Anopheles mosquitoes, leading to a heterogeneity in malaria transmission. In agricultural areas, heterogeneity of malaria transmission is often associated with the presence of hotspots consisting of localized clusters of higher transmission intensity. This study aims to identify micro-geographic hotspots of malaria transmission in an agricultural setting using a multidisciplinary approach.Wetlands and irrigated agricultural crops create potential breeding sites for Anopheles exposure  were compared with demographic, agricultural, and geographic data to identify drivers of malaria transmission. Heat maps combining these data were used to identify households with ongoing malaria transmission throughout the year.Two cross-sectional surveys were conducted at the end of the dry season and at the peak of the rainy season in rural and urban sites in Bouna, northeastern Côte d'Ivoire. A total of 296 individuals from 148 farming households were randomly selected and sociological, geographical, entomological, and clinical data as well as blood samples were collected during each visit. Parasitological data and Plasmodium prevalence was consistent between the dry and the rainy seasons, with roughly half of the population infected. In urban areas, malaria transmission indicators were lower, with a parasite prevalence of less than 20%, which remained comparable between the dry and the rainy season. The presence of irrigated crops and proximity to wetlands were associated with increased Anopheles exposure. By mapping Plasmodium infection and Anopheles exposure, two different types of hotspots of malaria transmission were identified: micro-geographical scale and local scale hotspots.In rural areas, The presence of wetlands in urban areas and irrigated agriculture in rural areas resulted in heterogeneity in malaria transmission on a micro-geographical scale. These specific households present particular risk of malaria transmission and could fuel malaria transmission in surrounding households. The identification of micro-geographical areas using heat maps combining several epidemiological parameters can help to identify hotspots of malaria transmission. The implementation of malaria control measures, such as seasonal chemoprophylaxis or vector control, in these areas could help to reduce the incidence of malaria and facilitate its elimination. Plasmodium falciparum malaria is the leading cause of mortality among children [Substantial reductions in the global burden of malaria were noted during the past two decades in response to improvement of control measures with the mass distribution of long-lasting insecticidal nets (LLIN), access to diagnosis with rapid diagnostic tests (RDT) and prompt treatment with artemisinin-based combination therapy (ACT). Over the last few years, progress has stagnated with global malaria incidence and deaths remain stable with over 200 million malaria cases and more than 600,000 deaths in 2021 [Plasmodium falciparum transmission is driven by ecological factors including those that favoured Anopheles breeding sites and thus Anopheles populations. The presence of wetland as well the type of agricultural crops and practices, particularly irrigated cultures can create suitable breeding habitats for Anopheles mosquitoes, because mosquitoes require stagnant water for their larval habitat. A study in Kenya showed that irrigated agriculture was associated with a higher malaria transmission rate, likely due to increased mosquito breeding in the irrigation canals [n canals . Similarn canals . The watn canals , 6. Thusn canals . As a reAnopheles bites. More specifically, the IgG response to the Anopheles gambiae gSG6-P1 salivary peptide has been identified as a proxy of exposure to Anopheles bites [Anopheles bites [In recent years, serological markers have been developed to assess individual level of exposure of human population to es bites . Studieses bites , 10, to es bites , 12.This present study aimed to assess the role of wetlands and agricultural practices in malaria transmission in agricultural households in rural and urban settings in Bouna, Côte d’Ivoire, using several epidemiological indicators of malaria transmission. Mapping together these epidemiological parameters helped us to identify households the most at risk of malaria transmission in the different settings.The study was conducted in the city of Bouna located in the North-East of Côte d'Ivoire  at the northern border to Burkina Faso and Ghana. The climate is tropical with two seasons including a dry season which runs from November through May and a rainy season from June to October. The annual rainfall recorded in 2020 was estimated at 847.4 mm with an average temperature around 26.7 °C. The study was carried out in 6 sites: 3 villages in rural setting  and 3 neighbourhoods in urban setting   and Anopheles coluzzii [Excepted Gborotchara and Bromakoté, all these study sites are characterized by the presence of large areas of wetlands, some of which are used for irrigated rice cultivation and market gardening. The presence of domestic animals, such as cats and dogs, are quite remarkable as well as the breeding practices of cattle, goats, and poultry. The duration of the malaria transmission season is perennial with a peak in the rainy season. The most important malaria vector in this area is coluzzii , 14.Two cross-sectional surveys were carried out at the end of dry season (Mai 2021) and at the peak of the rainy season (August 2021), respectively. One hundred and forty-eight (148) agricultural worker households were randomly selected from the 2020 malaria registry from the city's general hospital. The malaria registry refers to a notebook used to collect and record information on malaria cases and related data (demographic). Three neighbourhoods and the 3 rural villages of Bouna with the highest malaria prevalence were selected. In each selected site, thirty households per site were randomly selected according to the inclusion criteria: households belonged to a selected site, households included one child who had been infected with malaria in the previous year and treated at the general hospital, and parents had an agricultural activity. Two people (at least one child) from each household were included. For households that were absent or whose members refused to participate, the nearest household was selected and included with their consent, resulting in a total of 296 participants.Plasmodium species. Thick blood smears were fixed and stained with 10% Giemsa and read at double blind by certified microscopists. Asexual parasite densities were counted against 200 microscope fields white blood cells assuming 8,000 white blood cells per microlitre. A blood smear was considered negative if no parasites were observed. For immunological assays, dried blood spots (DBS) were collected at the fingertips on Whatman 3 MM filter, air-dried and stored in plastic bags at + 4 °C until immunological analysis. A household was defined as infected when at least one individual from this household was infected with Plasmodium (positive smear and Plasmodium density > 1 parasite/µL) during the survey.Each household received a long-lasting insecticidal nets (LLINs) at the time of inclusion in late May 2021 during LLINs mass campaign distribution by the national malaria control program (NMCP). At each visit, sociological, geographical, entomological, and clinical data were collected. Participant’s axillary temperature was measured, and thick films and blood smears were performed to determine parasite density and An. gambiae was calculated as the average number of mosquitoes collected per person per night . The mosquitoes from HLC methods were identified morphologically at the species level. This identification was made according to the determination key of Gillies and De Meillon [Adult mosquitoes were collected by human landing catches (HLC) in June and August in two reference households in each of the 6 sites. In each reference household, two catching points, one indoor and one outdoor were used to collect mosquitoes by landing catches on adult volunteers from 6.00 pm. to 6.00 am. Adult mosquito catchers gave prior informed consent, were vaccinated against yellow fever and were treated for malaria according to the national treatment guidelines. The mosquitoes were hourly collected, and carefully stored in closed hemolysis tubes with cotton and kept in plastic bag by time slot and by catching point. The human biting rate (HBR) of  Meillon .The use and physical integrity of the LLINs was recorded by the administration of questionnaires in all study households. Community health workers verified bednet installation after distribution of the news LLINs during the mass campaign. The questionnaires also recorded data on agricultural practices: nature of culture and type of irrigation practiced by household members.An. gambiae was measured by enzyme-linked immunosorbent assay (ELISA). Standardized dried blood spots (diameter: 1 cm) of each participant at two time points were eluted each in 300 µL phosphate buffered saline containing 0.1% Tween 20 (0.1% PBST) at 4 °C for 24 h. Subsequently, 96-well Maxisorp micro-assay plates  were coated with 100 µl of the gSG6-P1 salivary peptide (20 µg/mL in PBS) for 2 h and 30 min at 37 °C. Plates were blocked for 1 h with 200 μL of protein-free blocking buffer, pH7.4 . After washing, individual eluate was incubated in duplicate wells at 4 °C overnight wells at 1/40 dilution in 0.1% PBST. Mouse biotinylated anti-human IgG antibody  was added at a 1:2000 dilution in 1%-PBST (1 h and 30 min at 37 °C), and peroxidase-conjugated streptavidin  was then added . Colorimetric development was carried out using ABTS (2.2′-azino-bis (3 ethylbenzthiazoline 6-sulfonic acid) diammonium; Roche Diagnostics, Lyon, France) in 50 mM citrate buffer (pH 4) containing 4% H2O2 and the Optical Density (OD) was measured 2 h later at 405 nm. Individual results (ΔOD) are expressed as: ΔOD = ODx-ODn where ODx represents the mean of individual OD value in both wells containing the salivary antigen and ODn the individual OD value for each eluate without gSG6-P1 antigen.Human IgG level against the gSG6-P1 salivary antigen of Plasmodium density, IgG level to the gSG6-P1 salivary peptide and the Anopheles HBR were spatially linked to the GPS data of each household. Once these results were entered into the attribute table of the QGIS software, different intervals were defined automatically for mapping purposes. Finally, the HLC site location were plotted in the map. An interpolation using the inverse distance weighting method was carried out with pixels of equal columns and rows of 254 for a better rendering of the capture points. The maps were analysed on the basis of the spatial and temporal dynamics of epidemiological parameters related to malaria transmission . Hotspots represent groups of households with high values of malaria transmission parameters in the dry and in the rainy season. Hotspots were categorized into two categories according to their spatial scale: micro-geographical hotspots refer to small spatial areas (within a radius of 100 m), involving clusters of few houses, while local hotspots encompass a larger spatial extent, from 0.1 to 1 km, including an entire neighbourhood or village.The geographic coordinates of the households were recorded using Global Positioning System 60 (GPS) units  with an accuracy of 5 m. The houses selected for the entomological study and the main breeding sites of vectors were georeferenced. The data on The measurement of the distance between household and the nearest wetland (edge) was conducted using direct measurements with a GPS. During this phase, the GPS automatically recorded the traveled path as a line and a succession of points. Participants were divided into 2 groups according to the distance between households and the nearest wetland. The arbitrary threshold (= 400 m) was determined on the basis of the value of the median (= 423 m) and mean (= 390 m) of the distance between households and the wetland.Plasmodium infection. The HBR was compared between sites by using the prop.test testing the null hypothesis that the proportions in several groups are the same. All differences were considered significant at p < 0.05.A database was developed using Microsoft Excel software and then the data was analysed with Graph Pad Prism 9  and R software . After checking that the data did not follow a Gaussian distribution , the non-parametric Mann–Whitney U-test was used to compare the IgG levels between two independent groups, and the non-parametric Kruskal–Wallis test was used for comparison of the IgG levels between more than two groups and the Dunn’s post-hoc test was also performed for two-by-two comparisons in more than two groups. The paired Wilcoxon test was used to compare IgG response levels between the two time points in each setting or site. The Spearman’s rank correlation test was used to analyse the correlation between the distance of the household to the nearest wetland with the ΔOD of tested sera and with the parasitic density (log10). Logistic regression was performed to assess the relationship between the distance of the household to the nearest wetland and the prevalence of P. falciparum density) and entomological data (Anopheles Human Biting Rate) are presented according to study sites and season in Table Characteristics of the study population (gender ratio and age), parasitological  were included in the study. Mean age of the participants was similar between study sites (p = 0.22).P. falciparum. According to village, in dry season it ranged from 39,1% (Assoum1) to 57,7% (Téguiduo) and from 43,5% (Assoum1) to 61,5% (Téguiduo) in rainy season. The malaria prevalence was not significantly different between the 3 rural sites in dry (p = 0.137) and rainy season (p = 0.193) and the prevalence was similar in each site between dry and rainy season. Globally, geometric mean parasite density was significantly different between the dry and the rainy season (p = 0.019). It was different between the 3 rural sites only during the dry season (p = 0.036) and two-by-two comparison using Dunn’s test indicated a statistical difference between Assoum1 and the other sites. The geometric parasite means in Assoum1 significantly increased between the dry and the rainy season (p < 0.001) while it was not significantly different in Bromakote (p = 0.928) and Téguiduo (p = 0.438). A high mean level of Anopheles bites was recorded in rural setting in the dry season  and in the rainy season (78.3 BHN). The aggressivity of An. gambiae was higher in Assoum1 and Téguiduo in the dry season with about 65 BHN while 27 BHN was recorded in Bromakote. During the rainy season, the HBR significantly increased (double) to 109,5 BHN in Assoum (p < 0.001), and to 58 BHN in Bromakote (p = 0.001), while it stayed similar in Téguiduo.In rural setting, the parasite prevalence was similar between the dry and the rainy season (p = 0.646) with an average of half of the population presented an infection to Plasmodium prevalence was observed in Dassikeledougou (26.1%) while the sites of Gborotchara and Doropo presented a prevalence of 16% but the difference between the 3 urban sites was not significant (p = 0.384). In the rainy season, the prevalence was also similar between the 3 urban sites (p = 0.758) with Gborotchara (20.45%) and Doropo (19.6%) presented the highest rate. The prevalence was similar in each urban site between the dry and the rainy season. Geometric parasite mean was similar between the 3 urban sites during the dry (p = 0.842) and the rainy season (p = 0.705). No significant changes in the geometric parasite mean were noted between the dry and the rainy season in the urban setting and in each site. The HBR of An. gambiae was also globally lower than in rural setting with approximately 5 BHN recorded in Gborotchara and Dassikeledougou in the dry season and about 55 BHN in rainy season. Doropo presented the highest An. gambiae HBR both in the dry (77.5 BHN) and in the rainy (115.25 BHN) season. Anopheles aggressiveness significantly increased in all urban sites between the two seasons (p < 0.01).In urban setting, epidemiological indicators of malaria transmission were lower, with a mean of parasite prevalence less than 20% in the dry and rainy season. In dry season, the highest Anopheles gSG6-P1 salivary peptide represents an individual proxy of the level of exposure to Anopheles bites and was assessed in participants in each site during the dry and the rainy season. Participants presented a wide range in ∆ODgSG6-P1 within and between the different sites, both in the dry and the rainy season  Fig. A, B. DurIn urban setting, the IgG responses were significantly different between the 3 neighbourhoods both in the dry and the rainy season (p < 0.0001) Fig. C, D. DasAnopheles gSG6-P1 salivary peptide were compared according to the agricultural practices of participants from each setting and site according to season , while non-irrigated crops included shea, cashew, coffee, cocoa, and yam.Considering the 2 settings together, IgG median level responses to gSG6-P1 peptide was significantly higher in participants practicing irrigated crops compared to those producing non-irrigated crops, both during the dry (p = 0.011) and rainy season (p = 0.006) Fig. A. The saThe distance of each household from the nearest wetland was measured and households were then categorized in two groups according to the distance: households located less than 400 m from the wetland, or more than > 400 m  and the rainy season (p = 0.096)  and the distance to wetland  and in the rainy season . No correlation was found in the rural setting between the IgG level and the distance to wetland. Similar statistical analyses were performed to assess the correlation between Plasmodium prevalence and the distance to wetland in rural setting in rainy season (p = 0.033).A significant positive association between parasite density and distance from wetlands to household was showed in rainy season in rural setting . We also observed a positive association between Maps were generating by combining indicators of malaria transmission , and Plasmodium prevalence and density. Maps indicated variation in the distribution of the IgG levels to the gSG6-P1 peptide and the levels of parasitaemia across space and season according to the sites. In Bromakoté, there was a high homogeneous risk of exposure to Anopheles bites and infected households were scattered throughout the village both during the dry and the rainy season  that indicates the mean number of bites that an individual may receive per night, appreciates as an approximate proxy the level of exposure to Anopheles at site scale. Second, a serological biomarker of exposure based on the quantification of the IgG response specific to the An. gambiae gSG6-P1 salivary peptide was used to evaluate the human–Anopheles contact at the individual level. This tool integrates the individual risk factors of being bitten and provides for each participant a proxy of the individual level of exposure to Anopheles bites [Anopheles gSG6-P1 salivary peptide represents a reliable and complementary tool to entomological methods for assessing spatial and temporal heterogeneity of exposure to Anopheles bites at the individual level [Plasmodium infection ranging from 15% to nearly 60% in dry season and in rainy season according to site. Malaria transmission was higher in rural sites where almost half of the population was infected compared to urban neighborhoods. Exposure to Anopheles bites was also heterogeneous in Bouna during the study, with various level of Anopheles aggressiveness according to site. Heterogeneity between and within sites is also reflected by the heterogeneity in the individuals’ anti-gSG6-P1 levels.Exposure to es bites . It is mes bites . Numeroual level . In the Plasmodium prevalence was similar in each site between the dry and the rainy season both in the rural and the urban setting, indicating the malaria transmission is perennial throughout the year in the city of Bouna and in its surroundings. It may also suggest that persistent asymptomatic infections occurred in the urban setting, where only few Anopheles were caught during the dry season. In the rural setting, entomological studies reported the presence of a high density of Anopheles mosquitoes throughout the year with a mean of 52 bpn and 78 bpn recorded during the dry season and the rainy season, respectively. The presence of wetlands and the agricultural practices (irrigated rice culture and market gardening) could create potential breeding sites for Anopheles mosquitoes during the dry season that may sustained exposure to Anopheles and thus malaria transmission throughout the year. In the rainy season, new temporary Anopheles breeding sites could be created with the water rains and came to be added to the permanent breeding sites that wetland could represent. Interestingly, Bromakote and Gborotchara, the two sites without the presence of wetlands, had the lowest density of Anopheles for each setting, both in the dry and the rainy season.Anopheles bites. In rural setting, individuals that practiced irrigated culture  presented a significant higher exposure to Anopheles compared to individuals practicing non–irrigated cultures, both during the dry and the rainy season. Individuals can be either more exposed during the field activities or surrounding their households. In rural setting, irrigated crops or market gardening are commonly grown near households, and thus can increase the risk of being bitten [Anopheles mosquitoes throughout the year. In urban neighborhoods, there is limited space between dwellings and cultural practices are restricted in peri-urban districts [Anopheles mosquitoes. This is consistent with previous studies that have identified the role of agricultural activities and the presence of stagnant water in promoting malaria transmission [To decipher the role of agricultural environment in the risk of malaria exposure, the variation of the IgG level to the gSG6-P1 salivary peptide during each survey (dry and rainy season) and in each setting according to agricultural practices was first studied. The type of culture influenced the individual exposure to g bitten . This hiistricts . This issmission , 19. In smission , 21.Plasmodium density and prevalence. A significant positive association was observed in rural setting in rainy season. Altogether, this means that individuals living near wetlands were more exposed to Anopheles but did not present a higher risk of malaria transmission. Such apparent paradox has already been described, namely the paddy paradox [In this study, no association was observed between the distance to wetlands and the  paradox , 22.Then, we mapped the different epidemiological indicators of malaria transmission on maps for the dry and the rainy season, with the aim to identifying households or groups of households at high risk of malaria transmission throughout the year. Two types of hotspots which differed according to their spatial scale were identified. The first type is represented by micro-geographical areas within a study site, which is composed of a group of households where the risk of exposure and infection was localized and persistent between seasons. In Assoum1 and Gborotchara, malaria hotspots were composed of a group of infected households concentrated in a patch, persisting during the two seasons and from which transmission spread during period of high transmission with surrounding households infected in rainy season. In other sites, Téguiduo, Doropo2 and Bromakoté, malaria transmission was homogeneous, and thus the entire site is at risk of malaria transmission thus representing a local hotspot.Anopheles [The contrasting outcomes concerning malaria transmission pattern within irrigated areas highlight the significance of considering local context, environmental variations, and human behavior when assessing malaria risk. Targeted interventions that consider the specific factors of risk in different settings would be more effective in reducing malaria transmission and ultimately improving public health outcomes . Also imnopheles , 25. A hPlasmodium reservoir and preventing the spread of infection.In sites where the risk is high and homogeneous, such as Doropo2, Bromakoté, and Téguiduo, seasonal malaria chemoprophylaxis could be initiated before the start of the rainy season, with the aim reducing Anopheles was extrapolated from these 2 capture points, and the interpolation on the maps should be interpreted with caution. Nevertheless, measuring individual exposure using the serological approach overcomes this limitation. In addition, the identification and counting of potential Anopheles mosquito breeding sites close to households would have enabled them to be taken into account. A more complete characterization of the wetland, such as the measurement of standing water levels and the study of Anopheles larvae, would also have provided additional environmental characteristics to be tested, in addition to the type of agricultural crops. The intricate interplay between agricultural practices, notably rice crops, and malaria transmission underscores the need for a comprehensive understanding of factors influencing vector dynamics. Members of the Anopheles gambiae complex, particularly Anopheles arabiensis, exhibit a preference for breeding in open and sunlit puddles, often abundant in flooded rice fields [Anopheles mosquito species have varying preferences for breeding habitats, which can be influenced by factors such as water quality, vegetation, sunshine and temperature. In addition, agricultural practices can introduce pesticides or alter the hydrology of the area, which can affect mosquito populations and the dynamics of malaria transmission. In addition, more intensive monitoring of the human population studied would also have enabled us to characterize the dynamics of malaria transmission over time and space, in order to better identify hotspots.This study has several limitations. Firstly, due to logistical constraints, only 2 capture points in each site were used for the entomological studies. As a result, the aggressiveness of e fields . In factAnopheles mosquito bites also varied significantly within the study area. The presence of wetlands and agricultural activities, particularly irrigated crops, played a role in sustaining malaria transmission throughout the year. Proximity to wetlands increased the risk of malaria transmission in urban areas. Mapping efforts identified both micro-geographical and larger hotspot areas with persistent transmission. This study underscores the importance of considering local environmental factors for effective malaria risk assessment and management. Targeted interventions and hotspot targeting can contribute to reducing malaria incidence and facilitate malaria elimination efforts.In conclusion, this study investigated the transmission of malaria in an agricultural context, focusing on the influence of wetlands and agricultural practices on malaria heterogeneity in rural and semi-urban areas. The findings showed different malaria transmission patterns across rural and semi-urban sites, with higher prevalence in rural settings. Exposure to


Severe malaria in pregnancy causes maternal mortality, morbidity, and adverse foetal outcomes. The factors contributing to adverse maternal and foetal outcomes are not well defined. We aimed to identify the factors predicting higher maternal mortality and to describe the foetal mortality and morbidity associated with severe falciparum malaria in pregnancy.A retrospective cohort study was conducted of severe falciparum malaria in pregnancy, as defined by the World Health Organization severe malaria criteria. The patients were managed prospectively by the Shoklo Malaria Research Unit (SMRU) on the Thailand-Myanmar border or were included in hospital-based clinical trials in six Southeast Asian countries. Fixed-effects multivariable penalised logistic regression was used for analysing maternal mortality.p = 0.0002), hypotension  and respiratory failure  were associated with maternal mortality. Pregnant women with one or more of these three criteria had a mortality of 29.1% (25/86) (95%CI 19.5 to 38.7%) whereas there were no deaths in 88 pregnant women with hyperparasitaemia (> 10% parasitised erythrocytes) only or severe anaemia (haematocrit < 20%) only. In the SMRU prospective cohort, in which the pregnant women were followed up until delivery, the risks of foetal loss  and small-for-gestational-age  after severe malaria were high. Maternal death, foetal loss and preterm birth occurred commonly within a week of diagnosis of severe malaria.We included 213  episodes of severe falciparum malaria in pregnancy managed between 1980 and 2020. The mean maternal age was 25.7 (SD 6.8) years, and the mean gestational age was 25.6 (SD 8.9) weeks. The overall maternal mortality was 12.2% (26/213). Coma (adjusted odds ratio [aOR], 7.18, 95% CI 2.01–25.57, Vital organ dysfunction in pregnant women with severe malaria was associated with a very high maternal and foetal mortality whereas severe anaemia or hyperparasitaemia alone were not associated with poor prognosis, which may explain the variation of reported mortality from severe malaria in pregnancy. Access to antenatal care must be promoted to reduce barriers to early diagnosis and treatment of both malaria and anaemia.The online version contains supplementary material available at 10.1186/s12916-023-02991-8. Plasmodium falciparum infection remains the main cause of death from malaria worldwide [orldwide –3. Althoorldwide . If treaorldwide . Since 2orldwide . In pregorldwide  (2–3 timorldwide ), and thorldwide , 10. Howorldwide . Other sorldwide , 11. TheIn contrast to the large prospective series of severe malaria in children and non-pregnant adults that have been reported , 12, theThe data of severe falciparum malaria in pregnancy in Southeast Asia were derived from two different series: the SMRU pregnancy cohort on the Thailand-Myanmar border and the MORU/OUCRU clinical studies of hospitalised patients in Bangladesh, India, Indonesia, Myanmar, Thailand and Vietnam. Clinical data from birth records of pregnant women without severe malaria  collected from 1989 to 2020 at SMRU was additionally extracted for comparison of maternal and birth outcomes. We describe the SMRU cohort in detail and provide birth outcomes as these women were followed up systematically until delivery. The MORU/OUCRU studies were of patients hospitalised with severe malaria and were included to the analyses of maternal mortality, but these studies did not follow surviving women to delivery.P. falciparum were excluded.We used the current WHO severe malaria criteria  to definSMRU provides primary health care and antenatal care (ANC) for refugees and migrants in clinics along the North-western border of Thailand, an area of low seasonal malaria transmission , 18. SerAt SMRU, women with malaria parasitaemia were treated with effective antimalarial drugs , renal failure (anuria) and pulmonary oedema  were diagnosed clinically. Metabolic acidosis, which is based on the laboratory results as defined in the WHO severe criteria, was therefore not available for the analyses.PfHRP2-based rapid diagnostic test  for inclusion. The quantitative assessment of blood smear was conducted later. Haematology and biochemistry were tested on site. Last menstrual period was used for estimating gestational age in these studies.The MORU/OUCRU patients were from prospective clinical studies of hospitalised patients conducted in Southeast Asia and included data from three RCTs on severe malaria as described previously , 20, 21.The primary outcome was case fatality of mother , and secondary outcomes included foetal loss, preterm birth and birthweight of the foetus. Foetal loss, including death in utero, was categorised as miscarriage (< 28 weeks) or stillbirth (≥ 28 weeks), depending on EGA. Preterm birth was defined as live birth before 37 complete weeks (37 weeks + 0 days) . Small-fMedian with interquartile range (IQR) was used for describing continuous characteristics, and Wilcoxon’s rank sum test was used for comparing them. For describing outcomes, confidence intervals of proportions were calculated by the Wilson method. The number of missing information was excluded from the denominators of proportions. For those women who had more than one episode of severe malaria, only the final severe episode was used for assessing pregnancy outcomes.jomo command in R [p < 0.05 by Wald test as the cut-off [To characterise the predicting factors for maternal death, the baseline characteristics and the WHO severe malaria criteria were assessed using the pooled dataset of the two series. All the available WHO severe criteria, calendar year, maternal age, maternal body weight, parity, EGA at malaria, parasite density and presence of gametocytaemia, schizontaemia, malaria pigment either in neutrophils or monocytes and fever were assessed. Firth’s penalised logistic regression was conducted with fixed-effects for each site to take account of the variability among the sites. For missingness, joint-modelling multilevel multiple imputation was conducted using and in R   after severe malaria. Preterm birth was assessed among those who had severe malaria before 37 complete weeks. The prevalence of adverse pregnancy outcomes was described for the three clinical management groups. Proportions of these outcomes among women with uncomplicated falciparum malaria in pregnancy at SMRU were shown for reference. As a sensitivity analysis, assessment of birthweight was also conducted only for those who were weighed within 3 days of the date of birth . Stata MI2 was used for quantifying heterogeneity. We used metaprop command in Stata [A meta-analysis on the mortality from severe malaria in pregnancy in Asia was conducted, including the current study data. A previous systematic review on malaria in pregnancy in Asia  was condin Stata .n = 18), India (n = 1), Indonesia (n = 10), Myanmar (n = 21), Thailand (n = 13) / Thailand-Myanmar border (n = 123) and Vietnam (n = 27).In total, 213 episodes of severe falciparum malaria in pregnancy were included in this pooled analysis  and severe anaemia  were the most common severe malaria criteria fulfilled , but was not statistically different from the severe malaria with vital organ dysfunction group .Thirty-eight episodes were categorised as severe malaria with vital organ dysfunction, 50 episodes were categorised as severe malaria with hyperparasitaemia only, and 35 episodes were severe malaria with severe anaemia only Table . The patFirst-line antimalarial treatment for severe malaria changed from quinine to artemisinin derivatives during the study period according to the local guidelines . Mortality occurred only in women presenting with vital organ dysfunction; 26.3% (10/38) of this group died. There were no deaths in the other two groups (0/85) in which most women  were treated with oral antimalarials. Mortality was 8.3% (2/24) after intravenous artesunate, 25.0% (1/4) after intramuscular artemether, and 75.0% (3/4) after intravenous quinine. Most of the deaths  occurred within 24 h of admission. All deaths following intravenous artesunate or intramuscular artemether occurred within 24 h, while two patients died on day 4 of intravenous quinine. One woman died of severe malaria with eclampsia. Three other women had pre-eclampsia, and all survived.The hospital-based cohorts included 90 hospitalised pregnant women who fulfilled the WHO severe malaria criteria between 1980 and 2016. The most common severe criterion was coma 52.2%, 47/90) . A forest plot is shown in Additional file The maternal mortality of severe malaria in pregnancy reported in 14 studies , 28–39 ip < 0.0001), renal failure , hypotension  and respiratory failure . Neither EGA (continuous) nor trimester  was associated with maternal mortality. In the multivariable analysis adjusting for calendar year and treatment, coma , hypotension  and respiratory failure  were each independently associated with an increased risk of maternal death. Among women who had any of these three criteria, mortality was 29.1% (25/86). There were no deaths in 88 pregnant women with severe malaria with hyperparasitaemia (> 10%) or severe anaemia (haematocrit < 20%) only. Excluding these 88 women without organ dysfunction resulted in a mortality of 20.8% (26/125). Sensitivity analyses showed similar results . Factors associated with maternal death were assessed by pooling the two series  of women excluding three postpartum episodes, which were all live-born Table . Foetal All 72 live-born babies were singletons, and there was one congenital abnormality . Median estimated gestational age at delivery was 39.3 (IQR 38.1–40.2) weeks. Among women who had severe malaria before the 37th week of gestation and did not have foetal loss, the overall prevalence of preterm birth was 14.7% (10/68), which was not different from 13.8% (463/3353) in pregnant women who had uncomplicated falciparum malaria before the 37th week of gestation.n = 60). The proportion of SGA was 38.3% (23/60). Compared with those who had uncomplicated falciparum malaria in pregnancy , the proportion of SGA was higher in the severe malaria with organ dysfunction group , but not different in the groups with hyperparasitaemia only  or severe anaemia only . These figures were similar when only those whose birthweight had been assessed within 3 days of birth were included  of cases Fig. : all 16 I2 87.1%). This study included two different series of pregnant women with severe falciparum malaria, one community-based and the other hospital-based, showed clearly that, whereas falciparum malaria causing vital organ dysfunction carries a high mortality, severe anaemia or hyperparasitaemia only can present in ambulant women and carry a good prognosis if they are treated properly. Indeed, oral treatment under careful supervision was sufficient in 70% of the groups with either hyperparasitaemia only or severe anaemia only. This marked difference in mortality between the different WHO severe malaria criteria probably explains the variation in reported malaria-related mortality in pregnancy in the international literature, and it raises the question of whether these should be included in the criteria for a diagnosis of severe malaria in pregnancy.Severe falciparum malaria is an important cause of maternal death in malaria-endemic areas, particularly in lower-transmission areas such as those in most of Asia , 11. TheDefinitions of severe malaria are valuable in triage and in prompting emergency treatment. In this study, coma, respiratory failure and hypotension were each independently associated with mortality in pregnant women. Similar findings have been reported previously in both children and adults showing that coma, increased blood urea, metabolic acidosis, shock and pulmonary oedema were associated with increased mortality . In areaHyperparasitaemia reflects low immunity against falciparum malaria, such as in younger children or pregnant women , 3, 43. All three maternal deaths after parenteral artesunate/artemether in the SMRU cohort occurred within 24 h [Increased risks of foetal loss and SGA after severe malaria in pregnancy, particularly among those with organ dysfunction, were reported previously in a small case series . The majThere are several limitations to this study. First, some of the WHO severe malaria criteria were unavailable. Important determinants of outcome  could not be always assessed and blood glucose was not monitored frequently particularly when the patient was conscious. These missing criteria require laboratory investigation and are frequently unavailable at the primary healthcare level in malaria-endemic countries. The results of this study have practical utility for settings where most malaria is diagnosed and treated, i.e. in rural and remote settings. The number of fulfilled criteria  can be aAnaemia and malaria are common in pregnant women in tropical settings. Hyperparasitaemia is more common in low than high-transmission settings. However, anaemia and hyperparasitaemia often are not associated with concomitant vital organ dysfunction requiring parenteral malaria treatment. On the contrary, they carry a good prognosis for the mother with ready access to oral artemisinin treatments and if necessary, blood transfusion. The reported variability in the mortality of severe malaria in pregnancy is probably explained largely by the different prevalence of these two severe malaria criteria in different series. Maternal mortality is consistently high in severe malaria with vital organ dysfunction, notably cerebral malaria, requiring immediate life-saving intravenous artesunate administration. Severe malaria in pregnancy increases the immediate risk of foetal loss and preterm delivery, and the risk that the baby is born small-for-gestational-age.Greater malaria control efforts in the non-pregnant population along the Thailand-Myanmar border has resulted in a significant decline in malaria in pregnancy and hence mortality in all patients from severe malaria, including pregnant women . Waning Additional file 1:Table S1. The World Health Organization Severe Malaria Criteria .Additional file 2:Table S2. Treatment for each severe falciparum malaria sub-group group over time at the Shoklo Malaria Research Unit.Additional file 3. Supplemental Methods of Multiple imputation.Additional file 4:Table S3. The numbers and proportion of pregnant women who met each severe malaria criterion.Additional file 5:Figure S1. Forest plot of the maternal mortality among pregnant women with severe malaria in Asia.Additional file 6:Table S4. The adjusted odds ratio of maternal death by complete case analysis model and multiple imputation model.Additional file 7:Table S5. Univariable and multivariable penalised logistic regression on the potential prognostic factors for maternal death using the WHO severe malaria criteria for research purposes.Additional file 8:Table S6. Birthweight assessment by clinical severity groups on the Thailand-Myanmar border including only newborns who were weighed within three days from birth.


Ascaris lumbricoides, Trichuris trichiura, hookworm spp. and intestinal Schistosoma eggs. Results: A total of 402 participants were included in this study. An amount of 44.3% of them lived in urban areas, and only 51.9% of them reported having bed nets. Malaria infections were detected in 34.8% of the participants, while 50% of malaria infections were reported in children aged 10–17 years. Females had a lower prevalence of malaria (28.8%) compared with males (41.7%). Children of 1–9 years carried more gametocytes compared with other age groups. An amount of 49.3% of the participants infected with T. trichiura had malaria parasites compared with those infected with A. lumbricoides (39.6%) or both (46.8%). Conclusions: The overlapping problem of STH and malaria is neglected in Bata. The current study forces the government and other stakeholders involved in the fight against malaria and STH to consider a combined control program strategy for both parasitic infections in Equatorial Guinea.Introduction: Malaria and soil-transmitted helminth (STH) co-infection is an important parasitic infection affecting populations in co-endemic countries including Equatorial Guinea. To date, the health impact of STH and malaria co-infection is inconclusive. The current study aimed to report the malaria and STH infection epidemiology in the continental region of Equatorial Guinea. Methods: We performed a cross-sectional study between October 2020 and January 2021 in the Bata district of Equatorial Guinea. Participants aged 1–9 years, 10–17 years and above 18 were recruited. Fresh venous blood was collected for malaria testing via mRDTs and light microscopy. Stool specimens were collected, and the Kato–Katz technique was used to detect the presence of  Plasmodium spp. in endemic countries [Malaria continues to be a disease of public health importance despite the tremendous efforts invested in the control of ountries ,2. The eountries . In 2021Plasmodium infection with a year-round malaria transmission pattern [Plasmodium falciparum  malaria in EG has been reported to be high in the continental region of Bata compared with Bioko Island, which is most likely due to ongoing intensive and successful vector control programs that are ongoing on Bioko Island [Equatorial Guinea (EG) is a Central African country and constitutes two regions: the insular and the continental regions. The continental region comprises a large part of the country’s surface area, while the insular region is characterized by two islands, namely, Bioko and Annobón. The country is holoendemic for  pattern . A malar pattern ,6,7. In o Island ,9,10.The combination of malaria control strategies, such as malaria vaccines, vector control, and improved diagnosis and treatment, could be crucial for sustainable disease control ,12,13. AAge and sex are among the most studied factors that have been shown to influence different disease outcomes. Several studies have reported that malaria prevalence is affected by age  or age-dAscaris lumbricoides (A. lumbricoides), Trichuris trichiura (T. trichiura), Necator americanus (N. americanus) and Ancylostoma duodenale  [Soil-transmitted helminths (STHs) refer to intestinal worms transmitted to humans through contaminated soil, causing substantial disease and disability to more than a quarter of the world’s population ,28. STHsodenale) . While sodenale) . Such inFurthermore, malaria and helminth co-infection is the most common predominant infection affecting populations in Central Africa including EG due to their overlapping disease geographical distributions . To dateThe cross-sectional survey study took place in the two municipalities of the Bata district in the continental region of EG, selected using multi-stage cluster sampling. First, one district was randomly (simple random) selected, and within the district, two municipalities were selected. Second, from each municipality, four communities were selected using simple random sampling. Thereafter, 26 households were selected using systematic random sampling from each community based on a computer-generated random number list applied to the community register of households. Lastly, two individuals were selected from each household using stratified random sampling. A randomized list of the age categories for each household was produced. In cases where more than one person in the selected house was within the same age group, participants were chosen by tossing a coin. With the above sampling, 406 individuals were selected to participate in this study.This study was conducted in two municipalities of the Bata district (Bata and Rio campo) in the continental region of EG between October 2020 and January 2021. These municipalities represent the urban (Bata) and rural (Rio Campo) settings of the most populated district in the mainland (the Bata district). The sites were selected based on their population sizes as well as based on the convenience to perform this study.Volunteers were equally categorized into 3 age groups—pre-school children (1–9 years), school-age children (10–17 years), and above 18 years—and were recruited from the two municipalities of the Bata district, Continental Region of EG. The participants who resided in the study area for at least 3 months before the survey, provided signed or thumb-printed and witnessed informed consent/permission/assent, and met the above age criteria were included in this study. Participants with no thick blood smear (TBS) results were excluded from the analysis.The sample size was calculated based on the ability to estimate a prevalence of malaria of approximately 50% with a margin of error of approximately 5%; hence, a minimum of 400 volunteers needed to be surveyed (including 5% of the volunteers who were not able to provide a blood specimen for this study).Plasmodium spp. using optical light microscopy. The thick blood smears (TBSs) were prepared by evenly spreading 10 µL of fresh venous blood on a 1 cm × 2 cm rectangle for a thick smear and 6 µL of blood to obtain a thin smear [The commercially available RDT  Ag Combo, ACCESSBIO, USA ) was used throughout the participant recruitment process in the field, according to the manufacturer’s instructions and as detailed elsewhere . Two milin smear . The smein smear . The mRDA. lumbricoides, T. trichiura, hookworm spp. and Schistosoma spp., as described elsewhere [The Kato–Katz technique was used for the diagnosis of lsewhere . Briefly® . Descriptive statistics were used to summarize the data. For categorical data frequency, counts and percentages were used, and continuous variables were summarized with means, standard deviation and ranges. The associations between categorical variables were tested using Chi-squared tests. In the univariate logistic regression, a variable that showed association at a 20% significance level was considered in the multivariate analysis. Backward elimination with the use of a likelihood ratio test at a significance level of 5% was used to select the final model. A p-value of 0.05 or less was considered statistically significant unless stated otherwise. The data analysis was performed with STATA 15 standard editions .Data were collected and entered into Microsoft ExcelThe protocol received approval from the EG National Ethics Committee . Furthermore, this study was also approved by the public health direction of the Ministry of Health and Social Welfare (reference number 56-150), the regional delegation of Bata of the Ministry of Health and Social Welfare (reference number 2018), and the government delegation of Bata, Littoral from the Ministry of Interiors and Local Corporations (reference number 937). In addition, the protocol was submitted and approved by the training host institution, the Centre de Recherches Médicales de Lambaréné (CERMEL) for scientific and technical advice. All study procedures were conducted according to Good Clinical Practice (GCP). All eligible participants were asked to provide their consent by signing an informed consent form before enrollment in this study.A total of 406 participants were screened, 4 [P. falciparum was the most frequent species identified, followed by P. malariae  was detected during the analysis and was most frequent in the 1–9 years age group  participants had malaria-positive results via mRDT that were confirmed using TBS. The prevalence of malaria was higher (50%) in children aged 10–17 years compared with those of 1–9 years (42.2%) and above 18 years (20%). The prevalence of malaria was lower in females (28.8%) compared with males (41.7%), as shown in The results of the univariate logistics regression indicate that the risk of malaria infection decreased with age , wherebyp-value > 0.05).In the multivariate logistics regression, only the differences amongst ages (as continuous) and sex remained significant. The results of the final model are presented in A. lumbricoides had more malaria parasites compared with those who were infected with T. trichiura or both , Ancylostoma spp., Taenia solium and Strongyloides stercoralis mono, double and triple infection were detected during the analysis  compared with females (28.8%), affirming the finding of previous studies conducted in similar settings in Nigeria and Cameroon, and in Malaysia ,43,44. TOn the contrary, a number of studies have also reported higher malaria prevalence in females compared with males ,45,46, tWhen the current study compared the prevalence by age groups, the data showed that older children and early teenagers (10–17 years) had a higher prevalence of malaria (50%) followed by toddlers (1–9 years) (42.2%), while adults above 18 years had the least prevalence (20%). The analysis suggests that the higher malaria prevalence reported in the 10–17 years age group could be attributed to their active habits of staying outside houses during early nights, which increases exposure to mosquito bites, or/and the delayed acquisition of natural immune responses due to interventions implemented at a young age . SimilarNext, there is a need to investigate the distributions of parasite density among age groups. Herein, the data show that malaria parasite density declines as individuals increase in age. This study also showed that the risk of malaria decreased with age, whereby each year an increase in age was associated with a 2% decrease in the risk of malaria. The findings of the current study are in line with several studies that have also reported similar findings ,51,52 anAnopheles mosquitos [Gametocytes are drivers of malaria infection as they determine the transmission of malaria from one individual to another via osquitos . Therefoosquitos ,57. Thisosquitos .Bed nets ) have been the most successful malaria intervention to date . Herein,T.trichiuras (49.3%), followed by those who were multiply infected with both A. lumbricoides and T. trichiuras (46.8%). Moreover, when comparing the parasite densities amongst participants infected with different types of STH, we found that those who had malaria co-infected with A. lumbricoides had a slightly higher median density compared with T. trichiuras alone or T. trichiuras and A. lumbricoides mixed infections, although the evidence of association did not reach a level of statistical significance. Contrary to the findings of the current study, a positive association between STH and Plasmodium parasite density has been reported elsewhere [The body of evidence suggests that soil-transmitted helminths (STHs) have some modulatory effect on the pathophysiology of malaria infection ,63. Therlsewhere .The current study had some limitations. Amongst these were a lack of qPCR data for the malaria parasite, HRP2 gene deletion and STH diagnosis. This might have led to an underestimation due to the use of TBS and mRDT, which are not as sensitive as qPCR, or an overestimation of the cases due to false positive reporting. On the other hand, the inclusion of individuals who had stayed in the study areas for at least 3 months might also have led to an overestimation of prevalence, as individuals may come from other areas with infection. The current study also used a single fecal sample collection to estimate STH infection. This may have contributed to an underestimation of STH diagnosis, especially when the densities of some species were low. However, the use of a single sampling time point from cross-sectional studies may be sufficient to obtain a close estimate of current STH infection. Furthermore, there were no data on malaria prevalence just before COVID-19 started, hence hindering a proper comparison within the current study.This study demonstrated that despite global interventions against malaria, cases of malaria have plateaued in Bata, the continental region of EG. This study reinforces the importance of the government and other stakeholders involved in the fight against malaria in EG re-thinking new interventions. The data from the current study suggest that the risk of contracting malaria and STH is high in EG; hence, a combined strategy to fight both protozoa and helminth infection will benefit the interventions for parasitic infection in EG. However, further studies covering more areas of the continental region and with more sensitive diagnostics methods will supplement the data provided by the current study.


Plasmodium and is transmitted by the female Anopheles mosquito. The parasitic infection is endemic in 90 countries, with approximately 500 million cases reported annually and an estimated annual mortality of 1.5-2.7 million individuals. Historically, the use of antimalarial drugs has been promising for the chemoprophylaxis and treatment of malaria, mitigating the annual mortality rate. Notably, these antimalarial drugs have been associated with various adverse effects, including gastrointestinal upset and headaches. However, the adverse cutaneous manifestations these antimalarial drugs may lead to are poorly documented and understood. We aim to describe the lesser-studied adverse cutaneous pathologies of malaria treatment to better educate physicians on the proper treatment of their patients.Malaria is a life-threatening parasitic disease caused by various forms of the protozoa Our narrative review describes the skin manifestations associated with specific antimalarial treatments and their associated prognoses and treatments. The cutaneous pathologies discussed include aquagenic pruritus (AP), palmoplantar exfoliation, Steven-Johnson syndrome, toxic epidermal necrolysis, cutaneous vasculitis, psoriasis, ecchymosis, and tropical lichenoid dermatitis. Further studies and vigilant documentation of the cutaneous adverse events of antimalarial drugs need to be performed and emphasized to prevent potential life-threatening adverse outcomes. Plasmodium and spread by the female Anopheles mosquito. Every year, around two billion individuals are prone to malaria infection with around 500 million cases of malaria confirmed in those at risk. With rising global temperatures in the 90 malaria-endemic countries across the globe, it is no surprise that 1.5-2.7 million people annually succumb to the virus [Plasmodium cause infection in humans, with P. falciparum infection leading to the most severe complications and mortality. Plasmodium falciparum is most prevalent in Africa, specifically in western and sub-Saharan Africa, where the mortality rate post infection is around 90% [Malaria is a life-threatening disease caused by several species of the parasite P. falciparum [The most common symptom of malaria is a long-standing fever. Other common symptoms include headache, malaise, gastrointestinal pain, and muscle aches. Severe malaria cases can even lead to seizures, cerebral malaria, anemia, sepsis, renal failure, acute respiratory distress syndrome, disseminated intravascular coagulation, and pulmonary edema. Around 80% of malaria-associated deaths are due to cerebral malaria with lciparum . To comblciparum . Recent ObjectivesOur narrative review summarizes adverse cutaneous effects due to antimalarial drugs used for the treatment and chemoprophylaxis against malaria in an attempt to better prepare physicians in identifying and treating these skin manifestations.MethodsA literature search was performed using PubMed, Scopus, and Google Scholar. Our search was focused on the various adverse skin pathologies the patients noted to have experienced after malaria treatment and chemoprophylaxis, using primarily case reports supplemented with narrative reviews and systematic reviews. Articles were selected and narratively reviewed by two reviewers. In the initial article selection process, a third reviewer was included in times of incongruity between the two primary reviewers.ResultsAquagenic Pruritus (AP) Induced by Antimalarial DrugsIn 1981, aquagenic pruritus (AP) was established as a separate diagnosis from aquagenic urticaria . AP is dIt has been found that antimalarial drugs have the potential to induce non-aquagenic pruritus in almost 75% of patients . This geA case study involving a 36-year-old non-lupus-afflicted African female detailed a lifelong history of generalized pruritus in relation to a malaria-endemic environment . She wasThis diagnosis of AP can be quite challenging as AP includes no additional symptoms nor visible rash, a negative symptomatic dermographism, and a negative TempTest for cold/heat contact urticaria . AdditioPalmoplantar Exfoliation Due to ChloroquineP. falciparum infection in the majority of virus-endemic regions due to the global spread of resistant parasites, still can be utilized effectively in certain instances of malaria treatment [Chloroquine, although discontinued from the treatment of reatment . RegardiNair and Patel documented an incidence of photosensitivity and palmoplantar exfoliation in a 40-year-old female five days after taking a chloroquine tablet for malaria treatment . The patUnusual Cutaneous Manifestations With MefloquinePlasmodium. It is effective as an antimalarial drug as it targets multiple proteins in the parasite [Mefloquine is an antimalarial drug often used for chemoprophylaxis against parasite . The mosparasite -9.The most commonly reported adverse skin reaction of mefloquine includes pruritus, with severe cases described as "an excruciating burning" . The secSmith et al. described a review wherein a 66-year-old female undergoing malaria prophylaxis using mefloquine developed a blister on the lower part, which gradually transformed into ulcerating lesions involving her oral mucosa, upper and lower extremities, and back . After 3Chew and Ponampalam described a 46-year-old individual who developed ecchymosis of the trunk, waist, and buttocks with associated rectal bleeding three days after taking a prophylactic dose of mefloquine . After rPotasman and Seligmann reported that the usage of mefloquine resulted in a psoriasis flare in a 50-year-old male with a history of well-controlled psoriasis limited to extensor regions . After cQuinacrine Hydrochloride-Induced Tropical Lichenoid DermatitisThe Allied forces used quinacrine hydrochloride for malaria prevention during World War II when quinine was unavailable after Japan invaded Southeast Asia . HoweverBauer further classified the permanent sequelae as inactive (first presentation) and active (recent or chronic lesions) . The actWith the extensive benign to potentially life-threatening antimalarial-induced adverse cutaneous effects, physicians need to properly understand these events to provide competent care for their patients. Given the rare nature of these various antimalarial chemoprophylaxis- and treatment-induced adverse skin pathologies, it can be a challenge to truly encapsulate an accurate depiction of the aforementioned cutaneous presentations. Additionally, as drug metabolism varies from individual to individual, some patients may present with a more severe adverse effect than others. Lastly, had there existed extensive literature regarding antimalarial cutaneous adverse effects, further insight into the pathologies of the adverse skin effects could have been deduced from the cases presented. The development of rare but severe manifestations such as Steven-Johnson syndrome, toxic epidermal necrolysis, and cutaneous vasculitis, along with the exacerbation of chronic conditions such as psoriasis, requires further studies and extensive documentation to be performed and emphasized.


P. vivax predominated in GM; in PM, the proportion of P. vivax and P. falciparum was similar; in CM, P. falciparum predominated. The main clinical findings were headache (49%), anemia (32%), fever (24%), and musculoskeletal pain (13%). The clinical manifestations were statistically higher in P. vivax infections. In submicroscopic GM (positive with qPCR and negative with thick blood smear), the frequency of anemia, sore throat, and a headache was statistically higher compared with pregnant women without malaria. GM, PM, and CM reduce birth weight and head circumference. In Colombia, this is the first research on the clinical characteristics of GM, PM, and CM; contrary to evidence from other countries, P. vivax and submicroscopic infections are associated with clinical outcomes.This study compared the clinical–parasitological profiles of gestational (GM), placental (PM), and congenital (CM) malaria in northwestern Colombia. A cross-sectional study with 829 pregnant women, 549 placentas, and 547 newborns was conducted. The frequency of GM was 35.8%, PM 20.9%, and CM 8.5%.  Plasmodium spp. in maternal peripheral blood, placental malaria (PM) or the presence of the parasite or its pigment hemozoin in this organ or in placental blood, and congenital malaria (CM), which corresponds to malaria of the newborn during the first week of life or later if there is no possibility of infection through a mosquito bite  AND “clinical manifestations”[Title/Abstract] and “malaria pregnant*”[Title/Abstract] AND “clinical profile”[Title/Abstract], with which only one Colombian study was found, this research concluded that most cases in pregnant women correspond to uncomplicated infections , the othP. falciparum; therefore, the main manifestations of P. vivax and its risk of causing PM and CM are unknown. (iii) Diagnosis is based on TBS, which generates underreporting and leads to ignorance of the clinical and epidemiological importance of submicroscopic infections. (iv) Surveillance of PAM in Colombia is limited to clinical cases, and paradoxically there are no clinical profiles for this disease. (v) In the search for PAM, only febrile symptomatic cases are screened, so this manuscript would help to expand the number of useful signs and symptoms to guide the search of patients or probable cases. (vi) Clinical–parasitological profile on PAM can help physicians to guide an early diagnosis, opportune and species-specific treatment, and avoid the consequences of PAM. The objective of this research was to compare the clinical–parasitological profile of GM, PM, and CM malaria, in northwestern Colombia. The specific objectives were as follows: (i) compare the frequency of clinical findings in each one of the three forms of PAM  comparing positive GM, PM, and CM versus negative pregnant women; (ii) compare the clinical findings between P. vivax, P. falciparum, mixed-malaria infections in GM, PM, and CM; (iii) compare the frequency of clinical findings in microscopic GM, PM, and CM versus the submicroscopic infections and negative pregnant women.Knowing the clinical–parasitological profile of PAM in the main endemic area of Colombia is important because of the following: (i) It generates evidence in an unexplored topic of malaria in the country. (ii) Clinical evidence is focused on countries with a predominance of P. vivax predominates (60–70% of cases), but P. falciparum also circulates [Cross-sectional in three different analysis units: for GM, we included 829 pregnant women; for PM, 549 placentas were included; and for CM, 547 newborns were included . Pregnant women were recruited in three local hospitals in the main malaria-endemic area of Colombia, located in the northwest of the country. This region reports approximately 60% of annual malaria cases in Colombia; it is highly endemic with an annual parasite index >25/1000 exposed, transmission is stable throughout the year, and rculates .It was not possible to have the same number of pregnant women, placentas, and newborns for multiple economic, social, or health system factors, such as the following examples: a pregnant woman was included, and we could not obtain the placenta or newborns sample because she presented a complication or risk for which her delivery was attended in another health institution ; some only consented to take one of the samples (for example blood from the pregnant woman or from the cord); others entered during pregnancy but did not sign (or withdrew) the consent for the placenta or newborn samples; the team that attended the delivery or the family of the pregnant women did not contact the research group to notify them of the date of delivery, among other economic and cultural reasons that prevented the delivery care at the local hospital .Pregnant women and newborns met the following inclusion criteria: receiving antenatal care or delivery at the local hospital of their municipality, pregnant women residing in the study region for at least one year, and having TBS and qPCR results for malaria. Pregnant women and newborns diagnosed with other diseases, infections, or complications of their health status, on antimalarial treatment at the time of the study, or without signing informed consent were excluded. The samples were collected between 2010 and 2019 using the same standardized procedures for collecting information and diagnosing malaria, which consist of applying the same form for extracting variables from the medical chart and using the same survey. For the processing of this information, the research group trained and standardized three nursing assistants who led the information collection.TBS and qPCR were performed on the same blood samples (at the same time). The diagnosis of GM was made with peripheral blood collected by venipuncture . In PM, placental blood was taken from a point near the insertion of the umbilical cord and another in the distal part of this organ; in CM, peripheral blood from the newborn by heel puncture or umbilical cord was used. In the case of a pregnant woman or newborn positive for TBS, antimalarial treatment was performed in accordance with the Colombian clinical practice guideline. In submicroscopic cases, we notified the physician of the result of the qPCR, and depending on his clinical evaluation, the doctor decided on the treatment.Plasmodium and primers polymorphic specific to P. falciparum, P. vivax, P. malariae, and P. ovale [P. falciparum, P. vivax, or mixed malaria is defined. The latter corresponds to the observation of parasitic forms of P. vivax and concomitant gametocytes of P. falciparum or regular asexual forms compatible with P. falciparum in a proportion of ≥40% of the 100 parasitic forms observed [For qPCR, Whatmann #3 filter paper was used for DNA extraction with the Saponin-Chelex method. PCR is the main molecular diagnosis of malaria with a detection limit of <0.02 parasites/μL. qPCR avoids post-amplification manipulation and quantifies the number of microorganisms; it includes a highly conserved region 18S rRNA of P. ovale . TBS is observed .The following variables were extracted from the medical chart of pregnant women: hemoglobin  , presencP. falciparum, P. vivax, or mixed malaria was performed with the Pearson chi-square test or Fisher’s exact test (n < 5). When the comparison of P. falciparum, P. vivax, or mixed malaria showed significant p values, multiple comparisons were made with the Bonferroni statistic. In order to compare the continuous variables with PM and CM, the Mann–Whitney U test was used; for causal species and microscopic or submicroscopic GM, the Kruskal–Wallis H with post hoc of Dunnett was used. A p-value < 0.05 was considered statistically significant.Categorical variables were described with absolute (#) and relative (%) frequencies, and the continuous variables were described with median and interquartile range . The comparison of the clinical findings between positive and negative for PAM and those affected by The Declaration of Helsinki and the specifications of Resolution 8430 of Colombia for research with pregnant women were applied. All pregnant women signed the informed consent  or assent (under 18 years of age) obtained in writing with the signature of the pregnant woman and a witness external to the research group. This study was classified as minimal risk, endorsed by the Ethics Committee of the University Research Headquarters (SIU), University of Antioquia, Act 21-101-961 of the year 2021. All data were anonymized to guarantee confidentiality.P. vivax, 34.3% were P. falciparum, and 2.7% were mixed malaria. The frequency of PM was 20.9% (115/549), with 94.8% submicroscopic, an equal proportion of P. vivax and P. falciparum (44.3%), and 11.3% mixed malaria. CM was 12.4% in umbilical cord blood and 2.2% in peripheral blood of the newborn, all submicroscopic cases, and with P. falciparum as the main causal species with 63.5% of the cases (The frequency of GM was 35.8% (297/829). Among the 297 positives, 45.1% were submicroscopic, 63% were he cases . The conhe cases , 24 , fever (23.8%), musculoskeletal pain (13.0%), shaking chills (10.9%), and vomiting (10.9%). Previous abortions occurred in 15.4% (87/566) and stillbirths in 2.1% (12/566). The following medians (interquartile range) were presented in the newborn: birth weight 3100 g (2852–3400), height 50 cm (49–51), head circumference 34 cm (33–34), and APGAR score 8 (7–9).P. vivax, except for sore throat and cough (p Chi2 = 0.293), stillbirths (p Chi2 = 0.342), or ITN use (p Chi2 = 0.086).We did not find an association between GM and diarrhea, but with all other clinical manifestations, there was a statistical association. According to the causal species, clinical findings were more frequent in women with nd cough . There wp Chi2 = 0.677) or stillbirths (p Chi2 = 0.498).In submicroscopic GM, a statistically higher frequency of anemia, cough, sore throat, and headaches was found compared to negative pregnant women; the first three symptoms were statistically the same as those found in pregnant women with microscopic malaria (positive with both diagnostic tests) . We did p Chi2 = 0.490) or stillbirths (p Chi2 = 0.193). PM presented statistical differences with anemia, and there was no significant association with the other clinical findings . There was no statistical association of PM with previous abortions (findings . We did p = 0.012) was only found between height and mixed GM. In the mixed-GM group, the median was 45 cm (IR 45–46), and in negatives and pregnant women with P. falciparum and P. vivax, the median was 50 (IR 49–51).In the outcomes in the newborn, GM, PM, and CM did not present a statistical relationship with the APGAR score or with the height at birth; when disaggregating these comparisons according to the causal species, an association  were statistically more frequent in P. vivax ; this isSubmicroscopic GM presented an association with anemia, cough, sore throat, and headache, showing the need to implement molecular diagnostics, given the false negatives of TBS. Other publications report the same situation but focus their arguments on the sensitivity problems of TBS in non-febrile patients, the need to interrupt their transmission or the achievement of the goals of pre-elimination or elimination ,24,25,26In addition, our results are relevant to support subsequent research on the clinical utility of PAM molecular diagnosis since some authors indicate that PCR does not provide information on the viability of the microorganism; therefore, its clinical use is inadequate , so the search for symptomatic cases and the prescription of the treatment of malaria should continue to be carried out with TBS. In this sense, this study shows that submicroscopic cases presented some clinical findings statistically similar to those of microscopic PAM .P. vivax. Although higher pathogenicity has been reported for P. falciparum [P. vivax with serious effects such as anemia and other hematological complications, severe malaria, acute respiratory distress, and multiple organ failure [P. vivax in PAM [In PM, the frequency of anemia was higher in lciparum , the evi failure , as wellx in PAM ,9,10. Itx in PAM ,30.P. falciparum. This coincides with the available evidence on this topic [CM was associated with a reduction in weight and head circumference at birth. The effect on birth weight was higher in mixed malaria and is topic ,7,10,19 is topic ,32. AddiP falciparum or fetal and neonatal outcomes avoided when GM is treated during pregnancy [Regarding head circumference at birth, several studies have reported similar results, evidencing an association of PM with a decrease in head circumference; newborns with a small head in pregnant women infected with regnancy ,34,35,36The way in which health care is structured in Colombia restricts the number of times pregnant women are attended by health personnel; thus, important data from the medical chart are frequently omitted. The foregoing resulted in many women in this investigation not having a complete record of clinical manifestations. Molecular diagnosis with PCR is excluded as part of the treatment guidelines, with the placenta as a waste organ in hospitals, which leads to difficulties for studies of PM and structural barriers to accessing antenatal care in dispersed rural areas that are most affected by malaria, leading to problems of recruitment of all pregnant women exposed or at risk.P. vivax are associated with clinical findings. The differences in the causal species of GM, PM, and CM evidence the complexity of the parasitological component of PAM. The need to improve the completion of the medical chart and increase the number of studies on medical aspects of gestational, placental, and congenital malaria was also demonstrated.This research is one of the few available in Colombia on the clinical characteristics of PAM. Contrary to evidence from other countries, this study showed that submicroscopic infections and those caused by


Plasmodium vivax malaria is known for its recurring febrile episodes, typically considered less severe than its counterparts. This case study presents a distinctive case of a 22-year-old male from a malaria-endemic region, experiencing spleen rupture and infarction as rare complications of vivax malaria. We explore the uncommon aspects of this case, emphasizing the importance of early diagnosis and tailored management. Despite substantial progress in malaria control, the disease remains a significant public health challenge, particularly in tropical regions. Plasmodium vivax, one of the causative agents of malaria, is characterized by its recurring nature. While often perceived as less severe than Plasmodium falciparum malaria, vivax malaria can manifest severe complications, such as spleen rupture and infarction. This case study delves into the atypical presentation, diagnosis, and management of these infrequent complications in a vivax malaria patient .A 22-year-old, previously healthy male from Pakistan presented to our emergency department with a chief complaint of sudden left-sided abdominal pain, which had been persisting for one day. He described the pain as localized to the left hypochondrium, non-radiating, and associated with intermittent fever and multiple episodes of non-bloody bilious vomiting. He mentioned that his most recent trip was six months ago, back to his home country.Upon examination, the patient appeared pale and tachycardic, with a pulse rate of 100 beats per minute. His respiratory rate was 18 breaths per minute, and his initial blood pressure measured 148/99 mmHg. Physical examination revealed a rigid abdomen with tenderness throughout, more pronounced in the left hypochondriac region. While awaiting the results of blood tests, the patient became dizzy, and his blood pressure dropped. Intravenous fluids were promptly administered, and a focused assessment with sonography identified free fluid in the right hepato-renal and left spleno-renal spaces, along with inferior vena cava collapse.Laboratory investigations revealed a hemoglobin level of 8.5 mg/dL, with a platelet count of 36,000 per microliter of blood. Elevated inflammatory markers were noted, with a C-reactive protein level of 173.7 mg/dL and a procalcitonin level of 97.96 ng/ml. A subsequent blood smear confirmed the presence of malaria vivax, with a parasitemia of 0.1% (Table After hemodynamic stabilization, the patient underwent computed tomography, which revealed splenomegaly with spontaneous rupture and multiple infarcts, leading to hemoperitoneum Figures , 2. Due Following surgery, the patient was transferred to the general ward, where he received close monitoring of vital signs, blood chemistries, and input-output measurements. He was initiated on antimalarial therapy with intravenous artesunate 2.4 mg/kg at 0, 12, and 24 hours. On the fifth day of hospitalization, he was discharged with a prescription for primaquine 30 mg daily for two weeks and received appropriate vaccinations, which included pneumococcal, Haemophilus influenzae type b, meningococcal, and seasonal influenza vaccinations.Splenic rupture is an exceptionally rare yet critical complication that can occur during a primary acute attack of vivax malaria. In the existing body of literature, the majority of cases have been linked to infections caused by Plasmodium falciparum and Plasmodium vivax. Unfortunately, this complication remains underreported and often goes undiagnosed, with reported mortality rates estimated at approximately 38% among travelers and around 10% in indigenous populations residing in endemic regions .Spontaneous splenic rupture represents a rare but highly lethal complication, with a mortality rate of 38%. The causes can be categorized into infectious and hematological factors, with infectious mononucleosis being the predominant infectious cause, followed by malaria infection.The exact mechanisms behind splenic rupture during malaria infection remain unclear. Nonetheless, existing studies propose two primary hypotheses -4: 1. Sudden splenic congestion due to the engorgement of sinusoids by red blood cells, particularly in the presence of young trophozoites.2. Microcirculation disorders caused by parasitized red blood cells, leading to localized disseminated intravascular coagulation.The preferred therapy may differ among patients based on factors such as the severity of splenic rupture, the patient's hemodynamic condition, the accessibility of endovascular treatment, and the preferences of the attending physician. The primary goal of treatment should be the preservation of splenic tissue. For patients experiencing hemoperitoneum and ongoing instability, splenectomy continues to be the preferred treatment option .We present a case study involving a 22-year-old male from an endemic area who exhibited signs and symptoms of splenic rupture concurrent with asymptomatic malaria infection. This observation may be attributed to repeated malaria infections over the course of his life, resulting in the gradual acquisition of immunity against the disease, subsequently leading to asymptomatic infections.This case underscores the importance of early diagnosis and immediate initiation of tailored antimalarial therapy in vivax malaria cases to avert rare complications, including spleen rupture and infarction. Healthcare providers in malaria-endemic regions should maintain vigilance in assessing and managing patients, recognizing the distinctive aspects of each case, and customizing treatment accordingly. Further research is needed to unravel the unique features of these rare complications and develop more effective prevention and management strategies.