Malaria Journal最新文献

Background: Malaria remains a significant global health challenge despite remarkable declines in incidence, in Isfahan Province, Iran, historically considered an endemic area. Although national elimination programmes have reduced transmission, imported cases continue to sustain malaria risk. This study aimed to assess the epidemiological and clinical characteristics of malaria in Isfahan Province from 2009 to 2025.

Methods: A retrospective observational analysis was conducted using surveillance data from the Isfahan Center for Disease Control. All microscopically confirmed malaria cases reported between January 2009 and January 2025 were included. Demographic, epidemiological, and clinical data were extracted via a standardized checklist. Descriptive statistics and multivariable logistic regression were applied to identify trends and risk factors for severe malaria.

Results: A total of 569 cases were reported during the study period, with incidence declining sharply after 2009, but fluctuating during subsequent years, including a resurgence in 2024. Most cases occurred in males (96.1%) and individuals aged 15-24 years (53.6%), with Afghan nationals comprising 80.8% of infections. Imported cases represented 80.8% of the total burden, underscoring migration-related risks. Plasmodium vivax accounted for 88.0% of cases, while Plasmodium falciparum (4.6%) was strongly associated with severe disease (adjusted odds ratio 22.6; 95% CI 1.24-410.8; p = 0.035). Seasonal peaks were observed in spring and summer, and per capita incidence was higher in rural counties despite absolute urban predominance.

Conclusions: Malaria incidence in Isfahan Province has markedly declined over the past 16 years; however, imported cases, predominantly among migrant workers, remain the central challenge to elimination. The dominance of P. vivax alongside the clinical severity of P. falciparum highlights the need for species-specific strategies. Strengthened cross-border collaboration, targeted interventions for migrant populations, and enhanced surveillance in high-risk rural areas are essential to sustain elimination efforts.

Background: Coinfection has the potential to affect key traits describing the infection dynamics, the severity of the disease and in fine parasite fitness. However, despite its pervasiveness, experimental work investigating how parasites adapt to the conditions provided by a coinfected host is mostly missing.

Methods: We adopted an experimental evolution approach to investigate if coinfection with the nematode Heligmosomoides polygyrus (Hp) affected the infection dynamics and virulence of the murine malaria parasite Plasmodium yoelii (Py). To this purpose, lines of Py were passaged either in single infected hosts (SI-lines) or in hosts that had been previously infected with Hp (COI-lines). After five and seven passages, the infection dynamics and virulence of evolved lines were compared to the ancestral Py population during single infection trials. COI-lines were also used to infect hosts during coinfection trials, allowing us to compare within-host Py replication when the environment during the evaluation trials matched the environment experienced during the passages and when the two environments were mismatched.

Results: We found that serial passages increased parasitemia and Py virulence, due to the competitive advantage of genotypes with the fastest replication rate, but SI-lines and COI-lines had relatively similar replication rate and virulence. Hosts infected with evolved lines of Py were also less tolerant (steeper slope between red blood cell counts and parasitemia) but there was no difference between SI-lines and COI-lines. Finally, we found that when COI-lines were used during single infection trials (mismatched environments), they had a slower early replication rate compared to matched-environment trials.

Conclusions: We did not find strong evidence supporting a divergence between the virulence of SI-lines and COI-lines, possibly due to the cost of virulence paid by COI-lines. However, Py rapidly adapted to the environmental conditions provided by single infected or coinfected hosts, as shown by the slower replication rate found in mismatched-environment trials.

Background: Malaria remains a major public health challenge in sub-Saharan Africa, and its burden may be influenced by access to clean water, sanitation, and childhood vitamin A supplementation. Understanding how these indicators relate to malaria incidence can help inform targeted prevention strategies.

Methods: Country-level data from global health databases were analyzed using nonparametric statistical tests and machine learning models. The Kruskal-Wallis test and Dunn's post hoc comparisons were used to assess differences in malaria incidence across categories of water and sanitation access. Cliff's delta was used to measure effect sizes. Tree-based machine learning models and logistic regression were trained to evaluate the predictive strength of the three indicators.

Results: Significant differences in malaria incidence were found across water and sanitation access groups, with the lowest access groups consistently exhibiting the highest incidence. Cliff's delta indicated large effect sizes, particularly between low and high access categories. Vitamin A supplementation showed statistically significant group differences, though effect sizes were generally small. Tree-based machine learning models showed moderate predictive performance and outperformed logistic regression in classification accuracy and recall.

Conclusions: Access to clean water and adequate sanitation are strongly associated with lower malaria incidence, underscoring their importance in malaria control efforts. While vitamin A supplementation shows weaker associations, it may still interact with broader health conditions. These findings highlight the essential role of basic infrastructure in reducing malaria burden and demonstrate the potential of predictive modeling to support future global health research.

Background: Innovative, equitable, and sustainable multisectoral solutions are required to address persistently high global malaria deaths, widespread insecticide and antimalarial resistance, and falling funding for malaria control. Housing modification presents a promising option. Alongside a cluster-randomized control trial in Eastern Region, Uganda, we analysed the costs and households' willingness to pay (WTP) for two housing modification interventions, screening and eave tubes, focusing on equity and scale-up potential.

Methods: Taking a disaggregated societal perspective, we assessed financial and economic costs of installing two housing modification interventions in approximately 4000 homes (20000 people). We collected WTP data through three cross-sectional household surveys (n = 1500 households each) using modified structured haggling and calculated price elasticity of demand. We used multivariable regressions and concentration indices to analyse how costs and WTP varied by household characteristics. To identify potential financing gaps, we compared WTP to costs and examined variation by household wealth quintiles.

Results: Screening cost a mean of $116 (societal economic costs; 95%CI $112-120) United States Dollars (2022 USD) per house; eave tubes cost $50 (95%CI $48-52). When annualized over 5 years, screening cost $4.22 per person protected per year and eave tubes cost $3.03. Installation cost more in the wealthiest versus poorest quintiles for both screening ($151 vs $69) and eave tubes ($95 vs $31). Over 75% of respondents were willing to pay something for the interventions, but these values represented only a small fraction of the costs, with a higher fraction in the wealthiest vs poorest quintiles (screening: 12% vs 7%; eave tubes: 18% vs 14%).

Conclusions: While housing modification has relatively high upfront costs, its annual cost per person protected is comparable to other malaria interventions. Households, especially the poorest, are unwilling or unable to pay the full cost of housing modifications. Equitable scale-up would require additional financing and/or demand-boosting interventions.

Trial registration: NCT04622241 (clinicaltrials.gov).

Background: Rapid Diagnostic Tests (RDTs) are the primary means of malaria diagnosis in sub-Saharan Africa. Outside large health facilities, individuals performing RDTs have little or no formal laboratory training, and performing RDTs is by job aids derived from manufacturers' instructions for use (IFU). Furthermore, in many countries, RDT products are interchanged often without associated training or notification to users of differences in characteristics not immediately obvious to non-laboratory workers. This leads to common deviations from IFUs the consequences of which have not been systematically studied. This study investigated how these errors impact RDT results.

Methods: Six RDT products were tested using cultured Plasmodium falciparum diluted to represent infections with a range of parasitaemia. Tests were performed according to IFU (baseline) then with deviations from the IFU including changes in buffer volume, blood volume and incubation time. Effects of the deviations on test validity and overall test result compared to baseline were captured. Also captured, were effects of deviations on test band intensity, and ease of reading result due to test window abnormalities.

Results: Increasing sample volume beyond the recommended 5µL impaired RDT performance, with 4 of 6 RDT products showing 83.3% (30/36) invalid results due to faulty sample migration. No invalid results were observed for the remaining two products. The shortest incubation period (5 min) led to the most deviations from baseline, whereas longer periods aligned more with baseline results. Insufficient buffer volumes caused at least one invalid outcome [10/27 (37%)] in over half the products. Conversely, exceeding buffer volumes led to reductions in the proportion of invalid results among all tests with 0 of 45 invalid results. Higher parasitaemia was associated with increased band intensity and resulted in the fewest deviations from baseline among all products. At 1,000 parasites/µL and 5 µL sample, three products achieved 100% agreement with baseline regardless of incubation time and buffer volume.

Conclusion: Although malaria RDTs are tolerant of some errors, in general, procedural errors adversely affect results, particularly in low parasitaemia samples. Understanding how sample and buffer volumes, alongside incorrect incubation times, influence RDT performance can be incorporated into training and continuous quality improvement.

Background: Asymptomatic malaria represents a major challenge for malaria control and elimination efforts, particularly in endemic regions such as Gabon, where adult reservoirs are under-investigated. This study aimed to assess the burden and determinants of asymptomatic Plasmodium falciparum infection among adults in urban and rural communities in Gabon.

Methods: A community-based cross-sectional survey was conducted between January and December 2023 in Bitam (rural), Libreville, and Owendo (urban). Adults aged ≥ 18 years with no malaria symptoms or recent antimalarial treatment were included. Demographic, socio-economic, and ITN-use data were collected via structured questionnaire. Malaria was diagnosed by microscopy. Logistic regression models were used to identify factors associated with asymptomatic infection.

Results: Among 1,496 participants, the overall prevalence of asymptomatic P. falciparum infection was 15.3%, significantly higher in rural areas (22.4%) than in urban settings (4.1%; p < 0.01). Parasite densities were also higher in rural areas. Independent risk factors for asymptomatic malaria included rural residence (aOR: 7.1; 95% CI: [4.4-9.8]), being a worker (aOR: 5.2; 95% CI: [3.4-7.8]), attending school (p < 0.01). ITN use was low (32.7%) and not significantly protective in multivariate analysis.

Conclusion: The substantial burden of asymptomatic malaria in adults, particularly in rural Gabon, underscores the need to broaden malaria control strategies. These interventions must be broadened to include adult populations, considering occupational exposure and local transmission dynamics. Expanding screening and treatment and improving ITN access and use are critical to reduce the hidden reservoir and achieve malaria elimination.

Background: Building dams and irrigation schemes as resilience measures against growing food insecurity and water scarcity may increase malaria risk in endemic settings. This study aims to assess the clinical and asymptomatic carriage of Plasmodium falciparum throughout the year and explores their association with socio-economic and weather factors in Nanoro, Burkina Faso.

Methods: A monthly household-based surveys were conducted from March 2022 to February 2023 in five villages located at variable distance (3-40 km) from the Soum dam located in the Nanoro Health district catchment area. Socio-demographic, weather, and economic data were collected using a standardized questionnaire. Capillary blood samples were analyzed for P. falciparum infection by microscopy. A mixed-effects logistic regression model adjusted for socio-economic and environmental factors was used to assess the infection probability and to analyze how village-level and month-level factors contributed to the malaria infection risk.

Results: A total of 13,786 participants were included. The overall prevalence of asymptomatic carriage (24.5%) was higher than clinical cases (19.5%). The 12-month malaria prevalence (clinical cases and asymptomatic carriage) were 39.6% (95%CI 38.79-40.42) with the highest rate (42.1% with 95% CI 40.7-43.47) reported from Soum near the dam and lowest rate (33.2%;95% CI 31.21-35.32) from Séguédin located far from the dam. Regardless of village location and transmission period, participants aged 5-19 years old had the highest prevalence of malaria infection with values ranged from 43.6% (95% CI 38.34-49.01) in Séguédin to 69.4% (95% CI 64.94-73.57) in Soum. Monthly rainfall measured in millimeters, was unexpectedly associated with decreased risk of malaria infection (OR = 0.77, 95%CI 0.66-0.9).

Conclusion: The risk of malaria infection was higher in villages close to the dam, with Soum having the highest prevalence and Séguédin the lowest. This study highlights the impact of dam construction on the epidemiological profile of malaria and underscores the need for multi-sectoral approaches integrating health, water management, and socio-economic interventions to tackle the risk of the disease occurrence.

Background: Primaquine (PQ) is widely used to prevent Plasmodium vivax relapses. However, the most efficacious and safest dose is unknown, particularly in children. This trial assessed the safety, tolerability, and efficacy of two high-dose PQ regimens compared with standard of care (SoC) in children with P. vivax infections in the Brazilian Amazon.

Methods: CHILDPRIM was an open-label, randomized clinical trial conducted in Manaus and Cruzeiro do Sul, Brazilian Amazon, from August 2021 to January 2025. The study evaluated the non-inferiority of high-dose PQ regimens in terms of safety, tolerability, and parasitological response at day 180 compared to the low-dose regimen in children under 15 years of age with uncomplicated P. vivax malaria. Participants were randomized (1:1:1) to receive: (1) Brazilian routine standard-dose PQ (3.5 mg/kg over 7 days)-0.5 mg/kg/day; (2) high-dose PQ long-course (7.0 mg/kg over 14 days)-0.5 mg/kg/day; or (3) high-dose PQ short-course (7.0 mg/kg over 7 days)-1.0 mg/kg/day, after glucose-6-phosphate dehydrogenase (G6PD) deficiency screening using the quantitative SD Biosensor. All participants were followed for 180 days. The primary outcomes were the proportion of participants experiencing adverse events of any intensity and the proportion of failures up to day 180 between groups.

Results: A total of 100 individuals were randomized: 32 in the PQ 3.5 mg/kg over 7d arm, 34 in the PQ 7.0 mg/kg over 14d arm, and 34 in the PQ 7.0 mg/kg over 7d arm. The most common adverse events were methaemoglobinaemia, anaemia, and gastrointestinal symptoms. Higher doses of PQ resulted in more adverse events, but no more serious adverse events. Participants in the PQ 3.5 mg/kg over 7d arm presented a higher risk of recurrence at 42 and 180 days, which is why the trial was halted after the second interim analysis. Kaplan-Meier estimates of the percentage of participants who were free from recurrence at day 180 were 50% in PQ 3.5 mg/kg over 7d arm (n = 16), 82.3% in PQ 7.0 mg/kg over 14d arm (n = 28), and 79.4% in PQ 7.0 mg/kg over 7d arm (n = 27) (log-rank; p = 0.0065).

Conclusions: High-dose PQ regimens (7.0 mg/kg total) were safe, well tolerated, and significantly reduced P. vivax recurrence in children without G6PD deficiency. Both 7- and 14-day schedules showed comparable efficacy, with rare SAEs and normalization of Hb and methaemoglobinaemia by day 28. Given their similar efficacy, the shorter regimen may offer advantages for adherence and programmatic implementation in endemic settings. Trial registration ClinicalTrials.gov, TRN: NCT05044637, Registration Date: 20 August 2021.

Background: The Duffy binding ligand domain of Plasmodium vivax (PvDBPII) interacts with Duffy blood-group antigen on the surface of reticulocytes during host cell invasion process. Although diversity of this domain has been analysed among worldwide isolates, the evolution of the complete PvDBP gene remains to be explored.

Methods: In total, 232 P. vivax isolates from northwestern, northeastern, eastern, and southern Thailand were included for analyses of the complete gene sequence, copy number variation and duplication genotypes of Pvdbp. The Duffy blood-group genotypes of the patient were also determined.

Results: Pvdbp duplication, all of the Cambodian type, was detected in 22 isolates (9.48%), characterized by identical copies (n = 17) and microheterogeneity between copies (n = 5). Across 254 sequences including duplicated copies, nucleotide diversity was highest in PvdbpII. Positive selection, evidenced by excess nonsynonymous over synonymous substitutions, occurred in both the 5' region and PvdbpII. Codon-based analysis revealed 26 positively selected codons distributed across the protein; 22 of these overlapped predicted B cell and/or T cell epitopes. Insertions and deletions including frameshift mutations were found outside PvdbpII apart from an indel in this domain, while recombination breakpoints were confined to PvdbpII and the 3' region. Parasite isolates from each endemic region displayed population structure. No significant difference in Duffy phenotype frequencies was found between malaria patients in this study and healthy blood donors from reported data.

Conclusions: While PvdbpII remains the most variable domain, sequence diversity occurred outside this domain. Cambodian-type Pvdbp duplications, often with identical sequences, may enhance immune evasion via increased gene dosage. Positive selection is broadly distributed and likely driven by host immune pressure. Whether positive selection outside PvdbpII is relevant for vaccine design requires further investigation.

Background: Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection, characterized by coma, seizures, and multiorgan dysfunction. MRI findings in adult CM are underreported, particularly in cases with fulminant progression despite treatment.

Case presentation: A 54-year-old woman with a history of hypertension and hypothyroidism presented with fever, seizures, and altered sensorium. On admission, the patient was in shock with severe metabolic acidosis and multiorgan failure. A rapid diagnostic test and peripheral smear confirmed P. falciparum infection. CT brain was normal. However, MRI revealed bilateral T₂/FLAIR hyperintensities in the basal ganglia, thalami, centrum semiovale, and periventricular white matter, with patchy diffusion restriction, findings suggestive of cytotoxic oedema. Despite the timely initiation of artesunate, dialysis, and organ support, the patient succumbed to refractory multiorgan failure.

Discussion: The imaging findings reflect microvascular sequestration and cytotoxic injury, consistent with the known CM pathology. Deep gray and white matter involvement, along with diffusion restriction suggestive of cytotoxic and vasogenic oedema and associated haemorrhagic transformation, are critical MRI markers correlating with disease severity and poor prognosis.

Conclusion: This case highlights the diagnostic value of MRI in adult CM, especially when CT findings are inconclusive. Recognition of cytotoxic oedema patterns without haemorrhagic transformation may aid in early diagnosis and risk stratification.