Vivax Infection Research Articles

Impact of a large-scale fruit and vegetable irrigation scheme on the micro-epidemiology of malaria in southwest Ethiopia

BackgroundMalaria continues to represent an important public health problem in Ethiopia. The expansion of irrigated agricultural development projects turns out to be a major impediment to long-lasting and sustainable malaria prevention and control efforts in the country. The aim of this study was to determine the micro-epidemiology of malaria and associated risk factors in and around Gojeb Horizon Irrigation Plantation in southwest Ethiopia.MethodsA community-based comparative cross-sectional study was conducted from May to June 2018 in Gimbo District, southwest Ethiopia. A total of 186 households (94 from irrigated village and 92 from non-irrigated village) were randomly selected from among the communities living around the Gojeb Horizon plantation. In total, 718 individuals (368 from irrigated village and 350 from non-irrigated village) were recruited from the selected households. A finger-prick blood sample was obtained from each participant. Socio-demographic data from the households and individual study participants were collected using a semi-structured questionnaire. Multivariate regression was used to assess factors associated with micro-epidemiology of malaria. P-value < 0.05 was considered statistically significant.ResultsThe prevalence of malaria in irrigated and non-irrigated villages was 8.2% and 3.4%, respectively. Plasmodium falciparum, Plasmodium vivax and mixed infections accounted for 57.1%, 38.1%, and 4.8% of the cases, respectively. Individuals living in the irrigated villages were 2.53 (95% CI: 1.23–5.20) times at higher risk of Plasmodium infection as compared to those living in the non-irrigated village. Age (AOR = 1.03, 95% CI: 1.01–1.06) and non-use of long-lasting insecticidal net (AOR = 2.72, 95% CI: 1.03–7.22) were co-predictors of malaria infection in the area.ConclusionThis study revealed that communities living in irrigation village were at a higher risk of Plasmodium infection than those living in non-irrigated village, which necessitates the development of tailored interventions that are both targeted and customized.

Development and longevity of naturally acquired antibody and memory B cell responses against Plasmodium vivax infection.

Plasmodium vivax malaria causes significant public health problems in endemic regions. Considering the rapid spread of drug-resistant parasite strains and the development of hypnozoites in the liver with potential for relapse, development of a safe and effective vaccine for preventing, controlling, and eliminating the infection is critical. Immunity to malaria is mediated by antibodies that inhibit sporozoite or merozoite invasion into host cells and protect against clinical disease. Epidemiologic data from malaria endemic regions show the presence of naturally acquired antibodies to P. vivax antigens during and following infection. But data on the persistence of these antibodies, development of P. vivax-specific memory B cells (MBCs), and their relation to reduction of malaria severity and risk is limited. This review provides an overview of the acquisition and persistence of naturally acquired humoral immunity to P. vivax infection. Also, we summarize and discuss current progress in assessment of immune responses to candidate vaccine antigens in P. vivax patients from different transmission settings. Longitudinal studies of MBC and antibody responses to these antigens will open new avenues for developing vaccines against malaria infection and its transmission.

Transmission-blocking activities of artesunate, chloroquine, and methylene blue on Plasmodium vivax gametocytes.

Plasmodium vivax is now the main cause of malaria outside Africa. The gametocytocidal effects of antimalarial drugs are important to reduce malaria transmissibility, particularly in low-transmission settings, but they are not well characterized for P. vivax. The transmission-blocking effects of chloroquine, artesunate, and methylene blue on P. vivax gametocytes were assessed. Blood specimens were collected from patients presenting with vivax malaria, incubated with or without the tested drugs, and then fed to mosquitos from a laboratory-adapted colony of Anopheles dirus (a major malaria vector in Southeast Asia). The effects on oocyst and sporozoite development were analyzed under a multi-level Bayesian model accounting for assay variability and the heterogeneity of mosquito Plasmodium infection. Artesunate and methylene blue, but not chloroquine, exhibited potent transmission-blocking effects. Gametocyte exposures to artesunate and methylene blue reduced the mean oocyst count 469-fold (95% CI: 345 to 650) and 1,438-fold (95% CI: 970 to 2,064), respectively. The corresponding estimates for the sporozoite stage were a 148-fold reduction (95% CI: 61 to 470) and a 536-fold reduction (95% CI: 246 to 1,311) in the mean counts, respectively. In contrast, high chloroquine exposures reduced the mean oocyst count only 1.40-fold (95% CI: 1.20 to 1.64) and the mean sporozoite count 1.34-fold (95% CI: 1.12 to 1.66). This suggests that patients with vivax malaria often remain infectious to anopheline mosquitos after treatment with chloroquine. Use of artemisinin combination therapies or immediate initiation of primaquine radical cure should reduce the transmissibility of P. vivax infections.

Single-cell analyses of polyclonal Plasmodium vivax infections and their consequences on parasite transmission

Most Plasmodium vivax infections contain genetically distinct parasites, but the consequences of this polyclonality on the development of asexual parasites, their sexual differentiation, and their transmission remain unknown. We describe infections of Saimiri monkeys with two strains of P. vivax and the analyses of 80,024 parasites characterized by single cell RNA sequencing and individually genotyped. In our model, consecutive inoculations fail to establish polyclonal infections. By contrast, simultaneous inoculations of two strains lead to sustained polyclonal infections, although without detectable differences in parasite regulation or sexual commitment. Analyses of sporozoites dissected from mosquitoes fed on coinfected monkeys show that all genotypes are successfully transmitted to mosquitoes. However, after sporozoite inoculation, not all genotypes contribute to the subsequent blood infections, highlighting an important bottleneck during pre-erythrocytic development. Overall, these studies provide new insights on the mechanisms regulating the establishment of polyclonal P. vivax infections and their consequences for disease transmission.

Investigation of P. vivax elimination via mass drug administration: A simulation study

Plasmodium vivax is the most geographically widespread malaria parasite. P. vivax has the ability to remain dormant (as a hypnozoite) in the human liver and subsequently reactivate, which makes control efforts more difficult. Given the majority of P. vivax infections are due to hypnozoite reactivation, targeting the hypnozoite reservoir with a radical cure is crucial for achieving P. vivax elimination. Stochastic effects can strongly influence dynamics when disease prevalence is low or when the population size is small. Hence, it is important to account for this when modelling malaria elimination. We use a stochastic multiscale model of P. vivax transmission to study the impacts of multiple rounds of mass drug administration (MDA) with a radical cure, accounting for superinfection and hypnozoite dynamics. Our results indicate multiple rounds of MDA with a high-efficacy drug are needed to achieve a substantial probability of elimination. This work has the potential to help guide P. vivax elimination strategies by quantifying elimination probabilities for an MDA approach.

Clinical burden of Plasmodium infection and associated risk factors among the local population of Chakwal, Punjab, Pakistan (2019–2023)

BackgroundThis study aimed to determine the clinical burden, spatial dynamics, and associated risk factors of Plasmodium infection among the natives of Chakwal, Punjab Pakistan from 2019 to 2023 to guide targeted screening and treatment interventions.MethodA community-based cross-sectional study was conducted using primary and secondary data sources. Participants were recruited using a multi-stage cluster sampling by taking informed consent for the primary data sources. Whereas a secondary dataset of Plasmodium infection was obtained from the database of surveyed hospitals after ethical consideration. All the participants living in the study area for at least 3 months were included, while patients with chronic illness were excluded. Sociodemographic and environmental data were collected using a structured questionnaire. Plasmodium infection was diagnosed using microscopy, rapid diagnostic tests (RDTs), and nested polymerase chain reaction (PCR) as the reference standard. A Zero-inflated negative binomial logistic regression model and interpolation of malaria distribution to environmental variables were employed to determine the association and spatiotemporal patterns of malaria in Chakwal.ResultsAmong the 2457 participants, the prevalence of Plasmodium vivax infection (99%) was significantly higher than P. falciparum (0.8%) and mixed infection (0.2%). Females had a higher infection rate than males and the infection rate was higher in adults (21–40 years) and children (0–20 years). Age category (61–100), P. vivax species, temperature, rainfall, monsoon season, and mixed infection factors were significantly associated (p < 0.05) with increased Plasmodium infection risk. Geospatial mapping indicated potential malaria hotspots in Sarkal Kasar, Chak Baili, Mulkwal, Chohan, and other close areas of the Potohar region.ConclusionThe clinical burden of P. vivax was the highest during monsoon season in Chakwal. Age, gender, climatic factors, and mixed infection were significant risk factors for malaria transmission in this region. Targeted screening and treatment strategies should prioritize identified hotspots and high-risk groups to effectively control malaria in Potohar region of Pakistan.

Lineage-informative microhaplotypes for recurrence classification and spatio-temporal surveillance of Plasmodium vivax malaria parasites

Challenges in classifying recurrent Plasmodium vivax infections constrain surveillance of antimalarial efficacy and transmission. Recurrent infections may arise from activation of dormant liver stages (relapse), blood-stage treatment failure (recrudescence) or reinfection. Molecular inference of familial relatedness (identity-by-descent or IBD) can help resolve the probable origin of recurrences. As whole genome sequencing of P. vivax remains challenging, targeted genotyping methods are needed for scalability. We describe a P. vivax marker discovery framework to identify and select panels of microhaplotypes (multi-allelic markers within small, amplifiable segments of the genome) that can accurately capture IBD. We evaluate panels of 50–250 microhaplotypes discovered in a global set of 615 P. vivax genomes. A candidate global 100-microhaplotype panel exhibits high marker diversity in the Asia-Pacific, Latin America and horn of Africa (median HE = 0.70–0.81) and identifies 89% of the polyclonal infections detected with genome-wide datasets. Data simulations reveal lower error in estimating pairwise IBD using microhaplotypes relative to traditional biallelic SNP barcodes. The candidate global panel also exhibits high accuracy in predicting geographic origin and captures local infection outbreak and bottlenecking events. Our framework is open-source enabling customised microhaplotype discovery and selection, with potential for porting to other species or data resources.

Copy Number Variations of Plasmodium vivax DBP1, EBP/DBP2, and RBP2b in Ethiopians Who Are Duffy Positive and Duffy Negative.

Recent evidence challenges the belief that individuals who are Duffy-negative are resistant to Plasmodium vivax due to lacking the Duffy antigen receptor for chemokines. Erythrocyte-binding protein (EBP/DBP2) has shown moderate binding to Duffy-negative erythrocytes in vitro. Reticulocyte-binding protein 2b (RBP2b) interactions with transferrin receptor 1 suggest involvement in Duffy-negative infections. Gene copy number variations in PvDBP1, PvEBP/DBP2, and PvRBP2b were investigated in Duffy-positive and Duffy-negative P vivax infections from Ethiopia. Among Duffy-positive samples, 34% displayed PvDBP1 duplications (Cambodian type). In Duffy-negative infections, 30% showed duplications, mostly Cambodian type. For PvEBP/DBP2 and PvRBP2b, Duffy-positive samples exhibited higher duplication rates (1-8 copies for PvEBP/DBP2, 46%; 1-5 copies for PvRBP2b, 43%) as compared with Duffy-negative samples (20.8% and 26%, respectively). The range of copy number variations was lower in Duffy-negative infections. Demographic and clinical factors associated with gene multiplications in both Duffy types were explored, enhancing understanding of P vivax evolution in Africans who are Duffy negative.

Structure-based design of a Plasmodium vivax Duffy-binding protein immunogen focuses the antibody response to functional epitopes.

The Duffy-binding protein (DBP) is a promising antigen for a malaria vaccine that would protect against clinical symptoms caused by Plasmodium vivax infection. Region II of DBP (DBP-II) contains the receptor-binding domain that engages host red blood cells, but DBP-II vaccines elicit many non-neutralizing antibodies that bind distal to the receptor-binding surface. Here, we engineered a truncated DBP-II immunogen that focuses the immune response to the receptor-binding surface. This immunogen contains the receptor-binding subdomain S1S2 and lacks the immunodominant subdomain S3. Structure-based computational design of S1S2 identified combinatorial amino acid changes that stabilized the isolated S1S2 without perturbing neutralizing epitopes. This immunogen elicited DBP-II-specific antibodies in immunized mice that were significantly enriched for blocking activity compared to the native DBP-II antigen. This generalizable design process successfully stabilized an integral core fragment of a protein and focused the immune response to desired epitopes to create a promising new antigen for malaria vaccine development.

Detection through the use of RT-MqPCR of asymptomatic reservoirs of malaria in samples of patients from the indigenous Comarca of Guna Yala, Panama: Essential method to achieve the elimination of malaria.

Plasmodium vivax is the main causative agent of malaria in Panama. However, the prevalence of asymptomatic infections in the different endemic regions remains unknown. Understanding the epidemiological behavior of asymptomatic infections is essential for the elimination of malaria. This study aimed to determine the prevalence of asymptomatic malarial infections in one of the main endemic regions of Panama using multiplex real-time reverse transcription RT-MqPCR. A cross-sectional study was conducted in three communities in the Guna Yala Comarca. A total of 551 thick blood smears and their respective samples on filter paper were collected from volunteers of different ages and sexes from June 20 to 25, 2016. Infections by the Plasmodium spp. were diagnosed using microscopy and RT-MqPCR. All statistical analyses were performed using the R software. The average prevalence of asymptomatic infections by P. vivax in the three communities detected by RT-MqPCR was 9.3%, with Ukupa having the highest prevalence (13.4%), followed by Aidirgandi (11.1%) and Irgandi (3.3%). A total of 74 samples were diagnosed as asymptomatic infections using RT-MqPCR. Light microscopy (LM) detected that 17.6% (13/74) of the asymptomatic samples and 82.4% (61/74) were diagnosed as false negatives. A 100% correlation was observed between samples diagnosed using LM and RT-MqPCR. A total of 52.7% (39/74) of the asymptomatic patients were female and 85.1% (63/74) were registered between the ages of 1 and 21 years. Factors associated with asymptomatic infection were community (aOR = 0.38 (95% CI 0.17-0.83), p < 0.001) and age aOR = 0.98 (95% CI 0.97-1.00), p < 0.05); F = 5.38; p < 0.05). This study provides novel evidence of the considerable prevalence of asymptomatic P. vivax infections in the endemic region of Kuna Yala, representing a new challenge that requires immediate attention from the National Malaria Program. The results of this study provide essential information for the health authorities responsible for developing new policies. Furthermore, it will allow program administrators to reorient and design effective malaria control strategies that consider asymptomatic infections as a fundamental part of malaria control and move towards fulfilling their commitment to eliminate it.

Efficacy and safety of chloroquine plus primaquine for the treatment of Plasmodium vivax malaria in Hamusit site, Northwestern Ethiopia

BackgroundPlasmodium vivax malaria is still an important public health problem in Ethiopia. Unlike Plasmodium falciparum, P. vivax has a dormant liver stage (hypnozoite) that can be a risk of recurrent vivax malaria unless treated by radical cure with primaquine. Drug resistance to chloroquine is threatening malaria control and elimination efforts. This study assessed the therapeutic efficacy and safety of chloroquine plus 14 days of primaquine on P. vivax infection based on parasitological, clinical, and haematological parameters.MethodsA single-arm in vivo prospective therapeutic efficacy study was conducted to assess the clinical and parasitological response to the first-line treatment of P. vivax in Ethiopia, chloroquine plus 14 days low dose of (0.25 mg/kg/day) primaquine between December 2022 and March 2023 at Hamusit Health Centre using the standard World Health Organization (WHO) protocol. A total of 100 study participants with P. vivax mono-infection who were over 6 months old were enrolled and monitored for adequate clinical and parasitological responses for 42 days. The WHO double-entry Excel sheet and SPSS v.25 software were used for Kaplan–Meier survival analysis, and a paired t-test was used for analysis of haemoglobin improvements between follow up days.ResultsA total of 100 patients were enrolled among those, 96% cases were rural residents, 93% had previous malaria exposure, and predominant age group was 5–15 years (61%). 92.6% (95% CI 85.1–96.4%) of enrolled patients were adequate clinical and parasitological response, and 7.4% (95% CI 3.6–14.9%) recurrences were observed among treated patients. The fever and parasite clearance rate on day 3 were 98% and 94%, respectively. The baseline haemoglobin levels improved significantly compared to those days 14 and 42 (p < 0.001). No serious adverse event was observed during the study period.ConclusionsIn this study, co-administration of chloroquine with primaquine was efficacious and well-tolerated with fast resolution of fever and high parasites clearance rate. However, the 7.4% failure is reported is alarming that warrant further monitoring of the therapeutic efficacy study of P. vivax.

Spatiotemporal Epidemiology of Malaria in India from 2007 to 2022.

India is a major contributor to the global burden of malaria, especially Plasmodium vivax infection. Understanding the spatiotemporal trends of malaria across India over the last two decades may assist in targeted intervention. The population-normalized spatiotemporal trends of malaria epidemiology in India from 2007 to 2022 were analyzed using a geographic information system with the publicly available "malaria situation" report of the National Vector Borne Disease Control Program (NVBDCP). The NVBDCP data showed malaria cases to have steeply declined from 1.17 million in 2015 to 0.18 million cases in 2022; this is 10.1 and 18.7 fold lower than the WHO's estimate of 11.93 million and 3.38 million cases in 2015 and 2022, respectively. From 2007 to 2022, Mizoram, Meghalaya, Tripura, Odisha, Chhattisgarh, and Jharkhand consistently reported high caseloads of Plasmodium falciparum. In the same period, the P. vivax caseload was high in Arunachal Pradesh, Mizoram, Nagaland, Jharkhand, Odisha, Chhattisgarh, Goa, Daman and Diu, Dadra and Nagar Haveli, and Andaman and Nicobar Islands. The distribution of forest cover, annual rainfall, and proportion of the Scheduled Tribe population (the most underprivileged in Indian society) spatially correlated with malaria cases and deaths. Mizoram is the only state where cases were higher in 2022 than in 2007. Overall, India has made tremendous progress in controlling malaria and malaria-related deaths in the last decade. The decline could be attributed to the effective vector and parasite control strategies implemented across the country.

Seasonal Dynamics of Symptomatic and Asymptomatic Plasmodium falciparum and Plasmodium vivax Infections in Coendemic Low-Transmission Settings, South Ethiopia.

Ethiopia has a plan to eliminate malaria in selected low-transmission districts by 2025. However, complex factors such as seasonality, focal heterogeneity, and coendemicity of Plasmodium vivax and Plasmodium falciparum, and asymptomatic cases, along with other factors, pose challenges. This longitudinal study assessed these dynamics and associated factors in three elimination-targeted settings in southern Ethiopia. The study included rural districts (Wonago and Yirgacheffe) and an urban setting (Dilla town) with 504 participants from 168 households per season. The study covered the peak and minor malaria transmission seasons and the dry season. Finger-prick blood was collected for microscopy, rapid diagnostic tests, and 18S-rRNA-based quantitative polymerase chain reaction (qPCR). During the dry season, P. vivax accounted for most infections (64.5%, 71/110) and symptomatic malaria (50.9%, 29/57), whereas P. falciparum dominated during the peak transmission season (45.7%, 42/92 infections and 58.1%, 25/43 of symptomatic cases). Treatment-seeking behavior was low, with 65.3% (143/219) of symptomatic individuals not seeking treatment. Dilla town had significantly higher infection prevalence (29.6%, 149/504, P <0.001) in all seasons compared with the rural sites. The incidence rate was 12/1,000 person-seasons by qPCR and 5/1,000 person-seasons by microscopy. Urban residents, those with low hemoglobin levels, nonuse of mosquito nets, and proximity to stagnant water had a significantly higher risk of infection (P <0.001). Tailored approaches are needed in elimination-targeted areas, focusing on urban settings, Plasmodium species, and strengthening community-level interventions for behavioral change and active case detection.

Plasmodium vivax Infections among Immigrants from China Traveling to the United States.

Beginning in 2023, we observed increased Plasmodium vivax malaria cases at an institution in Los Angeles, California, USA. Most cases were among migrants from China who traveled to the United States through South and Central America. US clinicians should be aware of possible P. vivax malaria among immigrants from China.

Plasmodium vivax serological exposure markers: PvMSP1-42-induced humoral and memory B-cell response generates long-lived antibodies.

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.

Asymptomatic Malaria Reservoirs in Honduras: A Challenge for Elimination.

Efforts on a global scale for combating malaria have achieved substantial progress over the past twenty years. Two Central American nations have accomplished their goal of eliminating malaria: El Salvador and Belize. Honduras has decreased the incidence of malaria and now reports fewer than 4000 malaria cases annually, aspiring to reach elimination by 2030. To accomplish this goal, it is essential to assess the existing strategies employed for malaria control and to address the task of incorporating novel intervention strategies to identify asymptomatic reservoirs. A survey for detecting asymptomatic cases was carried out in the community of Kaukira, in Gracias a Dios, Honduras, focusing on malaria transmission during 2023. Asymptomatic community members were recruited as participants, malaria screening was performed through a rapid diagnostic test in situ, and a blood sample was collected on filter paper. Highly sensitive molecular assays based on photo-induced electron transfer PCR (PET-PCR) were performed to detect the two species of Plasmodium circulating in Honduras: Plasmodium vivax and Plasmodium falciparum. In addition, the identification of the parasite species was verified by amplifying three genetic markers (Pvmsp3α, Pvmsp3ß, and Pfmsp1). A total of 138 participants were recruited, mostly adult women. All individuals tested negative on the rapid diagnostic test. Positive results for malaria were detected by PET-PCR in 17 samples (12.3%). Most samples (12 out of 17) were amplified with a Ct value between 37 and 42, indicating very low parasitemias. Out of the 17 samples, 16 of them also showed amplification in the species assays. There were nine cases of P. falciparum infections and seven cases of P. vivax infections that were further confirmed by nested PCR (nPCR) of Pvmsp3 and Pfmsp1. Parasitemias ranged from 100 p/μL to less than 0.25 p/μL. One sample showed mixed infection. The existence of asymptomatic malaria reservoirs in Honduras can contribute to disease transmission and pose a challenge that may hinder elimination efforts, requiring public health authorities to modify surveillance strategies to identify the disease and treat this population accordingly.

Effectiveness, Safety, and Acceptability of Primaquine Mass Drug Administration in Low-Endemicity Areas in Southern Thailand: Proof-of-Concept Study.

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. 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. 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. 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. 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. Thai Clinical Trials Registry TCTR20190806004; https://www.thaiclinicaltrials.org/show/TCTR20190806004.

Improved serodiagnosis of Trypanosoma vivax infections in cattle reveals high infection rates in the livestock regions of Argentina.

Bovine trypanosomosis, caused by Trypanosoma vivax, currently affects cattle and has a significant economic impact in sub-Saharan Africa and South America. The development of new diagnostic antigens is essential to improve and refine existing methods. Our study evaluated the efficacy of two recombinant antigens in detecting specific antibodies in cattle. These antigens are derivatives of an invariant surface glycoprotein (ISG) from T. vivax. A fraction of a previously described antigen (TvY486_0045500), designated TvISGAf, from an African strain was evaluated, and a new ISG antigen from an American isolate, TvISGAm, was identified. The two antigens were expressed as fusion proteins in Escherichia coli: TvISGAf was fused to the MBP-His-tag, and TvISGAm was obtained as a His-tag fused protein. An ELISA evaluation was conducted using these antigens on 149 positive and 63 negative bovine samples. The diagnostic performance was enhanced by the use of a combination of both antigens (referred to as TvISG-based ELISA), achieving a sensitivity of 89.6% and specificity of 93.8%. Following the validation of the TvISG-based ELISA, the seroprevalence of T. vivax infection in 892 field samples from cattle in the central region of Argentina was determined. The mean seroprevalence of T. vivax was 53%, with variation ranging from 21% to 69% among the six departments studied. These results support the use of the TvISG ELISA as a valuable serological tool for the detection and monitoring of T. vivax infection in cattle. Furthermore, we report for the first time the seroprevalence of T. vivax in Argentina, which highlights the widespread endemic nature of the disease in the region. In order to effectively manage the increasing spread of T. vivax in the vast livestock production areas of South America, it is essential to implement consistent surveillance programs and to adopt preventive strategies.

Detection of Duffy blood group genotypes and submicroscopic Plasmodium infections using molecular diagnostic assays in febrile malaria patients

BackgroundMalaria remains a severe parasitic disease, posing a significant threat to public health and hindering economic development in sub-Saharan Africa. Ethiopia, a malaria endemic country, is facing a resurgence of the disease with a steadily rising incidence. Conventional diagnostic methods, such as microscopy, have become less effective due to low parasite density, particularly among Duffy-negative human populations in Africa. To develop comprehensive control strategies, it is crucial to generate data on the distribution and clinical occurrence of Plasmodium vivax and Plasmodium falciparum infections in regions where the disease is prevalent. This study assessed Plasmodium infections and Duffy antigen genotypes in febrile patients in Ethiopia.MethodsThree hundred febrile patients visiting four health facilities in Jimma town of southwestern Ethiopia were randomly selected during the malaria transmission season (Apr–Oct). Sociodemographic information was collected, and microscopic examination was performed for all study participants. Plasmodium species and parasitaemia as well as the Duffy genotype were assessed by quantitative polymerase chain reaction (qPCR) for all samples. Data were analysed using Fisher’s exact test and kappa statistics.ResultsThe Plasmodium infection rate by qPCR was 16% (48/300) among febrile patients, of which 19 (39.6%) were P. vivax, 25 (52.1%) were P. falciparum, and 4 (8.3%) were mixed (P. vivax and P. falciparum) infections. Among the 48 qPCR-positive samples, 39 (13%) were negative by microscopy. The results of bivariate logistic regression analysis showed that agriculture-related occupation, relapse and recurrence were significantly associated with Plasmodium infection (P < 0.001). Of the 300 febrile patients, 85 (28.3%) were Duffy negative, of whom two had P. vivax, six had P. falciparum, and one had mixed infections. Except for one patient with P. falciparum infection, Plasmodium infections in Duffy-negative individuals were all submicroscopic with low parasitaemia.ConclusionsThe present study revealed a high prevalence of submicroscopic malaria infections. Plasmodium vivax infections in Duffy-negative individuals were not detected due to low parasitaemia. In this study, an improved molecular diagnostic tool was used to detect and characterize Plasmodium infections, with the goal of quantifying P. vivax infection in Duffy-negative individuals. Advanced molecular diagnostic techniques, such as multiplex real-time PCR, loop-mediated isothermal amplification (LAMP), and CRISPR-based diagnostic methods. These techniques offer increased sensitivity, specificity, and the ability to detect low-parasite-density infections compared to the employed methodologies.

Modeling and investigating malaria P. Falciparum and P. Vivax infections: Application to Djibouti data

Malaria is an infectious and communicable disease, caused by one or more species of Plasmodium parasites. There are five species of parasites responsible for malaria in humans, of which two, Plasmodium Falciparum and Plasmodium Vivax, are the most dangerous. In Djibouti, the two species of Plasmodium are present in different proportions in the infected population: 77% of P. Falciparum and 33% of P. Vivax. In this study we present a new mathematical model describing the temporal dynamics of Plasmodium Falciparum and Plasmodium Vivax co-infection. We focus briefly on the well posedness of this model and on the calculation of the basic reproductive numbers for the infections with each Plasmodium species that help us understand the long-term dynamics of this model (i.e., existence and stability of various eqiuilibria). Then we use computational approaches to: (a) identify model parameters using real data on malaria infections in Djibouti; (b) illustrate the influence of different estimated parameters on the basic reproduction numbers; (c) perform global sensitivity and uncertainty analysis for the impact of various model parameters on the transient dynamics of infectious mosquitoes and infected humans, for infections with each of the Plasmodium species. The originality of this research stems from employing the FAST method and the LHS method to identify the key factors influencing the progression of the disease within the population of Djibouti. In addition, sensitivity analysis identified the most influential parameter for Falciparium and Vivax reproduction rates. Finally, the uncertainty analysis enabled us to understand the variability of certain parameters on the infected compartments.