Practices of herbal management of malaria among trading mothers in Shai Osudoku District, Accra.

BACKGROUND: Malaria is one of the leading causes of morbidity in the world. It is a significant health concern in most developing countries, including Ghana. Even though there are several orthodox medications used for decades in treating malaria effectively, a substantial number of individuals in developing countries are resorting to the use of herbs in the treatment of malaria. The study aim at exploring the practices of herbal management of malaria among trading mothers in Shai Osudoku District, Accra. METHODS: A qualitative approach with an exploratory, descriptive design was adopted in analyzing the research problem. Purposive sampling technique was used to select twenty (20) participants to partake in a face-face interview, guided by a semi-structured interview guide. The data were transcribed verbatim and analysed by adopting content analysis. RESULTS: Two significant themes and seven subthemes were generated following the analysis of this study. The main themes were; preferences for herbal malaria treatment and the practices and effectiveness of herbal medicine used for malaria treatment. It was worth noting that the women's cultural beliefs did not influence their preference for herbal malaria treatment. The main challenge associated with the herbal malaria treatment was inappropriate dosage specification. CONCLUSION: This study discovered that several factors influenced participants' preferences for malaria treatment. Participants further listed some traditional ways of treating malaria which implies that there is herbal malaria practice. However, literature in this area is inadequate, and most herbs lack specifications for use. It is therefore recommended that future research focus on scientific herbal malaria treatment. Also, regulating bodies should ensure that quality herbal drugs are sold for consumption.

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.

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.

Proximity of Residence to Irrigation Determines Malaria Risk and Anopheles Abundance at an Irrigated Agroecosystem in Malawi.

As countries of sub-Saharan Africa expand irrigation to improve food security and foster economic growth, it is important to quantify the malaria risk associated with this process. Irrigated ecosystems can be associated with increased malaria risk, but this relationship is not fully understood. We studied this relationship at the Bwanje Valley Irrigation Scheme (800 hectares) in Malawi. Household prevalence of malaria and indoor Anopheles density were quantified in two cross-sectional studies in 2016 and 2017 (5,829 residents of 1,091 households). Multilevel logistic regression was used to estimate the association between distance to the irrigation scheme and malaria infection and mosquito density. The prevalence of malaria infection was 50.2% (2,765/5,511) by histidine-rich protein 2-based malaria rapid diagnostic tests and 30.1% (1,626/5,403) by microscopy. Individuals residing in households within 3 km of the scheme had significantly higher prevalence of infection (adjusted odds ratio [aOR] = 1.41; 95% confidence interval [CI] 1.18, 1.68); school-aged children had the highest prevalence among age groups (aOR = 1.34; 95% CI 1.11, 1.63). Individuals who reported bed net use, and households with higher socioeconomic status and higher level of education for household head or spouse, had lower odds of malaria infection. Female Anopheles mosquitoes (2,215 total; Anopheles arabiensis, 90.5%, Anopheles funestus, 9.5%) were significantly more abundant in houses located within 1.5 km of the scheme. Proximity of human dwellings to the irrigation scheme increased malaria risk, but higher household wealth index reduced risk. Therefore, multisectoral approaches that spur economic growth while mitigating increased malaria transmission are needed for people living close to irrigated sites.

Smart Safety Surveillance (3S): Multi-Country Experience of Implementing the 3S Concepts and Principles.

INTRODUCTION: The Smart Safety Surveillance (3S) concept is based on the understanding that, when faced with competing pharmacovigilance priorities, countries will have to invest judiciously, by focusing on new priority products, sharing work and resources with other countries when possible and building national competence for those activities that cannot be delegated. METHOD: The 3S principles were applied to Armenia, Brazil, Ethiopia, India, Peru and Thailand using three priority products: bedaquiline, rotavirus vaccine and tafenoquine. A baseline assessment of pharmacovigilance preparedness was used to identify gaps and establish a work plan. The impact was measured by comparing pre and post 3S-intervention outcomes, which included the number and quality of reports (completeness scores) in the WHO global database of Individual Case Safety Reports, VigiBase, and number of structural indicators met. The implementation period was 9-18 months, ranging from March 2018 (earliest started) until May 2020 (latest). RESULT: An increase in adverse drug reaction (ADR) reporting was demonstrated in Armenia (bedaquiline), Brazil (TB and malaria medicines), India (rotavirus vaccine) and Ethiopia (TB medicines). Completeness scores were above 0.5 at baseline in all countries, and reports improved in quality for Brazil (TB), Peru (malaria), Thailand (malaria) and India (immunization). The number of structural indicators met increased by more than double for Ethiopia. Ethiopia and India demonstrated an increased capacity for signal detection and signal evaluation. Armenia, Brazil, Peru and Thailand showed increased capacity to assess risk management plans following the implementation of 3S principles. CONCLUSION: The 3S concept has demonstrated success in different ways across the six countries. Activities focused on three products for a proof of concept of the 3S principles, with the expectation that the project impact will be sustained through strengthened systems, to guide pharmacovigilance activities of other products in the future. It is important to continue monitoring the countries to understand if the gains and successes of the current 3S project are sustainable.

The high risk of malarial recurrence in patients with Plasmodium-mixed infection after treatment with antimalarial drugs: a systematic review and meta-analysis.

BACKGROUND: Malaria mixed infections are often unrecognized by microscopists in the hospitals, and a delay or failure to treat Plasmodium-mixed infection may lead to aggravated morbidity and increased mortality. The present study aimed to quantify the pooled proportion and risk of malarial recurrences after the treatment of Plasmodium-mixed infection. The results of the study may provide benefits in the management of Plasmodium-mixed infection in co-endemic regions. METHODS: This systematic review and meta-analysis searched the international Prospective Register of Systematic Reviews (PROSPERO; ID = CRD42020199709), MEDLINE, Web of Science, and Scopus for potentially relevant studies in any language published between January 1, 1936, and July 20, 2020, assessing drug efficacy in patients with Plasmodium-mixed infection. The primary outcome was the pooled prevalence of Plasmodium parasitemia after initiating antimalarial treatment for Plasmodium-mixed infection. The secondary outcome was the pooled risk ratio (RR) of malarial recurrence in Plasmodium-mixed infection compared with those in Plasmodium falciparum and Plasmodium vivax mono-infection. The pooled analyses were calculated by random-effects meta-analysis. After the initial treatment in different days of recurrences (≤ 28 days or > 28 days), the risk of Plasmodium parasitemia was compared in subgroup analysis. RESULTS: Out of 5217 screened studies, 11 were included in the meta-analysis, including 4390 patients from six countries. The pooled prevalence of all recurrences of Plasmodium-mixed parasitemia was 30% (95% confidence interval (CI) 16-43; I2: 99.2%; 11 studies). The RR of malarial recurrence within 28 days after the initial treatment (clinical treatment failure) of Plasmodium-mixed parasitemia compared with the treatment of P. falciparum was 1.22 (p: 0.029; 95% CI 1.02-1.47; Cochran Q: 0.93; I2: 0%; six studies), while there was no significant difference in the risk of recurrence 28 days after initial treatment compared with the treatment of P. falciparum (p: 0.696, RR: 1.14; 95% CI 0.59-2.18; Cochran Q < 0.05; I2: 98.2%; four studies). The subgroup analysis of antimalarial drugs showed that significant malarial recurrence within 28 days was observed in patients treated with artemisinin-based combination therapies (ACTs) with no significant heterogeneity (p: 0.028, RR: 1.31; 95% CI 1.03-1.66; Cochran Q: 0.834; I2: 0%). CONCLUSIONS: The present findings showed a high prevalence of malarial recurrence after the initial treatment of Plasmodium-mixed infection. Moreover, significant malaria recurrence of mixed infection occurred within 28 days after treatment with ACTs.

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.

Epidemiology of malaria among HIV/AIDS patients in sub-Saharan Africa: A systematic review and meta-analysis of observational studies.

Malaria related HIV morbidity and death is a concern in sub-Saharan Africa. Understanding the epidemiology of malaria among people living with HIV is vital for adequate intervention. We conducted a systematic review and meta-analysis to estimate the prevalence of malaria in HIV patients in sub-Saharan Africa. We searched PubMed, AJOL, Web of Science and Google Scholar databases. The overall pooled prevalence and pooled Odds Ratio (OR) with their 95% Confidence Intervals (CI) were estimated using the random-effects model and potential causes of heterogeneity in prevalence estimates were investigated using subgroup and meta-regression analysis. 58 studies, including 23,911 HIV patients, were identified between January 1990 and October 2020. The overall pooled prevalence of malaria in HIV patients was 22.7% (95% CI 18.0; 28.1). The Prevalence of malaria among HIV/AIDS patients was 33.1%, 30.2%, 15.3%, and 12.6% in Southern, Western, Central, and Eastern regions of SSA respectively. Prevalence of malaria in the central and western was higher [26.7% (95% CI 20.6; 33.9)] than 13.6% reported in the southern and eastern regions (95% CI 8.8; 20.5). There was a significant decrease in malaria prevalence among HIV/AIDS patients in the Eastern and Southern SSA regions from 21.9% (95% CI 15.5; 30.0) in the 2000-2010 period to 9.7% (95% CI 5.5-16.4) in the post-2010 period compared to the central and western regions. HIV infected patients with low CD4 + T cell count (CD4 < 200 cells/mm3) were 2.19 times more likely to become infected with malaria than those with high CD4 + T cell count (CD4 ≥ 200 cells/mm3) (pooled odds ratio (POR): 2.19 (95%CI 1.20;3.98), while patients on antiretroviral therapy (POR): 0.37 (0.23; 0.59), and in WHO clinical stages I and II (POR): 0.64 (0.28; 1.46), had a lower odds of been infected with malaria. Our review suggests that due consideration should be given to malaria among HIV/AIDS patients in SSA. In particular, the assessment and improvement of preventive measures for malaria/HIV co-infection in high-prevalence regions is important. For the treatment of both diseases, prophylaxis with cotrimoxazole and antiretroviral therapy should also be encouraged.

Polymorphisms in Fc Gamma Receptors and Susceptibility to Malaria in an Endemic Population.

Repeated infections by Plasmodium falciparum result in a humoral response that could reduce disease symptoms and prevent the development of clinical malaria. The principal mechanism underlying this humoral response is that immunoglobulin G (IgG) binds directly to the parasites, thus causing their neutralization. However, the action of antibodies alone is not always sufficient to eliminate pathogens from an organism. One key element involved in the recognition of IgG that plays a crucial role in the destruction of the parasites responsible for spreading malaria is the family of Fc gamma receptors. These receptors are expressed on the surface of immune cells. Several polymorphisms have been detected in the genes encoding these receptors, associated with susceptibility or resistance to malaria in different populations. In this review, we describe identified polymorphisms within the family of Fc gamma receptors and the impact of these variations on the response of a host to infection as well as provide new perspectives for the design of an effective vaccine for malaria.

Effects of Mosquito coil Smoke Inhalation on Spatial Memory in Mice.

BACKGROUND: Mosquito coil (MC) is widely used to repel mosquitoes in order to prevent malaria in many malaria-endemic countries. Although we are fully aware and concerned about carbon monoxide (CO) and its toxicity, exposure to CO from common, though occult sources like MC smoke is often overlooked. Equally, the adverse health effects, especially to the brain, are usually underestimated. OBJECTIVE: To assess the effects of exposure to CO from MC smoke inhalation on spatial memory in mice. METHODS: Sixteen, adult, male, mice, were randomly assigned to either the experimental or the control group; each having 8 mice. The experimental group was exposed to the MC smoke (Wavetide, China) that was allowed to burn inside the gas chamber (75 cm x 50 cm x 50 cm) for 15 minutes, daily, for 14 days. Digital CO meter (PCMM05 Pyle) was used to measure the amount of CO and Barnes maze protocol to assess the spatial memory. RESULTS: Our results indicate that burning MC for 15 minutes produced up to 312 parts per million (ppm) of CO and raised the blood carboxy-hemoglobin (COHb) level by 15.8%. This is higher than the WHO recommended limit (<100 mg/m3 or 87 ppm for 15 min.) of CO exposure and the %COHb level of <2%. Mosquito coil smoke was also associated with impaired spatial memory. However, the dose and duration of exposure did not significantly affect weight gain in the mice. CONCLUSION: Although widely used to prevent malaria, MC could serve as a potential source of CO and other neurotoxins that could be harmful to the brain; the use and toxicity of which is mostly overlooked even by the public health professionals.

Parents' perception on cause of malaria and their malaria prevention experience among school-aged children in Kutcha district, Southern Ethiopia; qualitative study.

INTRODUCTION: School-aged children become a highly vulnerable group for malaria, yet they are less likely to use malaria prevention interventions. Previous studies exploring perception on cause of malaria mainly focused on pregnant mothers or parents of children under age five years. Exploring parent's perception on cause of malaria and their experiences on the prevention of malaria and associated challenges among school-aged children is important to develop a malaria prevention education package for school-aged children to reduce malaria and malaria related morbidities among school-aged children. METHODS: A descriptive qualitative study is conducted in Kutcha district by recruiting 19 parents of school-aged children for semi-structured interviews, 6 key informants and 6 focus group discussion which consists of parents, health development army and health extension workers. A semi-structured interview guide is used to guide the interview process. The collected data is analyzed thematically with a focus on the three major areas of concern: perceived cause of malaria, experience of malaria prevention and challenges of bed net use for prevention of malaria. RESULTS: Five causes of malaria were identified, namely hunger, mosquito bite, exposure to hot sunshine, poor sanitation and hygiene and eating some sweet foods and unripe maize. Participants perceived that eating sweet foods and unripe maize lead to enlargement of the spleen that ends in malaria while poor hygiene and sanitation leads to either development of the ova of mosquito and the landing of the housefly to contaminate food for consumption. The experiences of malaria prevention were largely influenced by their perceived cause of malaria. The malaria prevention measures undertaken by parents were vectors control measures, homemade herbal remedies and restricting children from eating sweet foods. The challenges of malaria prevention by using bed nets were related to a negative attitude, sleeping behaviors of children; use of bed nets for unintended purposes, shortage of bed nets and delays in the distribution of bed nets. CONCLUSION: There were misconceptions about the cause of malaria and associated experiences of malaria prevention. Control of malaria among school-aged children need health education targeting the challenges and correcting identified misconceptions by parents in Kutcha district and in other similar settings.

Predictors of anaemia among adolescent schoolchildren of Ghana.

Anaemia is a public health problem in Ghana. We sought to identify factors associated with haemoglobin concentration (Hb) and anaemia among school-attending adolescents. We analysed data from 2948 adolescent girls and 609 boys (10-19 years) selected from 115 schools from regions of Ghana as a secondary analysis of baseline surveys conducted at two time-points. We measured Hb, malaria from capillary blood, anthropometry and used a modified food frequency questionnaire to assess diet. Multivariable linear and Poisson regression models were used to identify predictors of Hb and anaemia. The prevalence of anaemia, malaria and geophagy were 24, 25, and 24 %, respectively, among girls and 13, 27 and 6 %, respectively, among boys. Girls engaging in geophagy had a 53 % higher adjusted prevalence of anaemia and 0⋅39 g/dl lower Hb. There were similar results among those who tested positive for malaria (+52 % anaemia; -0⋅42 g/dl Hb). Among girls, lower anaemia prevalence and higher Hb were associated with consumption of foods rich in haeme iron (-22 %; +0⋅18 g/dl), consumption of iron-fortified cereal/beverages consumed with citrus (-50 %; +0⋅37 g/dl) and being overweight (-22 %; +0⋅22 g/dl). Age was positively associated with anaemia among girls, but negatively associated among boys. Boys who tested positive for malaria had 0⋅31 g/dl lower Hb. Boys who were overweight or had obesity and consumed flour products were also more likely to be anaemic (119 and 56 %, respectively). Factors associated with Hb and anaemia may inform anaemia reduction interventions among school-going adolescents and suggest the need to tailor them uniquely for boys and girls.

Evaluation of Imported Malaria Cases in Northern Cyprus between 2016 and 2019: First Data Series

Objective: In present times, malaria remains an infectious disease with a high mortality rate in some regions of the world. It is predicted to preserve its importance as a disease in the future because of the traveling human populations from malaria-endemic African countries into the regions where malaria has been eradicated. The objective of this study is to evaluate the increasing imported malaria cases in the Turkish Republic of Northern Cyprus. Methods: In this study, we investigated 13 patients who were diagnosed with malaria between 2016 and 2019. We clinically evaluated all the cases. More importantly, we made the diagnosis of these patients by Giemsa-stained thin and thick blood smears, rapid malaria antigen tests, and genotyping (only for five patients) by real-time polymerase chain reaction. Additionally, we evaluated patients with malaria in terms of age, gender, and seasons. Results: In the diagnosed malaria cases, 11 (84.4%) of them were male and 2 (15.6%) were female. There was no significance between malaria infection and gender (p=0.358). Plasmodium falciparum, Plasmodium vivax, and Plasmodium ovale infection were detected in ten patients (76.9%), two (15.4%) patients, and one (7.7%) patient, respectively. There was a significant increase (p=0.003) in the malaria cases in 2019 (n=9). The seasonal comparison revealed that malaria infections are most common in autumn (8/13, 61.5%). Conclusion: Despite the eradication of malaria in Turkish Republic of Northern Cyprus, the rising number of recently imported cases increases the risk of emerging local cases. Malaria infection should be immediately suspected, particularly, in foreign patients who travel from the malaria-endemic region and present with symptoms such as fever and shivering if the laboratory findings especially detect thrombocytopenia.

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.

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.

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.

Estudio descriptivo de los casos de malaria en la población pediátrica en un hospital de referencia de Valencia, España, entre 1993 y 2015 / Descriptive study of malaria cases in the paediatric population in a reference hospital in Valencia, Spain, between 1993 and 2015

Introducción: La malaria es considerada la cuarta causa de mortalidad infantil después de la neumonía, las complicaciones por parto prematuro y la asfixia perinatal. Material y métodos: Estudio retrospectivo y descriptivo de los casos de paludismo confirmados y tratados en la Unidad de Enfermedades Infecciosas Pediátricas (edad inferior a 15 años) del Hospital La Fe (Valencia) en el período comprendido entre 1993 y 2015. Resultados: Durante el período 1993-2015 se diagnosticaron 54 casos de malaria infantil, el 51,8% en varones. El 46,2% eran menores de 5 años. La mayoría de los niños procedían de Guinea Ecuatorial (68,5%). Solo en el 5,6% de los pacientes se pudo constatar que recibieran profilaxis antimalárica. Se evidenció que Plasmodium falciparum fue la especie causal del 81,4% de los episodios. Siete casos (13%) presentaron malaria complicada. El tratamiento más empleado fue la quinina, sola o en combinación con otros fármacos: atovacuona-proguanil fue empleada a partir del año 2010 y estuvo indicada en el 20,3% de los pacientes. A partir del año 2013 se inició la utilización de: artesunato, piperaquina y dihidroartemisina. No hubo mortalidad ni efectos adversos relevantes, siendo la respuesta clínica favorable en el 100% de los niños. Conclusiones: La malaria sigue siendo una enfermedad vigente en nuestra población, consecuencia de la inmigración y del turismo a países endémicos. Debe ser considerada como diagnóstico probable ante un niño febril que procede o ha viajado a un área endémica en el último año

Introduction: Malaria is considered to be the fourth leading cause of infant mortality after pneumonia, complications related to premature birth, and perinatal asphyxia. Material and methods: A retrospective and descriptive study of cases of malaria confirmed and treated by the Paediatric Infectious Diseases Unit (age lower than 15 years) at the La Fe Hospital, Valencia, over the period 1993 to 2015. Results: A total of 54 cases of paediatric malaria were diagnosed in the period 1993-2015, with 51.8% of these occurring in males, and 46.2% of patients were aged below 5 years. The majority of children came from Equatorial Guinea (68.5%). Only 5.6% had received antimalarial prophylaxis. Plasmodium falciparum was found to be the causal species in 81.4% of cases. Seven patients (13%) presented with complicated malaria. The most widely used treatment was quinine, either alone or in combination with other drugs. Atovaquone/proguanil was used from 2010 onwards and was indicated in 20.3% of the patients. The combination of artesunate/piperaquine/dihydroartemisinin began to be used in 2013. No deaths or relevant side effects were reported, and the clinical response was favourable in all children (100%). Conclusions: Malaria is still a prevalent disease in this population, a consequence of immigration, and tourism to endemic countries. Malaria should be considered as a likely diagnosis in a febrile child who comes from, or has travelled to, an endemic region in the past year

Assessing the relative importance of social determinants of health in malaria and anemia classification based on machine learning techniques.

Disparate types of data including biological and environmental have been used in supervised learning to predict a specific disease outcome. However, social determinants of health, which have been explored very little, promise to be significant predictors of public health problems such as malaria and anemia among children. We considered studying their contribution power in malaria and anemia predictions based on Variable Importance in Projection (VIP). This innovative method has potential advantages as it analyzes the impact of independent variables on disease prediction. In addition, we applied five machine learning algorithms to classify both diseases, using social determinants of health data, and compared their results. Of them all, artificial neural networks gave the best results of 94.74% and 84.17% accuracy for malaria and anemia prediction, respectively. These results are consistent and reflect the significance of non-medical factors in disease prediction.

Antibiotic exposure among children younger than 5 years in low-income and middle-income countries: a cross-sectional study of nationally representative facility-based and household-based surveys.

BACKGROUND: Antibiotic resistance is a major threat to global health. Although detailed information about antibiotic use in high-income countries is available, little is known regarding the use of antibiotics and cumulative exposure to antibiotics in low-income and middle-income countries (LMICs). We aimed to quantify antibiotic exposure in children younger than 5 years in LMICs. METHODS: We did a cross-sectional study in sick children younger than 5 years who attended a health-care facility in eight LMICs (Haiti, Kenya, Malawi, Namibia, Nepal, Senegal, Tanzania, and Uganda) between May, 2006, and December, 2016. Demographic and Health Surveys were used to estimate the cumulative number of illnesses related to a fever or cough and the cumulative number of visits to a health-care facility because of these illnesses for each country. We also used clinical observation data from nationally representative health-care facility-based Service Provision Assessment (SPA) surveys to estimate the proportion of children who were prescribed an antibiotic during a visit to a health-care facility and the number of antibiotic prescriptions issued that were unrelated to fever or respiratory problems. By combining these estimates, and using bootstrap analysis to compute uncertainty intervals, we estimated cumulative antibiotic exposure in children from birth up to age 5 years in each LMIC. FINDINGS: From SPA surveys, we identified 22 519 clinical observations of children younger than 5 years who visited a health-care facility because of an illness between July, 2007, and December, 2016. From DHS surveys, we identified 68 826 children younger than 5 years who visited a health-care facility between May, 2006, and November, 2016. 85·4% of health-care facility visits were related to either a fever or cough. Antibiotics were prescribed to 80·5% of children diagnosed with respiratory illness, 50·1% with diarrhoea, and 28·3% with malaria. The mean number of antibiotic prescriptions issued to children between birth and age 5 years across the eight LMICs was 24·5 (95% CI 22·6-26·7), ranging from 7·1 (6·3-7·9) in Senegal to 59·1 (54·1-64·6) in Uganda. INTERPRETATION: Between birth and age 5 years, children in LMICs are prescribed a remarkably high number of antibiotics. A large proportion of these prescriptions appear to be unnecessary. National and local efforts to reduce unnecessary prescription of antibiotics to children would likely improve both patient wellbeing (in terms of preventing side-effects) and reduce the global threat of antimicrobial resistance. FUNDING: None.