Malaria Journal最新文献

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.

Background: The northern Brazilian state of Roraima has recently experienced an increase in malaria cases, mainly caused by illegal mining activities on indigenous lands. These activities mainly affect the Yanomami Indigenous people, whose territory accounts for nearly 30% of Roraima. In January 2023, the severity of the malaria outbreak led to a Public Health Emergency declaration in the Yanomami Indigenous Land (YIL) and prompted government intervention. This study examines malaria trends before and after the 2023 federal government's response in the YIL.

Methods: A descriptive retrospective study was performed using secondary data from Brazil's Health Information System (HIS), covering reported malaria cases, hospitalizations, and deaths in Roraima from 2021 to 2024.

Results: Between January 2021 and December 2024, Roraima reported 117,214 indigenous malaria cases. After the federal intervention in the YIL in 2023, cases increased significantly (52,210 to 65,004; p = 0.0005), while hospitalizations decreased (787-638; p = 0.0304), and deaths remained steady (111 total; p = 0.9089). Throughout the study, Plasmodium vivax was the dominant species. Cases were highest among men, Indigenous people, and the 20-39 age group. Post-intervention, case detection increased for all species but shifted from adults (20-59 years) to vulnerable groups (0-19, 60 + years). Indigenous cases rose sharply. Hospitalizations for P. vivax, declined after the intervention, especially in men and the 20-39 age group. Mortality was highest in children under 10 and Indigenous populations. Within the Yanomami Special Indigenous Health District (Yanomami-DSEI), cases decreased in Mucajaí, Iracema, and Caracaraí but increased in Alto Alegre in 2024. Exported cases from Roraima to Maranhão (- 95.5%), Pará (- 86.8%), and Amazonas (- 71.5%) dropped sharply.

Conclusions: After federal government intervention in the YIL, malaria case detection increased, hospitalizations decreased, and mortality stayed steady. Cases among the Yanomami in Alto Alegre rose, while exports to other states declined. Ongoing progress relies on strengthening primary care, enhancing surveillance, and fostering cross-border cooperation.

Background: Malaria continues to impose a significant public health burden in Sudan, where fragile health systems and conflict exacerbate transmission. The introduction of RTS,S/AS01 and R21/Matrix-M vaccines offers a potential breakthrough. However, the success of such programs depends heavily on healthcare workers (HCWs), whose knowledge and attitudes can influence vaccine uptake; this study explored these factors among Sudanese HCWs' knowledge and attitudes toward malaria vaccination.

Methods: An exploratory cross-sectional survey was conducted between January and April 2025 among HCWs across Sudan. A total of 222 eligible participants were recruited via an online, self-administered questionnaire. Knowledge was assessed using eight malaria vaccine-related items, with scores ≥ 70% indicating adequate knowledge. Attitudes were measured through six Likert-scale items, with ≥ 70% considered positive. Descriptive statistics, Chi-square tests, independent t-tests, and regression analyses were applied.

Results: The mean age of respondents was 31.5 years, and 66.7% were female. Pharmacists represented the largest professional group (44.6%). Only 9% (n = 20) demonstrated adequate knowledge of malaria vaccination, and 21.6% (n = 48) displayed positive attitudes. While 66.2% (n = 147) had heard of malaria vaccines, 71.2% (n = 158) were unaware of WHO recommendations, and 76.6% (n = 170) did not know the vaccine's target parasite. Negative attitudes were reported by 78.4% (n = 174), particularly concerning safety, affordability, and trust in authorities. Positive attitudes were more common among males, HCWs with > 5 years of experience, and those in the private sector (all p < 0.05).

Conclusion: The study highlights critical gaps in knowledge and predominantly unfavorable attitudes toward malaria vaccination among Sudanese HCWs, indicating a risk of vaccine hesitancy in frontline delivery. Targeted training and awareness programs are urgently needed to strengthen HCWs' capacity, dispel misconceptions, and build trust in the malaria vaccine as Sudan scales up immunization efforts.

Background: Genotyping Plasmodium falciparum polymorphic merozoite genes to describe parasite genetic diversity and the complexity of malaria infections (COI) is routinely used to assess the effectiveness of malaria control interventions. They are also utilized in anti-malarial drug therapeutic efficacy studies (TES) to differentiate recrudescent parasites from new infections. However, these polymorphic genes are usually under selection. Therefore, neutral microsatellite markers are preferred as they are also easier to genotype. The current study investigated the genetic diversity and COI using the poly-α microsatellite marker to provide background information on circulating genotypes before its applied to TES in Kenya.

Methods: Dried blood spot (DBS) samples were obtained from 93 participants from a TES in Busia County in 2016 and 92 participants from a malaria monitoring study conducted in Kilifi in 2020. Genotyping of the poly-α microsatellite was done by PCR, capillary electrophoresis and the fragment data analysed using GeneMarker.

Results: About 97% and 87% of the samples from Busia and Kilifi, respectively, were successfully genotyped. The infections in Busia were mainly polyclonal (80%) with a significantly higher mean COI of 2.9 (p < 0.0001), while those in Kilifi were mostly monoclonal (52.5%) with a mean COI of 1.7. Despite on average a younger population and lower parasite density in Busia, both regions had similar expected heterozygosity (He) (Busia = 0.92; Kilifi = 0.90) while Kilifi recorded a slightly lower number of effective alleles (Ne) (Kilifi = 9.3; Busia = 10.8).

Conclusions: The poly-α microsatellite genotyping revealed high genetic diversity of malaria parasites in Busia and Kilifi. These findings define the genotypes (fragment sizes) observed in the two Kenyan populations, providing a proof of concept for the utility of poly-α in TES studies as a molecular correction tool and for the evaluation of the effectiveness of malaria interventions in Kenya.

Background: Unique patient identification is necessary for detecting malaria recurrence and facilitates individualised treatment. Reliable patient identification in settings with poor information technology infrastructure is challenging. A before-and-after study was conducted to investigate whether the use of biometric fingerprinting alongside an existing physical 'malaria card' system improved unique identification of patients with malaria at a busy, publicly-funded clinic in Papua, Indonesia.

Methods: A three-phase study was conducted at Wania clinic in Timika over a 16-month period. In Phase 1 (the 'pre-intervention period'-3 months), patient identification practices using the standard 'malaria card' system were documented. In Phase 2 ('training'-6 months), fingerprinting was introduced, troubleshooting was undertaken, and biometric data were gradually accrued. In Phase 3 ('consolidation'-7 months), fingerprinting continued to be incorporated into routine clinic practice. The main outcome of interest was the proportion of malaria patients visiting the clinic's 'Malaria Corner' who could be linked to a pre-existing malaria card number in Phase 1 versus Phase 3. Analyses were descriptive.

Results: During the 16-month study period, 7471 patients with malaria visited the Malaria Corner at Wania clinic, 1487 in Phase 1 (80.3%), 3228 in Phase 2 (59.6%), and 2756 in Phase 3 (59.1%). The proportion of patients who attended the Malaria Corner with a malaria card was 33.1% (492/1487) in Phase 1, 36.3% (663/1828) in Phase 2, and 46.9% (938/2001) in Phase 3. Overall, 56.6% (1828/3228) of patients attending the Malaria Corner had biometric fingerprinting in Phase 2 and 72.6% (2001/2756) in Phase 3. The proportion of all patients attending the Malaria Corner who could be linked to a pre-existing malaria card number increased from 44.4% (660/1487) in Phase 1 to 48.9% (1348/2756) in Phase 3 (difference = 4.5%, 95% Confidence Interval (CI) 1.4-7.7%). In Phase 3, 55.8% (1117/2001) of patients who had fingerprinting were linked to a pre-existing malaria card number (difference compared with Phase 1 = 11.4%, 95% CI 8.1-14.8%). Of the 2714 patients who were offered biometric fingerprinting for the first time, 0.39% (6/1556) refused in Phase 2 and 0.26% (3/1158) refused in Phase 3. Challenges in implementation included unreadable fingerprints, particularly among children.

Conclusion: This study demonstrates the potential use of biometrics to improve patient identification in resource-limited settings and to streamline workflows. Expanding biometric systems to include complementary methods, such as facial recognition, could further address challenges in uniquely identifying specific patient groups, such as young children.

Background: Malaria is a significant cause of under-five child mortality in sub-Saharan Africa (SSA). The World Health Organization (WHO)-approved rapid diagnostic tests (RDT) for malaria offer a resource-efficient alternative to gold-standard diagnostic methods and may improve timely access to care through self-testing.

Methods: The feasibility of use of RDT for self-testing was evaluated in 100 households each in Migori County, Kenya; KwaZulu-Natal Province, South Africa; and Copperbelt Province, Zambia. Surveys assessed perceived usability, acceptability, and preferences for RDTs among consenting participants.

Results: Among 225 participants in Kenya, 80 in South Africa, and 163 in Zambia, 25 (11.5%), 0 (0.0%), and 3 (1.8%) tested positive for malaria, respectively. In Kenya and Zambia, 89% of participants reported previous malaria diagnoses. Participants across all three sites interpreted the RDT with 100% sensitivity and 99.7% specificity compared to RDT interpretation performed by a trained study team member, with only one individual interpreting their test incorrectly. Over 96% of participants across all three sites felt the RDT would be easy to use for specimen collection, test operation, and result interpretation, and 160 (100%) Kenyan participants, 74 (96.1%) South African participants, and 157 (99.4%) Zambian participants felt confident that they had interpreted their own test correctly. Participants' perceived comfort for future self-testing with an RDT was high in Kenya (92%) and Zambia (86%), and moderate in South Africa (66%).

Conclusions: These findings indicate that RDT self-testing is highly acceptable and feasible in SSA settings with a high malaria burden.

Background: Mosquitoes transmit several infectious diseases, including malaria. Due to the increasing resistance of mosquitoes to synthetic insecticides and the non-selective nature of these chemicals, larviciding has emerged as an effective and environmentally safer method of mosquito control. This study focused on the larvicidal activity of the essential oils (EOs) isolated from Cymbopogon citratus (lemongrass) stalks and leaves collected in Morogoro, Tanzania, against Anopheles gambiae sensu stricto (s.s.) larvae.

Methods: The EOs were extracted by hydrodistillation and characterized by Gas Chromatography-Mass Spectroscopy (GC-MS). Larvicidal bioassays were performed on laboratory-reared larvae, and mortality data were analysed using probit analysis to determine LC₅₀ and LC₉₀ values at 95% confidence intervals.

Results: A total of 195 and 99 components from the lemongrass leaves and stalks, respectively, were identified. The higher concentration of EOs was obtained from stalks in comparison to the leaf's counterpart, in which the geranial (31.89%) and neral (27.02%) were determined to be the major components. The EOs isolated from lemongrass stalks demonstrated greater larvicidal activity than those obtained from lemongrass leaves, with LC₅₀ values of 146.6 ppm and 209.5 ppm, respectively. These results demonstrated the potent larvicidal properties of lemongrass stalk EOs against An. gambiae s.s. larvae.

Conclusion: The EOs from lemongrass stalks exhibit greater larvicidal efficacy against An. gambiae s.s. larvae compared to those obtained from lemongrass leaves.