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Parasitology Research Jun 2016Malaria recurrences after an initially successful therapy and malarial fever occurring a long time after infection are well-known problems in malariology. Currently, two... (Review)
Review
Malaria recurrences after an initially successful therapy and malarial fever occurring a long time after infection are well-known problems in malariology. Currently, two distinct types of malaria recurrences are defined: recrudescence and relapse. A recrudescence is thought to originate from circulating Plasmodium blood stages which do not cause fever before a certain level of a microscopically detectable parasitemia is reached. Contrary, a relapse is thought to originate from quiescent intracellular hepatic parasite stages called hypnozoites. Recrudescences would typically occur in infections due to Plasmodium falciparum. Plasmodium knowlesi, and Plasmodium malariae, whereas relapses would be caused exclusively by Plasmodium vivax and Plasmodium ovale. This schematic view is, however, insufficiently supported by experimental evidence. For instance, hypnozoites of P. ovale have never been experimentally documented. On the other hand, the nonfinding of P. malariae hypnozoites turned into the proof for the nonexistence of P. malariae hypnozoites. Clinical relapse-type recurrences have been observed in both P. ovale and P. malariae infections, and decade-long incubation times have also been reported in P. falciparum infections. We propose a gradual hypothesis in accordance with the continuity concept of biological evolution: both, relapse and recrudescence may be potentially caused by all Plasmodium spp. We hypothesize that the difference between the various Plasmodium spp. is quantitative rather than qualitative: there are Plasmodium spp. which frequently cause relapses such as P. vivax, particularly the P.v. Chesson strain, species which cause relapses less frequently, such as P. ovale and sometimes P. malariae, and species which may exceptionally cause relapses such as P. falciparum. All species may cause recrudescences. As clinical consequences, we propose that 8-aminquinolines may be considered in a relapse-type recrudescence regardless of the causal Plasmodium sp., whereas primaquine relapse prevention might not be routinely indicated in malaria due to P. ovale.
Topics: Aminoquinolines; Antimalarials; Humans; Liver; Malaria; Parasitemia; Plasmodium; Plasmodium falciparum; Plasmodium knowlesi; Plasmodium malariae; Plasmodium ovale; Plasmodium vivax; Primaquine; Recurrence; Species Specificity
PubMed: 27079460
DOI: 10.1007/s00436-016-5043-0 -
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 -
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 -
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 -
Expert Opinion on Pharmacotherapy Oct 2014Chemotherapy of malaria has become a rapidly changing field. Less than two decades ago, treatment regimens were increasingly bound to fail due to emerging drug... (Review)
Review
INTRODUCTION
Chemotherapy of malaria has become a rapidly changing field. Less than two decades ago, treatment regimens were increasingly bound to fail due to emerging drug resistance against 4-aminoquinolines and sulfa compounds. By now, artemisinin-based combination therapies (ACTs) constitute the standard of care for uncomplicated falciparum malaria and are increasingly also taken into consideration for the treatment of non-falciparum malaria.
AREAS COVERED
This narrative review provides an overview of the state-of-art antimalarial drug therapy, highlights the global portfolio of current Phase III/IV clinical trials and summarizes current developments.
EXPERT OPINION
Malaria chemotherapy remains a dynamic field, with novel drugs and drug combinations continuing to emerge in order to outpace the development of large-scale drug resistance against the currently most important drug class, the artemisinin derivatives. More randomized controlled studies are urgently needed especially for the treatment of malaria in first trimester pregnant women. ACTs should be used for the treatment of imported malaria more consequently. Gaining sufficient efficacy and safety information on ACT use for non-falciparum species including Plasmodium ovale and malariae should be a research priority. Continuous investment into malaria drug development is a vital factor to combat artemisinin resistance and successfully improve malaria control toward the ultimate goal of elimination.
Topics: Antimalarials; Artemisinins; Drug Discovery; Drug Resistance; Drug Therapy, Combination; Female; Humans; Malaria; Plasmodium; Pregnancy
PubMed: 25110058
DOI: 10.1517/14656566.2014.944499 -
Malaria Journal Nov 2016Malaria, due to Plasmodium ovale, can be challenging to diagnose due to clinically mild disease and low parasite burden. Two genetically distinct sub-species of P. ovale...
BACKGROUND
Malaria, due to Plasmodium ovale, can be challenging to diagnose due to clinically mild disease and low parasite burden. Two genetically distinct sub-species of P. ovale exist: Plasmodium ovale curtisi (classic) and Plasmodium ovale wallikeri (variant). It is presently unknown if the sub-species causing infection affects performance of malaria diagnostic tests. The aim of this work was to understand how the genetically distinct sub-species, P. o. curtisi and P. o. wallikeri, affect malaria diagnostic tests.
METHODS
Plasmodium ovale-positive whole blood specimens were sub-speciated by PCR and sequencing of 18S rRNA and dhfr-ts. Parasitaemia, morphology, pan-aldolase positivity, 18S copy number, and dhfr-ts sequences were compared between sub-species.
RESULTS
From 2006 to 2015, 49 P. ovale isolates were identified, of which 22 were P. o. curtisi and 27 P. o. wallikeri; 80% were identified in the last five years, and 88% were acquired in West Africa. Sub-species did not differ by parasitaemia, 18S copy number, or pan-aldolase positivity. Lack of Schüffner's stippling was over-represented among P. o. wallikeri isolates (p = 0.02). Several nucleotide polymorphisms between the sub-species were observed, but they do not occur at sites believed to relate to antifolate binding.
CONCLUSIONS
Plasmodium ovale is increasing among travellers to West Africa, although sub-species do not differ significantly by parasitologic features such as parasitaemia. Absence of Schüffner's stippling may be a feature specific to P. o. wallikeri and is a novel finding.
Topics: Africa, Western; DNA, Protozoan; DNA, Ribosomal; Diagnostic Tests, Routine; Fructose-Bisphosphate Aldolase; Humans; Malaria; Parasite Load; Parasitemia; Plasmodium ovale; Polymerase Chain Reaction; RNA, Ribosomal, 18S; Sequence Analysis, DNA
PubMed: 27832785
DOI: 10.1186/s12936-016-1601-2 -
Microorganisms Jun 2022was until recently thought to be a single unique species. However, the deployment of more sensitive tools has led to increased diagnostic sensitivity, including new...
was until recently thought to be a single unique species. However, the deployment of more sensitive tools has led to increased diagnostic sensitivity, including new evidence supporting the presence of two sympatric species: (Poc) and (Pow). The increased reports and evolution of subspecies are concerning for sub-Saharan Africa where the greatest burden of malaria is borne. Employing published sequence data, we set out to decipher the genetic diversity and phylogenetic relatedness of and using the tryptophan-rich protein and small subunit ribosomal RNA genes from Gabon, Senegal, Ethiopia and Kenya. Higher number of segregating sites were recorded in Poc isolates from Gabon than from Ethiopia, with a similar trend in the number of haplotypes. With regards to Pow, the number of segregating sites and haplotypes from Ethiopia were higher than from those in Gabon. Poc from Kenya, had higher segregating sites (20), and haplotypes (4) than isolates from Senegal (8 and 3 respectively), while nucleotide from Senegal were more diverse (θw = 0.02159; π = 0.02159) than those from Kenya (θw = 0.01452; π = 0.01583). Phylogenetic tree construction reveal two large clades with Poc from Gabon and Ethiopia, and distinct Gabonese and Ethiopian clades on opposite ends. A similar observation was recorded for the phylogeny of Poc isolates from Kenya and Senegal. With such results, there is a high potential that ovale malaria control measures deployed in one country may be effective in the other since parasite from both countries show some degree of relatedness. How this translates to malaria control efforts throughout the continent would be next step deserving more studies.
PubMed: 35744665
DOI: 10.3390/microorganisms10061147 -
Open Forum Infectious Diseases Jul 2022The majority of symptomatic malaria in sub-Saharan Africa is caused by . Infection with is often not recorded and not considered clinically relevant. Here, we describe...
The majority of symptomatic malaria in sub-Saharan Africa is caused by . Infection with is often not recorded and not considered clinically relevant. Here, we describe 8 cases of infection from 3 African countries-all of which were misdiagnosed at the presenting health facility.
PubMed: 35854985
DOI: 10.1093/ofid/ofac261 -
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