CD4+ICOS+Foxp3+: a sub-population of regulatory T cells contribute to malaria pathogenesis.

BACKGROUND: Regulatory T cells are known to play a key role to counter balance the protective immune response and immune mediated pathology. However, the role of naturally occurring regulatory cells CD4+CD25+Foxp3+ in malaria infection during the disease pathogenesis is controversial. Beside this, ICOS molecule has been shown to be involved in the development and function of regulatory T cell enhance IL-10 production. Therefore, possible involvement of the ICOS dependent regulatory CD4+ICOS+Foxp3+ T cells in resistance/susceptibility during malaria parasite is explored in this study. METHODS: 5 × 105 red blood cells infected with non-lethal and lethal parasites were inoculated in female Balb/c mice by intra-peritoneal injection. Infected or uninfected mice were sacrificed at early (3rd day post infection) and later stage (10th day post infection) of infection. Harvested cells were analysed by using flow cytometer and serum cytokine by Bioplex assay. RESULTS: Thin blood films show that percentages of parasitaemia increases with disease progression in infections with the lethal malaria parasite and mice eventually die by day 14th post-infection. Whereas in case of non-lethal malaria parasite, parasitaemia goes down by 7th day post infection and gets cleared within 13th day. The number of CD4+ ICOS+ T cells increases in lethal infection with disease progression. Surprisingly, in non-lethal parasite, ICOS expression decreases after day 7th post infection as parasitaemia goes down. The frequency of CD4+ICOS+FoxP3+ Tregs was significantly higher in lethal parasitic infection as compared to the non-lethal parasite. The level of IL-12 cytokine was remarkably higher in non-lethal infection compared to the lethal infection. In contrast, the level of IL-10 cytokines was higher in lethal parasite infection compared to the non-lethal parasite. CONCLUSION: Taken together, these data suggest that lethal parasite induce immunosuppressive environment, protecting from host immune responses and help the parasite to survive whereas non-lethal parasite leads to low frequencies of Treg cells seldom impede immune response that allow the parasite to get self-resolved.

Imported Malaria in Countries where Malaria Is Not Endemic: a Comparison of Semi-immune and Nonimmune Travelers.

The continuous increase in long-distance travel and recent large migratory movements have changed the epidemiological characteristics of imported malaria in countries where malaria is not endemic (here termed non-malaria-endemic countries). While malaria was primarily imported to nonendemic countries by returning travelers, the proportion of immigrants from malaria-endemic regions and travelers visiting friends and relatives (VFRs) in malaria-endemic countries has continued to increase. VFRs and immigrants from malaria-endemic countries now make up the majority of malaria patients in many nonendemic countries. Importantly, this group is characterized by various degrees of semi-immunity to malaria, resulting from repeated exposure to infection and a gradual decline of protection as a result of prolonged residence in non-malaria-endemic regions. Most studies indicate an effect of naturally acquired immunity in VFRs, leading to differences in the parasitological features, clinical manifestation, and odds for severe malaria and clinical complications between immune VFRs and nonimmune returning travelers. There are no valid data indicating evidence for differing algorithms for chemoprophylaxis or antimalarial treatment in semi-immune versus nonimmune malaria patients. So far, no robust biomarkers exist that properly reflect anti-parasite or clinical immunity. Until they are found, researchers should rigorously stratify their study results using surrogate markers, such as duration of time spent outside a malaria-endemic country.

Risk factors associated with house entry of malaria vectors in an area of Burkina Faso with high, persistent malaria transmission and high insecticide resistance.

BACKGROUND: In rural Burkina Faso, the primary malaria vector Anopheles gambiae sensu lato (s.l.) primarily feeds indoors at night. Identification of factors which influence mosquito house entry could lead to development of novel malaria vector control interventions. A study was therefore carried out to identify risk factors associated with house entry of An. gambiae s.l. in south-west Burkina Faso, an area of high insecticide resistance. METHODS: Mosquitoes were sampled monthly during the malaria transmission season using CDC light traps in 252 houses from 10 villages, each house sleeping at least one child aged five to 15 years old. Potential risk factors for house entry of An. gambiae s.l. were measured, including socio-economic status, caregiver's education and occupation, number of people sleeping in the same part of the house as the child, use of anti-mosquito measures, house construction and fittings, proximity of anopheline aquatic habitats and presence of animals near the house. Mosquito counts were compared using a generalized linear mixed-effect model with negative binomial and log link function, adjusting for repeated collections. RESULTS: 20,929 mosquitoes were caught, of which 16,270 (77.7%) were An. gambiae s.l. Of the 6691 An. gambiae s.l. identified to species, 4101 (61.3%) were An. gambiae sensu stricto and 2590 (38.7%) Anopheles coluzzii. Having a metal-roof on the child's sleeping space (IRR = 0.55, 95% CI 0.32-0.95, p = 0.03) was associated with fewer malaria vectors inside the home. CONCLUSION: This study demonstrated that the rate of An. gambiae s.l. was 45% lower in sleeping spaces with a metal roof, compared to those with thatch roofs. Improvements in house construction, including installation of metal roofs, should be considered in endemic areas of Africa to reduce the burden of malaria.

The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease.

Cholesterol homeostasis is essential in normal physiology of all cells. One of several proteins involved in cholesterol homeostasis is the ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein widely expressed in many tissues. One of its main functions is the efflux of intracellular free cholesterol and phospholipids across the plasma membrane to combine with apolipoproteins, mainly apolipoprotein A-I (Apo A-I), forming nascent high-density lipoprotein-cholesterol (HDL-C) particles, the first step of reverse cholesterol transport (RCT). In addition, ABCA1 regulates cholesterol and phospholipid content in the plasma membrane affecting lipid rafts, microparticle (MP) formation and cell signaling. Thus, it is not surprising that impaired ABCA1 function and altered cholesterol homeostasis may affect many different organs and is involved in the pathophysiology of a broad array of diseases. This review describes evidence obtained from animal models, human studies and genetic variation explaining how ABCA1 is involved in dyslipidemia, coronary heart disease (CHD), type 2 diabetes (T2D), thrombosis, neurological disorders, age-related macular degeneration (AMD), glaucoma, viral infections and in cancer progression.

Environmental and anthropogenic factors associated with increased malaria incidence in South-Kivu Province, Democratic Republic of the Congo.

OBJECTIVE: To examine environmental and human factors that affect the spatial and temporal dynamism of malaria in DRC's South-Kivu province. METHODS: In a cross-sectional study conducted between 1 January 2010 and 31 December 2015, spatial distribution was determined through thematic maps of malaria attack rate. SatScan ™ software and Monte Carlo test were used to identify spatial risk clusters. Temporal evolutions were analysed using the Cleveland algorithm. Generalized Additive Models for Location Scale and Shape and negative binomial regression were used to assess the independent human and environmental factors associated with incident malaria. RESULTS: The cumulative annual incidence of malaria increased from 10 968/100 000 in 2013 to 15 501/100 000 in 2015 (P for trend ˂0.001); malaria lethality increased from 0.1% in 2013 to 0.3% in 2015 (P for trend = 0.62). Between 2010 and 2015, 18 of 34 health zones consistently reported the highest attack rates, which ranged from 25 000 to 50 000/100 000. Four risk clusters areas were identified, with relative risk (RR) of 1.2 to 3.0, from which malaria was reported continuously during each year. Factors significantly associated with malaria cases were agro-pisciculture practices (Incidence Risk Ratio [IRR]: 1.96; 95% CI: 1.23-3.13) and the presence of a lake in the health zone (IRR: 2.48, 95% CI: 1.51-4.42). CONCLUSIONS: Malaria control in this setting must be intensified in peri-lacustrine areas and those in which the population is intensively engaged in standing water-associated activities.

OBJECTIF: Examiner les facteurs environnementaux et humains qui affectent le dynamisme spatial et temporel du paludisme dans la province du Sud-Kivu en RDC. MÉTHODES: Dans une étude transversale menée entre le 1er janvier 2010 et le 31 décembre 2015, la distribution spatiale a été déterminée à l'aide de cartes thématiques du taux de cas de paludisme. Le logiciel SatScan™ et le test Monte Carlo ont été utilisés pour identifier les grappes de risques spatiaux. Les évolutions temporelles ont été analysées à l'aide de l'algorithme de Cleveland. Des modèles additifs généralisés pour l'échelle et la forme de l'emplacement et la régression binomiale négative ont été utilisés pour évaluer les facteurs humains et environnementaux indépendants associés à l'incidence du paludisme. RÉSULTATS: L'incidence annuelle cumulée du paludisme est passée de 10.968/100 000 en 2013 à 15.501/100 000 en 2015 (p pour la tendance ˂0,001); la létalité du paludisme est passée de 0,1% en 2013 à 0,3% en 2015 (p pour tendance = 0,62). Entre 2010 et 2015, 18 des 34 zones de santé ont constamment rapporté des taux de cas les plus élevés, qui variaient de 25.000 à 50.000/100 000. Quatre zones de risques de grappes ont été identifiées, avec un risque relatif (RR) de 1,2 à 3,0 à partir desquelles le paludisme a été rapporté en continu chaque année. Les facteurs significativement associés aux cas de paludisme étaient: les pratiques agro-piscicoles (Ratio d'Incidence de Risque [IRR]: 1,96 ; IC95%: 1,23-3,13) et la présence d'un lac dans la zone de santé (TRI: 2,48 ; IC95%: 1,51-4,42). CONCLUSIONS: La lutte contre le paludisme dans ce contexte doit être intensifiée dans les zones péri-lacustres et celles dans lesquelles la population est intensément engagée dans des activités liées à l'eau stagnante.

Levels of knowledge regarding malaria causes, symptoms, and prevention measures among Malawian women of reproductive age.

BACKGROUND: Malawi is a malaria-endemic country and approximately 6 million cases are reported annually. Improving knowledge of malaria causes and symptoms, and the overall perception towards malaria and its preventive measures is vital for malaria control. The current study investigated the levels of knowledge of the causes, symptoms and prevention of malaria among Malawian women. METHODS: Data from the 2017 wave of the Malawi Malaria Indicator Survey (MMIS) were analysed. In total, 3422 women of reproductive age (15-49 years) were sampled and analysed. The levels of women's knowledge about: (1) causes of malaria; (2) symptoms of malaria; and, (3) preventive measures were assessed. The tertiles of the composite score were used as the cut-offs to categorize the levels of knowledge as 'low', 'medium' and 'high'. Multinomial logistic regression models were constructed to assess the independent factors while taking into account the complex survey design. RESULTS: Approximately 50% of all respondents had high levels of knowledge of causes, symptoms and preventive measures. The high level of knowledge was 45% for rural women and 55% for urban dwellers. After adjusting for the a wide range of factors, women of age group 15-19 years adjusted odds ratio ((aOR): 2.58; 95% Confidence Interval (CI) 1.69-3.92), women with no formal education (aOR: 3.73; 95% CI 2.20-6.33), women whose household had no television (aOR: 1.50; 95% CI 1.02-2.22), women who had not seen/heard malaria message (aOR: 1.53; 95% CI 1.20-1.95), women of Yao tribe (aOR: 1.95; 95% CI 1.10-3.46), and women from rural areas had low levels of knowledge about the causes of malaria, symptoms of malaria and preventive measures. Additionally, the results also showed that women aged 15-19 years (beta [ß] = - 0.73, standard error [SE] = 0.12); P < .0001, women with no formal education (ß = - 1.17, SE = 0.15); P < .0001, women whose household had no radio (ß = - 0.15, SE = 0.0816); P = 0.0715 and women who had not seen or heard malaria message (ß = - 0.41, SE = 0.07); P < .0001 were likely to have a lower knowledge score. CONCLUSIONS: The levels of malaria knowledge were reported to be unsatisfactory among adult women, underscoring the need to scale up efforts on malaria education. Beside insecticide-treated bed nets (ITNs) and prompt diagnosis, malaria can be best managed in Malawi by increasing knowledge of malaria causes, and symptoms especially for younger women, women with no formal education, women whose households have no media, women from Yao tribes, and rural dwellers.

The Effect of ABO Blood Groups, Hemoglobinopathy, and Heme Oxygenase-1 Polymorphisms on Malaria Susceptibility and Severity.

Malaria is one of the most important public health problems in tropical areas on the globe. Several factors are associated with susceptibility to malaria and disease severity, including innate immunity such as blood group, hemoglobinopathy, and heme oxygenase-1 (HO-1) polymorphisms. This study was carried out to investigate association among ABO blood group, thalassemia types and HO-1 polymorphisms in malaria. The malarial blood samples were collected from patients along the Thai-Myanmar border. Determination of ABO blood group, thalassemia variants, and HO-1 polymorphisms were performed using agglutination test, low pressure liquid chromatography and polymerase chain reaction, respectively. Plasmodium vivax was the major infected malaria species in the study samples. Distribution of ABO blood type in the malaria-infected samples was similar to that in healthy subjects, of which blood type O being most prevalent. Association between blood group A and decreased risk of severe malaria was significant. Six thalassemia types (30%) were detected, i.e., hemoglobin E (HbE), ß-thalassemia, α-thalassemia 1, α-thalassemia 2, HbE with α-thalassemia 2, and ß-thalassemia with α-thalassemia 2. Malaria infected samples without thalassemia showed significantly higher risk to severe malaria. The prevalence of HO-1 polymorphisms, S/S, S/L and L/L were 25, 62, and 13%, respectively. Further study with larger sample size is required to confirm the impact of these 3 host genetic factors in malaria patients.

An analysis of the influence of the local effects of climatic and hydrological factors affecting new malaria cases in riverine areas along the Rio Negro and surrounding Puraquequara Lake, Amazonas, Brazil.

A study was conducted at three sampling regions along the Rio Negro and surrounding Puraquequara Lake, Amazonas, Brazil. The aim was to determine the influence of the local effects of climatic and hydrological variables on new malaria cases. Data was gathered on the river level, precipitation, air temperature, and the number of new cases of autochthonous malaria between January 2003 and December 2013. Monthly averages, time series decompositions, cross-correlations, and multiple regressions revealed different relationships at each location. The sampling region in the upper Rio Negro indicated no statistically significant results. However, monthly averages suggest that precipitation and air temperature correlate positively with the occurrence of new cases of malaria. In the mid Rio Negro and Puraquequara Lake, the river level positively correlated, and temperature negatively correlated with new transmissions, while precipitation correlated negatively in the mid Rio Negro and positively on the lake. Overall, the river level is a key variable affecting the formation of breeding sites, while precipitation may either develop or damage them. A negative temperature correlation is associated with the occurrence of new annual post-peak cases of malaria, when the monthly average exceeds 28.5 °C. This suggests that several factors contribute to the occurrence of new malaria cases as higher temperatures are reached at the same time as precipitation and the river levels are lowest. Differences between signals and correlation lags indicate that local characteristics have an impact on how different variables influence the disease vector's life cycle, pathogens, and consequently, new cases of malaria.

Safety and benefits of antenatal oral iron supplementation in low-income countries: a review.

The World Health Organization recommends universal iron supplementation of 30-60 mg/day in pregnancy but coverage is low in most countries. Its efficacy is uncertain, however, and there has been a vigorous debate in the last decade about its safety, particularly in areas with a high burden of malaria and other infectious diseases. We reviewed the evidence on the safety and efficacy of antenatal iron supplementation in low-income countries. We found no evidence that daily supplementation at a dose of 60 mg leads to increased maternal Plasmodium infection risk. On the other hand, recent meta-analyses found that antenatal iron supplementation provides benefits for maternal health (severe anaemia at postpartum, blood transfusion). For neonates, there was a reduced prematurity risk, and only a small or no effect on birth weight. A recent trial showed, however, that benefits of antenatal iron supplementation on maternal and neonatal health vary by maternal iron status, with substantial benefits in iron-deficient women. The benefits of universal iron supplementation are likely to vary with the prevalence of iron deficiency. As a consequence, the balance between benefits and risks is probably more favourable in low-income countries than in high-income countries despite the higher exposure to infectious pathogens.

High Iron Stores in the Low Malaria Season Increase Malaria Risk in the High Transmission Season in a Prospective Cohort of Rural Zambian Children.

Background: Higher iron stores, defined by serum ferritin (SF) concentration, may increase malaria risk.Objective: We evaluated the association between SF assessed during low malaria season and the risk of malaria during high malaria season, controlling for inflammation.Methods: Data for this prospective study were collected from children aged 4-8 y (n = 745) participating in a biofortified maize efficacy trial in rural Zambia. All malaria cases were treated at baseline (September 2012). We used baseline SF and malaria status indicated by positive microscopy at endline (March 2013) to define exposure and outcome, respectively. Iron status was defined as deficient (corrected or uncorrected SF <12 or <15 µg/L, depending on age <5 or ≥5 y, respectively), moderate (<75 µg/L, excluding deficient), or high (≥75 µg/L). We used a modified Poisson regression to model the risk of malaria in the high transmission seasons (endline) as a function of iron status assessed in the low malaria seasons (baseline).Results: We observed an age-dependent, positive dose-response association between ferritin in the low malaria season and malaria incidence during the high malaria season in younger children. In children aged <6 y (but not older children), we observed a relative increase in malaria risk in the moderate iron status [incidence rate ratio (IRR) with SF: 1.56; 95% CI: 0.64, 3.86; IRR with inflammation-corrected SF: 1.92; 95% CI: 0.75, 4.93] and high iron status (IRR with SF: 2.66; 95% CI: 1.10, 6.43; or IRR with corrected SF: 2.93; 95% CI: 1.17, 7.33) categories compared with the deficient iron status category. The relative increase in malaria risk for children with high iron status was statistically significant only among those with a concurrently normal serum soluble transferrin receptor concentration (<8.3 mg/L; IRR: 1.97; 95% CI: 1.20, 7.37).Conclusions: Iron adequacy in 4- to 8-y-old children in rural Zambia was associated with increased malaria risk. Our findings underscore the need to integrate iron interventions with malaria control programs. This trial was registered at clinicaltrials.gov as NCT01695148.

Caretakers' understanding of malaria, use of insecticide treated net and care seeking-behavior for febrile illness of their children in Ethiopia.

BACKGROUND: Local understandings of malaria and use of preventive measures-are critical factors in sustained control of malaria. This study assessed caretakers' knowledge on malaria, use of Long Lasting Insecticide Treated Nets (LLINs) and care-seeking behavior for their children's illness in different malaria transmission settings of Ethiopia. METHODS: Data were collected from 709 caretakers of children of 2-9 years of age during in 2016. A standard questionnaire was used to assess caretakers' perceptions of malaria, use of LLIN and care seeking behavior for febrile illness of children aged 2-9 years. RESULTS: The caretakers recognized malaria mostly by chills (70.4%, 499/709), fever (45.7%, 324/709) and headache (39.8%, 282/709). Overall, only 66.4% (471) of the caretakers knew that mosquito bite caused malaria and that it was quite heterogeneous by localities (ranging from 26.1% to 89.4%) and altitude (p < 0.05). Majority, 72.2% (512), of the caretakers knew that sleeping under LLIN could prevent malaria. Overall knowledge on malaria (mean = 51.2%) was very low with significant variations by localities, altitude and levels of malaria transmission, being low in high altitude and low in transmission areas (p < 0.05). Four hundred ninety-one (69.3%, 491/709) of the children slept under LLIN in the previous night. Of malaria related knowledge items, only knowledge of LLIN was associated with net use; non-use of LLN was higher among caretakers who did not know the role of LLIN (AOR = 0.47, 95%CI: 0.28-0.77, p = 0.003). Of course, attributing causation of malaria to stagnant water discouraged use of net (p = 0.021). Of febrile children (n = 122), only 50 (41.0%) sought care with only 17 (34.0%) seeking the care promptly. There was no significant link between knowledge of malaria and care seeking behavior (p > 0.05). However, knowledge of malaria had some level of influence on treatment source preference where caretakers with greater knowledge preferred pharmacy as source of care. CONCLUSIONS: The findings demonstrated that caretakers' understanding of malaria was unsatisfactory with marked heterogeneity by localities. The present evidence suggests that knowledge is not sufficient enough to drive LLIN use and care seeking. Yet, context-specific health education interventions are important besides ensuring access to necessary preventive tools.

Epidemiological and clinical profile of paediatric malaria: a cross sectional study performed on febrile children in five epidemiological strata of malaria in Cameroon.

BACKGROUND: In the wake of a decline in global malaria, it is imperative to describe the epidemiology of malaria in a country to inform control policies. The purpose of this study was to describe the epidemiological and clinical profile of paediatric malaria in five epidemiological strata of malaria in Cameroon including: the Sudano-sahelian (SS) strata, the High inland plateau (HIP) strata, the South Cameroonian Equatorial forest (SCEF) strata, the High western plateau (HWP) strata, and the Coastal (C) strata. METHODS: This study involved 1609 febrile children (≤15 years) recruited using reference hospitals in the five epidemiological strata. Baseline characteristics were determined; blood glucose level was measured by a glucometer, malaria parasitaemia was assessed by Giemsa microscopy, and complete blood count was performed using an automated hematology analyser. Severe malaria was assessed and categorized based on WHO criteria. RESULTS: An overall prevalence of 15.0% (95% CI: 13.3-16.9) for malaria was observed in this study. Malaria prevalence was significantly higher in children between 60 and 119 months (p < 0.001) and in Limbe (C strata) (p < 0.001). The overall rate of severe malaria (SM) attack in this study was 29.3%; SM was significantly higher in children below 60 months (p < 0.046). Although not significant, the rate of SM was highest in Maroua (SS strata) and lowest in Limbe in the C strata. The main clinical phenotypes of SM were hyperparasitaemia, severe malaria anaemia and impaired consciousness. The majority (73.2%) of SM cases were in group 1 of the WHO classification of severe malaria (i.e. the most severe form). The malaria case-fatality rate was 5.8%; this was higher in Ngaoundere (HIP strata) (p = 0.034). CONCLUSION: In this study, malaria prevalence decreased steadily northward, from the C strata in the South to the SS strata in the North of Cameroon, meanwhile the mortality rate associated with malaria increased in the same direction. On the contrary, the rate of severe malaria attack was similar across the different epidemiological strata. Immunoepidemiological studies will be required to shed more light on the observed trends.

The correlation between malaria RDT (Paracheck pf.®) faint test bands and microscopy in the diagnosis of malaria in Malawi.

BACKGROUND: Faint test bands of Paracheck Pf.® are interpreted as malaria positive according to world health organization (WHO) guideline. However if there are conspicuous number of faint test bands, a performance of Paracheck Pf.® could be influenced depending on whether interpreting faint test bands as malaria positive or negative. Finding out the frequency and accurate interpretation of faint test bands are important to prevent the overdiagnosis and drug resistance. METHODS: A cross-sectional, descriptive study was conducted to find out the frequency of faint test bands and evaluate the performance of Paracheck Pf.® by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of diagnosis of Paracheck Pf.® using microscopy as the gold standard. 388 suspected patients with malaria in Malawi were recruited in this study. Malaria rapid diagnostic tests (RDTs) and microscopy were used and patients' information which includes age, sex, body temperature and signs or symptoms of malaria were recorded. RESULTS: Among all patients involved in the study, 29.1% (113/388) were found malaria positive by RDT. Overall 5.4% (21/388) of all Paracheck Pf.® tests resulted in a "faint test band" and 85.7% (18/21) corresponded with malaria negative by microscopy. Faint test bands which corresponded with malaria positive by microscopy were lower parasite density and there are no patients who showed definitive symptom of malaria, such as fever. When Paracheck Pf.® "faint test bands" were classified as positive, accuracy of diagnosis was 76.5% (95% CI 72%-80.7%) as compared to 80.4% (95% CI 76.1%-84.2%) when Paracheck Pf.® "faint test bands" were classified as negative. CONCLUSIONS: This study shows that frequency of faint test bands is 5.4% in all malaria RDTs. The accuracy of diagnosis was improved when faint test bands were interpreted as malaria negative. However information and data obtained in this study may not be enough and more intensive research including a frequency and property of faint test bands is needed for significant interpretation of faint test bands.

Prevalence and associated risk factors of malaria among adults in East Shewa Zone of Oromia Regional State, Ethiopia: a cross-sectional study.

BACKGROUND: Malaria is one of the most important causes of morbidity and mortality in sub-Saharan Africa. The disease is prevalent in over 75% of the country's area making it the leading public health problems in the country. Information on the prevalence of malaria and its associated factors is vital to focus and improve malaria interventions. METHODS: A cross-sectional study was carried out from October to November 2012 in East Shewa zone of Oromia Regional State, Ethiopia. Adults aged 16 or more years with suspected malaria attending five health centers were eligible for the study. Logistic regression models were used to examine the effect of each independent variable on risk of subsequent diagnosis of malaria. RESULTS: Of 810 suspected adult malaria patients who participated in the study, 204 (25%) had microscopically confirmed malaria parasites. The dominant Plasmodium species were P. vivax (54%) and P. falciparum (45%), with mixed infection of both species in one patient. A positive microscopic result was significantly associated with being in the age group of 16 to 24 years [Adjusted Odds Ratio aOR 6.7; 95% CI: 2.3 to 19.5], 25 to 34 years [aOR 4.2; 95% CI: 1.4 to 12.4], and 35 to 44 years [aOR 3.7; 95% CI: 1.2-11.4] compared to 45 years or older; being treated at Meki health center [aOR 4.1; 95% CI: 2.4 to 7.1], being in Shashemene health center [aOR = 2.3; 95% CI: 1.5 to 4.5], and living in a rural area compared to an urban area [aOR 1.7; 95% CI: 1.1 to 2.6)]. CONCLUSION: Malaria is an important public health problem among adults in the study area with a predominance of P. vivax and P. falciparum infection. Thus, appropriate health interventions should be implemented to prevent and control the disease.

Transfusion-transmitted malaria not preventable by current blood donor screening guidelines: a case report.

BACKGROUND: Transfusion-transmitted malaria (TTM) is a well-known, though rare, entity in the United States with only 100 cases previously reported. With no Food and Drug Administration-approved screening tests of donated blood for malaria in the United States, prevention relies solely on deferral of the highest-risk donors. We present a case of TTM not preventable by these guidelines. CASE REPORT: A 76-year-old male presented with fever, hypotension, tachycardia, and a urinalysis consistent with a urinary tract infection. He was admitted to the intensive care unit and initiated on broad-spectrum antibiotics. On Hospital Day 2, he was incidentally found to have intraerythrocytic parasites on a peripheral smear, identified as Plasmodium malariae by polymerase chain reaction and was treated successfully with atovaquone-proguanil. The patient had no recent foreign travel or exposure to malaria but had received 15 units of blood products in the past 6 years. Index samples from the 10 most recent units were obtained, with one testing positive for P. malariae via serology. The donor was a 20-year-old male who immigrated to the United States from Liberia at the age of 5 with no subsequent travel or exposure to malaria. DISCUSSION: A review of current literature demonstrated that 71% of TTM cases occur from imperfect application of the current deferral guidelines. In this case, however, 15 years had elapsed between the donor's immigration and the transmission of the disease, placing him well outside any current deferral period. As such, the case demonstrates the need for continued development of highly sensitive and cost-effective laboratory screening for high-risk donors.

A retrospective chart review study to describe selected zoonotic and arboviral etiologies in hospitalized febrile patients in the Republic of Armenia.

BACKGROUND: Scant information is available on the infectious causes of febrile illnesses in Armenia. The goal of this study was to describe the most common causes, with a focus on zoonotic and arboviral infections and related epidemiological and clinical patterns for hospitalized patients with febrile illnesses of infectious origin admitted to Nork Infectious Diseases Clinical Hospital, the referral center for infectious diseases in the capital city, Yerevan. METHOD: A chart review study was conducted in 2014. Data were abstracted from medical charts of adults (≥18 years) with a fever (≥38 °C), who were hospitalized (for ≥24 h) in 2010-2012. RESULTS: Of the 600 patients whose charts were analyzed, 76 % were from Yerevan and 51 % were male; the mean age (± standard deviation) was 35.5 (±16) years. Livestock exposure was recorded in 5 % of charts. Consumption of undercooked meat and unpasteurized dairy products were reported in 11 and 8 % of charts, respectively. Intestinal infections (51 %) were the most frequently reported final medical diagnoses, followed by diseases of the respiratory system (11 %), infectious mononucleosis (9.5 %), chickenpox (8.3 %), brucellosis (8.3 %), viral hepatitis (3.2 %), and erysipelas (1.5 %). Reviewed medical charts included two cases of fever of unknown origin (FUO), two cutaneous anthrax cases, two leptospirosis cases, three imported malaria cases, one case of rickettsiosis, and one case of rabies. Engagement in agricultural activities, exposure to animals, consumption of raw or unpasteurized milk, and male gender were significantly associated with brucellosis. CONCLUSION: Our analysis indicated that brucellosis was the most frequently reported zoonotic disease among hospitalized febrile patients. Overall, these study results suggest that zoonotic and arboviral infections were not common etiologies among febrile adult patients admitted to the Nork Infectious Diseases Clinical Hospital in Armenia.

Malarial hemozoin: from target to tool.

BACKGROUND: Malaria is an extremely devastating disease that continues to affect millions of people each year. A distinctive attribute of malaria infected red blood cells is the presence of malarial pigment or the so-called hemozoin. Hemozoin is a biocrystal synthesized by Plasmodium and other blood-feeding parasites to avoid the toxicity of free heme derived from the digestion of hemoglobin during invasion of the erythrocytes. SCOPE OF REVIEW: Hemozoin is involved in several aspects of the pathology of the disease as well as in important processes such as the immunogenicity elicited. It is known that the once best antimalarial drug, chloroquine, exerted its effect through interference with the process of hemozoin formation. In the present review we explore what is known about hemozoin, from hemoglobin digestion, to its final structural analysis, to its physicochemical properties, its role in the disease and notions of the possible mechanisms that could kill the parasite by disrupting the synthesis or integrity of this remarkable crystal. MAJOR CONCLUSIONS: The importance and peculiarities of this biocrystal have given researchers a cause to consider it as a target for new antimalarials and to use it through unconventional approaches for diagnostics and therapeutics against the disease. GENERAL SIGNIFICANCE: Hemozoin plays an essential role in the biology of malarial disease. Innovative ideas could use all the existing data on the unique chemical and biophysical properties of this macromolecule to come up with new ways of combating malaria.

Fevered Decisions: Race, Ethics, and Clinical Vulnerability in the Malarial Treatment of Neurosyphilis, 1922-1953.

Physicians deliberately inoculated marginalized patients with malaria, using them as reservoirs to facilitate malarial fever therapy for syphilitic patients. The history presents ethical questions in an evolving historical context.

Semiparametric models for malaria rapid diagnosis test result.

BACKGROUND: More than 75% of the total of Ethiopia is malarious. Therefore, malaria is a leading public health problem in Ethiopia. This study aims to identify socio-economic, geographic and demographic factors contributing to the spread of malaria and is based on the results of a malaria Rapid Diagnosis Test survey. METHODS: The data used in this study originates from the baseline malaria indicator survey, conducted in the Amhara, Oromiya and Southern Nation Nationalities and People (SNNP) regions of Ethiopia from December 2006 to January 2007. The study applies the method of generalized additive mixed model (GAMM) to analyse data. The response variable is the presence or absence of malaria, using the malaria Rapid Diagnosis Test (RDT). RESULTS: The results provide an improved insight into the distribution of malaria in relation to the age of affected people, the altitude, the total number of rooms, the total number of mosquito nets, family size, and the number of months that their rooms have been sprayed. The results confirm that positive malaria RDT test results are high for children under 15 years and for older persons. Gender, source of drinking water, time needed to fetch water, toilet facilities, main materials used for the construction of walls, floors and roofs, and use of mosquito nets were all found to have a significant impact on the results of the malaria rapid diagnosis test. CONCLUSION: The result of the analysis identifies poor socio-economic conditions as a major contributing factor or determinant for the spread of malaria. With the correct use of mosquito nets, indoor residual spraying with insecticide and other preventative measures, the incidence of malaria could be decreased. In addition, improving housing conditions is a means to reduce the risk of malaria. Other measures such as creating awareness of the use of mosquito nets, indoor residual spraying with insecticide, and malaria transmission, can lead to a further reduction in the number of malaria cases.