Malaria Journal最新文献

Background: Seasonal Malaria Chemoprevention (SMC) has been implemented in Moissala Health District, southern Chad, since 2013 using the standard regimen of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ). Although not the sole determinant, SMC can play an important role in generating parasite drug resistance. Three studies spanning a ten-year period were conducted to monitor evolving trends of molecular markers of resistance to SP and AQ in implementation areas.

Methods: In 2014, 2021, and 2023, a total of 136, 256, and 219 blood samples, respectively, were collected from children with clinical malaria residing in eight health zones. Samples were analysed for known molecular mutations associated with emerging Plasmodium falciparum resistance to SP (dhfr N51I, C59R, and S108N; dhps A437G and K540E) and to AQ (pfcrt K76T and pfmdr-1 N86Y).

Results: The proportion of triple dhfr mutants was very high in 2014 and 2021 (100% and 96.9%, respectively), but significantly lower in 2023 (83.9%, p < 0.001). The proportion of quadruple mutants (triple dhfr + dhps A437G) significantly increased from 28.0% in 2014 to 41.0% in 2021 and 47.9% in 2023 (p < 0.001). The proportion of quintuple mutants (triple dhfr + double dhps) was low and did not significantly increase over the years studied (7.6%, 2.8%, and 5.9% in 2014, 2021, and 2023, respectively). The proportion of samples with the pfcrt K76T mutation decreased from 44.6% in 2014 to approximately 11% in 2021 and 2023, while the proportion of samples with the pfmdr-1 N86Y mutation remained consistently low across all three studies. One sample in 2014 exhibited all seven point-mutations investigated, while none were detected in samples in 2021 or 2023.

Conclusion: Surveillance of molecular markers of resistance conducted over a ten-year period in Moissala Health District indicates that SP and AQ remain effective despite prolonged use. However, the rise in quadruple mutants-linked to partial SP resistance-is concerning, and monitoring is needed to detect any increase in quintuple mutants, which confer stronger resistance. These findings underscore the importance of sustained molecular surveillance to guide policy decisions and enable timely adaptations of SMC strategies as resistance patterns evolve.

Background: Placental malaria is caused by the binding of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) protein VAR2CSA, found on the surface of infected erythrocytes, to placental tissue. Complications include maternal anaemia, low birth weight, small for gestational age and preterm delivery. Acquisition of antibodies against VAR2CSA during pregnancy has been linked to immunity against infection.

Methods: Pregnant Malawian women were enrolled at their first antenatal care visit at 16-28 weeks' gestation into a trial of malaria prevention. Women with malaria infection at enrolment (n = 321) or any later point in pregnancy (n = 145) were selected. The IgG and IgM plasma levels against the VAR2CSA DBL1X-ID2a domain were measured at enrolment and delivery. Associations between the DBL1X-ID2a VAR2CSA-specific IgG and IgM antibody levels at enrolment or delivery and low birth weight, small for gestational age, maternal anaemia at delivery, and preterm delivery were assessed using logistic regression with confounder adjustment.

Result: Women with malaria infection at enrolment had higher antibody levels to DBL1X-ID2a than uninfected women, and these declined from enrolment to delivery. There were no significant associations between the IgG antibody level measured at enrolment and the birth outcomes of interest, but the IgG antibody level at delivery in women uninfected at enrolment was associated with a lower risk of low birth weight, adjusted odds ratio (aOR) 0.43 (95% CI 0.19-0.97) p = 0.04. Additionally, in women infected at enrolment, one log higher IgM antibodies to DBL1X-ID2a VAR2CSA at enrolment were associated with a significant 23% decrease in maternal anaemia at delivery, aOR 0.77 (95% CI 0.60-0.99), p = 0.04.

Conclusion: VAR2CSA-specific IgG and IgM antibodies are markers of malaria infection and protection against placental malaria outcomes.

Background: Asymptomatic malaria presents a significant barrier to malaria elimination efforts, particularly in endemic countries like Nigeria. Despite its public health relevance, no national-level pooled estimate of its prevalence and associated risk factors currently exists for Nigeria. This systematic review and meta-analysis aimed to synthesize existing data to estimate the prevalence of asymptomatic malaria and identify affected populations and risk factors across Nigeria.

Methods: A systematic search of PubMed, Google Scholar, and Scopus was conducted to identify observational studies reporting the prevalence of asymptomatic malaria in Nigeria. The review protocol was registered with PROSPERO (CRD42024591788). Eligible studies were screened using Rayyan software, and relevant data were extracted into Microsoft Excel. Meta-analysis was performed using Stata version 15.0. A random-effects model was applied to estimate the pooled prevalence. Heterogeneity was assessed using meta-regression and subgroup analyses, while publication bias was evaluated using funnel plot visualization.

Results: A total of 25 studies were included in the meta-analysis. The pooled prevalence of asymptomatic malaria in Nigeria was estimated at 33% (95% CI 26-41). Prevalence varied by population subgroup, ranging from 25% in the general population to 52% in children. Risk factor analysis revealed an overall prevalence of 19% related to education level, 36% based on sex, and 39% associated with insecticide-treated net (ITN) usage.

Conclusion: This review highlights a high prevalence of asymptomatic malaria in Nigeria, particularly among children. While asymptomatic infections sustain transmission, current evidence underscores the need to prioritize proven transmission-reduction tools. With reduced transmission, the asymptomatic reservoir can then be more effectively addressed through complementary strategies.

Background: Malaria is a leading cause of illness and death in pregnant women and newborns. In 2023, an estimated 12.4 million pregnant women were infected with malaria parasites, resulting in 351,000 low birth weight deliveries. Maternal and household factors associated with malaria in pregnancy and low birth weight were investigated in a high-transmission area of Uganda.

Methods: Data come from a randomized controlled trial of intermittent preventive treatment in pregnancy (IPTp) conducted from December 2020 to July 2024 in Busia District. Maternal and household data were collected using structured questionnaires. Women were followed through delivery including monthly assessment of microscopic parasitemia, assessment of placental malaria by histopathology, and birth weight. Associations between maternal and household factors were assessed: (1) parasitaemia at enrolment, (2) parasitaemia during pregnancy after starting IPTp, (3) high-grade placental malaria, and (4) low birth weight (< 2500 gm).

Results: Of 2,757 women enrolled, 2,728 (98.9%) had a household survey completed and were included in study. Overall, 38.1% had parasitemia at enrolment, 6.5% had parasitemia following initiation of IPTp, 6.4% had high-grade placental malaria, and 6.8% of live births had low birth weight. Parasitemia at enrolment was more common in those 16-21 years of age (RR = 1.62, 95% CI 1.31-1.99 p < 0.001), primigravida (RR = 1.86, 95% CI 1.57-2.21, p < 0.001)), and living in traditional houses (RR-1.17 95% CI 1.06-1.30, p = 0.002). These associations persisted after IPTp initiation: younger age (RR = 1.72, 95% CI 1.22-2.43, p < 0.002), primigravida (RR = 2.40, 95% CI 1.81-3.20, p < 0.001), and traditional housing (RR = 1.30 95% CI 1.01-1.60, p = 0.02). Maternal level of education was not associated with malaria parasitaemia both at enrollment and after initiation of IPTp. Primigravida was strongly associated with high-grade placental malaria (RR = 4.20, 95% CI 2.33-7.59, p < 0.001)) and low birth weight (RR = 2.14, 95% CI 1.18-3.89, p = 0.01). However, there were no significant associations between maternal age, level of education, household wealth, and household construction with high-grade placental malaria or low birthweight.

Conclusions: In an area of high malaria transmission, young primigravida women and those living in traditionally constructed houses had the greatest risk of malaria parasitemia during pregnancy. Primigravida women also had higher risks of low birth weight and high grade placental malaria.

Background: Malaria remains a major public health challenge in Ghana. However, heterogeneous transmission necessitates localized data for effective subnational targeting of control measures. The Ho Municipality, characterized by high rainfall and humidity ideal for year-round mosquito breeding, exemplifies a setting where such detailed epidemiological intelligence is needed but currently scarce. This study aimed to bridge this gap by analysing facility-based trends to inform precision public health interventions in this vulnerable region.

Methods: A retrospective cross-sectional study, performing a census of all available malaria microscopy records from three major healthcare facilities in Ho Municipality over 36 months (January 2020-December 2022) was conducted. Data were extracted from both paper-based logbooks and electronic health records. Descriptive statistics and multivariable regression analyses-specifically, a log-linear model was employed to identify factors associated with parasite density (presented as Geometric Mean Ratios, GMR) and a Poisson regression model to identify factors associated with test positivity (presented as Adjusted Prevalence Ratios, APR). All models were adjusted for age, sex, facility, and year.

Results: Among 27,171 tests, the overall test positivity rate (TPR) was 8.8%, showing a decline from 9.9% in 2020 to 7.2% in 2022. Significant disparities were observed: school-age children (5-12 years) had the highest TPR (18.0%), and a fourfold disparity existed between Ho Municipal Hospital (21.0% TPR) and Ho Teaching Hospital (5.2% TPR). Transmission peaked seasonally in August (13.9% TPR). Plasmodium falciparum was dominant (79.9% of confirmed cases). School-age children and adolescents demonstrated significantly higher parasite densities than adults (aGMR = 3.69 and aGMR = 3.57, respectively). Regression confirmed school-age children (aPR = 3.26) and adolescents (aPR = 3.49) as the highest-risk groups, with a significant age-sex interaction revealing elderly females were also at markedly increased risk (aPR = 2.15).

Conclusion: This study identifies persistent, significant disparities in malaria burden linked to specific age groups, sex, and health facilities in Ho Municipality. These findings underline the urgent need for a targeted intervention strategy, including school-based chemoprevention programs, enhanced diagnostic support and staffing for high-burden facilities, and pre-emptive vector control ahead of peak rainfall seasons to accelerate progress towards malaria elimination.

Background: Community engagement (CE) is essential for public health interventions. This is particularly important when introducing novel technologies, such as the Sterile Insect Technique (SIT), that require strong community understanding and acceptance. Against this background, arts-based CE strategies, including music, drama, and radio short stories, were developed and piloted, but their effectiveness remained unevaluated. This study assessed whether exposure to arts-based CE approaches influenced community knowledge, attitudes, and acceptance of the SIT in uMkhanyakude District, KwaZulu-Natal, South Africa.

Methods: A cross-sectional survey to understand the influence of arts-based CE approaches was conducted in the Jozini municipality, uMkhanyakude District, after community exposure to these CE productions. Structured interviews were conducted with randomly sampled community members. Data were collected on CE exposure and SIT-related knowledge, attitudes, and acceptance. A chi-square test and a stepwise ordinal logistic regression were used to analyse the data after adjusting for sociodemographic factors.

Results: Among 614 participants, only 26.2% (n = 161) were exposed to arts-based CE approaches. Those exposed were more likely to correctly identify that female mosquitoes feed on blood as compared to the unexposed (95.0% vs. 85.8%, p = 0.008), and to express support for SIT (e.g., 98.1% vs. 89.4% agreed with upcoming releases, p = 0.003). Exposure remained a significant predictor of SIT acceptance in multivariate models (OR 0.65, 95% CI 0.45-0.94). Positive attitudes and accurate knowledge also independently predicted greater acceptance.

Conclusion: Arts-based CE tools were effective in supporting the introduction of SIT by improving knowledge and acceptance. However, limited exposure suggests the need for more sustained and widely accessible engagement strategies to maximize reach and long-term impact. These findings suggest that artistic productions, especially when delivered through culturally relevant, multimodal formats, play a meaningful role in shaping community receptiveness to novel vector control methods like the SIT.

Background: From August to October 2022, a therapeutic efficacy study of Niger's first-line antimalarial, artemether-lumefantrine (AL), was conducted in four sites (Aderbissinat, Boboye, Aguié, and Baban Tabki) to evaluate its therapeutic efficacy and investigate for molecular markers of antimalarial drug resistance.

Methods: Children aged 5 to 15 years old with uncomplicated malaria were assessed in a 28 day in vivo efficacy study. Genotyping using three markers (msp1, msp2 and the PolyA microsatellite) and match counting using the WHO three-out-of-three algorithm, were used to distinguish recrudescences from new infections. A two-out-of-three algorithm was also utilized as a sensitivity analysis.

Results: PCR uncorrected and corrected efficacy results at day 28 were calculated. Resistance markers were analysed by next-generation sequencing. Uncorrected treatment efficacies were 62.0% (95% CI 54-74) in Aderbissinat, 95.4% (95% CI 91-100) in Aguié, 98.7% (95% CI 96-100) in Boboye, and 50.6% (95% CI 42-62) in Baban Tabki. After PCR correction, AL efficacy was 100%, 97.5%, 100%, and 93.5%, respectively. Marker analysis revealed a high prevalence of S108N, C59R, and N51I mutations in the pfdhfr gene, and S436A and A437G mutations in the pfdhps gene. No validated or candidate pfkelch13 mutations were observed.

Conclusion: In all four sites evaluated, AL retains therapeutic efficacies above the 90% WHO-recommended threshold using the primary three-out-of-three match criteria. In Aguié and Baban Tabki, efficacy remained above the threshold with certain match criteria and statistical approaches but fell below the cutoff using two-out-of-three matching and per-protocol methods, suggesting emerging efficacy concerns in southern parts of the country.

Background: The innovative automated haematology analyzer XN-31 has demonstrated comparable or, in some settings, superior performance to microscopy and rapid diagnostic tests (RDTs), and good concordance with polymerase chain reaction (PCR) in various endemic areas, particularly where Plasmodium falciparum is prevalent. The XN-31 applies the principle of flow cytometry to measure cell size and nucleic acid content to generate a two-dimensional cytogram in approximately one minute. This technique identifies P. falciparum and other species and provides % parasitaemia (MI-RBC%). This study evaluated the diagnostic performance of the XN-31 in Thailand, where Plasmodium vivax is predominant.

Methods: From November 2019 to June 2022, 349 patients suspected of having malaria were enrolled at the Hospital for Tropical Medicine, Mahidol University, Bangkok. Blood samples were collected via venipuncture and analysed using the XN-31, thick and thin film microscopy, RDTs, and PCR. The qualitative diagnostic accuracy of the XN-31 for detecting malaria parasites and identifying their species was compared with other methods. The quantitative diagnostic ability of the XN-31 was assessed by correlating the MI-RBC% values with % parasitaemia from thin film microscopy.

Results: Among the 349 samples, 125 were positive according to thick film microscopy (103 P. vivax, 17 P. falciparum, 3 Plasmodium knowlesi, 1 Plasmodium ovale, and 1 Plasmodium malariae). The XN-31 demonstrated 98.4% sensitivity relative to thick film microscopy as the reference method, outperforming the RDT (88.0%). All XN-31-positive samples were confirmed via PCR. The information on the parasite species, flagged as 'Malaria? (P.f)' or 'Malaria? (others)' by the XN-31, which depicts P. falciparum or other Plasmodium species, respectively, matched 100% with microscopic determination. The quantitative performance of the XN-31 was strongly correlated with that of thin film microscopy (correlation coefficient [r] = 0.903).

Conclusions: This is the first study to confirm the accuracy of the XN-31 for both qualitative and quantitative diagnoses in a malaria-endemic region dominated by P. vivax. The XN-31 is expected to be a useful diagnostic tool in similar endemic regions.

Background: Insecticide-treated nets (ITNs) remain a key intervention in malaria prevention. However, their protective effectiveness may decline with physical deterioration, even when usage remains high. This study assessed the impact of ITN physical integrity on children's exposure to Anopheles mosquito bites over a three-year period in Mali, using gSG6-P1 biomarker as an innovative immuno-epidemiological indicator of human exposure.

Methods: A three-year prospective cohort study was conducted from 2018, 2019, and 2020 in two rural health districts of Mali: Kéniéba using Yorkool^® ITNs and Kita using PermaNet^® 2.0 ITNs. A total of 586 children under five years old were enrolled and followed annually across 30 villages randomly selected into the two districts. Household surveys captured ITN ownership, usage patterns, and net condition. Net physical integrity was evaluated using proportional hole index (pHI). Blood samples were collected each year and analysed for anti-gSG6-P1 IgG levels, expressed as ΔOD. Net condition and specific IgG levels were analysed across time points and stratified by site and ITNs type.

Results: ITN usage remained high (> 75%) across all survey years, but the proportion of serviceable nets declined significantly, particularly for Yorkool^® (49% at 36 months versus 78% for PermaNet^® 2.0). Median anti-gSG6-P1 IgG levels increased concurrently, indicating rising exposure to Anopheles bites as net integrity deteriorated. Children sleeping under Yorkool^® nets showed higher specific IgG levels than those using PermaNet^® 2.0, suggesting reduced protective performance of Yorkool^® over time.

Conclusion: This study demonstrates that ITN effectiveness decreases as physical deterioration advances, even when usage is maintained. Monitoring net integrity through the gSG6-P1 biomarker provides an innovative, field-adapted approach to anticipate ITN protection failures and to support evidence-based decision-making in malaria control programmes.

Introduction: Accurate diagnosis of malaria, caused by Plasmodium falciparum, remains challenging in endemic resource-limited settings. Molecular diagnostics, like PCR, offer a higher sensitivity, but are often impractical at the point-of-care. A relatively simple molecular diagnostic test has been developed to overcome the technological challenges frequently encountered during the implementation of molecular tools. We present here the results of the field evaluation of this novel mini direct-on-blood PCR platform with lateral flow readout (dbPCR-NALFIA), in a rural setting of Burkina Faso.

Methods: A phase 3 diagnostic accuracy study was conducted over one year in a high P. falciparum transmission setting in Burkina Faso. Febrile patients of all ages (n = 438) were screened using PfHRP2-based RDT, microscopy, and the investigational dbPCR-NALFIA test. Reference diagnostic test was qPCR targeting the P. falciparum varATS gene. Diagnostic accuracy metrics (sensitivity, specificity, predictive values) and agreement (Cohen's kappa) were calculated for each method.

Results: Malaria prevalence by qPCR was 65.5% (287/438). A total of 99.2% (259/261) of P. falciparum microscopy-positive samples were detected by qPCR, 97.7% (253/259) detected with RDT and 99.6% (258/259) with the investigational dbPCR-NALFIA. Overall, 85.2% (149/177) of microscopy negative samples were also confirmed negative with qPCR. Among these qPCR negative samples, 80.5% (120/149) were concordantly negative by RDT, while 98.0% (146/149) were confirmed negative by dbPCR-NALFIA. Using qPCR as reference, the dbPCR-NALFIA demonstrated a sensitivity of 96.5% and specificity of 98.0%, comparable to RDT sensitivity (95.1%) and microscopy specificity (98.7%), but out-performed RDT specificity (80.8%) and microscopy sensitivity (90.2%). dbPCR-NALFIA detected 67.9% of sub microscopic qPCR-positive samples missed by the microscopy. Agreement with qPCR was the highest for dbPCR-NALFIA (kappa value = 0.90), compared to microscopy (kappa value = 0.80) and RDT (kappa value = 0.71).

Conclusion: The dbPCR-NALFIA shows excellent diagnostic performance to detect P. falciparum under field conditions. It addresses key limitations of other diagnostics and could play a vital role in case detection.