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Alzheimer's disease (AD) is the most common neurodegenerative disorder to date. Neuropathological hallmarks are β-amyloid (Aβ) plaques and neurofibrillary tangles, but the inflammatory process has a fundamental role in the pathogenesis of AD. Inflammatory components related to AD neuroinflammation include brain cells such as microglia and astrocytes, the complement system, as well as cytokines and chemokines. Cytokines play a key role in inflammatory and anti-inflammatory processes in AD. An important factor in the onset of inflammatory process is the overexpression of interleukin (IL)-1, which produces many reactions in a vicious circle that cause dysfunction and neuronal death. Other important cytokines in neuroinflammation are IL-6 and tumor necrosis factor (TNF)-α. By contrast, other cytokines such as IL-1 receptor antagonist (IL-1ra), IL-4, IL-10, and transforming growth factor (TGF)-β can suppress both proinflammatory cytokine production and their action, subsequently protecting the brain. It has been observed in epidemiological studies that treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the risk for developing AD. Unfortunately, clinical trials of NSAIDs in AD patients have not been very fruitful. Proinflammatory responses may be countered through polyphenols. Supplementation of these natural compounds may provide a new therapeutic line of approach to this brain disorder.

Background Malaysia has declared its aim to eliminate malaria with a goal of achieving zero local transmission by the year 2020. However, targeting the human reservoir of infection, including those with asymptomatic infection is required to achieve malaria elimination. Diagnosing asymptomatic malaria is not as straightforward due to the obvious lack of clinical manifestations and often subpatent level of parasites. Accurate diagnosis of malaria is important for providing realistic estimates of malaria burden and preventing misinformed interventions. Low levels of parasitaemia acts as silent reservoir of transmission thus remains infectious to susceptible mosquito vectors. Hence, the aim of this study is to investigate the prevalence of asymptomatic submicroscopic malaria (SMM) in the District of Belaga, Sarawak. Methods In 2013, a total of 1744 dried blood spots (DBS) were obtained from residents of 8 longhouses who appeared healthy. Subsequently, 251 venous blood samples were collected from residents of 2 localities in 2014 based on the highest number of submicroscopic cases from prior findings. Thin and thick blood films were prepared from blood obtained from all participants in this study. Microscopic examination were carried out on all samples and a nested and nested multiplex PCR were performed on samples collected in 2013 and 2014 respectively. Results No malaria parasites were detected in all the Giemsa-stained blood films. However, of the 1744 samples, 29 (1.7%) were positive for Plasmodium vivax by PCR. Additionally, of the 251 samples, the most prevalent mono-infection detected by PCR was Plasmodium falciparum 50 (20%), followed by P. vivax 39 (16%), P. knowlesi 9 (4%), and mixed infections 20 (8%). Conclusions This research findings conclude evidence of Plasmodium by PCR, among samples previously undetectable by routine blood film microscopic examination, in local ethnic minority who are clinically healthy. SMM in Belaga district is attributed not only to P. vivax , but also to P. falciparum and P. knowlesi. In complementing efforts of programme managers, there is a need to increase surveillance for SMM nationwide to estimate the degree of SMM that warrant measures to block new transmission of malaria.

Background The emergence of drug resistance in Plasmodium falciparum has been a major contributor to the global burden of malaria. Drug resistance complicates treatment, and it is one of the most important problems in malaria control. This study assessed the level of mutations in P. falciparum genes, pfdhfr , pfdhps , pfmdr1 , and pfcrt , related to resistance to different anti-malarial drugs, in the Continental Region of Equatorial Guinea, after 8 years of implementing artesunate combination therapies as the first-line treatment. Results A triple mutant of pfdhfr (51I/59R/108N), which conferred resistance to sulfadoxine/pyrimethamine (SP), was found in 78% of samples from rural settings; its frequency was significantly different between urban and rural settings (p = 0.007). The 164L mutation was detected for the first time in this area, in rural settings (1.4%). We also identified three classes of previously described mutants and their frequencies: the partially resistant ( pfdhfr 51I/59R/108N +  pfdhps 437G), found at 54% (95% CI 47.75–60.25); the fully resistant ( pfdhfr 51I/59R/108N +  pfdhps 437G/540E), found at 28% (95% CI 7.07–14.93); and the super resistant ( pfdhfr 51I/59R/108N +  pfdhps 437G/540E/581G), found at 6% (95% CI 0.48–4.32). A double mutation in pfmdr1 (86Y + 1246Y) was detected at 2% (95% CI 0.24–3.76) frequency, distributed in both urban and rural samples. A combination of single mutations in the pfmdr1 and pfcrt genes (86Y + 76T), which was related to resistance to chloroquine and amodiaquine, was detected in 22% (95% CI 16.8–27.2) of samples from the area. Conclusions The high level of mutations detected in P. falciparum genes related to SP resistance could be linked to the unsuccessful withdrawal of SP treatment in this area. Drug resistance can reduce the efficacy of intermittent prophylactic treatment with SP for children under 5 years old and for pregnant women. Although a high number of mutations was detected, the efficacy of the first-line treatment, artemisinin/amodiaquine, was not affected. To avoid increases in the numbers, occurrence, and spread of mutations, and to protect the population, the Ministry of Health should ensure that health centres and hospitals are supplied with appropriate first-line treatments for malaria.

Background In non-endemic countries, malaria can be transmitted through blood donations from imported cases. To ensure standards of quality and safety of human blood, the European Union and Spanish national law, requires a deferral period, or a screening by immunological or genomic test among those donors with potential risk of malaria. Scientific societies, European Committee on Blood Transfusion, and Spanish Society of Haematology and Haemotherapy, refer only to the result of the immunological test. Methods An observational retrospective study was performed in potential donors with a positive immunological test for malaria done in the Regional Transfusion Center in Madrid and referred to the National Reference Unit for Tropical Diseases in Madrid between 2015–2020. At consultation a Polymerase Chain Reaction (PCR) for malaria was performed. Results During the study period, 121 possible donors attended for consultation at NRU-Trop. Median age: 38.5 (IQR:33–48); median time to consultation was 32 months (IQR:12.5–110). Eighty-two (67.8%) donors were migrants and thirty-nine were travellers (32.2%). ELISA values were available for 109 subjects (90.1%), 56 individual left malaria endemic area > 3 years before. All donors tested negative for Plasmodium spp PCR test (n = 121, 100%). Conclusions None of the subjects with a positive immunologic test deferred as blood donors had a positive genomic test. The presence of Plasmodium spp in collected blood was not detected by molecular techniques. To avoid the loss of potential blood donors, especially those with low incidence red blood cell antigens, as more precise microbiology techniques become available, updating the existing legislation becomes necessary to increase the availability of donated blood.

In Spain, a patient’s unexpected relapse with Plasmodium falciparum raises questions about genetic influences on treatment efficacy. Meanwhile, in a separate case, a recurrence of Plasmodium malariae prompts speculation on latent reservoirs and treatment strategies. Here, we delve into these complex cases that underscore the evolving landscape of malaria.

Background Mansonella perstans is a vector-borne filarial parasite widely endemic in sub-Saharan Africa, with sporadic cases in Latin America. Infection is often overlooked; treatment is not standardized, and effectiveness of common regimes is difficult to ascertain. Anti- Wolbachia macrofilaricidal treatment with doxycycline has been applied, but there are scant and contrasting reports about the presence of Wolbachia in M. perstans isolates from different geographical locations. Taking advantage of a network of European centres expert in traveller and migrant health, we aimed to expand the knowledge concerning the distribution of Wolbachia in M. perstans to contribute to the design of optimal treatment approaches. Methods We analysed 19 samples of concentrated microfilariae or whole blood from M. perstans -infected patients who reported having resided or travelled in one or more of 10 West African countries. Wolbachia was detected by PCR targeting 16S and ftsZ genes and phylogenetic analysis of M. perstans was performed based on COX1 gene sequencing. Results Wolbachia was identified in 14/19 (74%) samples. With the possible inaccuracy deriving from potential origin of infection being identified retrospectively from routine clinical visit’s documents, this study identified Wolbachia in M. perstans from Burkina Faso, Equatorial Guinea, Republic of Guinea and Senegal for the first time to our knowledge. Furthermore, Wolbachia might also be present in M. perstans from Democratic Republic of the Congo, Mali, Niger and Nigeria. Conclusions The retrieval of Wolbachia -positive and Wolbachia -negative M. perstans samples can either be explained by technical limitations or reflect the real existence of Wolbachia -positive and Wolbachia -negative M. perstans populations. However, this latter hypothesis was not supported by our phylogenetic analysis. Our results suggest that doxycycline could be used for the treatment of M. perstans infection upfront or, if possible, after ascertaining the presence of Wolbachia by PCR performed on concentrated microfilariae using two targets to avoid false-negative results. Graphical Abstract

Altered lipid profiles have been observed in acute malaria, though mechanisms remain unclear. The impact of asymptomatic submicroscopic malaria infection (AMI) on lipids is unexploredAn observational, comparative, retrospective study was conducted of 1278 asymptomatic Sub-Saharan African migrants (ASSAMs) screened for malaria and lipid profiles during health exams (2010-2022). A systematic screening protocol for infectious disease was performed, including screening for Plasmodium spp. infection by polymerase chain reaction (PCR).Among 800 ASSAMs screened for malaria, 104 (13%) were PCR-positive: P. falciparum (68.72%), P. malariae (18.27%), P. ovale (9.62%), and mixed infections (3.8%). Participants with AMIs exhibited lower baseline lipid levels: total cholesterol (146 vs. 163 mg/dL; p < 0.001), HDL (43 vs. 47 mg/dL; p < 0.001), and LDL (87.5 vs. 98 mg/dL; p < 0.001), with no differences in triglycerides. After treatment, lipid levels partially equalized: total cholesterol (156 vs. 166; p equivalent 0.01), HDL (44 vs. 47.5; p equivalent 0.05), LDL (102 vs. 108.5; p equivalent 0.31), with no changes in triglycerides. Patients with AMI showed higher rates of co-infections (Strongyloides 20.61% vs. 14.35%; p < 0.001; filariae 7.69% vs. 1.91%; p equivalent 0.02) and lower mean corpuscular volume (87.2 vs. 85; p < 0.001). Conclusions: These findings suggest that cholesterol reductions in AMI are not solely due to acute inflammation but May reflect chronic inflammatory processes triggered by asymptomatic malaria. This supports a potential link between AMI and lipid profile changes, underscoring its role in subclinical chronic inflammation.

The risk of non-human primate (NHP) malaria transmission to humans is increasing, with Plasmodium knowlesi and Plasmodium cynomolgi emerging as significant zoonotic threats, particularly in Malaysia. While P. knowlesi is well-documented, P. cynomolgi infections in humans remain underreported, largely due to diagnostic challenges. Routine microscopy and standard molecular diagnostic tools often misdiagnose P. cynomolgi infections as P. vivax due to morphological similarities and genetic homology. We report a new case of a human P. cynomolgi infection misdiagnosed as Plasmodium vivax in a 32-year-old male with no prior malaria history or travel to endemic countries. The initial diagnoses made by the microscopy and qPCR conducted by the Kota Bharu Public Health Laboratory in Kelantan identified the infection as P. vivax. However, cross-examination by the Institute for Medical Research (IMR) revealed the presence of mixed-species infection, prompting further analysis. The real-time PCR and sequencing performed at MAPELAB, Spain, confirmed the co-infection of P. vivax and P. cynomolgi. This case highlights the diagnostic limitations in detecting P. cynomolgi, which shares high genetic similarity with P. vivax, leading to potential cross-reactivity and diagnostic inaccuracies. As P. cynomolgi emerges as the second zoonotic malaria species after P. knowlesi capable of infecting humans in Southeast Asia, improved diagnostic methods are urgently needed. Enhanced molecular diagnostics and comprehensive epidemiological studies are essential to elucidate transmission dynamics, assess public health implications, and inform effective malaria control strategies.

Background Routine field diagnosis of malaria is a considerable challenge in rural and low resources endemic areas mainly due to lack of personnel, training and sample processing capacity. In addition, differential diagnosis of Plasmodium species has a high level of misdiagnosis. Real time remote microscopical diagnosis through on-line crowdsourcing platforms could be converted into an agile network to support diagnosis-based treatment and malaria control in low resources areas. This study explores whether accurate Plasmodium species identification—a critical step during the diagnosis protocol in order to choose the appropriate medication—is possible through the information provided by non-trained on-line volunteers. Methods 88 volunteers have performed a series of questionnaires over 110 images to differentiate species ( Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax, Plasmodium malariae, Plasmodium knowlesi ) and parasite staging from thin blood smear images digitalized with a smartphone camera adapted to the ocular of a conventional light microscope. Visual cues evaluated in the surveys include texture and colour, parasite shape and red blood size. Results On-line volunteers are able to discriminate Plasmodium species ( P. falciparum , P. malariae, P. vivax , P. ovale , P. knowlesi ) and stages in thin-blood smears according to visual cues observed on digitalized images of parasitized red blood cells. Friendly textual descriptions of the visual cues and specialized malaria terminology is key for volunteers learning and efficiency. Conclusions On-line volunteers with short-training are able to differentiate malaria parasite species and parasite stages from digitalized thin smears based on simple visual cues (shape, size, texture and colour). While the accuracy of a single on-line expert is far from perfect, a single parasite classification obtained by combining the opinions of multiple on-line volunteers over the same smear, could improve accuracy and reliability of Plasmodium species identification in remote malaria diagnosis.