage agents, had a greater risk of delayed onset of illness. The impact of chemoprophylaxis on the outcomes of infection with relapse-causing species calls for new chemoprophylaxis acting against erythrocytic and liver stages.
Topics: Humans; Atovaquone; Plasmodium vivax; Antimalarials; Plasmodium ovale; Case-Control Studies; Travel; Malaria; Malaria, Vivax; Chloroquine; Chemoprevention
PubMed: 35962785
DOI: 10.1093/cid/ciac641