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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 -
Tropical Medicine and Infectious Disease Sep 2023Up-to-date knowledge of key epidemiological aspects of each species is necessary for making informed decisions on targeted interventions and control strategies to...
Up-to-date knowledge of key epidemiological aspects of each species is necessary for making informed decisions on targeted interventions and control strategies to eliminate each of them. This study aims to describe the epidemiology of plasmodial species in Mali, where malaria is hyperendemic and seasonal. Data reports collected during high-transmission season over six consecutive years were analyzed to summarize malaria epidemiology. Malaria species and density were from blood smear microscopy. Data from 6870 symptomatic and 1740 asymptomatic participants were analyzed. The median age of participants was 12 years, and the sex ratio (male/female) was 0.81. Malaria prevalence from all species was 65.20% (95% CI: 60.10-69.89%) and 22.41% (CI: 16.60-28.79%) for passive and active screening, respectively. was the most prevalent species encountered in active and passive screening (59.33%, 19.31%). This prevalence was followed by (1.50%, 1.15%) and (0.32%, 0.06%). Regarding frequency, was more frequent in symptomatic individuals (96.77% vs. 93.24%, = 0.014). In contrast, was more frequent in asymptomatic individuals (5.64% vs. 2.45%, < 0.001). remained the least frequent species (less than 1%), and no was detected. The most frequent coinfections were and (0.56%). Children aged 5-9 presented the highest frequency of infections (41.91%). Non- species were primarily detected in adolescents (10-14 years) with frequencies above 50%. Only infections had parasitemias greater than 100,000 parasites per µL of blood. gametocytes were found with variable prevalence across age groups. Our data highlight that represented the first burden, but other non- species were also important. Increasing attention to and is essential if malaria elimination is to be achieved.
PubMed: 37755899
DOI: 10.3390/tropicalmed8090438 -
Malaria Journal Sep 2023The routine surveillance of asymptomatic malaria using nucleic acid-based amplification tests is essential in obtaining reliable data that would inform malaria policy...
BACKGROUND
The routine surveillance of asymptomatic malaria using nucleic acid-based amplification tests is essential in obtaining reliable data that would inform malaria policy formulation and the implementation of appropriate control measures.
METHODS
In this study, the prevalence rate and the dynamics of Plasmodium species among asymptomatic children (n = 1697) under 5 years from 30 communities within the Hohoe municipality in Ghana were determined.
RESULTS AND DISCUSSION
The observed prevalence of Plasmodium parasite infection by polymerase chain reaction (PCR) was 33.6% (571/1697), which was significantly higher compared to that obtained by microscopy [26.6% (451/1697)] (P < 0.0001). Based on species-specific analysis by nested PCR, Plasmodium falciparum infection [33.6% (570/1697)] was dominant, with Plasmodium malariae, Plasmodium ovale and Plasmodium vivax infections accounting for 0.1% (1/1697), 0.0% (0/1697), and 0.0% (0/1697), respectively. The prevalence of P. falciparum infection among the 30 communities ranged from 0.0 to 82.5%. Following artesunate-amodiaquine (AS + AQ, 25 mg/kg) treatment of a sub-population of the participants (n = 184), there was a substantial reduction in Plasmodium parasite prevalence by 100% and 79.2% on day 7 based on microscopy and nested PCR analysis, respectively. However, there was an increase in parasite prevalence from day 14 to day 42, with a subsequent decline on day 70 by both microscopy and nested PCR. For parasite clearance rate analysis, we found a significant proportion of the participants harbouring residual Plasmodium parasites or parasite genomic DNA on day 1 [65.0% (13/20)], day 2 [65.0% (13/20)] and day 3 [60.0% (12/20)] after initiating treatment. Of note, gametocyte carriage among participants was low before and after treatment.
CONCLUSION
Taken together, the results indicate that a significant number of individuals could harbour residual Plasmodium parasites or parasite genomic DNA after treatment. The study demonstrates the importance of routine surveillance of asymptomatic malaria using sensitive nucleic acid-based amplification techniques.
Topics: Child; Humans; Ghana; Malaria; Artemisinins; Malaria, Falciparum; Plasmodium malariae; Nucleic Acids
PubMed: 37710288
DOI: 10.1186/s12936-023-04712-1 -
The American Journal of Tropical... Oct 2023There are many techniques for malaria diagnosis. Currently, the nested polymerase chain reaction (PCR) method based on a small subunit ribosomal RNA gene (18S rRNA) has...
A Novel Nested Multiplex Polymerase Chain Reaction Assay for Malaria Diagnosis Using the Hydroxymethyl Dihydropterin Pyrophosphokinase-Dihydropteroate Synthase (hppk-dhps) Gene.
There are many techniques for malaria diagnosis. Currently, the nested polymerase chain reaction (PCR) method based on a small subunit ribosomal RNA gene (18S rRNA) has been used as a confirmatory method. However, this method is time-consuming, laborious, and costly. Therefore, the objective of this study was to develop nested multiplex PCR for Plasmodium species identification using the dihydropterin pyrophosphokinase-dihydropteroate synthase (hppk-dhps) gene. Genus- and species-specific primers for the hppk-dhps gene were designed. The performance of the novel nested multiplex PCR was compared with 18S rRNA nested PCR. A total of 115 blood samples were used in this study, including 84 infected samples and 31 uninfected samples. Analysis of the blood samples by nested multiplex PCR targeting the hppk-dhps gene identified 81 infected cases. The level of agreement between this novel method and 18S rRNA nested PCR was 97.4%. Further, the novel method successfully detected all human malaria parasites except Plasmodium ovale and detected mixed Plasmodium falciparum/Plasmodium vivax infections. The sensitivity and specificity obtained from this novel method were 96.4% and 100%, respectively. The limit of detection of the hppk-dhps nested multiplex PCR for P. falciparum and P. vivax was 500 parasites/µL and 4 parasites/µL, respectively. The lowest parasite gDNA detected by this method was 0.5 ng/µL for P. falciparum and 0.1 ng/µL for P. vivax. These results corroborate that the hppk-dhps gene is a novel amplification target for the detection of human malaria. This novel target PCR-based method is a beneficial approach for malaria diagnosis, as well as species identification and differentiation.
PubMed: 37696509
DOI: 10.4269/ajtmh.23-0130 -
MedRxiv : the Preprint Server For... Aug 2023The worldwide decline in malaria incidence is revealing the extensive burden of non-malarial febrile illness (NMFI), which remains poorly understood and difficult to...
The worldwide decline in malaria incidence is revealing the extensive burden of non-malarial febrile illness (NMFI), which remains poorly understood and difficult to diagnose. To characterize NMFI in Senegal, we collected venous blood and clinical metadata from febrile patients and healthy controls in a low malaria burden area. Using 16S and unbiased sequencing, we detected viral, bacterial, or eukaryotic pathogens in 29% of NMFI cases. Bacteria were the most common, with relapsing fever and spotted fever found in 15% and 3.7% of cases, respectively. Four viral pathogens were found in a total of 7 febrile cases (3.5%). Sequencing also detected undiagnosed , including one putative infection. We developed a logistic regression model to distinguish from NMFIs with similar presentation based on symptoms and vital signs. These results highlight the challenge and importance of improved diagnostics, especially for , to support diagnosis and surveillance.
PubMed: 37662407
DOI: 10.1101/2023.08.24.23294564 -
Tropical Medicine and Infectious Disease Jul 2023The global malaria community has picked up the theme of malaria elimination in more than 90% of the world's population in the next decade. Recent reports of () in... (Review)
Review
The global malaria community has picked up the theme of malaria elimination in more than 90% of the world's population in the next decade. Recent reports of () in sub-Saharan Africa, including in Duffy-negative individuals, threaten the efforts aimed at achieving elimination. This is not only in view of strategies that are tailored only to elimination but also due to currently revealed biological characteristics of concerning the relapse patterns of hypnozoites and conservation of large biomasses in cryptic sites in the bone marrow and spleen. A typical scenario was observed in Botswana between 2008 and 2018, which palpably projects how could endanger malaria elimination efforts where the two parasites co-exist. The need for the global malaria community, national malaria programs (NMPs), funding agencies and relevant stakeholders to engage in a forum to discuss and recommend clear pathways for elimination of malaria, including , in sub-Saharan Africa is warranted.
PubMed: 37624330
DOI: 10.3390/tropicalmed8080392 -
The American Journal of Tropical... Sep 2023We report the first known case of hemophagocytic lymphohistiocytosis (HLH) secondary to imported Plasmodium ovale wallikeri infection in a 58-year-old white woman. A...
We report the first known case of hemophagocytic lymphohistiocytosis (HLH) secondary to imported Plasmodium ovale wallikeri infection in a 58-year-old white woman. A delayed diagnosis of malaria and HLH was made after protracted fever and pancytopenia failed to respond adequately to antimalarial treatment, which required intravenous methylprednisolone and gamma-globulin therapy to resolve.
Topics: Female; Humans; Middle Aged; Plasmodium ovale; Lymphohistiocytosis, Hemophagocytic; Malaria; Antimalarials; Pancytopenia
PubMed: 37580024
DOI: 10.4269/ajtmh.23-0180 -
Malaria Journal Aug 2023Anopheles funestus, which is considered as secondary vector of malaria in Ethiopia, is known to have several morphologically indistinguishable (sibling) species....
BACKGROUND
Anopheles funestus, which is considered as secondary vector of malaria in Ethiopia, is known to have several morphologically indistinguishable (sibling) species. Accurate identification of sibling species is crucial to understand their biology, behaviour and vector competence. In this study, molecular identification was conducted on the Ethiopian An. funestus populations. Moreover, insecticide resistance mechanism markers were detected, including ace N485I, kdr L1014F, L1014S, and CYP6P9a TaqMan qPCR was used to detect the infective stage of the parasite from field collected adult female An. funestus populations.
METHODS
Adult female mosquito collection was conducted from Lare, Gambella Regional State of Ethiopia between June 2018 to July 2020 using CDC light traps and HLC. Sub-samples of the morphologically identified An. funestus mosquitoes were molecularly identified using species-specific PCR, and the possible presence of insecticide resistance alleles was investigated using TaqMan qPCR (N485I-Ace-1), PCR-Sanger sequencing (L1014F-kdr), and PCR-RFLP (CYP6P9a resistance allele). Following head/thorax dissection, the TaqMan qPCR assay was used to investigate the presence of the infective stage Plasmodium parasite species.
RESULTS
A total of 1086 adult female An. funestus mosquitoes were collected during the study period. All sub-samples (N = 20) that were morphologically identified as An. funestus sensu lato (s.l.) were identified as An. funestus sensu stricto (s.s.) using species- specific PCR assay. The PCR-RFLP assay that detects the CYP6P9a resistance allele that confers pyrethroid resistance in An. funestus was applied in N = 30 randomly selected An. funestus s.l.
SPECIMENS
None of the specimens showed a digestion pattern consistent with the presence of the CYP6P9a resistance allele in contrast to what was observed in the positive control. Consequently, all samples were characterized as wild type. The qPCR TaqMan assay that detects the N485I acetylcholinesterase-1 mutation conferring resistance to organophosphates/carbamates in An. funestus was used in (N = 144) samples. All samples were characterized as wild type. The kdr L1014F and L1014S mutations in the VGSC gene that confer resistance to pyrethroids and DDT were analysed with direct Sanger sequencing after PCR and clean-up of the PCR products were also characterized as wild type. None of the samples (N = 169) were found positive for Plasmodium (P. falciparum/ovale/malariae/vivax) detection.
CONCLUSION
All An. funestus s.l. samples from Lare were molecularly identified as An. funestus s.s. No CYP6P9, N485I acetylcholinesterase 1, kdr L1014F or L1014S mutations were detected in the An. funestus samples. None of the An. funestus samples were positive for Plasmodium. Although the current study did not detect any insecticide resistant mechanism, it provides a reference for future vector monitoring programmes. Regular monitoring of resistance mechanisms covering wider geographical areas of Ethiopia where this vector is distributed is important for improving the efficacy of vector control programs.
Topics: Animals; Female; Anopheles; Acetylcholinesterase; Alleles; Ethiopia; Mosquito Vectors; Insecticides; Pyrethrins; Insecticide Resistance; Malaria
PubMed: 37573300
DOI: 10.1186/s12936-023-04667-3 -
Parasites & Vectors Aug 2023Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease has been underestimated. Plasmodium ovale curtisi...
BACKGROUND
Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease has been underestimated. Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII) is an essential ligand for reticulocyte recognition and host cell invasion by P. ovale curtisi. However, the genomic variation, antigenicity and immunogenicity of PocDBP-RII remain major knowledge gaps.
METHODS
A total of 93 P. ovale curtisi samples were collected from migrant workers who returned to China from 17 countries in Africa between 2012 and 2016. The genetic polymorphism, natural selection and copy number variation (CNV) were investigated by sequencing and real-time PCR. The antigenicity and immunogenicity of the recombinant PocDBP-RII (rPocDBP-RII) protein were further examined, and the humoral and cellular responses of immunized mice were assessed using protein microarrays and flow cytometry.
RESULTS
Efficiently expressed and purified rPocDBP-RII (39 kDa) was successfully used as an antigen for immunization in mice. The haplotype diversity (Hd) of PocDBP-RII gene was 0.105, and the nucleotide diversity index (π) was 0.00011. No increased copy number was found among the collected isolates of P. ovale curtisi. Furthermore, rPocDBP-RII induced persistent antigen-specific antibody production with a serum IgG antibody titer of 1: 16,000. IFN-γ-producing T cells, rather than IL-10-producing cells, were activated in response to the stimulation of rPocDBP-RII. Compared to PBS-immunized mice (negative control), there was a higher percentage of CD4CD44CD62L T cells (effector memory T cells) and CD8CD44CD62L T cells (central memory T cells) in rPocDBP-RII‑immunized mice.
CONCLUSIONS
PocDBP-RII sequences were highly conserved in clinical isolates of P. ovale curtisi. rPocDBP-RII protein could mediate protective blood-stage immunity through IFN-γ-producing CD4 and CD8 T cells and memory T cells, in addition to inducing specific antibodies. Our results suggested that rPocDBP-RII protein has potential as a vaccine candidate to provide assessment and guidance for malaria control and elimination activities.
Topics: Animals; Mice; Plasmodium ovale; Interferon-gamma; CD8-Positive T-Lymphocytes; DNA Copy Number Variations; Protein Domains; Malaria
PubMed: 37553591
DOI: 10.1186/s13071-023-05897-9