Malaria Journal最新文献

Malaria remains a significant global health challenge, with nearly half of the world's population at risk of infection. In 2022 alone, malaria claimed approximately 608,000 lives, with 76% of these fatalities occurring in children under the age of five, underscoring the disease's disproportionate impact on vulnerable populations. Africa bears the highest burden, accounting for 94% of global malaria cases. For over 60 years, the development of a malaria vaccine has been a critical objective for scientists and governments, with substantial efforts directed toward this goal. Recent progress has led to the approval of the first malaria vaccines, RTS,S/AS01 (Mosquirix^®) and the R21/Matrix-M vaccine. Inspired by the promise of these vaccines, the global malaria community has renewed its focus on malaria eradication, 50 years after flawed earlier eradication efforts in the mid-twentieth century. Since the World Health Organization's endorsement of RTS,S in 2021 and R21 in 2023, several African countries, beginning with Cameroon, have integrated these vaccines into routine immunization programmes. This review examines the role of routine malaria vaccination in Africa as a key strategy toward malaria elimination, explores challenges and solutions for widespread vaccine implementation, and discusses future directions in the ongoing fight to eliminate malaria on the continent.

Background: In western Kenya, a cluster-randomized trial is assessing the impact of attractive targeted sugar baits (ATSBs) on malaria in children enrolled in three consecutive cohorts. Here, characteristics of children and households at enrolment, and factors associated with baseline malaria prevalence are described.

Methods: Children aged 1 to < 15 years were randomly selected by cluster (n = 70) from a census database. Cohorts were enrolled in March-April 2022, September-October 2022, and March-April 2023. ATSBs were deployed in March 2022. At enrolment, all participants were tested for malaria by rapid diagnostic test (RDT). After enrolment a household survey was conducted. Household structures were classified as 'improved' (finished walls and roofs, and closed eaves) or 'traditional' (all other construction). A generalized linear mixed model was used to assess factors associated with malaria prevalence.

Results: Of 3705 children screened, 220 declined and 523 were excluded, due to plans to leave the study area (n = 392), ineligible age (n = 64) or other reason (n = 67). Overall, 2962 children were enrolled. Bed net use the previous night was more common in children aged 1-4 years (746/777 [96%]) than those aged 5-<15 years (1806/2157 [84%], p < 0.001). Of the 2644 households surveyed (for 2,886 participants), information on house construction was available for 2595. Of these, only 199 (8%) were categorized as 'improved', as most houses had open eaves. While 99% of households owned at least one bed net, only 51% were adequately covered (one net per two household residents). Among 999 children enrolled in the first cohort (baseline), 498 (50%) tested positive by RDT. In an adjusted multivariable analysis, factors associated with RDT positivity included sub-county (Alego-Usonga vs Rarieda, adjusted odds ratio [aOR] 4.81; 95% CI: 2.74-8.45; p < 0.001), house construction (traditional vs improved, aOR 2.80; 95% CI: 1.59-4.95; p < 0.001), and age (5-< 15 vs 1-4 years, aOR 1.64; 95% CI: 1.13-2.37; p = 0.009).

Conclusions: In western Kenya, the burden of malaria in children remains high. Most households owned a bed net, but coverage was inadequate. Residents of Alego-Usonga sub-county, those living in traditionally constructed households, and older children were more likely to test positive by RDT. Additional tools are needed to effectively control malaria in this area. Trial registration The ATSB trial is registered under Clinicaltrials.gov NCT05219565.

Background: The national malaria control programmes in Cambodia, Nepal, and Bhutan aim to achieve malaria elimination by 2025-2030. While the vivax malaria burden remains challenging, the consistent decline in falciparum malaria in these countries over the last five years suggests that the goal is achievable. However, unexpected cases in previously falciparum malaria-free districts continue to occur. A virtual meeting was convened in May 2024, followed by smaller meetings, to discuss and share experiences among regional partners, focusing on falciparum malaria elimination.

Main text: The discussion among regional partners from these three countries was prompted by an isolated outbreak of falciparum malaria in April 2022 in a previously malaria-free district in Pursat province, Cambodia. The National Center for Parasitology, Entomology and Malaria Control (CNM) worked with stakeholders to contain the outbreak, which was likely to have originated in forest goers. Community-based village malaria workers (VMWs) were augmented with the additional resources required to test and treat malaria among forest goers under the supervision of health centres and district hospitals. This response rapidly reduced malaria cases in the subsequent months. Regional partners from Nepal and Bhutan, who are also engaged in the final phase of malaria elimination, reported that isolated malaria outbreaks in their countries were not unusual and were mostly imported from a neighbouring country, India. Importation of cases was facilitated by unsupervised transborder travel including the movement of migrant workers. The imported cases were only established during the case investigation such as when responding to the isolated outbreaks. In contrast, in Cambodia, spread of malaria was known to be facilitated by mobile and migrant workers, and forest goers within the country. The specific differences between Nepal and Bhutan (South Asia), and Cambodia (Greater Mekong Subregion) offered insights into strategies for malaria elimination. A relevant component for countries embarking on malaria elimination included strengthening of local malaria surveillance and response in collaboration with the community health workers, and community members targeting the 'at risk' population.

Conclusion: In countries approaching malaria elimination, resourcing community-based health workers could play a critical role in enhancing malaria surveillance, early case detection and treatment, including interventions targeting migrant populations such as forest goers and seasonal migrant workers.

Background: Rapid diagnostic tests (RDTs) based on the detection of Plasmodium falciparum histidine rich protein 2 (PfHRP2) are widely used for the diagnostic of P. falciparum in Africa. However, deletions of the pfhrp2 and pfhrp3 genes can lead to false negative test results and compromise appropriate case management. Due to the high burden of malaria in Mozambique, it is crucial to monitor the potential emergence of parasites with pfhrp2/3 gene deletions in the country.

Methods: The presence of pfhrp2/3 deletions was assessed during the 2023 high transmission season in 34 health facilities from 9 districts across 6 provinces in Mozambique. Children between 2 and 10 years of age attending the health facility with fever were tested by both the routine HRP2-RDT and a P. falciparum lactate dehydrogenase (PfLDH)-RDT, and dried blood spots (DBS) were collected from those testing positive by one or both RDTs. DBS from children with a negative HRP2-RDT but positive PfLDH-RDT were tested for the presence of pfhrp2/3 deletions by multiplex real time quantitative polymerase chain reaction (qPCR).

Results: 3208 children attended the health facilities during the study. 81.6% (2612/3208) participants were positive for at least one malaria RDT and, among them, 0.8% (210/2612) had discrepant RDT results (22 HRP2 - but LDH + and 188 HRP2 + but LDH -). The overall prevalence of suspected false-negative HRP2-RDT results in Mozambique was 0.91% (95% CI 0.58-1.39; 22/2424). pfhrp2/3 gene deletions were confirmed in 4 cases (1 in Nampula and 3 in Inhambane). Therefore, the prevalence of P. falciparum confirmed cases with pfhrp2/3 gene deletions in the six provinces sampled was 0.16% (95% CI 0.15-2.57; 4/2424), being 0.27% (95% CI 0.01-1.75; 1/367) in Nampula and 0.59% (95% CI 0.15-1.88; 3/503) in Inhambane.

Conclusion: pfhrp2/3 gene deletions were detected in 2 out of 6 provinces surveyed in Mozambique, but at a prevalence far below the 5% threshold recommended for a change in HRP2-based-RDT.

Background: Malaria remains a threat in sub-Saharan Africa, particularly in Côte d'Ivoire, where it is endemic and represents the leading cause of hospital consultations, morbidity and mortality. The strong climatic variations that exist between coastal and savannah areas of Côte d'Ivoire suggest that vector control interventions should be scheduled according to the eco-epidemiological diversity. This study evaluates bioecological parameters of vectors and malaria transmission in two health districts, one coastal and one central of Côte d'Ivoire.

Methods: The study was conducted in the coastal (Jacqueville) and savannah (Béoumi) areas of Côte d'Ivoire from November 2018 to March 2019. Human Landing Catches (HLC) were conducted monthly at the study sites to determine Anopheles vector species composition, biting behaviour as well as entomological parameters of malaria transmission. Mosquitoes were collected over 12 h, from 6:00 pm to 6:00 am during 2 days per month. Mosquitoes infectivity was revealed by enzyme-linked immunosorbent assay (ELISA) for Plasmodium falciparum circumsporozoite protein. A random sample of 100 Anopheles gambiae sensu lato (s.l.) including all CSP-positive females, were further classified by polymerase chain reaction (PCR) at the species and molecular form levels.

Results: In Jacqueville, 853 (99.7%) An. gambiae s.l., and 3 (0.35%) Anopheles pharoensis were collected. In Béoumi, 811 (96.3%) An. gambiae s.l., 23 (2.73%) Anopheles funestus and 8 (0. 95%) An. pharoensis have been found. Anopheles coluzzii represented the only species of the An. gambiae complex in Jacqueville. Among the An. gambiae s.l. samples tested in Beoumi, 29 (58%) were An. coluzzii and the rest 21 (42%) was An. gambiae sensu stricto. The human biting rate (HBR) in Jacqueville increased from 5.7 (b/p/n) in November to 17.3 (b/p/n) in March. Conversely in Béoumi the HBR decreased from 16.4 (b/p/n) in November to 0.69 (b/p/n) in March. In Jacqueville, the entomological inoculation rate (EIR) varies from 0.21 to 0.56 (ib/p/n) with the pic of 0.56 (ib/p/n) in February. In Béoumi no infection was detected in the parous An. gambiae s.l. samples tested during the study period.

Conclusions: This study evaluates bioecological parameters of vectors and malaria transmission in two health districts, one coastal and one central of Côte d'Ivoire.

Background: Molecular methods play an important role in clinical trials assessing anti-malarial drugs and vaccines, as well as in epidemiological studies aimed at detecting Plasmodium species, especially when dealing with large sample sizes. Molecular techniques are more sensitive and generally have a higher throughput compared to the gold standard microscopy. Further optimization can be achieved with automation of nucleic acid isolation, allowing for rapid and precise extraction. This study evaluated the isolation of total nucleic acids from Plasmodium falciparum mocked samples using an automated extraction method with a magnetic bead-based kit compared to a manual silica column-based kit. Additionally, two different RNA preservation solutions were compared.

Methods: Plasmodium falciparum Dd2 parasites were serially diluted and spiked into whole blood. The dilutions were stored in two different RNA preservation solutions and total nucleic acids extracted with an automated magnetic bead-based kit and a manual silica column-based kit. Subsequently, a reverse transcription (RT) qPCR for Plasmodium detection targeting Plasmodium 18S rRNA and DNA in a single reaction was performed and the quantification cycle (Cq) values across the different sample groups were compared.

Results: Comparable Cq values across the various sample preparations were obtained, suggesting minimal influence from RNA preservation solutions (p = 0.686) or extraction methods (p = 0.119) on RT-qPCR outcomes. Automated nucleic acids extraction allowed processing numerous samples in a shorter timeframe and showed similar efficiency in detecting Plasmodium in blood samples by RT-qPCR as manual extraction.

Conclusions: The automated method for nucleic acid isolation is a valuable tool for the detection of Plasmodium infections in large-scale studies. It is efficient, reliable, and cost-effective. Its potential applications extend to other molecular surveillance studies to support malaria control measures.

Background: To eliminate malaria by 2035, Brazil must address Plasmodium vivax. Previously, first-line treatment was chloroquine plus 7-day primaquine (PQ) without glucose-6-phosphate dehydrogenase (G6PD) deficiency testing. In 2021, point-of-care quantitative G6PD testing and single-dose tafenoquine (TQ) were piloted in two municipalities. This study evaluated healthcare professional (HCP) and patient perceptions of TQ implementation.

Methods: This qualitative observational study in Manaus and Porto Velho municipalities evaluated the pilot implementation of the new P. vivax malaria treatment algorithm in high/medium-complexity healthcare units (phase one), then low-complexity units (phase two). Qualitative data collection began 30 days after the first TQ treatment in each phase, i.e., October 2021 and March 2022. Perceptions of TQ were assessed using semi-structured in-depth interviews and field notes until saturation. Data were analysed through debriefing sessions, and systematic organization in Excel and MAXQDA, with themes derived by inductive and deductive analysis.

Results: The study included 55 patients who received TQ and 94 HCPs. HCPs viewed the TQ single-dose regimen as a significant advancement over 7-day PQ, enhancing adherence. Patients appreciated the shorter duration of treatment and perceived a rapid clinical recovery and fewer side effects. HCPs also noted that TQ resulted in fewer recurrences of P. vivax. The single-dose administration of TQ facilitated complete supervision of the treatment, reduced HCP workload and ensured that patients received the necessary care and did not share the medication with family members. TQ packaging instilled patient trust, though HCPs working in the community found the packaging too bulky. Prescription insecurities among HCPs after initial training prompted requests for additional training. While some patients initially doubted single-dose efficacy, confidence grew with experience. TQ implementation increased awareness of pharmacovigilance and enhanced patient communication, with HCPs adhering to protocols for monitoring haemolysis symptoms.

Conclusion: Single-dose TQ for P. vivax malaria in Brazil's Amazon region was positively received by HCPs and patients. Positive perceptions of the medication may aid in improving patient adherence to malaria treatment, thereby reducing malaria recurrences. The findings underscore the importance of adaptive training to optimize P. vivax radical cure implementation.

Studies on Plasmodium falciparum transmission require blood-feeding infectious gametocytes to mosquitoes using standard membrane-feeding assays (SMFAs). SMFAs are routinely performed using electric heating coils or glass membrane feeders connected to a circulatory water bath using tubing and clamps. Each of these approaches is expensive and requires a complex setup, hence restricting the number of assays that can be performed simultaneously. Furthermore, existing methods cannot be easily applied in low-resource field settings. This study presents a low-cost and simplified method for feeding mosquitoes with an infectious blood meal using 35 mm Petri dishes where temperature is maintained by using reusable gel warmers. The intensity and prevalence of infection in mosquitoes (Anopheles stephensi and Anopheles gambiae) fed via a Petri dish overlaid with gel warmers were comparable to mosquitoes fed using standard glass membrane feeders. The methodology described here can be easily applied in low-resource and field settings due to its low cost, ease of set up, and use of easily available supplies, such as Petri dishes, and reusable gel warmers. We believe a wide range of laboratories can easily adapt this method for P. falciparum transmission studies.

Background: Effective vector control interventions, notably insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are indispensable for malaria control in Tanzania and elsewhere. However, the emergence of widespread insecticide resistance threatens the efficacy of these interventions. Monitoring of insecticide resistance is, therefore, critical for the selection and assessment of the programmatic impact of insecticide-based interventions.

Methods: The study was conducted country-wide across 22 sentinel districts of Tanzania between May and July 2023 using standard World Health Organization susceptibility test with 1×, 5×, and 10× of deltamethrin, permethrin, and alpha-cypermethrin and discriminating concentrations of 0.25% pirimiphos-methyl. Synergist assays were conducted to explore the underlying mechanisms of the observed phenotypic pyrethroid-resistant mosquitoes. Three- to five-day-old wild adult females in the first filiar generation of Anopheles gambiae sensu lato (s.l.) were used for the susceptibility bioassays.

Results: Anopheles gambiae s.l. were resistant to all pyrethroids at the discriminating dose in most sentinel districts except in Rorya, which remains fully susceptible, and Ushetu, which remains susceptible to deltamethrin but not permethrin. In 5 sites (Bukombe, Ukerewe, Kilwa, Kibondo, and Kakonko), the An. gambiae s.l. species exhibited strong resistance to pyrethroids surviving the 10 X concentrations (mortality rate < 98%). However, they remained fully susceptible to pirimiphos-methyl in almost all the sites except in Kibondo and Shinyanga. Likewise, there was full restoration to susceptibility to pyrethroid following pre-exposure of An. gambiae s.l. to piperonyl-butoxide (PBO) in 13 out of 16 sites. The 3 sites that exhibited partial restoration include Kakonko, Tandahimba, and Newala.

Conclusion: The evidence of widespread pyrethroid resistance of the major malaria vector justifies the decision made by the Tanzania National Malaria Control Programme to transition to PBO-based ITNs. Without this switch, the gains achieved in malaria control could be compromised. Equally important, the lack of full restoration to susceptibility observed in three sentinel districts upon pre-exposure to PBO merits close monitoring, as there could be other underlying resistance mechanisms besides oxidase metabolic resistance.