Assessment of Culicidae collection methods for xenomonitoring lymphatic filariasis in malaria co-infection context in Burkina Faso.

BACKGROUND: Entomological surveillance of lymphatic filariasis and malaria infections play an important role in the decision-making of national programs to control, or eliminate these both diseases. In areas where both diseases prevalence is low, a large number of mosquitoes need to be sampled to determine vectors infection rate. To do this, efficient mosquito collection methods must be used. This study is part in this framework, to assess appropriate mosquito collection methods for lymphatic filariasis xenomonitoring in a coexistence context with malaria in Burkina Faso. METHODOLOGY/PRINCIPAL FINDINGS: Mosquito collections were performed between August and September 2018 in four villages (Koulpissi, Seiga, and Péribgan, Saptan), distributed in East and South-West health regions of Burkina Faso. Different collection methods were used: Human Landing Catches (HLC) executed indoor and outdoor, Window Exit-Trap, Double Net Trap (DNT) and Pyrethrum Spray Catches (PSC). Molecular analyses were performed to identify Anopheles gambiae s.l. sibling species and to detect Wuchereria bancrofti and Plasmodium falciparum infection in Anopheles mosquitoes. A total of 3 322 mosquitoes were collected among this, Anopheles gambiae s.l. was the vector caught in largest proportion (63.82%). An. gambiae s.l. sibling species molecular characterization showed that An. gambiae was the dominant specie in all villages. The Human Landing Catches (indoor and outdoor) collected the highest proportion of mosquitoes (between 61.5% and 82.79%). For the sampling vectors infected to W. bancrofti or P. falciparum, PSC, HLC and Window Exit-Trap were found the most effective collection methods. CONCLUSIONS/SIGNIFICANCE: This study revealed that HLC indoor and outdoor remained the most effective collection method. Likewise, the results showed the probability to use Window Exit-Trap and PSC collection methods to sample Anopheles infected.

Apolipoprotein E genetic variation, atherogenic index and cardiovascular disease risk assessment in an African population: An analysis of HIV and malaria patients in Ghana.

BACKGROUND: Apolipoprotein E is involved in lipid transport and clearance of lipoprotein through low-density lipoprotein receptors (LDLR). ApoE variation has been linked to cardiovascular disease (CVD) risk. There are 3 isoforms of ApoE which originate from two non-synonymous single nucleotide polymorphisms denoted as ε2, ε3 and ε4. The ε2 isoform is implicated in higher levels of atherogenic lipoprotein with the ε4 isoform causing LDLR downregulation. This leads to variable effects and differential CVD risk. Malaria and HIV are life-threatening diseases affecting several countries globally especially in sub-Saharan Africa. Parasite and viral activities have been implicated in lipid dysregulation leading to dyslipidaemia. This study examined ApoE variation and CVD risk assessment in malaria and HIV patients. METHODS: We compared 76 malaria-only, 33 malaria-HIV coinfected, 21-HIV-only and 31 controls from a tertiary health facility in Ghana. Fasting venous blood samples were taken for ApoE genotyping and lipid measurements. Clinical and laboratory data were collected with ApoE genotyping performed using Iplex Gold microarray and PCR-RFLP. Cardiovascular disease risk was calculated using the Framingham BMI and cholesterol risk and Qrisk3 tools. RESULTS: The frequency of C/C genotype for rs429358 was 9.32%, whiles T/T genotype for rs7412 was found in 2.48% of all participants. ε3/ε3 was the most distributed ApoE genotype accounting for 51.55% of the total participants whiles ε2/ε2 was found in 2.48% of participants, with 1 in malaria-only and 3 in HIV-only patients. There was a significant association between ε4+ and high TG (OR = 0.20, CI; 0.05-0.73; p = 0.015), whiles ε2+ was significantly associated with higher BMI (OR; 0.24, CI; 0.06-0.87; p = 0.030) and higher Castelli Risk Index II in females (OR = 11.26, CI; 1.37-92.30; p = 0.024). A higher proportion of malaria-only participants had a moderate to high 10-year CVD risk. CONCLUSION: Overall malaria patients seem to have a higher CVD risk though the means through which this occurs may be poorly understood. ε2/ε2 genotypes was observed in our population at a lower frequency. Further studies are vital to determine CVD risk in malaria and how this occurs.

Sociodemographic factors associated with anemia among reproductive age women in Mali; evidenced by Mali malaria indicator survey 2021: spatial and multilevel mixed effect model analysis.

INTRODUCTION: Anemia is a severe global public health problem that threatens human health as well as social and economic development in both developing and developed nations. Anemia is a significant public health issue because; it affects people from all backgrounds. Anemia affected about one-third of non-pregnant women, 41.8% of pregnant women, and more than a quarter of the world's population. Any stage of a woman's life might result in anemia, due to physiological factors, infections, hormonal imbalances, pregnancy related complications, genetic factors, nutritional deficiency and environmental factors. Mali is a developing country with substantial anemia prevalence, particularly in the developing areas. In order to reduce anemia among women of reproductive age, the Mali government worked to enhance preventative and integrative interventions. One of the government's objectives is to reduce the prevalence of anemia in order to decrease maternal and infant mortality and morbidity. METHODS: Secondary data analysis was conducted using data from Mali Malaria Indicator Survey 2021 datasets. The study comprised a total of 10,765 reproductive-age women. Spatial and multilevel mixed effect analysis, chi-square, bivariate and multivariate logistic regression were employed on determinant factors of anemia among reproductive age women in Mali. Finally, the percentage and odd ratio, its 95% confidence intervals, and the result of spatial analysis were reported. RESULTS: This study includes a total weighted sample of 10,765 reproductive-age women from Mali Malaria Indicator Survey 2021. The prevalence of anemia was 38%. Of them, 1.4%, were severely anemic, while 23.5% and 13.1% were moderately and mildly anemic, respectively in Mali. In the spatial analysis, the spatial distribution of anemia showed that a higher proportion of anemia found in southern and south west region of Mali. The northern and north east region of Mali had a low of proportion of anemia. being youngest age [20-24] years [ AOR = 0.817; 95% CI = (0.638,1.047); P = 0.000], attending higher education [AOR = 0.401; 95% CI= (0.278,0.579); P = 0.000], being male headed household [AOR = 0.653; 95% CI= (0.536,0.794); P = 0.000] and being richest [AOR = 0.629; 95% CI= (0.524,0.754) P = 0.000] were protective factors for anemia among reproductive age women. In contrast to this, living in rural area [ AOR = 1.053; 95% CI = (0.880,1.260); P = 0.000], being animist religion follower [AOR = 3.10; 95% CI= (0.763,12.623) P = 0.04], using unimproved drinking water sources [AOR = 1.117; CI= (1.017,1.228); P = 0.021} and using unimproved toilet facility [AOR = 1.018; CI= (0.917,1.130); P = 0.041} were considered as the risk factors for anemia among reproductive age women. CONCLUSION: In this study, anemia was linked to socio-demographic characteristics, and there were regional variations in the frequency of anemia among women of reproductive age. The most important measures to prevent anemia among women of reproductive age in Mali included empowering women to have higher levels of education, raising the wealth index, rise in awareness of improved drinking water sources and toilet facilities, spreading anemia education through religiously acceptable routes, and using an integrated approach to prevention and intervention in high-prevalent regions of the country.

Uptake and usage of proguanil as malaria chemoprophylaxis and the socio-economic determinants of proguanil usage in children with sickle cell anemia in Benin City.

Background: Proguanil is currently the recommended drug used for malaria chemoprophylaxis in children with Sickle cell anaemia (SCA). Aims: This study aims to determine the uptake and usage of proguanil as malaria chemoprophylaxis and the socioeconomic determinants of its usage in children aged 6-59 months. This was a descriptive cross-sectional study carried out in two major sickle cell clinics in Benin City, Edo state, Nigeria. A total of 420 participants were interviewed using semistructured questionnaires. Patients and Methods: Descriptive, bivariate, and multivariate analysis of quantitative data were done using SPSS version 21. Results: The uptake of proguanil among study participants was 67.4%; of these number, 268 (94.7%) reported daily use of proguanil. Only 3 (0.7%) used pyrimethamine as chemoprophylaxis, while 134 (31.9%) used no form of malaria chemoprophylaxis. Having mothers with higher level of education (LOE) (P = 0.013, odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.15-3.17), attending clinic at the University of Benin Teaching Hospital (UBTH) (P = 0.044, OR = 2.15, 95% CI = 1.02-4.54), older age group (36-59 months) (P = 0.015, OR = 1.67, 95% CI = 1.11-2.51), and owning insecticide-treated net (ITN) (P = 0.000, OR = 3.11, 95% CI = 1.98-4.88) were significant positive predictors for the usage of proguanil. Conclusion: Proguanil uptake was low. Attending sickle-cell clinic at UBTH, having mothers with tertiary LOE, and owning ITN were social factors associated with high usage of proguanil amongst children with SCA. Continuous monitoring and evaluation of the uptake and usage of proguanil in children is important, so as to aid policy implementation and review.

The determinants of lipid profiles in early adolescence in a Ugandan birth cohort.

Dyslipidaemia in adolescence tracks into adulthood and is an important risk factor for cardiovascular disease. Little is known about the effects of environmental exposures and early-life exposure to infectious diseases common to tropical regions on lipids. In 1119 early adolescent participants in the Entebbe Mother and Baby Study, we used linear regression to examine whether prenatal, childhood or adolescent factors are associated with lipid levels. Reduced high-density lipoprotein (HDL) and elevated triglyceride levels were common (prevalence 31% and 14%, respectively), but elevated low-density lipoprotein (LDL) or total cholesterol (TC) were rare. Current malaria infection was associated with lower mean LDL (adjusted ß - 0.51; 95% CI - 0.81, - 0.21), HDL (adjusted ß - 0.40; 95% CI - 0.56, - 0.23), and TC levels (adjusted ß - 0.62; 95% CI - 0.97, - 0.27), but higher mean triglyceride levels (geometric mean ratio (GMR) 1.47; 95% CI 1.18-1.84). Early-life asymptomatic malaria was associated with modest reductions in HDL and TC. Body mass index (BMI) was positively associated with LDL, TC, and triglycerides. No associations with helminth infection were found. Our findings suggest that early-life factors have only marginal effects on the lipid profile. Current malaria infection and BMI are strongly associated with lipids and important to consider when trying to improve the lipid profile.

Assessment of the burden of malaria and bacteraemia by retrospective molecular diagnosis in febrile illnesses and first-line anti-infectives in Côte d'Ivoire.

BACKGROUND: The aetiologies of fever are poorly understood in sub-Saharan Africa. We aimed to assess the burden of malaria and bacteria in Côte d'Ivoire. METHODS: Blood samples from 438 febrile and 346 afebrile people were screened using molecular tools. RESULTS: Plasmodium falciparum was the most common microorganism associated with fever (46.8% in febrile, 23.4% in afebrile people; p < 0.001). Bacteraemia was detected in 21.7% of febrile people and 12.7% of afebrile people (p = 0.001). Streptococcus pneumoniae was the main cause of bacteraemia (7.1% of febrile and 0.6% of afebrile individuals; p < 0.001). Non-typhoidal Salmonella spp. was detected in 4.5% of febrile people and 1.2% of afebrile individuals (p < 0.001). Salmonella enterica Typhi and S. enterica Paratyphi were only detected in febrile subjects (1.4% and 2.1%), as well as Tropheryma whipplei (0.9%), Streptococcus pyogenes (0.7%), and Plasmodium ovale (4.6%). The prevalence in febrile and afebrile people was similar for Staphylococcus aureus (3.6-4.9%), Rickettsia felis (5.5-6.4%), Mansonella perstans (3.0-3.2%), and Plasmodium malariae (1.6-2.3%). Comorbidities were higher in febrile than in afebrile subjects (10.3% versus 5.5%; p = 0.01); 82% involving P. falciparum. All patients co-infected with P. falciparum and S. pneumoniae were febrile whereas 30% of those infected by P. falciparum alone were not (p = 0.02). Among febrile participants, 30.4% with malaria and 54.7% with bacteraemia had received neither antimalarial nor antibiotic therapy. CONCLUSION: Identification of etiologies of acute febrile diseases in sub-Saharan Africa proposes keys to successful treatment and prevention of infectious diseases. Vaccination campaigns may decrease the morbidity of mono- and co-infections by preventable microorganisms.

Prevalence and Clinical Management of Non-malarial Febrile Illnesses among Outpatients in the Era of Universal Malaria Testing in Malawi.

Increasing access to rapid diagnostic tests for malaria (mRDTs) has raised awareness of the challenges healthcare workers face in managing non-malarial febrile illnesses (NMFIs). We examined NMFI prevalence, clinical diagnoses, and prescribing practices in outpatient clinics across different malaria transmission settings in Malawi. Standardized facility-based malaria surveillance was conducted at three facilities one of every 4 weeks over 2 years. Information on demographics, presenting symptoms, temperature, clinical diagnosis, and treatment were collected from outpatients presenting with malaria-like symptoms. Of the 25,486 patients with fever, 69% had NMFI. Non-malarial febrile illness prevalence was lower in 5- to 15-year-old patients (55%) than in children < 5 years (72%) and adults > 15 years of age (77%). The most common clinical diagnoses among febrile patients with negative mRDTs in all age-groups and settings were respiratory infections (46%), sepsis (29%), gastroenteritis (13%), musculoskeletal pain (9%), and malaria (5%). Antibiotic prescribing was high in all age-groups and settings. Trimethoprim-sulfamethoxazole (40%) and amoxicillin (29%) were the most commonly prescribed antibiotics and were used for nearly all clinical diagnoses. In these settings with minimal access to diagnostic tools, patients with fever and a negative mRDT received a limited number of clinical diagnoses. Many were likely to be inaccurate and were associated with the inappropriate use of the limited range of available antibiotics. Prescription and diagnostic practices for NMFIs in the facilities require research and policy input. Resource-limited malaria-endemic countries urgently need more point-of-care diagnostic tools and evidence-based diagnosis and treatment algorithms to provide effective and cost-efficient care.

Evaluation of Psychometric Quality of EQ-5D-5L Scale for Assessing Health-Related Quality of Life of Malaria Patients.

OBJECTIVES: To evaluate the validity and reliability of the 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L) through classical test theory and the Rasch measurement model. METHODS: Three hundred patients treated for uncomplicated malaria in selected primary healthcare facilities of Plateau state, Nigeria, completed the EQ-5D-5L scale. Classical test theory was used to establish validity and Cronbach's alpha reliability of the scale. Rasch analysis was used to confirm the unidimensionality, item fitness, item and person separations and reliabilities, and targeting of item difficulty to patient ability levels and presentation on Wright map (item-person map). RESULTS: The outcome of classical test theory revealed unidimensional scale with average variance extracted values > 0.5, and the square root of the average variance extracted for construct was greater than the correlation coefficients, indicating convergent and discriminant validities of the scale whose Cronbach's alpha coefficient (α) was 0.87. Rasch analysis indicated variance explained values of 88.3% and the eigenvalues of the first contrast was 1.3, further confirming the unidimensionality of the scale, whose fit index values were within accepted ranges. The high item and person separation and reliability values indicated the instrument's strength in detecting and evenly spreading items and persons on the Wright map based on item difficulty and the respondents' ability levels, respectively. CONCLUSION: The EQ-5D-5L scale performed well in uncomplicated malaria, hence, it is recommended for use in the assessment of health-related quality of life in this patient population.

An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment.

Treating malaria in HIV-coinfected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly used antiretrovirals often induce or inhibit. A population pharmacokinetic meta-analysis was conducted using individual participant data from 10 studies with 6,100 lumefantrine concentrations from 793 nonpregnant adult participants (41% HIV-malaria-coinfected, 36% malaria-infected, 20% HIV-infected, and 3% healthy volunteers). Lumefantrine exposure increased 3.4-fold with coadministration of lopinavir-ritonavir-based antiretroviral therapy (ART), while it decreased by 47% with efavirenz-based ART and by 59% in the patients with rifampin-based antituberculosis treatment. Nevirapine- or dolutegravir-based ART and malaria or HIV infection were not associated with significant effects. Monte Carlo simulations showed that those on concomitant efavirenz or rifampin have 49% and 80% probability of day 7 concentrations <200 ng/ml, respectively, a threshold associated with an increased risk of treatment failure. The risk of achieving subtherapeutic concentrations increases with larger body weight. An extended 5-day and 6-day artemether-lumefantrine regimen is predicted to overcome these drug-drug interactions with efavirenz and rifampin, respectively.

Burden and etiopathogenesis of acute kidney injury in the tropics.

Acute kidney injury (AKI) is prevalent and is associated with high morbidity and mortality globally. The epidemiology differs remarkably between developing and developed economies. Infections, diarrheal illnesses, obstetric causes and nephrotoxins are very rampant in the tropics. Even though the etiologies are different, the final common pathway in the pathogenesis is similar - tubular damage or necrosis, tubular blockage, and back leak of glomerular filtrate. The mechanism of AKI in infections could be through ischemic insult consequent to hypovolemia and/or hemoglobinuria, as seen in malaria and viral hemorrhagic fevers, interstitial inflammation, or nephrotoxicity. On the contrary, the mechanism of nephrotoxin-induced AKI includes direct toxic effect on the renal tubules, intratubular precipitation of substances like djenkolic and oxalic acids (crystalluria) as well as intratubular obstruction and AKI. Toxicity could also be indirect by interacting with the pharmacokinetic profile of other coadministered medications. Bites and envenomation as well as obstetric complications also induce AKI through hypovolemia, interstitial nephritis, and other unclear mechanisms in eclampsia and preeclampsia. Outcome is variable and dependent on etiology. Prognosis appears to be significantly better in hypovolemic or prerenal and/or obstructive AKI compared to intrarenal or intrinsic AKI.

Risk factors for Burkitt lymphoma in East African children and minors: A case-control study in malaria-endemic regions in Uganda, Tanzania and Kenya.

Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in sub-Saharan African countries, however, few epidemiologic studies have been undertaken and none attempted enrolling cases from multiple countries. We therefore conducted a population-based case-control study of eBL in children aged 0-15 years old in six regions in Northern Uganda, Northern Tanzania and Western Kenya, enrolling 862 suspected cases and 2,934 population controls (response rates 98.5-100%), and processing ~40,000 vials of samples using standardized protocols. Risk factor questionnaires were administered, and malaria period prevalence was measured using rapid diagnostic tests (RDTs). A total of 80.9% of the recruited cases were diagnosed as eBL; 61.4% confirmed by histology. Associations with eBL risk were computed using logistic regression models adjusted for relevant confounders. Associations common in at least two countries were emphasized. eBL risk was decreased with higher maternal income and paternal education and elevated with history of inpatient malaria treatment >12 months before enrollment. Reporting malaria-attributed fever up to 6 months before enrollment and malaria-RDT positivity at enrollment were associated with decreased eBL risk. Conversely, reporting exposure to mass malaria suppression programs (e.g., indoor residual insecticide) was associated with elevated risk. HIV seropositivity was associated with elevated eBL risk, but the relative impact was small. The study shows that it is feasible to conduct networked, multisite population-based studies of eBL in Africa. eBL was inversely associated with socioeconomic status, positively associated with inpatient malaria treatment 12 months ago and with living in areas targeted for malaria suppression, which support a role of malaria in eBL.

Relative Contributions of Malaria, Inflammation, and Deficiencies of Iron and Vitamin A to the Burden of Anemia during Low and High Malaria Seasons in Rural Zambian Children.

OBJECTIVE: To estimate the burden of anemia attributable to malaria, inflammation, and deficiency of iron or vitamin A during low and high malaria seasons among Zambian children. STUDY DESIGN: From a cohort of children (n = 820), 4-8 years of age participating in a randomized controlled trial of pro-vitamin A, we estimated attributable fractions for anemia (hemoglobin of <110 or 115 g/L, by age) owing to current malaria or inflammation (C-reactive protein of >5 mg/L, or α-1 acid glycoprotein of >1 g/L, or both), and current or prior iron deficiency (ID; defined as low ferritin [<12 or 15 µg/L for age <5 or >5 years] or functional ID [soluble transferrin receptor of >8.3 mg/L] or both) and vitamin A deficiency (retinol of <0.7 µmol/L), during low and high malaria seasons, using multivariate logistic regression. Serum ferritin, soluble transferrin receptor, and retinol were adjusted for inflammation. RESULTS: The burden of anemia independently associated with current malaria, inflammation, ID, and vitamin A deficiency in the low malaria season were 12% (P < .001), 6% (P = .005), 14% (P = .001), and 2% (P = .07), respectively, and 32% (P < .001), 15% (P < .001), 10% (P = .06), and 2% (P = .06), respectively, in the high malaria season. In both seasons, functional ID was independently associated with more anemia (approximately 11%) than low ferritin (approximately 4%). Anemia and ID in the low malaria season, accounted for 20% (P < .001) and 4% (P = .095) of the anemia in the subsequent high malaria season. CONCLUSIONS: Anemia in this population is strongly linked to malaria, inflammation, and functional ID, and to a lesser extent, low iron stores. Integrated control strategies are needed.

Transfusion Volume for Children with Severe Anemia in Africa.

BACKGROUND: Severe anemia (hemoglobin level, <6 g per deciliter) is a leading cause of hospital admission and death in children in sub-Saharan Africa. The World Health Organization recommends transfusion of 20 ml of whole-blood equivalent per kilogram of body weight for anemia, regardless of hemoglobin level. METHODS: In this factorial, open-label trial, we randomly assigned Ugandan and Malawian children 2 months to 12 years of age with a hemoglobin level of less than 6 g per deciliter and severity features (e.g., respiratory distress or reduced consciousness) to receive immediate blood transfusion with 20 ml per kilogram or 30 ml per kilogram. Three other randomized analyses investigated immediate as compared with no immediate transfusion, the administration of postdischarge micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole. The primary outcome was 28-day mortality. RESULTS: A total of 3196 eligible children (median age, 37 months; 2050 [64.1%] with malaria) were assigned to receive a transfusion of 30 ml per kilogram (1598 children) or 20 ml per kilogram (1598 children) and were followed for 180 days. A total of 1592 children (99.6%) in the higher-volume group and 1596 (99.9%) in the lower-volume group started transfusion (median, 1.2 hours after randomization). The mean (±SD) volume of total blood transfused per child was 475±385 ml and 353±348 ml, respectively; 197 children (12.3%) and 300 children (18.8%) in the respective groups received additional transfusions. Overall, 55 children (3.4%) in the higher-volume group and 72 (4.5%) in the lower-volume group died before 28 days (hazard ratio, 0.76; 95% confidence interval [CI], 0.54 to 1.08; P = 0.12 by log-rank test). This finding masked significant heterogeneity in 28-day mortality according to the presence or absence of fever (>37.5°C) at screening (P=0.001 after Sidak correction). Among the 1943 children (60.8%) without fever, mortality was lower with a transfusion volume of 30 ml per kilogram than with a volume of 20 ml per kilogram (hazard ratio, 0.43; 95% CI, 0.27 to 0.69). Among the 1253 children (39.2%) with fever, mortality was higher with 30 ml per kilogram than with 20 ml per kilogram (hazard ratio, 1.91; 95% CI, 1.04 to 3.49). There was no evidence of differences between the randomized groups in readmissions, serious adverse events, or hemoglobin recovery at 180 days. CONCLUSIONS: Overall mortality did not differ between the two transfusion strategies. (Funded by the Medical Research Council and Department for International Development, United Kingdom; TRACT Current Controlled Trials number, ISRCTN84086586.).

Immediate Transfusion in African Children with Uncomplicated Severe Anemia.

BACKGROUND: The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes. METHODS: In this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter. The primary outcome was 28-day mortality. Three other randomizations investigated transfusion volume, postdischarge supplementation with micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole. RESULTS: A total of 1565 children (median age, 26 months) underwent randomization, with 778 assigned to the immediate-transfusion group and 787 to the control group; 984 children (62.9%) had malaria. The children were followed for 180 days, and 71 (4.5%) were lost to follow-up. During the primary hospitalization, transfusion was performed in all the children in the immediate-transfusion group and in 386 (49.0%) in the control group (median time to transfusion, 1.3 hours vs. 24.9 hours after randomization). The mean (±SD) total blood volume transfused per child was 314±228 ml in the immediate-transfusion group and 142±224 ml in the control group. Death had occurred by 28 days in 7 children (0.9%) in the immediate-transfusion group and in 13 (1.7%) in the control group (hazard ratio, 0.54; 95% confidence interval [CI], 0.22 to 1.36; P = 0.19) and by 180 days in 35 (4.5%) and 47 (6.0%), respectively (hazard ratio, 0.75; 95% CI, 0.48 to 1.15), without evidence of interaction with other randomizations (P>0.20) or evidence of between-group differences in readmissions, serious adverse events, or hemoglobin recovery at 180 days. The mean length of hospital stay was 0.9 days longer in the control group. CONCLUSIONS: There was no evidence of differences in clinical outcomes over 6 months between the children who received immediate transfusion and those who did not. The triggered-transfusion strategy in the control group resulted in lower blood use; however, the length of hospital stay was longer, and this strategy required clinical and hemoglobin monitoring. (Funded by the Medical Research Council and Department for International Development; TRACT Current Controlled Trials number, ISRCTN84086586.).

Treatment-seeking behaviour for febrile illnesses and its implications for malaria control and elimination in Savannakhet Province, Lao PDR (Laos): a mixed method study.

BACKGROUND: How people respond to febrile illness is critical to malaria prevention, control, and ultimately elimination. This article explores factors affecting treatment-seeking behaviour for febrile illnesses in a remote area of Lao PDR. METHODS: Household heads or their representatives (n = 281) were interviewed using a structured questionnaire. A total of twelve focus group discussions (FGDs) each with eight to ten participants were conducted in four villages. In addition, observations were recorded as field notes (n = 130) and were used to collect information on the local context, including the treatment seeking behaviour and the health services. RESULTS: Almost three-quarters (201/281) of respondents reported fever in past two months. Most (92%, 185/201) sought treatment of which 80% (149/185) sought treatment at a health centre. Geographic proximity to a health centre (AOR = 6.5; CI = 1.74-24.25; for those < 3.5 km versus those > 3.6 km) and previous experience of attending a health centre (AOR = 4.7; CI = 1.2-19.1) were strong predictors of visiting a health centre for febrile symptoms. During FGDs, respondents described seeking treatment from traditional healers and at health centre for mild to moderate illnesses. Respondents also explained how if symptoms, including fever, were severe or persisted after receiving treatment elsewhere, they sought assistance at health centres. Access to local health centres/hospitals was often constrained by a lack of transportation and an ability to meet the direct and indirect costs of a visit. CONCLUSION: In Nong District, a rural area bordering Vietnam, people seek care from health centres offering allopathic medicine and from spiritual healers. Decisions about where and when to attend health care depended on their economic status, mobility (distance to the health centre, road conditions, availability of transport), symptoms severity and illness recognition. Current and future malaria control/elimination programmes could benefit from greater collaboration with the locally accessible sources of treatments, such as health volunteers and traditional healers.

Comparative assessment of clinic-laboratory profile of different species of severe malaria in a tertiary care institute in southern India.

BACKGROUND & OBJECTIVES: Majority of the studies on severe malaria in India have concentrated on falciparum and have been done in northern part. The objective of the study was to compare the clinical spectrum and laboratory profile among severe Plasmodium vivax, P. falciparum and mixed malaria patients admitted at a tertiary care center in southern India. METHODS: This prospective, observational study was done in adult patients with severe malaria hospitalized in a tertiary care centre in southern India. Malaria was diagnosed by either quantitative buffy coat test or peripheral blood smear. In the cases of P. vivax malaria, an antigen detection test was done to rule out coexistent falciparum infection. Severe malaria was defined as per the WHO guidelines. The malaria severity score (MSS) was calculated for all patients based on the clinical features and laboratory parameters. RESULTS: A total of 204 cases of severe malaria were studied. Among them, 105 (51.5%) had vivax infection, 30 (14.7%) had falciparum and 69 (33.8%) patients had mixed malaria. The mean age of the study population was 39.8±15.7 yr. The majority were males (71.6%). Hypotension and prostration were the most common complications noted in the patients, irrespective of species. The maximum mean MSS was found to be highest in falciparum malaria, followed by mixed malaria and vivax. In vivax malaria, majority of patients (71.4%) had one or two complications and only 28.57% of patients had three more complications, whereas in falciparum malaria, the majority (53.33%) had three or more complications. Around 44.93% of mixed infection malaria patients had three or more complications. The number of patients with multi-organ dysfunction (>2 complications) was significantly more in patients with falciparum infections compared to the remaining patients. INTERPRETATION & CONCLUSION: Severe malaria in south India is predominantly due to vivax. Hypotension and prostration were the most common complication of severe malaria irrespective of the plasmodium species. The entire spectrum of severe malaria complications described for falciparum are seen in severe vivax malaria.

Framework for Evaluating the Health Impact of the Scale-Up of Malaria Control Interventions on All-Cause Child Mortality in Sub-Saharan Africa.

Concerted efforts from national and international partners have scaled up malaria control interventions, including insecticide-treated nets, indoor residual spraying, diagnostics, prompt and effective treatment of malaria cases, and intermittent preventive treatment during pregnancy in sub-Saharan Africa (SSA). This scale-up warrants an assessment of its health impact to guide future efforts and investments; however, measuring malaria-specific mortality and the overall impact of malaria control interventions remains challenging. In 2007, Roll Back Malaria's Monitoring and Evaluation Reference Group proposed a theoretical framework for evaluating the impact of full-coverage malaria control interventions on morbidity and mortality in high-burden SSA countries. Recently, several evaluations have contributed new ideas and lessons to strengthen this plausibility design. This paper harnesses that new evaluation experience to expand the framework, with additional features, such as stratification, to examine subgroups most likely to experience improvement if control programs are working; the use of a national platform framework; and analysis of complete birth histories from national household surveys. The refined framework has shown that, despite persisting data challenges, combining multiple sources of data, considering potential contributions from both fundamental and proximate contextual factors, and conducting subnational analyses allows identification of the plausible contributions of malaria control interventions on malaria morbidity and mortality.

Spectrum of kidney diseases in Africa: malaria, schistosomiasis, sickle cell disease, and toxins.

Kidney diseases have assumed epidemic proportions in both developed and developing countries, particularly chronic kidney disease (CKD). While treatment modalities are available and accessible in developed economies with improvement in outcomes, survival, and quality of life, they are either unavailable or inaccessible in nations with emerging economies, particularly in sub-Saharan Africa (SSA), with an attendant worsening outcome and survival for CKD patients. The epidemiology of CKD in SSA has revealed that it preferentially affects adults in their economically productive years, usually below the age of 50 years, with consequent drain on the economy. This derives mainly from the major etiologies in the region, which are infection-induced chronic glomerulonephritis and hypertension, compounded by poverty as well as societal and health underdevelopment, poor resource allocation to health, and underdeveloped health infrastructures. This has made preventive nephrology a major goal in the sub-region, although those who have already developed CKD must be managed up to tertiary levels. In this review, we assessed the contributions of parasitic diseases (i.e., malaria and schistosomiasis), sickle cell disease and nephrotoxins with the aim of espousing their contributions to the burden of kidney disease, and proposing management options with the goal of ultimately reducing the burden of kidney disease in these disadvantaged populations.

Assessment of the usage and effectiveness of intermittent preventive treatment and insecticide-treated nets on the indicators of malaria among pregnant women attending antenatal care in the Buea Health District, Cameroon.

BACKGROUND: Malaria in pregnancy is an immense public health problem with at least 50 million pregnant women living in malaria endemic areas. To prevent malaria and its complications in pregnancy the World Health Organization recommends the use of intermittent preventive treatment sulfadoxine-pyrimethamine (IPTp-SP), the use of insecticide-treated nets (ITNs), and effective case management. In most malaria endemic countries in Africa, 40% of pregnant women sleep under ITNs. In Cameroon, about 90% of pregnant women receive the first dose of SP, while 64% take the complete dose. Following the 2011 mass-campaign of free distribution of ITNs coupled with routine ANC distribution of ITN and adoption of IPTp in Cameroon, little has been done to assess the effectiveness of both interventions outside of Yaoundé, the capital city. This study sought to assess the usage and effectiveness of IPTp-SP and ITNs on malaria in pregnancy. METHODS: The research was a cross-sectional hospital-based study that included 410 pregnant women attending antenatal clinics in the Buea Health District. Capillary blood samples were collected to check malaria parasite by microscopy and haemoglobin levels by microhaematocrit technique. RESULTS: A prevalence of 13.4 and 41.7% was detected for malaria and anaemia, respectively. The Overall coverage of ITN was 32.4% while that of ITPp was 63.2%. Malaria prevalence was least (7.2%) amongst women using both IPTp-SP and ITN while those with no intervention had the highest malaria prevalence of 18.6% (χ2 = 6.188; P = 0.103). Of the women with malaria, 12.73% were using ITN and had taken at least one dose of SP, 38.18% had taken at least one dose IPTp only, 10.91% were using only ITN and 38.18% were not using any preventive measure. There was a difference in anaemia status within the different intervention groups (χ2 = 8.673; P = 0.034). Pregnant women using both interventions were less associated to malaria (OR = 0.341, 95% CI = 0.138-0.841) compared to those using only one control method. CONCLUSION: Repeated doses of SP in combination with ITN use are effective in reducing malaria parasitaemia and improving haemoglobin level of pregnant women.

Assessment of Point-of-Care Diagnostics for G6PD Deficiency in Malaria Endemic Rural Eastern Indonesia.

BACKGROUND: Patients infected by Plasmodium vivax or Plasmodium ovale suffer repeated clinical attacks without primaquine therapy against latent stages in liver. Primaquine causes seriously threatening acute hemolytic anemia in patients having inherited glucose-6-phosphate dehydrogenase (G6PD) deficiency. Access to safe primaquine therapy hinges upon the ability to confirm G6PD normal status. CareStart G6PD, a qualitative G6PD rapid diagnostic test (G6PD RDT) intended for use at point-of-care in impoverished rural settings where most malaria patients live, was evaluated. METHODOLOGY/PRINCIPAL FINDINGS: This device and the standard qualitative fluorescent spot test (FST) were each compared against the quantitative spectrophotometric assay for G6PD activity as the diagnostic gold standard. The assessment occurred at meso-endemic Panenggo Ede in western Sumba Island in eastern Indonesia, where 610 residents provided venous blood. The G6PD RDT and FST qualitative assessments were performed in the field, whereas the quantitative assay was performed in a research laboratory at Jakarta. The median G6PD activity ≥ 5 U/gHb was 9.7 U/gHb and was considered 100% of normal activity. The prevalence of G6PD deficiency by quantitative assessment (<5 U/gHb) was 7.2%. Applying 30% of normal G6PD activity as the cut-off for qualitative testing, the sensitivity, specificity, positive predictive value, and negative predictive value for G6PD RDT versus FST among males were as follows: 100%, 98.7%, 89%, and 100% versus 91.7%, 92%, 55%, and 99%; P = 0.49, 0.001, 0.004, and 0.24, respectively. These values among females were: 83%, 92.7%, 17%, and 99.7% versus 100%, 92%, 18%, and 100%; P = 1.0, 0.89, 1.0 and 1.0, respectively. CONCLUSIONS/SIGNIFICANCE: The overall performance of G6PD RDT, especially 100% negative predictive value, demonstrates suitable safety for G6PD screening prior to administering hemolytic drugs like primaquine and many others. Relatively poor diagnostic performance among females due to mosaic G6PD phenotype is an inherent limitation of any current practical screening methodology.