Gestational glucose intolerance among pregnant women at the Cape Coast Teaching Hospital.

BACKGROUND: Malaria in pregnancy can have adverse outcomes if untreated. Both malaria and pregnancy are associated with insulin resistance and diabetes. Although malaria is treated prophylactically with gestational diabetes mellitus (GDM) screened for in pregnancy as part a routine antenatal care, their impacts have not been examined in terms of other forms of dysglycaemia. This cross-sectional study examined insulin resistance and its relationship with dysglycaemia and malaria among pregnant women in the Cape Coast Teaching Hospital (CCTH). METHODS: Using a structured questionnaire, demographic and clinical information were obtained from 252 pregnant women aged 18-42 years. Weight and height were measured for computation of body mass index (BMI). Measurement of insulin, lipid profile and glucose were taken under fasting conditions followed by oral glucose tolerant test. Insulin resistance and beta-cell function were assessed by the homeostatic model as malaria was diagnosed by microscopy. RESULTS: The respective prevalence of GDM, gestational glucose intolerance (GGI) and insulin resistance were 0.8% (2/252), 19.44% (49/252) and 56.75% (143/252). No malaria parasite or dyslipidaemia was detected in any of the participants. Apart from BMI that increased across trimesters, no other measured parameter differed among the participants. Junior High School (JHS) education compared with no formal education increased the odds (AOR: 2.53; CI: 1.12-5.71; P = 0.03) but 2nd trimester of pregnancy compared to the 1st decreased the odds (AOR: 0.32; CI: 0.12-0.81; P = 0.02) of having insulin resistance in the entire sample. In a sub-group analysis across trimesters, pregnant women with JHS education in their 3rd trimester had increased odds (AOR: 4.41; CI: 1.25-15.62; P = 0.02) of having insulin resistance. CONCLUSION: Prevalence of GDM and GGI were 0.8% and 19.44% respectively. The odds of insulin resistance increased in pregnant women with JHS education in the 3rd trimester. Appropriate measures are needed to assuage the diabetogenic risk posed by GGI in our setting.

Hypertension Increases Susceptibility to Experimental Malaria in Mice.

Global prevalence of hypertension is on the rise, burdening healthcare, especially in developing countries where infectious diseases, such as malaria, are also rampant. Whether hypertension could predispose or increase susceptibility to malaria, however, has not been extensively explored. Previously, we reported that hypertension is associated with abnormal red blood cell (RBC) physiology and anemia. Since RBC are target host cells for malarial parasite, Plasmodium, we hypothesized that hypertensive patients with abnormal RBC physiology are at greater risk or susceptibility to Plasmodium infection. To test this hypothesis, normotensive (BPN/3J) and hypertensive (BPH/2J) mice were characterized for their RBC physiology and subsequently infected with Plasmodium yoelii (P. yoelii), a murine-specific non-lethal strain. When compared to BPN mice, BPH mice displayed microcytic anemia with RBC highly resistant to osmotic hemolysis. Further, BPH RBC exhibited greater membrane rigidity and an altered lipid composition, as evidenced by higher levels of phospholipids and saturated fatty acid, such as stearate (C18:0), along with lower levels of polyunsaturated fatty acid like arachidonate (C20:4). Moreover, BPH mice had significantly greater circulating Ter119+ CD71+ reticulocytes, or immature RBC, prone to P. yoelii infection. Upon infection with P. yoelii, BPH mice experienced significant body weight loss accompanied by sustained parasitemia, indices of anemia, and substantial increase in systemic pro-inflammatory mediators, compared to BPN mice, indicating that BPH mice were incompetent to clear P. yoelii infection. Collectively, these data demonstrate that aberrant RBC physiology observed in hypertensive BPH mice contributes to an increased susceptibility to P. yoelii infection and malaria-associated pathology.

Assessment of the impact of pregnancy and malaria infection on the variation of neutrophil levels in women from San, Mali.

BACKGROUND: In patients with severe neutropenia, infections can rapidly become serious and life-threatening. It is essential to understand whether pregnancy induces changes in neutrophil levels thereby posing an increased threat to the health of gravidae. METHODOLOGY: This cross-sectional study was conducted in San Health District (Mali) and involved pregnant women infected or not by malaria parasites and non-pregnant healthy volunteers. Subjects were categorized as having neutropenia, normal neutrophil levels, and neutrophilia regarding their neutrophil levels. A logistic regression analysis was performed to determine factors associated with neutrophil level variation in pregnant women. RESULTS: Whether or not the pregnant women were infected with malaria, 98 of the 202 cases (48.5%) showed neutrophilia. Surprisingly, 67 of the 71 cases of neutropenia (94.4%) observed in this study concerned healthy people who were not pregnant. The mean percentage of neutrophil levels was significantly (p < 0.001) lower (49.9%) in the first trimester compared to the second trimester of pregnancy (62.0%). A logistic regression model showed that compared to early pregnancy, the second (OR = 12.9, 95% CI 2.2-248.1, p = 0.018) and the third trimesters (OR = 13.7, 95% CI 2.3-257.5, p = 0.016) were strongly associated with the increase of neutrophil levels. CONCLUSIONS: Pregnancy can induce the production of mature neutrophils that are continually released into circulation. Neutrophil levels were lower during the first trimester of the pregnancy compared to the second and third trimesters, but not affected by the presence or absence of malaria infection.

Albumin levels in malaria patients: a systematic review and meta-analysis of their association with disease severity.

Albumin, a key protein in human blood plasma, has been linked to various health conditions. However, its association with malaria, particularly in assessing disease severity, remains inadequately understood. This comprehensive systematic review and meta-analysis aimed to elucidate the relationship between albumin levels and malaria severity. A comprehensive literature search was conducted across multiple databases, including Embase, Scopus, PubMed, MEDLINE, Ovid, and Google Scholar, to identify studies examining albumin levels in malaria patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Data were pooled using a random-effects model, and heterogeneity was assessed using I2 statistics. Subgroup and meta-regression analyses were performed based on publication year, study location, and Plasmodium species. A total of 37 studies were included in this review. The thematic synthesis indicated that albumin levels in malaria patients varied significantly based on geographical location. A meta-analysis of 28 studies found that albumin levels were significantly lower in malaria patients compared with non-malarial controls (P < 0.001, standardized mean differences [SMD] = -2.23, 95% CI - 3.25 to - 1.20, I2: 98%, random effects model, 28 studies). Additionally, subgroup analysis revealed variations in albumin levels based on geographical location and Plasmodium species. Regarding the association with disease severity, thematic synthesis showed that severe malaria cases generally had decreased albumin levels across various regions. However, one Brazilian study reported higher albumin levels in severe cases. A separate meta-analysis of five studies found significantly lower albumin levels in patients experiencing severe malaria relative to those with less severe forms of the disease (P < 0.001, SMD = -0.66, 95% CI - 1.07 to - 0.25), I2: 73%, random effects model, 5 studies). This study underscores the clinical significance of albumin as a potential biomarker for Plasmodium infection and the severity of malaria. The findings suggest that albumin level monitoring could be crucial in managing malaria patients, especially in assessing disease severity and tailoring treatment approaches. Additional studies are required to investigate the underlying mechanisms driving these associations and validate the clinical utility of albumin levels in malaria patient management.

Association of ABO, Rh-D and Kell blood groups with transfusion transmitted infections among blood donors from the Asir Region, Saudi Arabia: A retrospective observational study.

OBJECTIVES: To evaluate the association between transfusion-transmitted infections (TTIs) and ABO, Rh-D, and Kell blood systems among blood donors. METHODS: This was a retrospective study of 10,095 donors who visited the Blood Bank at Asir Hospital, Abha, Saudi Arabia. Data including demographic information, ABO, Rh-D, and Kell blood groups, and serological and molecular test results of TTIs (the TTIs were obtained from each donor's records). Chi-squared and Fisher's exact tests were employed to establish possible associations between blood groups and TTIs. RESULTS: The prevalence rate of TTIs among donors was 6.3%, with HBcAb (70%) being the most prevalent biomarker among positive donors. Donors with the O blood group were at a higher risk of contracting TTIs. Significant associations were observed between HIV and blood group A (χ2=6.30, p=0.01), HBsAg and group AB (χ2=17.3193, p=0.00003), malaria and group A (χ2=5.0567, p=0.02), and HBV-DNA and group AB (χ2=12.3163, p=0.0004). Also, Kell blood group was significantly associated with HIV (χ2=14.5, p=0.0001), HBcAb (χ2=78.51, p<0.0001), and syphilis (χ2=25.225, p<0.00001). CONCLUSION: ABO and Kell blood groups are associated with TTI markers. These findings highlight the need for improved strategies and approaches in screening and managing blood donations to minimize the risk of TTIs.

Altered haematological parameters in children with malaria infection, a systematic review and meta-analysis.

OBJECTIVE: This study aimed to illustrate the effect of malaria infection on red blood cell parameters in children and evaluate the diagnostic relevance of haematological parameters in predicting malaria. METHODS: The studies were identified through databases like PubMed, Google Scholar, and Scopus to retrieve related articles. Fourteen studies were selected by literature search based on inclusion and exclusion criteria, and a meta-analysis on different red blood cell parameters was performed. RESULTS: Haematocrit, haemoglobin concentration, and RBC count show statistically significant findings with p values of (<0.00001), (p<0.00001) and (p=0.0004), respectively. Other parameters like MCV, MCH, and MCHC show statistically non-significant results with p values of 0.21, 0.36, and 0.63, respectively. CONCLUSION: Considering the above findings, the combination of haemoglobin concentration, haematocrit, and RBC counts could be used as reliable parameters to predict the presence of infection and included in the diagnostic strategy for malaria in children.

The malarial blood transcriptome: translational applications.

The blood transcriptome of malaria patients has been used extensively to elucidate the pathophysiological mechanisms and host immune responses to disease, identify candidate diagnostic and prognostic biomarkers, and reveal new therapeutic targets for drug discovery. This review gives a high-level overview of the three main translational applications of these studies (diagnostics, prognostics, and therapeutics) by summarising recent literature and outlining the main limitations and future directions of each application. It highlights the need for consistent and accurate definitions of disease states and subject groups and discusses how prognostic studies must distinguish clearly between analyses that attempt to predict future disease states and those which attempt to discriminate between current disease states (classification). Lastly it examines how many promising therapeutics fail due to the choice of imperfect animal models for pre-clinical testing and lack of appropriate validation studies in humans, and how future transcriptional studies may be utilised to overcome some of these limitations.

A systematic review and meta-analysis of the relationship between magnesium levels and malaria severity.

Magnesium is associated with Plasmodium infections and malaria severity. This systematic review and meta-analysis was conducted to synthesize the link between Plasmodium infections and magnesium levels for improved clinical guidance and therapeutic interventions in malaria-affected regions. A systematic literature search was conducted across multiple databases, including ProQuest, Scopus, Embase, Ovid, MEDLINE, PubMed, and Google Scholar. The risk of bias in the selected studies was assessed using the Joanna Briggs Institute critical appraisal tools. A thematic synthesis was employed to demonstrate the magnesium levels across selected studies, for analyzing and grouping based on geographic regions, age demographics, and clinical manifestations of malaria. Meta-analyses determined differences in magnesium levels between individuals with malaria, uninfected controls, and patients with different clinical severities of malaria. The effect sizes from individual studies were pooled using the random-effects model. Out of 2533 records identified, 13 studies were included in the review. The thematic synthesis revealed complex and varied results, with studies showing different magnesium levels in malaria patients across different geographies, age groups, and clinical presentations. The meta-analysis indicated elevated magnesium levels in malaria patients compared with uninfected controls (P < 0.01, Hedges' g: 1.94, 95% CI 0.86-3.03, I2: 98.38%, 9 studies). No statistically significant difference was observed in magnesium levels between patients with severe and nonsevere malaria (P: 0.34, Hedges' g: 0.62, 95% CI - 0.64-1.88, I2: 91.46%, 2 studies). A significant increase in magnesium levels was seen in patients with malaria who died compared with those who survived (P < 0.01, Hedges' g: 0.39, 95% CI 0.13-0.64, I2: 3.39%, 3 studies). This systematic review and meta-analysis presented relationship between magnesium levels and malaria. While the meta-analysis indicated a general trend of increased magnesium levels in patients with malaria, the substantial heterogeneity and instability of the results hint toward a rich yet uncharted territory requiring more research depth. The intricate interplay between magnesium levels and malaria beckons a multidimensional approach in future studies.

Increased erythroferrone levels in malarial anaemia.

We assessed the diagnostic potential of erythroferrone as a biomarker for iron homeostasis comparing iron deficiency cases with anaemia of inflammation and controls. The dysregulation of the hepcidin axis was observed by Latour et al. in a mouse model of malarial anaemia induced by prolonged Plasmodium infection leading to increased erythroferrone concentrations. In line with that, we found significantly higher erythroferrone levels in cases with malaria and anaemia in an African population, compared to asymptomatic controls. Therefore, our findings extend the previous ones of the mouse model, suggesting also a dysregulation of the hepcidin axis in humans, which should be further corroborated in prospective studies and may lay the basis for the development of improved treatment strategies according to ERFE concentrations in such patients.

Genotyping of Anopheles mosquito blood meals reveals nonrandom human host selection: implications for human-to-mosquito Plasmodium falciparum transmission.

BACKGROUND: Control of malaria parasite transmission can be enhanced by understanding which human demographic groups serve as the infectious reservoirs. Because vector biting can be heterogeneous, some infected individuals may contribute more to human-to-mosquito transmission than others. Infection prevalence peaks in school-age children, but it is not known how often they are fed upon. Genotypic profiling of human blood permits identification of individual humans who were bitten. The present investigation used this method to estimate which human demographic groups were most responsible for transmitting malaria parasites to Anopheles mosquitoes. It was hypothesized that school-age children contribute more than other demographic groups to human-to-mosquito malaria transmission. METHODS: In a region of moderate-to-high malaria incidence in southeastern Malawi, randomly selected households were surveyed to collect human demographic information and blood samples. Blood-fed, female Anopheles mosquitoes were sampled indoors from the same houses. Genomic DNA from human blood samples and mosquito blood meals of human origin was genotyped using 24 microsatellite loci. The resultant genotypes were matched to identify which individual humans were sources of blood meals. In addition, Plasmodium falciparum DNA in mosquito abdomens was detected with polymerase chain reaction. The combined results were used to identify which humans were most frequently bitten, and the P. falciparum infection prevalence in mosquitoes that resulted from these blood meals. RESULTS: Anopheles females selected human hosts non-randomly and fed on more than one human in 9% of the blood meals. Few humans contributed most of the blood meals to the Anopheles vector population. Children ≤ 5 years old were under-represented in mosquito blood meals while older males (31-75 years old) were over-represented. However, the largest number of malaria-infected blood meals was from school age children (6-15 years old). CONCLUSIONS: The results support the hypothesis that humans aged 6-15 years are the most important demographic group contributing to the transmission of P. falciparum to the Anopheles mosquito vectors. This conclusion suggests that malaria control and prevention programmes should enhance efforts targeting school-age children and males.

The effect of malaria on childhood anemia in a quasi-experimental study of 7,384 twins from 23 Sub-Saharan African countries.

Background: Young children in Sub-Saharan Africa (SSA), particularly those from resource-limited settings, are heavily burdened by anemia and malaria. While malaria infected children frequently become anemic (hemoglobin < 110 g/L), anemia is a strongly multifactorial disease with many other risk factors than malaria. Due to the complex and often overlapping contributors to anemia, it remains challenging to isolate the true impact of malaria on population level hemoglobin concentrations. Methods: We quantified the malaria-induced effect on hemoglobin levels in children under 5 years of age, leveraging data from 7,384 twins and other multiples, aged 6 to 59 months, from 57 nationally representative Demographic and Health Surveys (DHSs) from 23 SSA countries from 2006 to 2019. The quasi-experimental twin fixed-effect design let us minimize the impact of potential confounders that do not vary between twins. Results: Our analyses of twins revealed a malaria-induced hemoglobin decrease in infected twins of 9 g/L (95% CI -10; -7, p<0.001). The relative risk of severe anemia was higher (RR = 3.01, 95% CI 1.79; 5.1, p<0.001) among malaria positive children, compared to malaria negative children. Conversely, malaria positive children are only half as likely to be non-anemic (RR = 0.51, 95% CI 0.43; 0.61, p<0.001). Conclusion: Even after rigorous control for confounding through a twin fixed-effects study design, malaria substantially decreased hemoglobin levels among SSA twins, rendering them much more susceptible to severe anemia. This effect reflects the population-level effect of malaria on anemia.

A portable brightfield and fluorescence microscope toward automated malarial parasitemia quantification in thin blood smears.

Malaria is often most endemic in remote regions where diagnostic microscopy services are unavailable. In such regions, the use of rapid diagnostic tests fails to quantify parasitemia measurements which reflect the concentration of Plasmodium parasites in the bloodstream. Thus, novel diagnostic and monitoring technologies capable of providing such information could improve the quality of treatment, monitoring, and eradication efforts. A low-cost, portable microscope for gathering quantitative parasitemia data from fluorescently stained thin blood smears is presented. The system employs bimodal imaging using components optimized for cost savings, system robustness, and optical performance. The microscope is novel for its use of monochromatic visible illumination paired with a long working distance singlet aspheric objective lens that can image both traditionally mounted and cartridge-based blood smears. Eight dilutions of red blood cells containing laboratory cultured wild-type P. falciparum were used to create thin smears which were stained with SYBR Green-1 fluorescent dye. Two subsequent images are captured for each field-of-view, with brightfield images providing cell counts and fluorescence images providing parasite localization data. Results indicate the successful resolution of sub-micron sized parasites, and parasitemia measurements from the prototype microscope display linear correlation with measurements from a benchtop microscope with a limit of detection of 0.18 parasites per 100 red blood cells.

Circulating IL-6, IL-10, and TNF-alpha and IL-10/IL-6 and IL-10/TNF-alpha ratio profiles of polyparasitized individuals in rural and urban areas of gabon.

Malaria, blood-borne filarial worms and intestinal parasites are all endemic in Gabon. This geographical co-distribution leads to polyparasitism and, consequently, the possibility of immune-mediated interactions among different parasite species. Intestinal protozoa and helminths could modulate antimalarial immunity, for example, thereby potentially increasing or reducing susceptibility to malaria. The aim of the study was to compare the cytokine levels and cytokine ratios according to parasitic profiles of the population to determine the potential role of co-endemic parasites in the malaria susceptibility of populations. Blood and stool samples were collected during cross-sectional surveys in five provinces of Gabon. Parasitological diagnosis was performed to detect plasmodial parasites, Loa loa, Mansonella perstans, intestinal helminths (STHs) and protozoan parasites. Nested PCR was used to detect submicroscopic plasmodial infection in individuals with negative blood smears. A cytometric bead array was used to quantify interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-α in the plasma of subjects with different parasitological profiles. Median IL-6 and IL-10 levels and the median IL-10/TNF-α ratio were all significantly higher among individuals with Plasmodium (P.) falciparum infection than among other participants (p<0.0001). The median TNF-α level and IL-10/IL-6 ratio were higher in subjects with STHs (p = 0.09) and P. falciparum-intestinal protozoa co-infection (p = 0.04), respectively. IL-6 (r = -0.37; P<0.01) and IL-10 (r = -0.37; P<0.01) levels and the IL-10/TNF-α ratio (r = -0.36; P<0.01) correlated negatively with age. Among children under five years old, the IL-10/TNF-α and IL-10/IL-6 ratios were higher in those with intestinal protozoan infections than in uninfected children. The IL-10/TNF-α ratio was also higher in children aged 5-15 years and in adults harbouring blood-borne filariae than in their control counterparts, whereas the IL-10/IL-6 ratio was lower in those aged 5-15 years with filariae and intestinal parasites but higher in adults with intestinal parasitic infections. Asymptomatic malaria is associated with a strong polarization towards a regulatory immune response, presenting high circulating levels of IL-10. P. falciparum/intestinal protozoa co-infections were associated with an enhanced IL-10 response. Immunity against malaria could differ according to age and carriage of other parasites. Helminths and intestinal protozoa can play a role in the high susceptibility to malaria currently observed in some areas of Gabon, but further investigations are necessary.

ABO blood group and risk of malaria during pregnancy: a systematic review and meta-analysis.

The association between the ABO blood group and the risk of malaria during pregnancy has not been clearly established. The present study summarised relevant knowledge and reassessed the association through meta-analysis. Articles in MEDICINE and PubMed published before 30 November 2021 were searched. Five studies satisfied the inclusion criteria and were enrolled in the meta-analysis. It was shown that primiparae with different ABO blood group, multiparae with blood group A and non-A, AB and non-AB had a comparable risk of malaria. However, multiparae with blood group B had a significantly higher risk than non-B group [odds ratio (OR) = 1.23, 95% confidence interval (CI) was 1.01 to 1.50, P = 0.04], while multiparae with blood group O had a significantly lower risk than non-O group (OR = 0.78, 95% CI was 0.63 to 0.97, P = 0.03). Therefore, the ABO blood group may not result in a different risk of malaria in primiparae. Blood group B is potentially a risk factor while blood group O is a protective factor for multiparae.

Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger.

The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1-59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29% (hazard ratio = 0.71, 95% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger.

Review of Microdevices for Hemozoin-Based Malaria Detection.

Despite being preventable and treatable, malaria still puts almost half of the world's population at risk. Thus, prompt, accurate and sensitive malaria diagnosis is crucial for disease control and elimination. Optical microscopy and immuno-rapid tests are the standard malaria diagnostic methods in the field. However, these are time-consuming and fail to detect low-level parasitemia. Biosensors and lab-on-a-chip devices, as reported to different applications, usually offer high sensitivity, specificity, and ease of use at the point of care. Thus, these can be explored as an alternative for malaria diagnosis. Alongside malaria infection inside the human red blood cells, parasites consume host hemoglobin generating the hemozoin crystal as a by-product. Hemozoin is produced in all parasite species either in symptomatic and asymptomatic individuals. Furthermore, hemozoin crystals are produced as the parasites invade the red blood cells and their content relates to disease progression. Hemozoin is, therefore, a unique indicator of infection, being used as a malaria biomarker. Herein, the so-far developed biosensors and lab-on-a-chip devices aiming for malaria detection by targeting hemozoin as a biomarker are reviewed and discussed to fulfil all the medical demands for malaria management towards elimination.

Characterising co-infections with Plasmodium spp., Mansonella perstans or Loa loa in asymptomatic children, adults and elderly people living on Bioko Island using nucleic acids extracted from malaria rapid diagnostic tests.

BACKGROUND: Regular and comprehensive epidemiological surveys of the filarial nematodes Mansonella perstans and Loa loa in children, adolescents and adults living across Bioko Island, Equatorial Guinea are lacking. We aimed to demonstrate that blood retained on malaria rapid diagnostic tests, commonly deployed for malaria surveys, could be used as a source of nucleic acids for molecular based detection of M. perstans and L. loa. We wanted to determine the positivity rate and distribution of filarial nematodes across different age groups and geographical areas as well as to understand level of co-infections with malaria in an asymptomatic population. METHODOLOGY: M. perstans, L. loa and Plasmodium spp. parasites were monitored by qPCR in a cross-sectional study using DNA extracted from a subset malaria rapid diagnostic tests (mRDTs) collected during the annual malaria indicator survey conducted on Bioko Island in 2018. PRINCIPAL FINDINGS: We identified DNA specific for the two filarial nematodes investigated among 8.2% (263) of the 3214 RDTs screened. Positivity rates of M. perstans and L. loa were 6.6% and 1.5%, respectively. M. perstans infection were more prominent in male (10.5%) compared to female (3.9%) survey participants. M. perstans parasite density and positivity rate was higher among older people and the population living in rural areas. The socio-economic status of participants strongly influenced the infection rate with people belonging to the lowest socio-economic quintile more than 3 and 5 times more likely to be L. loa and M. perstans infected, respectively. No increased risk of being co-infected with Plasmodium spp. parasites was observed among the different age groups. CONCLUSIONS/SIGNIFICANCE: We found otherwise asymptomatic individuals were infected with M. perstans and L. loa. Our study demonstrates that employing mRDTs probed with blood for malaria testing represents a promising, future tool to preserve and ship NAs at room temperature to laboratories for molecular, high-throughput diagnosis and genotyping of blood-dwelling nematode filarial infections. Using this approach, asymptomatic populations can be reached and surveyed for infectious diseases beyond malaria.

Blood meal analysis of Anopheles vectors of simian malaria based on laboratory and field studies.

Blood feeding and host-seeking behaviors of a mosquito play an imperative role in determining its vectorial capacity in transmitting pathogens. Unfortunately, limited information is available regarding blood feeding behavior of Anopheles species in Malaysia. Collection of resting Anopheles mosquitoes for blood meal analysis poses a great challenge especially for forest dwelling mosquitoes. Therefore, a laboratory-based study was conducted to evaluate the potential use of mosquitoes caught using human landing catch (HLC) for blood meal analysis, and subsequently to document blood feeding behavior of local Anopheles mosquitoes in Peninsular Malaysia. The laboratory-based experiment from this study revealed that mosquitoes caught using HLC had the potential to be used for blood meal analysis. Besides HLC, mosquitoes were also collected using manual aspirator and Mosquito Magnet. Overall, 47.4% of 321 field-caught Anopheles mosquitoes belonging to six species were positive for vertebrate host DNA in their blood meal. The most frequent blood meal source was human (45.9%) followed by wild boar (27.4%), dog (15.3%) and monkey (7.5%). Interestingly, only Anopheles cracens and Anopheles introlatus (Leucosphyrus Group) fed on monkey. This study further confirmed that members of the Leucosphyrus Group are the predominant vectors for knowlesi malaria transmission in Peninsular Malaysia mainly due to their simio-anthropophagic feeding behavior.

Spatial cluster analysis of Plasmodium vivax and P. malariae exposure using serological data among Haitian school children sampled between 2014 and 2016.

BACKGROUND: Estimation of malaria prevalence in very low transmission settings is difficult by even the most advanced diagnostic tests. Antibodies against malaria antigens provide an indicator of active or past exposure to these parasites. The prominent malaria species within Haiti is Plasmodium falciparum, but P. vivax and P. malariae infections are also known to be endemic. METHODOLOGY/PRINCIPAL FINDINGS: From 2014-2016, 28,681 Haitian children were enrolled in school-based serosurveys and were asked to provide a blood sample for detection of antibodies against multiple infectious diseases. IgG against the P. falciparum, P. vivax, and P. malariae merozoite surface protein 19kD subunit (MSP119) antigens was detected by a multiplex bead assay (MBA). A subset of samples was also tested for Plasmodium DNA by PCR assays, and for Plasmodium antigens by a multiplex antigen detection assay. Geospatial clustering of high seroprevalence areas for P. vivax and P. malariae antigens was assessed by both Ripley's K-function and Kulldorff's spatial scan statistic. Of 21,719 children enrolled in 680 schools in Haiti who provided samples to assay for IgG against PmMSP119, 278 (1.27%) were seropositive. Of 24,559 children enrolled in 788 schools providing samples for PvMSP119 serology, 113 (0.46%) were seropositive. Two significant clusters of seropositivity were identified throughout the country for P. malariae exposure, and two identified for P. vivax. No samples were found to be positive for Plasmodium DNA or antigens. CONCLUSIONS/SIGNIFICANCE: From school-based surveys conducted from 2014 to 2016, very few Haitian children had evidence of exposure to P. vivax or P. malariae, with no children testing positive for active infection. Spatial scan statistics identified non-overlapping areas of the country with higher seroprevalence for these two malarias. Serological data provides useful information of exposure to very low endemic malaria species in a population that is unlikely to present to clinics with symptomatic infections.

Safety and Tolerability of Mosquito Bite-Induced Controlled Human Infection with Plasmodium vivax in Malaria-Naive Study Participants-Clinical Profile and Utility of Molecular Diagnostic Methods.

BACKGROUND: Plasmodium vivax controlled human malaria infection (PvCHMI) is an important tool for evaluation of drugs, vaccines, and pathologies associated with this parasite. However, there are few data on safety due to limited numbers of PvCHMIs performed. METHODS: We report clinical and laboratory data, including hematological and biochemical profiles and adverse events (AEs), following mosquito bite-induced PvCHMI in malaria-naive study participants. Malaria diagnosis and treatment initiation was based on microscopic analysis of Giemsa-stained slides. Exploratory molecular assays were used to detect parasites using real-time polymerase chain reaction (PCR). RESULTS: AEs were mild to moderate and no study-related severe AEs were observed in any study participants. The majority of symptoms were transient, resolving within 48 hours. Molecular diagnostic methods detected parasitemia in 100% of study participants before malaria diagnosis using microscopy. Of reported AEs, microscopy detected 67%-100%, quantitative PCR 79%-100%, and quantitative real-time reverse-transcription PCR 96%-100% of study participants prior to appearance of symptoms. Almost all symptoms appeared after initiation of treatment, likely as known consequence of drug treatment. CONCLUSIONS: PvCHMI is safe with the majority of infections being detected prior to appearance of clinical symptoms, which can be further alleviated by using sensitive molecular methods for clinical diagnosis. Clinical Trials Registration. NCT01157897.