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PLoS Pathogens Jun 2024Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to...
Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to accelerate malaria elimination. To determine the dynamic profiles of SEMs in current and past P. vivax infections, we screened and selected 11 P. vivax proteins from 210 putative proteins using protein arrays, with a set of serum samples obtained from patients with acute P. vivax and documented past P. vivax infections. Then we used a murine protein immune model to initially investigate the humoral and memory B cell response involved in the generation of long-lived antibodies. We show that of the 11 proteins, especially C-terminal 42-kDa region of P. vivax merozoite surface protein 1 (PvMSP1-42) induced longer-lasting long-lived antibodies, as these antibodies were detected in individuals infected with P. vivax in the 1960-1970s who were not re-infected until 2012. In addition, we provide a potential mechanism for the maintenance of long-lived antibodies after the induction of PvMSP1-42. The results indicate that PvMSP1-42 induces more CD73+CD80+ memory B cells (MBCs) compared to P. vivax GPI-anchored micronemal antigen (PvGAMA), allowing IgG anti-PvMSP1-42 antibodies to be maintained for a long time.
PubMed: 38941356
DOI: 10.1371/journal.ppat.1012334 -
Infection, Genetics and Evolution :... Jun 2024In malaria parasites, the erythrocyte binding-like proteins (EBL) are a family of invasion proteins that are attractive vaccine targets. In the case of Plasmodium vivax,...
In malaria parasites, the erythrocyte binding-like proteins (EBL) are a family of invasion proteins that are attractive vaccine targets. In the case of Plasmodium vivax, the widespread malaria parasite, blood-stage vaccines have been largely focused on a single EBL candidate, the Duffy binding-like domain (DBL) of the Duffy binding protein (DBPII), due to its well-characterized role in the reticulocyte invasion. A novel P. vivax EBL family member, the Erythrocyte binding protein (EBP2, also named EBP or DBP2), binds preferentially to reticulocytes and may mediate an alternative P. vivax invasion pathway. To gain insight into the natural genetic diversity of the DBL domain of EBP2 (region II; EBP2-II), we analyzed ebp2-II gene sequences of 71 P. vivax isolates collected in different endemic settings of the Brazilian Amazon rainforest, where P. vivax is the predominant malaria-associated species. Although most of the substitutions in the ebp2-II gene were non-synonymous and suggested positive selection, the results showed that the DBL domain of the EBP2 was much less polymorphic than that of DBPII. The predominant EBP2 haplotype in the Amazon region corresponded to the C127 reference sequence first described in Cambodia (25% C127-like haplotype). An overview of ebp2-II gene sequences available at GenBank (n = 352) from seven countries (Cambodia, Madagascar, Myanmar, PNG, South Korea, Thailand, Vietnam) confirmed the C127-like haplotype as highly prevalent worldwide. Two out of 43 haplotypes (5 to 20 inferred per country) showed a global frequency of 60%. The results presented here open new avenues of research pursuit while suggesting that a vaccine based on the DBL domain of EBP2 should target a few haplotypes for broad coverage.
PubMed: 38936525
DOI: 10.1016/j.meegid.2024.105628 -
International Journal of Environmental... May 2024Multidrug- and artemisinin-resistant (ART-R) parasites represent a challenge for malaria elimination worldwide. Molecular monitoring in the Kelch domain region gene...
Multidrug- and artemisinin-resistant (ART-R) parasites represent a challenge for malaria elimination worldwide. Molecular monitoring in the Kelch domain region gene allows tracking mutations in parasite resistance to artemisinin. The increase in illegal miners in the Roraima Yanomami indigenous land (YIL) could favor ART-R parasites. Thus, this study aimed to investigate ART-R in patients from illegal gold mining areas in the YIL of Roraima, Brazil. A questionnaire was conducted, and blood was collected from 48 patients diagnosed with or mixed malaria (). The DNA was extracted and the gene was amplified by PCR. The amplicons were subjected to DNA-Sanger-sequencing and the entire amplified fragment was analyzed. Among the patients, 96% (46) were from illegal mining areas of the YIL. All parasite samples carried the wild-type genotypes/ART-sensitive phenotypes. These data reinforce the continued use of artemisinin-based combination therapies (ACTs) in Roraima, as well as the maintenance of systematic monitoring for early detection of parasite populations resistant to ART, mainly in regions with an intense flow of individuals from mining areas, such as the YIL. This is especially true when the achievement of falciparum malaria elimination in Brazil is planned and expected by 2030.
Topics: Artemisinins; Brazil; Plasmodium falciparum; Humans; Antimalarials; Drug Resistance; Malaria, Falciparum; Male; Mining; Adult; Female; Middle Aged; Young Adult; Adolescent; Genotype
PubMed: 38928926
DOI: 10.3390/ijerph21060679 -
Journal of Vector Borne Diseases Apr 2024Plasmodium knowlesi, a simian malaria species, is now known to infect humans. Due to disadvantages in the current diagnosis methods, many efforts have been placed into...
Detection of Plasmodium knowlesi in whole blood samples with sandwich enzyme-linked immunosorbent assay (ELISA) using rhoptry-associated protein 1 specific polyclonal antibodies.
BACKGROUND OBJECTIVES
Plasmodium knowlesi, a simian malaria species, is now known to infect humans. Due to disadvantages in the current diagnosis methods, many efforts have been placed into developing new methods to diagnose the disease. This study assessed the ability of the PkRAP-1 sandwich enzyme-linked immunosorbent (ELISA) to detect P knowlesi antigens in whole blood specimens.
METHODS
Western blot assay was conducted to evaluate the ability of raised mouse and rabbit anti-PkRAP-1 polyclonal antibodies to bind to the native proteins in P. knowlesi lysate. The polyclonal antibodies were then used in sandwich ELISA to detect P. knowlesi. In the sandwich ELISA, mouse and rabbit polyclonal antibodies were used as the capture and detection antibodies, respectively. The limit of detection (LOD) of the assay was determined using P. knowlesi A1H1 culture and purified recombinant PkRAP-1.
RESULTS
Western blot results showed positive reactions towards the proteins in P. knowlesi lysate. The LOD of the assay from three technical replicates was 0.068% parasitaemia. The assay performance in detecting P. knowlesi was 83% sensitivity and 70% specificity with positive and negative predictive values of 74% and 80%, respectively. The anti-PkRAP-1 polyclonal antibodies did not cross-react with P. falciparum and healthy samples, but P. vivax by detecting all 12 samples.
INTERPRETATION CONCLUSION
PkRAP-1 has the potential as a biomarker for the development of a new diagnostic tool for P. knowlesi detection. Further studies need to be conducted to establish the full potential of the usage of anti-PkRAP-1 antibodies for P. knowlesi detection.
Topics: Plasmodium knowlesi; Enzyme-Linked Immunosorbent Assay; Animals; Malaria; Antibodies, Protozoan; Rabbits; Sensitivity and Specificity; Mice; Protozoan Proteins; Humans; Antigens, Protozoan; Blotting, Western; Limit of Detection
PubMed: 38922654
DOI: 10.4103/jvbd.jvbd_55_23 -
Journal of Vector Borne Diseases Apr 2024Following World Health Organization (WHO) plans for thirty-five malaria-endemic countries, Indonesia will eliminate malaria by 2030. As one of the Indonesian provinces,...
BACKGROUND OBJECTIVES
Following World Health Organization (WHO) plans for thirty-five malaria-endemic countries, Indonesia will eliminate malaria by 2030. As one of the Indonesian provinces, West Java targeted subnational malaria elimination in 2022. This article aims to describe malaria surveillance data and elimination programs, including weaknesses in sustaining the program.
METHODS
This study used secondary data from malaria surveillance information system regencies/cities' case reports for 2019-2022 and achievement data of sub-national malaria elimination certification from each regency/city from 2014-2022. The data was confirmed from the evaluation study document, analysis of reported cases, and interviews.
RESULTS
Most cases were confirmed by microscopic examination (84.1% in 2021 and 94.4% in 2022) and rapid diagnostic tests (57% in 2019 and 58.1% in 2020). Malaria is more prevalent among men (93% in 2019, 95% in 2020, 96% in 2021, and 95.9% in 2022) and productive ages of 15-64 years (98.8% in 2019, 100% in 2020, 99.2% in 2021, and 98.8% in 2022), frequently occurs in the military (56.3% in 2019, 75.7% in 2020, 45.2% in 2021) and police (40.5% in 2022), often uses passive case detection for identifying cases (97.9% in 2019 and 2020, 95.2% in 2021, and 97.6% in 2022), and the majority undergo inpatient treatment (86.4% in 2019, 81.7% in 2021, and 82.6% in 2022). Most positive cases originated from imported cases, and last indigenous cases were still found in 2019. Plasmodium vivax dominated malaria cases and and relapses were high (55.0% in 2020, and 47.3% in 2022).
INTERPRETATION CONCLUSION
All regencies/cities have obtained sub-national malaria elimination certification in 2022. West Java has the potential to be verified for Java-Bali sub-national malaria elimination targeted in 2023, albeit cases of imported malaria still occur. It is imperative to address the issue of imported cases transitioning into locally transmitted cases (introduced) by effective coordination across all regencies/cities and inter-provincial efforts.
Topics: Indonesia; Humans; Adolescent; Adult; Male; Middle Aged; Young Adult; Disease Eradication; Female; Child; Child, Preschool; Malaria; Infant; Malaria, Vivax; Prevalence; Aged; Infant, Newborn
PubMed: 38922652
DOI: 10.4103/jvbd.jvbd_113_23 -
JMIR Public Health and Surveillance Jun 2024A challenge in achieving the malaria-elimination target in the Greater Mekong Subregion, including Thailand, is the predominance of Plasmodium vivax malaria, which has... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
A challenge in achieving the malaria-elimination target in the Greater Mekong Subregion, including Thailand, is the predominance of Plasmodium vivax malaria, which has shown extreme resilience to control measures.
OBJECTIVE
This proof-of-concept study aimed to provide evidence for implementing primaquine mass drug administration (pMDA) as a strategy for P. vivax elimination in low-endemicity settings.
METHODS
The study employed a mixed-methods trial to thoroughly evaluate the effectiveness, safety, acceptability, and community engagement of pMDA. The quantitative part was designed as a 2-period cluster-crossover randomized controlled trial. The intervention was pMDA augmented to the national prevention and control standards with directly observed treatment (DOT) by village health volunteers. The qualitative part employed in-depth interviews and brainstorming discussions. The study involved 7 clusters in 2 districts of 2 southern provinces in Thailand with persistently low P. vivax transmission. In the quantitative part, 5 cross-sectional blood surveys were conducted in both the pMDA and control groups before and 3 months after pMDA. The effectiveness of pMDA was determined by comparing the proportions of P. vivax infections per 1000 population between the 2 groups, with a multilevel zero-inflated negative binomial model adjusted for cluster and time as covariates and the interaction. The safety data comprised adverse events after drug administration. Thematic content analysis was used to assess the acceptability and engagement of stakeholders.
RESULTS
In the pre-pMDA period, the proportions of P. vivax infections in the pMDA (n=1536) and control (n=1577) groups were 13.0 (95% CI 8.2-20.4) and 12.0 (95% CI 7.5-19.1), respectively. At month 3 post-pMDA, these proportions in the pMDA (n=1430) and control (n=1420) groups were 8.4 (95% CI 4.6-15.1) and 5.6 (95% CI 2.6-11.5), respectively. No statistically significant differences were found between the groups. The number of malaria cases reduced in all clusters in both groups, and thus, the impact of pMDA was inconclusive. There were no major safety concerns. Acceptance among the study participants and public health care providers at local and national levels was high, and they believed that pMDA had boosted awareness in the community.
CONCLUSIONS
pMDA was associated with high adherence, safety, and tolerability, but it may not significantly impact P. vivax transmission. As this was a proof-of-concept study, we decided not to scale up the intervention with larger clusters and samples. An alternative approach involving a targeted primaquine treatment strategy with primaquine and DOT is currently being implemented. We experienced success regarding effective health care workforces at point-of-care centers, effective collaborations in the community, and commitment from authorities at local and national levels. Our efforts boosted the acceptability of the malaria-elimination initiative. Community engagement is recommended to achieve elimination targets.
TRIAL REGISTRATION
Thai Clinical Trials Registry TCTR20190806004; https://www.thaiclinicaltrials.org/show/TCTR20190806004.
Topics: Humans; Primaquine; Thailand; Mass Drug Administration; Male; Female; Adult; Adolescent; Malaria, Vivax; Antimalarials; Middle Aged; Young Adult; Proof of Concept Study; Child; Cross-Over Studies; Cross-Sectional Studies; Patient Acceptance of Health Care
PubMed: 38922648
DOI: 10.2196/51993 -
Cureus May 2024Prompt diagnosis of malaria infection is critical for effective management, yet it can be challenging due to varying incubation periods and the need for...
Prompt diagnosis of malaria infection is critical for effective management, yet it can be challenging due to varying incubation periods and the need for physician-initiated laboratory workups. We present a case of a 40-year-old male with fever and dark-colored urine, initially evaluated for sepsis. Plasmodium vivax was incidentally identified on a peripheral smear review after obtaining a remote travel history from a malaria-endemic area. Consultation with the Centers for Disease Control confirmed the diagnosis, emphasizing the importance of thorough travel history assessment and timely laboratory investigation in suspected cases of malaria. This case underscores the significance of early diagnosis in managing this potentially life-threatening infection.
PubMed: 38916004
DOI: 10.7759/cureus.61077 -
The National Medical Journal of India 2023Background Malaria in pregnancy (MIP) is a major public health problem due to the vulnerability of pregnant women to infections, resulting in adverse maternal/foetal...
Burden of malaria during pregnancy in perennial transmission settings of two densely forested and remote blocks (Baihar and Birsa) of district Balaghat, Madhya Pradesh, central India.
Background Malaria in pregnancy (MIP) is a major public health problem due to the vulnerability of pregnant women to infections, resulting in adverse maternal/foetal outcomes in endemic areas. Methods We did a field-based study to assess the burden of MIP (prevalence at the time of enrolment and follow-up) and to identify risk factors for MIP in the Birsa and Baihar blocks of district Balaghat in Madhya Pradesh, which have perennial malaria transmission. Malaria screening (during 2015-2017) was done by microscopy and bivalent rapid diagnostic test (SD Bioline RDT, malaria antigen Plasmodium falciparum/Plasmodium vivax Pf/Pv). Dried blood spots were used for haemoglobin estimation. Sociodemographic details with past and present pregnancy status were obtained. A subset of pregnant women were followed up for malaria during pregnancy. Women were also screened for malaria post delivery. Malaria treatment was given as per the National Guidelines of 2013. Multivariate analysis was done to assess independent risk factors for malaria. Results A total of 1728 pregnant women were screened, of which 1651 were included in the final analysis. Malaria prevalence at first screening was 23.4% (Pf 88%). Prevalence and Pf parasitaemia both were significantly higher among primigravid (G1) compared to multigravid (G>2; p value 0.012 and 0.019, respectively). Pregnant women of the Baiga ethnic group were more likely to have malaria compared to those belonging to the Gond group (OR [95% CI]; 2.4 [1.7-3.4]; p<0.00001) and non-indigenous group (OR [95% CI]; 8.3 [3.9-19.7]; p<0.00001). Primigravid status of women, first and second trimester of pregnancy, women belonging to indigenous ethnic tribal group and cash crop insufficiency for whole year (a socioeconomic indicator) in the family were the independent risk factors for malaria. Conclusion MIP is a major public health problem in forested tribal settlements of Birsa and Baihar blocks of Balaghat district in Madhya Pradesh and requires immediate intervention.
Topics: Humans; Female; Pregnancy; India; Adult; Pregnancy Complications, Parasitic; Prevalence; Risk Factors; Malaria, Falciparum; Young Adult; Malaria, Vivax; Forests; Adolescent; Antimalarials; Plasmodium falciparum
PubMed: 38909309
DOI: 10.25259/NMJI_535_21 -
Malaria Journal Jun 2024Imported malaria continues to be reported in Sri Lanka after it was eliminated in 2012, and a few progress to life-threatening severe malaria.
BACKGROUND
Imported malaria continues to be reported in Sri Lanka after it was eliminated in 2012, and a few progress to life-threatening severe malaria.
METHODS
Data on imported malaria cases reported in Sri Lanka from 2013 to 2023 were extracted from the national malaria database maintained by the Anti Malaria Campaign (AMC) of Sri Lanka. Case data of severe malaria as defined by the World Health Organization were analysed with regard to patients' general characteristics and their health-seeking behaviour, and the latter compared with that of uncomplicated malaria patients. Details of the last three cases of severe malaria in 2023 are presented.
RESULTS
532 imported malaria cases were diagnosed over 11 years (2013-2023); 46 (8.6%) were severe malaria, of which 45 were Plasmodium falciparum and one Plasmodium vivax. Most severe malaria infections were acquired in Africa. All but one were males, and a majority (87%) were 26-60 years of age. They were mainly Sri Lankan nationals (82.6%). Just over half (56.5%) were treated at government hospitals. The average time between arrival of the person in Sri Lanka and onset of illness was 4 days. 29 cases of severe malaria were compared with 165 uncomplicated malaria cases reported from 2015 to 2023. On average both severe and uncomplicated malaria patients consulted a physician equally early (mean = 1 day) with 93.3% of severe malaria doing so within 3 days. However, the time from the point of consulting a physician to diagnosis of malaria was significantly longer (median 4 days) in severe malaria patients compared to uncomplicated patients (median 1 day) (p = 0.012) as was the time from onset of illness to diagnosis (p = 0.042). All severe patients recovered without sequelae except for one who died.
CONCLUSIONS
The risk of severe malaria among imported cases increases significantly beyond 5 days from the onset of symptoms. Although patients consult a physician early, malaria diagnosis tends to be delayed by physicians because it is now a rare disease. Good access to expert clinical care has maintained case fatality rates of severe malaria at par with those reported elsewhere.
Topics: Sri Lanka; Humans; Male; Adult; Middle Aged; Female; Young Adult; Communicable Diseases, Imported; Malaria, Falciparum; Malaria, Vivax; Aged; Adolescent; Malaria; Disease Eradication
PubMed: 38909255
DOI: 10.1186/s12936-024-05014-w -
Revista Clinica Espanola Jun 2024The scarcity of epidemiological data on acute febrile illnesses from South Asia impairs evidence-based clinical decision-making. Our study aimed to explore the...
INTRODUCTION
The scarcity of epidemiological data on acute febrile illnesses from South Asia impairs evidence-based clinical decision-making. Our study aimed to explore the etiological spectrum of short-duration fever in patients admitted to a tertiary care hospital in West Bengal, India.
METHODS
We conducted a cross-sectional study from May 2021 to April 2022 involving 150 adult patients presenting with a fever lasting less than two weeks at Burdwan Medical College and Hospital (West Bengal, India). We performed comprehensive clinical assessments, including microbiological, serological, and other specific investigations, to identify the causes of the fever.
RESULTS
The demographic profile predominantly included individuals aged 21-40 years, with a male-to-female ratio of 1.9:1, and 60.7% of participants were from rural areas. The primary etiological agents identified were scrub typhus (25.3%), dengue (15.3%), and enteric fever (13.3%). Notably, 80% of patients presented with non-localizing symptoms, while 14.7% had respiratory symptoms. Blood cultures pinpointed Salmonella typhi and Staphylococcus aureus in a minority of cases (3.3%), and malaria, primarily Plasmodium vivax, was diagnosed in 12% of the cases.
CONCLUSION
Our findings highlight the complexity of diagnosing short-duration fevers, dominated by a wide range of etiological agents, with a notable prevalence of scrub typhus. These results underscore the urgent need for enhanced diagnostic facilities, including the availability of scrub typhus testing at primary healthcare centers. We recommend empirical doxycycline therapy for suspected cases and emphasize the need for further research to develop refined management guidelines for acute febrile illnesses. This study also highlights the importance of raising both community and clinician awareness to prevent irrational antibiotic use.
PubMed: 38906399
DOI: 10.1016/j.rceng.2024.06.009