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Background: Schistosomiasis is an important snail-borne parasitic disease whose transmission is exacerbated by water resource management activities. In Rwanda, meeting the growing population's demand for food has led to wetlands reclamation for cultivation and increased agrochemical enrichment for crop production. However, the ecological consequences of agrochemical enrichment on schistosomiasis transmission remain unexplored. Methods: A malacological survey was conducted in 71 villages selected from 15 schistosomiasis endemic districts. Snail sampling was done in wetlands used for agriculture, along lake Kivu and at constructed multipurpose water dams. Water physico-chemical parameters were collected at all snail sampling sites. Analysis of collected data was performed using Xgboost (gain) and Random Forest (mean decrease in accuracy), machine learning techniques, to construct models that evaluate and categorize the importance of all physico-chemical properties on the presence and abundance of intermediate host snails (IHS). Results: Different sets of parameters were relevant for the presence and abundance of Biomphalaria spp. and/or Bulinus spp. snails. Electrical conductivity, elevation, magnesium and lead content were deemed to shape the presence and abundance of Bulinus spp. snails. The impact of phosphate ion concentration, ammonia ions, total nitrogen and total organic carbon levels mirrored their importance towards the presence and abundance of Biomphalaria spp. Factors such as pH, electric conductivity, total nitrogen content and total organic carbon influenced the coexistence of both species. Our study highlights the value of integrating a wide range of predictor variables, enabling effective variable selection to uncover important predictors of snail distribution. Conclusion: The results suggest that agrochemical compounds can enhance the abundance of IHS leading to an increased risk of Schistosoma transmission. Snail surveillance could therefore be integrated into agricultural expansion projects in our match towards schistosomiasis elimination. Recognizing the impact of agrochemicals on IHS is crucial for minimizing schistosomiasis transmission among those working in wetlands while meeting the growing need for food. Author summary: Schistosomiasis is a neglected tropical disease (NTD) affecting more than 250 million people worldwide, the biggest burden being in Africa. In Rwanda, a national control program was established in 2008 and since then, regular mass deworming campaigns target populations at risk. However, quinquennial mapping surveys and epidemiological studies reveal areas with persistent infection and new foci of transmission. Since these foci often coincide with water bodies used for agricultural activities, this study aimed to investigate how agrochemical compounds and physical properties of water bodies influence the distribution and abundance of snails that are intermediate hosts for Schistosoma parasites. We used in comparison two machine learning approaches to analyze a wide range of physico-chemical parameters of water bodies in relation to snail abundance throughout the country. Findings indicate that water acidity and chemicals like those found in fertilizers influence the abundance of snails, confirming that agricultural expansion may carry the unwanted burden of schistosomiasis transmission. As the country aims to move towards schistosomiasis elimination as a public health problem, it is imperative to integrate infection control such as public health education, snail control (improved agricultural practices), and mass drug administration into efforts to improve agricultural production. [ABSTRACT FROM AUTHOR]

Abstract: Background: Intestinal schistosomiasis remains a worrying health problem, particularly in western Côte d'Ivoire, despite control efforts. It is therefore necessary to understand all the factors involved in the development of the disease, including biotic and abiotic factors. The aim of this study was to examine the factors that could support the maintenance of the intermediate host and its vectorial capacity in western Côte d'Ivoire. Methods: Data on river physicochemical, microbiological, and climatic parameters, the presence or absence of snails with Schistosoma mansoni, and human infections were collected between January 2020 and February 2021. Spearman rank correlation tests, Mann–Whitney, analysis of variance (ANOVA), and an appropriate model selection procedure were used to analyze the data. Results: The overall prevalence of infected snails was 56.05%, with infection reaching 100% in some collection sites and localities. Of 26 sites examined, 25 contained thermophilic coliforms and 22 contained Escherichia coli. Biomphalaria pfeifferi was observed in environments with lower land surface temperature (LST) and higher relative air humidity (RAH), and B. pfeifferi infection predominated in more acidic environments. Thermal coliforms and E. coli preferred higher pH levels. Lower maximum LST (LST_Max) and higher RAH and minimum LST (LST_Min) were favorable to E. coli, and lower LST_Max favored coliforms. The presence of B. pfeifferi was positively influenced by water temperature (T °C), LST_Min, RAH, and precipitation (Pp) (P < 0.05) and negatively influenced by pH, total dissolved solids (TDS), electrical conductivity (EC), LST_Max, and mean land surface temperature (LST). The parameters pH, TDS, EC, LST_Min, LST, and Pp had a positive impact on snail infection, while LST_Max had a negative impact on infection. Only pH had a positive effect on coliform and E. coli abundance. Of the 701 people examined for human schistosomiasis, 73.13% were positive for the point-of-care circulating cathodic antigen (POC-CCA) test and 12.01% for the Kato–Katz (KK) test. A positive correlation was established between human infections and the abundance of Biomphalaria (r2 = 0.879, P = 0.04959). Conclusions: The results obtained reflect the environmental conditions that are conducive to the maintenance of S. mansoni infection in this part of the country. To combat this infection as effectively as possible, it will be necessary not only to redouble efforts but also to prioritize control according to the level of endemicity at the village level. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma. The pathogen is transmitted via freshwater snails. These snails are highly tolerant to agricultural pesticides and indirectly benefit from exposure due to adverse effects on their more sensitive enemy species. Pesticides in surface waters may thus increase the risk of schistosomiasis transmission unless they also affect the pathogen. We tested the tolerance of the free-swimming life stages (miracidia and cercariae) of Schistosoma mansoni to the insecticides diazinon and imidacloprid. We also investigated whether these pesticides decrease the ability of miracidia to infect and further develop as sporocysts within the host snail Biomphalaria pfeifferi. Results: Exposure to imidacloprid for 6 and 12 h immobilized 50% of miracidia at 150 and 16 µg/L, respectively (nominal EC50); 50% of cercariae were immobilized at 403 and 284 µg/L. Diazinon immobilized 50% of miracidia at 51 and 21 µg/L after 6 and 12 h; 50% of cercariae were immobilized at 25 and 13 µg/L. The observed insecticide tolerance is lower than those of the host snail B. pfeifferi and comparable to those of other commonly tested freshwater invertebrates. Exposure for up to 6 h decreased the infectivity of miracidia at high sublethal concentrations (48.8 µg imidacloprid/L and 10.5 µg diazinon/L, i.e. 20–33% of EC50), but not at lower concentrations commonly observed in the field (4.88 µg imidacloprid/L and 1.05 µg diazinon/L). The development of sporocysts within the snail host was not affected at any of these test concentrations. Conclusions: Insecticides did not affect the performance of S. mansoni at environmentally relevant concentrations. Particularly within its host snail the pathogen can escape exposure peaks that have been shown to affect other sensitive invertebrates and their biological control of host snails. Our findings suggest that freshwater pollution with agricultural pesticides increases the risk of schistosomiasis; they illustrate the need to integrate an environmental and public health risk assessment and management. [ABSTRACT FROM AUTHOR]

Background: Multi-factorial reasons are an induction to cause cancer. Different infections and infestations with viruses, bacteria, and parasites have been detected for many years to be related to human carcinogenesis. Purpose: The study aimed to review all ideas of tumor carcinogenesis and its associations with parasitic infections and infestations. Methods: We reviewed several articles (published and imprinted) by selecting, extracting, and synthesizing data about the relationship between cancers and parasites. Results: Several helminths infections as schistosomiasis, are highly carcinogenic agents for bladder cancer, whereas trypanosomiasis has a bi-model role in cancer development. Leishmaniasis may be a cause of hepatocarcinoma, skin cancer, and lymphomas. In addition, malaria appears to be causative in the carcinogenesis of some cancers; as Burkitt lymphoma. Also, data from previous studies suggested that Strongyloides stercoralis may be a relevant co-factor in lymphomas. Conclusion: There are different mechanisms of parasitic infection to be enhancing in carcinogenesis of cancer in human. [ABSTRACT FROM AUTHOR]

Background: Patients' adherence to artemisinin-based combination therapy (ACT) is a malaria control strategy. Studies report varied experiences regarding patients' adherence to ACT. The study aimed at determining factors influencing patients' adherence to ACT for malaria in Kamuli, Uganda. Methods: In a longitudinal study, 1266 participants at 8 public health facilities were enrolled. Equal numbers (422) were assigned to the three arms (no follow-up, day 2 and day 4). To establish the mean difference between groups, Student t-test was used and a chi-square test was used for proportionality. A multivariate logistic regression analysis was used to establish the influence of predictor variables on the dependent variable. Statistical significance was established at p < 0.05. Results: A total of 844 patients were analysed. The median age was 20 years, majority (64.3%) were females. Overall patients' adherence was 588/844 (69.7%). At bivariate level, age (t-test = 2.258, p = 0.024), household head (χ2 = 14.484, p = 0.002), employment status (χ2 = 35.886, p < 0.0001), patients' preference of ACT to other anti-malarials (χ2 = 15.981, p < 0.0001), giving a patient/caregiver instructions on how to take the medication (χ2 = 7.134, p = 0.011), being satisfied with getting ACT at facility (χ2 = 48.261, p < 0.0001), patient/caregiver knowing the drug prescribed (χ2 = 5.483, p = 0.019), patient history of saving ACT medicines (χ2 = 39.242, p < 0.0001), and patient ever shared ACT medicines (χ2 = 30.893, p < 0.0001) were all associated with patients' adherence to ACT. Multivariate analysis demonstrated that adhering to ACT is 3.063 times higher for someone satisfied with getting ACT at the facility (OR = 3.063; p < 0.0001), 4.088 times for someone with history of saving ACT medicines (OR = 4.088; p < 0.0001), 2.134 times for someone who shared ACT (OR = 2.134; p = 0.03), and 2.817 times for someone with a household head (OR = 2.817; p = 0.008). Conclusion: Patients' adherence to ACT is generally good in the studied population. However, patients' tendencies to save ACT for future use and sharing among family members is a threat, amidst the benefits associated with adherence. There is a need to educate all about adherence to medicines as prescribed, and tighten government medicine supply chain to avoid stock-outs. [ABSTRACT FROM AUTHOR]

Urogenital schistosomiasis (UGS) caused by Schistosoma haematobium is endemic in the South West Region of Cameroon. An understanding of the abundance and distribution of the Bulinus snail, intermediate host can inform strategic snail control programmes at a local scale. This study investigated seasonal dynamics and environmental factors influencing occurrence and abundance of freshwater snail intermediate hosts in Tiko, a semi-urban endemic focus in the Mount Cameroon area. A longitudinal malacological field survey was conducted between December 2019 and December 2020 in the Tiko municipality. Snails were collected for one year monthly at 12 different human water contact sites along a stretch of the Ndongo stream using a standardized sampling technique. Freshwater snails were identified using shell morphological features. In addition, water temperature, pH, electrical conductivity, total dissolved solutes, salinity, water depth, width and flow velocity were measured, and vegetation cover as well as substrate type were determined. Bayesian regression models were used to identify the main environmental factors affecting the occurrence and abundance of Bulinus intermediate host. In total, 2129 fresh water snails were collected during the study period. Physa (51.4%) was the most abundant genus followed by Melanoides (28.6%) then, Bulinus (15.5%), Lymnaea (4.2%), Indoplanorbis (0.2%) and Potadoma (0.1%). Seasonality in abundance was significant in Bulinus sp as well as other genera, with greater numbers in the dry season (peaks between December and February). Water temperature, a rocky or sandy substrate type associated positively with Bulinus sp, meanwhile a higher water flow rate and medium vegetation negatively influenced the snail intermediate host population. These findings underscore the importance of timing behavioural and snail control interventions against schistosomiasis as well as increase vigilance of other trematode diseases in the study area. The continuous spread of planorbid snail hosts is a major concern. [ABSTRACT FROM AUTHOR]

Endemic Burkitt lymphoma (eBL) is a fast-growing germinal center B cell lymphoma, affecting 5–10 per 100,000 children annually, in the equatorial belt of Africa. We hypothesize that co-infections with Plasmodium falciparum (Pf) malaria and Epstein-Barr virus (EBV) impair host natural killer (NK) and T cell responses to tumor cells, and thus increase the risk of eBL pathogenesis. NK cell education is partially controlled by killer immunoglobulin-like receptors and variable expression of KIR3DL1 has been associated with other malignancies. Here, we investigated whether KIR3D-mediated mechanisms contribute to eBL, by testing for an association of KIR3DL1/KIR3DS1 genotypes with the disease in 108 eBL patients and 99 healthy Kenyan children. KIR3DL1 allelic typing and EBV loads were assessed by PCR. We inferred previously observed phenotypes from the genotypes. The frequencies of KIR3DL1/KIR3DL1 and KIR3DL1/KIR3DS1 did not differ significantly between cases and controls. Additionally, none of the study participants was homozygous for KIR3DS1 alleles. EBV loads did not differ by the KIR3DL1 genotypes nor were they different between eBL survivors and non-survivors. Our results suggest that eBL pathogenesis may not simply involve variations in KIR3DL1 and KIR3DS1 genotypes. However, considering the complexity of the KIR3DL1 locus, this study could not exclude a role for copy number variation in eBL pathogenesis. [ABSTRACT FROM AUTHOR]

The spatial and seasonal distribution, abundance, and infection rates of human schistosomiasis intermediate host snails and interactions with other freshwater snails, water physicochemical parameters, and climatic factors was determined in this study. A longitudinal malacology survey was conducted at seventy-nine sites in seven districts in KwaZulu-Natal province between September 2020 and August 2021. Snail sampling was done simultaneously by two trained personnel for fifteen minutes, once in three months. A total of 15,756 snails were collected during the study period. Eight freshwater snails were found: Bulinus globosus (n = 1396), Biomphalaria pfeifferi (n = 1130), Lymnaea natalensis (n = 1195), Bulinus tropicus (n = 1722), Bulinus forskalii (n = 195), Tarebia granifera (n = 8078), Physa acuta (n = 1579), and Bivalves (n = 461). The infection rates of B. globosus and B. pfeifferi are 3.5% and 0.9%, respectively. In our study, rainfall, pH, type of habitats, other freshwater snails and seasons influenced the distribution, abundance, and infection rates of human schistosomiasis intermediate host snails (p-value < 0.05). Our findings provide useful information which can be adopted in designing and implementing snail control strategies as part of schistosomiasis control in the study area. [ABSTRACT FROM AUTHOR]

Schistosomiasis is the second most devastating parasite prevalent in the tropical region of the world, posing significant public health impacts in endemic areas. Presently, several disease mitigation measures have shown a decline in transmission of the infection rate in risk localities using mass drug administration (MDA) of school-based or community-wide treatments. Despite all the endeavors made, the decline in transmission of infection rate has not been attained in the entire medicated segment of the population. Perhaps the current challenges of control of the disease appear to be strongly associated with a lack of appropriate diagnostic tools. It's well known that the current diagnosis of schistosomiasis greatly relies on conventional methods. On the other hand, minor symptoms of schistosomiasis and low sensitivity and specificity of diagnostic methods are still unresolved diagnostic challenges to clinicians. Numerous scholars have reviewed various diagnostic methods of schistosomiasis and attempted to identify their strengths and weaknesses, currently on function. As a result of the known limitations of the existing diagnostic tools, the need to develop new and feasible diagnostic methods and diagnostic markers is unquestionable for more precise detection of the infection. Hence, advances in diagnostic methods have been considered part of the solution for the control and eventual elimination strategy of the disease in endemic areas. As of today, easy, cheap, and accurate diagnostics for schistosomiasis are difficult to get, and this limits the concerted efforts towards full control of schistosomiasis. While looking for new diagnostic methods and markers, it is important to simultaneously work on improving the existing diagnostic methods for better results. This review tries to give new insights to the status of the existing diagnostic methods of schistosomiasis from conventional to modern via summarizing the strengths and limitations of the methods. It also tries to recommend new, sensitive and feasible diagnostic methods for future approaches. [ABSTRACT FROM AUTHOR]

The planorbid gastropod genus Bulinus consists of 38 species that vary in their ability to vector Schistosoma haematobium (the causative agent of human urogenital schistosomiasis), other Schistosoma species, and non-schistosome trematodes. Relying on sequence-based identifications of bulinids (partial cox1 and 16S) and Schistosoma (cox1 and ITS), we examined Bulinus species in the Lake Victoria Basin in Kenya for naturally acquired infections with Schistosoma species. We collected 6,133 bulinids from 11 sites between 2014–2021, 226 (3.7%) of which harbored Schistosoma infections. We found 4 Bulinus taxa from Lake Victoria (B. truncatus, B. tropicus, B. ugandae, and B. cf. transversalis), and an additional 4 from other habitats (B. globosus, B. productus, B. forskalii, and B. scalaris). S. haematobium infections were found in B. globosus and B. productus (with infections in the former predominating) whereas S. bovis infections were identified in B. globosus, B. productus, B. forskalii, and B. ugandae. No nuclear/mitochondrial discordance potentially indicative of S. haematobium/S. bovis hybridization was detected. We highlight the presence of Bulinus ugandae as a distinct lake-dwelling taxon closely related to B. globosus yet, unlike all other members of the B. africanus species group, is likely not a vector for S. haematobium, though it does exhibit susceptibility to S. bovis. Other lake-dwelling bulinids also lacked S. haematobium infections, supporting the possibility that they all lack compatibility with local S. haematobium, thereby preventing widespread transmission of urogenital schistosomiasis in the lake's waters. We support B. productus as a distinct species from B. nasutus, B. scalaris as distinct from B. forskalii, and add further evidence for a B. globosus species complex with three lineages represented in Kenya alone. This study serves as an essential prelude for investigating why these patterns in compatibility exist and whether the underlying biological mechanisms may be exploited for the purpose of limiting schistosome transmission. Author summary: Human schistosomiasis is a neglected tropical disease caused by members of the trematode genus Schistosoma. Every schistosome species is dependent on a particular species, or array of species, of intermediate gastropod host(s) for their transmission. In the Lake Victoria Basin in Kenya, two related schistosome species (Schistosoma haematobium and Schistosoma bovis) utilize multiple species within the genus Bulinus as intermediate hosts. Discerning which bulinid species vector S. haematobium or S. bovis, or both, and identifying the habitats for each, is critical to understanding local transmission patterns. Closely related bulinids cannot be confidently distinguished using morphological criteria so this study used DNA sequence-based methods to identify local bulinid species and to identify schistosomes shed from infected snails. We implicate two bulinid species in the transmission of S. haematobium and four species in the transmission of S. bovis. Both S. haematobium associated species were found exclusively in streams and dams in the Lake Victoria Basin thereby seemingly keeping the shores of Lake Victoria largely free of S. haematobium transmission. Further study as to why some species like B. globosus are susceptible to S. haematobium whereas other close relatives like B. ugandae are apparently refractory may reveal underlying resistance factors potentially useful for control programs. [ABSTRACT FROM AUTHOR]

Continuous field studies on the abundance and distribution of freshwater snails and cercarial populations are important for schistosomiasis control programs. In the present work, snail surveys and cercariometry were conducted for four successive seasons at 12 sites on the Nile River banks in the area of Greater Cairo to identify potential transmission foci for schistosomiasis. In addition, water physicochemical parameters were recorded. The results showed that the electrical conductivity, total dissolved solids, dissolved oxygen, and pH were within the permissible levels, except that the water temperature increased, especially in the spring season. Malacological surveys identified 10 native snail species at the studied sites of the Nile River, namely Bulinus truncatus, Biomphalaria alexandrina, Lymnaea natalensis, Lanistes carinatus, Cleopatra bulimoides, Melanoides tuberculata, Helisoma duryi, Bellamya unicolor, Physa acuta, Thedoxus niloticus, and one invasive snail species, Thiara scabra. The calculated diversity index indicated that the structure of snails' habitats was poor, while Evenness index indicated that the individuals were not distributed equally. Natural infection results identified no schistosome cercariae in B. truncatus and B. alexandrina. However, the cercariometry recovered Schistosoma cercariae in all the surveyed sites during all seasons with variable distribution. The preceding data suggest that there are still some active transmission foci for schistosomiasis infection in the Nile River. Moreover, the present finding highlights the importance of cercariomety as a complementary approach to snail samplings for identifying the transmission foci for schistosomiasis. [ABSTRACT FROM AUTHOR]

Summary: Memory B cells (MBCs) are an essential part of our immunological memory. They respond fast upon re-encountering pathogens and can differentiate into plasma cells that secrete protective antibodies. The focus of this review is on MBCs that lack, or express low levels of, CD21, hereafter referred to as CD21–/low. These cells are expanded in peripheral blood with age and during chronic inflammatory conditions such as viral infections, malaria, common variable immunodeficiency, and autoimmune diseases. CD21–/low MBCs have gained significant attention; they produce disease-specific antibodies/autoantibodies and associate with key disease manifestations in some conditions. These cells can be divided into subsets based on classical B-cell and other markers, e.g. CD11c, FcRL4, and Tbet which, over the years, have become hallmarks to identify these cells. This has resulted in different names including age-associated, autoimmune-associated, atypical, tissue-like, tissue-resident, tissue-restricted, exhausted, or simply CD21–/low B cells. It is however unclear whether the expanded 'CD21–/low' cells in one condition are equivalent to those in another, whether they express an identical gene signature and whether they have a similar function. Here, we will discuss these issues with the goal to understand whether the CD21–/low B cells are comparable in different conditions. CD21-/low memory B cells are expanded with age in healthy individuals and in patients with viral infections and autoimmune conditions and are associated with pathogen-specific antibodies as well as key disease manifestations. Depending on condition, CD21-/low memory B cells have been termed age-associated, autoimmune-associated, atypical, tissue-like, tissue-resident, tissue-restricted, exhausted or simply CD21-/low B cells. CD21-/low memory B cells are often CD27-IgD-CD11c+ and in some conditions they express Tbet, in others FcRL4 and in yet others both. [ABSTRACT FROM AUTHOR]

Digenetic trematodes form a major group of human parasites, affecting a large number of humans, especially in endemic foci. Over 100 species have been reported infecting humans, including blood, lung, liver and intestinal parasites. Traditionally, trematode infections have been diagnosed by parasitological methods based on the detection and the identification of eggs in different clinical samples. However, this is complicated due to the morphological similarity between eggs of different trematode species and other factors such as lack of sensitivity or ectopic locations of the parasites. Moreover, the problem is currently aggravated by migratory flows, international travel, international trade of foods and changes in alimentary habits. Although efforts have been made for the development of immunological and molecular techniques, the detection of eggs through parasitological techniques remains as the gold standard for the diagnosis of trematodiases. In the present chapter, we review the current status of knowledge on diagnostic techniques used when examining feces, urine, and sputum and also analyze the most relevant characteristics used to identify eggs with a quick key for the identification of eggs., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Almost 80% of health problems in the developing world are due to malnutrition and infectious diseases, which are mainly parasitic. Updated records on the prevalence of parasitic infections and the potential risk factors are essential to enhancing control strategies. Therefore, this study was conducted to evaluate the current situation of intestinal parasitism among patients attending teaching hospitals in Zagazig district, Northeastern Egypt. The study involved five hundred cases. They were all subjected to faecal examination using direct smear measure and two commercial faecal concentrators: Mini-Parasep® solvent-free and Mini-FLOTAC procedures. Mini-FLOTAC was performed with two solutions (FS2: saturated sodium chloride and FS7: zinc sulphate). The overall prevalence of intestinal parasitic infections was 56%. Different species were identified, like Giardia lamblia (12.6%), Entamoeba histolytica/dispar (10%), Ascaris lumbricoides (8.8%) and Hymenolepis nana (8.6%). Data analyses revealed a significant association of intestinal parasitism with different socio-demographic features of the participants. Our results showed a better diagnostic performance of Mini-Parasep® in the overall recovery of intestinal parasites. It was more accurate than Mini-FLOTAC in diagnosing both helminths and protozoan infections. Mini-FLOTAC (FS2) exhibited a higher sensitivity than FS7 for helminth recovery (74.6% vs 53.4%), while FS7 was more sensitive for protozoan infections (50.6% vs 43.8%). Intestinal parasitosis remains a challenging health problem in Zagazig city, wherever reliable diagnostic approaches are limited. Thus, our study has proposed the value of the commercial concentrators (Mini-Parasep® and Mini-FLOTAC) as alternative techniques for diagnosing a large variety of parasite species in resource-constrained settings. [ABSTRACT FROM AUTHOR]

Memory B cells (MBCs) and plasma antibodies against Plasmodium falciparum (Pf) merozoite antigens are important components of the protective immune response against malaria. To gain understanding of how responses against Pf develop in these two arms of the humoral immune system, we evaluated MBC and antibody responses against the most abundant merozoite antigen, full-length Pf merozoite surface protein 1 (PfMSP1FL), in individuals from a region in Uganda with high Pf transmission. Our results showed that PfMSP1FL-specific B cells in adults with immunological protection against malaria were predominantly IgG+ classical MBCs, while children with incomplete protection mainly harbored IgM+ PfMSP1FL-specific classical MBCs. In contrast, anti-PfMSP1FL plasma IgM reactivity was minimal in both children and adults. Instead, both groups showed high plasma IgG reactivity against PfMSP1FL, with broadening of the response against non-3D7 strains in adults. The B cell receptors encoded by PfMSP1FL-specific IgG+ MBCs carried high levels of amino acid substitutions and recognized relatively conserved epitopes on the highly variable PfMSP1 protein. Proteomics analysis of PfMSP119-specific IgG in plasma of an adult revealed a limited repertoire of anti-MSP1 antibodies, most of which were IgG1 or IgG3. Similar to B cell receptors of PfMSP1FL-specific MBCs, anti-PfMSP119 IgGs had high levels of amino acid substitutions and their sequences were predominantly found in classical MBCs, not atypical MBCs. Collectively, these results showed evolution of the PfMSP1-specific humoral immune response with cumulative Pf exposure, with a shift from IgM+ to IgG+ B cell memory, diversification of B cells from germline, and stronger recognition of PfMSP1 variants by the plasma IgG repertoire. [ABSTRACT FROM AUTHOR]

Background: Malaria case management relies on World Health Organization (WHO)-recommended artemisinin-based combination therapy (ACT), and a continuous understanding of local community knowledge, attitudes, and practices may be a great support for the success of malaria disease control efforts. In this context, this study aimed to identify potential facilitators or barriers at the community level to inform a health district-wide implementation of multiple first-line therapies (MFT) as a new strategy for uncomplicated malaria case management. Methods: A community-based cross-sectional study using a mixed-method design was carried out from November 2018 to February 2019, in the health district (HD) of Kaya in Burkina Faso. Quantitative data were collected using a standardized questionnaire from 1394 individuals who had fever/malaria episodes four weeks prior to the survey. In addition, 23 focus group discussions (FGDs) were conducted targeting various segments of the community. Logistic regression models were used to assess the predictors of community care-seeking behaviours. Results: Overall, 98% (1366/1394) of study participants sought advice or treatment, and 66.5% did so within 24 h of fever onset. 76.4% of participants preferred to seek treatment from health centres as the first recourse to care, 5.8% were treated at home with remaining drug stock, and 2.3% preferred traditional healers. Artemether-lumefantrine (AL) was by far the most used anti-malarial drug (98.2%); reported adherence to the 3-day treatment regimen was 84.3%. Multivariate analysis identified less than 5 km distance travelled for care (AOR = 2.7; 95% CI 2.1–3.7) and education/schooling (AOR = 1.8; 95% CI 1.3–2.5) as determinants of prompt care-seeking for fever. Geographical proximity (AOR = 1.5, 95% CI 1.2–2.1), having a child under five (AOR = 4.6, 95% CI 3.2–6.7), being pregnant (AOR = 6.5, 95% CI 1.9–22.5), and living in an urban area (AOR = 2.8, 95% CI 1.8–4.2) were significant predictors for visiting health centres. The FGDs showed that participants had good knowledge about malaria symptoms, prevention tools, and effective treatment. Behaviour change regarding malaria treatment and free medication for children under five were the main reasons for participants to seek care at health centres. Conclusions: The study showed appropriate knowledge about malaria and positive community care-seeking behaviour at health centres for fever/malaria episodes. This could potentially facilitate the implementation of a MFT pilot programme in the district. ClinicalTrials.gov Identifier: NCT04265573. [ABSTRACT FROM AUTHOR]

Identifying the mechanism of naturally acquired immunity against Plasmodium falciparum malaria could contribute to the design of effective malaria vaccines. Using a recently developed multiplexed FluoroSpot assay, we assessed cross-sectional pre-existing memory B-cells (MBCs) and antibody responses against six well known P. falciparum antigens (MSP-119, MSP-2 (3D7), MSP-2 (FC27), MSP-3, AMA-1 and CSP) and measured their associations with previous infections and time to clinical malaria in the ensuing malaria season in Kenyan children. These children were under active weekly surveillance for malaria as part of a long-term longitudinal malaria immunology cohort study, where they are recruited from birth. After performing Cox regression analysis, we found that children with a breadth of three or more antigen-specific MBC or antibody responses at the baseline had a reduced risk for malaria in the ensuing P. falciparum transmission season. Specifically, MBC responses against AMA-1, MSP-2 (3D7) and MSP-3, as well as antibody responses to MSP-2 (3D7) and MSP-3 were prospectively associated with a reduced risk for malaria. The magnitude or breadth of MBC responses were however not correlated with the cumulative number of malaria episodes since birth. We conclude that increased breadth for merozoite antigen-specific MBC and antibody responses is associated with protection against malaria. [ABSTRACT FROM AUTHOR]

Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in regions of equatorial Africa where P. falciparum malaria is holoendemic. The tumor is consistently associated with Epstein-Barr virus (EBV). Screening for EBV DNA in plasma in a high-risk population in Hong Kong has been shown to be useful in facilitating the early diagnosis of nasopharyngeal carcinoma, another EBV-associated tumor. Here, we investigate plasma EBV as a diagnostic marker for eBL in children in Uganda. We studied plasma specimens from 25 children with eBL and 25 controls matched for age (<3-16 years), gender and geography, including many with asymptomatic P. falciparum infection. These specimens were previously collected under the auspices of the EMBLEM (Epidemiology of Burkitt lymphoma in East African children and minors) study. After cell-free DNA isolation, plasma EBV DNA was measured using a quantitative PCR assay that amplifies the large internal repeats of the EBV genome. All children with eBL had measurable plasma EBV, as compared to 84% of control children. The median plasma EBV DNA level was 5.23 log10 copies/mL (interquartile range 3.54-6.08 log10 copies/mL) in children with eBL. In contrast, the median plasma EBV DNA level was 0.37 log10 copies/mL (interquartile range 0.18-1.05 log10 copies/mL) in children without lymphoma. An EBV threshold of 2.52 log10 copies/mL yielded a sensitivity of.88 and a specificity of 1. The estimated AUC was 0.936 (95% CI: 0.8496 – 1.00) for the corresponding ROC curve. Plasma EBV copy number did not depend on age, gender, or malaria screening status. However, two control children with asymptomatic P. falciparum infection and parasitemia also had high plasma EBV copy number. Our analysis suggests that measurements of EBV copy number in plasma may be useful in identifying children with eBL versus control children. A promising area for future research is the differentiation of high copy number associated with tumor versus high copy number associated with asymptomatic parasitemia. [ABSTRACT FROM AUTHOR]