human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND No comprehensive data on the clinical features and the prognosis of cerebral malaria in the South Pacific are available at present . We conducted a prospect i ve study in children with cerebral malaria to assess the case fatality rate ( CFR ) in the region and to identify potential risk factors for death . METHODS We recruited 134 children admitted to the Madang General Hospital between April 1991 and October 1993 with a strictly defined diagnosis of cerebral malaria . Besides clinical examination , we collected a blood sample for parasitological haematological and biochemical assessment .  RESULTS The CFR was 11.9 % and the prevalence of residual neurological sequelae at discharge was 1.5 % . The proportion of children presenting with deep coma ( 12 % ) or hypoglycaemia ( 17 % ) was lower in our study than in African ones , where severe complications are more frequent . Also mortality associated with hypoglycaemia on admission was lower . Clinical or laboratory conditions significantly associated with death were deep coma , malarial anaemia and hyperleucocytosis . CONCLUSIONS All conditions associated with deep coma , such as shock , hypoglycaemia and acidosis , should be corrected . Also prompt administration of blood transfusions to patients with anaemia is likely to reduce the occurrence of death in Papua New Guinean children with cerebral malaria BACKGROUND The relation between malnutrition and malaria is controversial . On the one h and , malaria may cause malnutrition , whereas on the other h and , malnutrition itself may modulate susceptibility to the disease . OBJECTIVE The objective was to investigate the association between Plasmodium falciparum malaria and malnutrition in a cohort of Kenyan children . DESIGN The study involved the longitudinal follow-up of children aged 0 - 95 [ corrected ] mo for clinical malaria episodes and anthropometric measurements through 4  cross-sectional surveys . We used Poisson regression analysis to investigate the association between malaria and nutritional status . RESULTS The crude incidence rate ratios ( IRRs ) for malaria during the 6-mo period before assessment in children defined as malnourished on the basis of low height-for-age or low weight-for-age z scores ( < -2 ) were 1.17 ( 95 % CI : 0.91 , 1.50 ; P=0.21 ) and 0.94 ( 0.71 , 1.25 ; P=0.67 ) , respectively , which suggests no association between malaria and the subsequent development of protein-energy malnutrition . However , we found that age acted as an effect modifier in the association between malaria episodes and malnutrition on prospect i ve follow-up . The IRR for malaria in children aged 0 - 2 y , who were subsequently characterized as underweight , was 1.65 ( 1.10 , 2.20 ; P=0.01 ) , and a significant overall relation between malaria and stunting was found on regression analysis after adjustment for the interaction with age ( IRR : 1.91 ; 1.01 , 3.58 ; P=0.04 ) . CONCLUSION Although children living on the coast of Kenya continue to experience clinical episodes of uncomplicated malaria throughout the first decade of life , the effect of malaria on nutritional status appears to be greatest during the first 2 y of life BACKGROUND Previous analyses derived the relative risk ( RR ) of dying as a result of low weight-for-age and calculated the proportion of child deaths worldwide attributable to underweight . OBJECTIVES The objectives were to examine whether the risk of dying because of underweight varies by cause of death and to estimate the fraction of deaths by cause attributable to underweight . DESIGN Data were obtained from investigators of 10 cohort studies with both weight-for-age category ( < -3 SDs , -3 to < -2 SDs , -2 to < -1 SD , and > -1 SD ) and cause of death information . All 10 studies contributed information on weight-for-age and risk of diarrhea , pneumonia , and all-cause mortality ; however , only 6 studies contributed information on deaths because of measles , and only 3 studies contributed information on deaths because of malaria or fever . With use of weighted r and om effects models , we related the log mortality rate by cause and anthropometric status in each study to derive cause-specific RRs of dying because of undernutrition . Prevalences of each weight-for-age category were obtained from analyses of 310 national nutrition surveys . With use of the RR and prevalence information , we then calculated the fraction of deaths by cause attributable to undernutrition . RESULTS The RR of mortality because of low weight-for-age was elevated for each cause of death and for all-cause mortality . Overall , 52.5 % of all deaths in young children were attributable to undernutrition , varying from 44.8 % for deaths because of measles to 60.7 % for deaths because of diarrhea . CONCLUSION A significant proportion of deaths in young children worldwide is attributable to low weight-for-age , and efforts to reduce malnutrition should be a policy priority Objective : To examine the relation of circulating appetite neuropeptides , CCK-8 sulphate ( CCK-8s ) and β-endorphin , and the tumour necrosis factor-alpha ( TNF-α ) and soluble TNF receptors ( sTNFR ) to the anorexia and wasting associated with HIV-infection . Design : Cross-sectional analysis . Setting : A university-based HIV/AIDS ambulatory clinic in Madrid , Spain . Participants : Thirty-six r and omly selected AIDS patients without concomitant diseases or secondary infections were classified into two groups : 19 patients with wasting and 17 with normal body weight , and 18 healthy controls . Measurements : Nutritional status was evaluated by anthropometry , laboratory parameters and  self-report of appetite . Plasma levels of TNF-α and sTNFR proteins p55 ( sTNFR-p55 )  and p75 ( sTNFR-p75 ) were determined by enzyme immunoassay , whereas CCK-8s and β-endorphin levels were measured by radioimmunoassay . Results : AIDS patients with wasting had significantly higher plasma concentrations of CCK-8s , but lower levels of β-endorphin when compared to well-nourished AIDS patients ( P < 0.01 ) or controls ( P < 0.001 ) . Mean levels of TNF-α , and sTNFR-p55 and sTNFR-p75 were greater in AIDS patients with wasting than in asymptomatic AIDS patients or in controls . No significant association was observed between any of these circulating peptides and the parameters of malnutrition . Conclusions : An activation of the TNF system , together with reciprocal changes in plasma concentrations of two neuropeptides with opposing appetite regulation , that is increased concentrations of CCK-8s but lower levels of β-endorphin , are associated with the presence of HIV wasting . We hypothesize that these changes may contribute to the development of HIV wasting by producing a pathological inhibition of appetite BACKGROUND Children 's development is affected by the interplay of internal and external factors and changes in one factor can precipitate changes in multiple developmental domains . AIMS The aim of this study was to test a theoretical model of children 's development using structural equation modeling . STUDY DESIGN This was design ed as a sub study of a r and omized , placebo-controlled , 2 × 2 factorial trial of the effects of daily supplementation with iron ( 12.5 mg ) + folic acid ( 50 μg ) ( FeFA ) with or without zinc ( 10 mg ) ( Zn ) on child mortality . SUBJECTS Zanzibari children aged 5 - 9 mo ( n = 106 ) and 10 - 14 mo ( n = 141 ) at baseline were included in this sub study . OUTCOME MEASURES Longitudinal data on children 's hemoglobin , growth , malaria infection , motor development , motor activity , and language development and caregiver behavior were used to test the fit of the theoretical model for two age groups and to examine the direct and indirect relationships among the variables in the model . RESULTS The theoretical models were a good fit to the data for both age groups and revealed that FeFA with or without Zn had positive effects on motor development . FeFA alone had negative effects on language development in both age groups and Zn alone had negative effects on language development in children aged 10 - 14 mo . The incidence of malaria had negative effects on the majority of health and development outcomes in children aged 5 - 9 mo , and on motor development and hemoglobin in children aged 10 - 14 mo . CONCLUSIONS These findings illustrate how nutrition and health factors can affect different domains of development and how these changes can precipitate changes in other domains . More work is needed to better underst and the multiple impacts of internal and external factors on children 's development and how changes in developmental domains interact with each other over time to determine children 's overall developmental trajectory . The r and omized , placebo-controlled study was registered as an International St and ard R and omized Controlled Trial , number IS RCT N59549825 BACKGROUND Previous studies on the association of malaria and stunted growth  delivered inconsistent results . These conflicting results may be due to different levels of confounding and to considerable difficulties in elucidating a causal relationship . R and omized experiments are impractical and previous observational studies have not fully controlled for potential confounding including nutritional deficiencies , breastfeeding habits , other infectious diseases and socioeconomic status . METHODS This study aims to estimate the causal effect between malaria episodes and stunted growth by applying a combination of Mendelian r and omization , using the sickle cell trait , and matching . We demonstrate the method on a cohort of children in the Ashanti Region , Ghana . RESULTS We found that the risk of stunting increases by 0.32 ( P-value : 0.004 , 95 % CI : 0.09 , 1.0 ) for every malaria episode . The risk estimate based on Mendelian r and omization substantially differs from the multiple regression estimate of 0.02 ( P-value : 0.02 , 95 % CI : 0.003 , 0.03 ) . In addition , based on the sensitivity analysis , our results were reasonably insensitive to unmeasured confounders . CONCLUSIONS The method applied in this study indicates a causal relationship between malaria  and stunting in young children in an area of high endemicity and demonstrates the usefulness of the sickle cell trait as an instrument for the analysis of conditions that might be causally related to malaria Negative consequences of malaria might account for seasonality in nutritional status in children in the Sahel . We report the impact of a r and omized , double-blind , placebo-controlled trial of seasonal intermittent preventive anti-malarial treatment on growth and nutritional status in 1,063 Senegalese preschool children .  A combination of artesunate and sulfadoxine-pyrimethamine was given monthly from September to November . In the intervention arm , mean weight gain was significantly greater ( 122.9 + /- 340 versus 42.9 + /- 344 [ SD ] g/mo , P < 0.0001 ) and losses in triceps and subscapular skinfold measurements were less ( -0.39 + /- 1.01 versus -0.66 + /- 1.01 mm/mo , and -0.15 + /- 0.64 versus -0.36 + /- 0.62 mm/mo , respectively , P < 0.0001 for both ) . There was no difference in height increments . The prevalence of wasting increased significantly in the control arm ( 4.6 % before versus 9.5 % after , P < 0.0001 ) , but remained constant in intervention children : 5.6 % versus 7.0 % ( P = 0.62 ) . The prevention of malaria would improve child nutritional status in areas with seasonal transmission BACKGROUND The mechanisms of severe malarial anemia and cerebral malaria , which are extreme manifestations of Plasmodium falciparum malaria , are not fully understood . METHODS Children aged < 6 years from southern Zambia presenting to the hospital with severe malarial anemia ( n = 72 ) , cerebral malaria ( n = 28 ) , or uncomplicated malaria ( n = 66 ) were studied prospect ively . Children with overlapping severe anemia and cerebral malaria were excluded . RESULTS Low interleukin 10 concentrations had the strongest association with severe anemia ( st and ard β = .61 ; P < .001 ) followed by high tumor necrosis factor α and sFas concentrations , low weight-for-age z scores , presence of stool parasites , and splenomegaly ( st and ard β = .15-.25 ; P ≤ .031 ) ; most of these factors were also associated with lower reticulocytes . Greater parasitemia was associated with higher interleukin 10 and tumor necrosis factor α concentrations , whereas sulfadoxizole/pyrimethamine therapy and lower weight-for-age z scores were associated with lower interleukin 10 levels . Thrombocytopenia and elevated tissue plasminogen activator inhibitor 1 levels had the strongest associations with cerebral malaria ( st and ard β = .37 or .36 ; P < .0001 ) , followed by exposure to traditional herbal medicine and hemoglobinuria ( st and ard β = .21-.31 ; P ≤ .006 ) . CONCLUSIONS Predictors of severe malarial anemia ( altered immune responses 
    Output:
    
agent
Conclusions This systematic review found that most of the evidence associating malaria and malnutrition comes from P. falciparum endemic areas , with a significant heterogeneity in studies ’ design .
Apparently malnutrition has not a great impact on malaria morbidity , but could have a negative impact on malaria mortality and severity .
Most studies show no association between malaria and subsequent malnutrition in P. falciparum areas .
In Plasmodium vivax endemic areas , malaria was associated with malnutrition in children .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND No comprehensive data on the clinical features and the prognosis of cerebral malaria in the South Pacific are available at present . We conducted a prospect i ve study in children with cerebral malaria to assess the case fatality rate ( CFR ) in the region and to identify potential risk factors for death . METHODS We recruited 134 children admitted to the Madang General Hospital between April 1991 and October 1993 with a strictly defined diagnosis of cerebral malaria . Besides clinical examination , we collected a blood sample for parasitological haematological and biochemical assessment .  RESULTS The CFR was 11.9 % and the prevalence of residual neurological sequelae at discharge was 1.5 % . The proportion of children presenting with deep coma ( 12 % ) or hypoglycaemia ( 17 % ) was lower in our study than in African ones , where severe complications are more frequent . Also mortality associated with hypoglycaemia on admission was lower . Clinical or laboratory conditions significantly associated with death were deep coma , malarial anaemia and hyperleucocytosis . CONCLUSIONS All conditions associated with deep coma , such as shock , hypoglycaemia and acidosis , should be corrected . Also prompt administration of blood transfusions to patients with anaemia is likely to reduce the occurrence of death in Papua New Guinean children with cerebral malaria BACKGROUND The relation between malnutrition and malaria is controversial . On the one h and , malaria may cause malnutrition , whereas on the other h and , malnutrition itself may modulate susceptibility to the disease . OBJECTIVE The objective was to investigate the association between Plasmodium falciparum malaria and malnutrition in a cohort of Kenyan children . DESIGN The study involved the longitudinal follow-up of children aged 0 - 95 [ corrected ] mo for clinical malaria episodes and anthropometric measurements through 4  cross-sectional surveys . We used Poisson regression analysis to investigate the association between malaria and nutritional status . RESULTS The crude incidence rate ratios ( IRRs ) for malaria during the 6-mo period before assessment in children defined as malnourished on the basis of low height-for-age or low weight-for-age z scores ( < -2 ) were 1.17 ( 95 % CI : 0.91 , 1.50 ; P=0.21 ) and 0.94 ( 0.71 , 1.25 ; P=0.67 ) , respectively , which suggests no association between malaria and the subsequent development of protein-energy malnutrition . However , we found that age acted as an effect modifier in the association between malaria episodes and malnutrition on prospect i ve follow-up . The IRR for malaria in children aged 0 - 2 y , who were subsequently characterized as underweight , was 1.65 ( 1.10 , 2.20 ; P=0.01 ) , and a significant overall relation between malaria and stunting was found on regression analysis after adjustment for the interaction with age ( IRR : 1.91 ; 1.01 , 3.58 ; P=0.04 ) . CONCLUSION Although children living on the coast of Kenya continue to experience clinical episodes of uncomplicated malaria throughout the first decade of life , the effect of malaria on nutritional status appears to be greatest during the first 2 y of life BACKGROUND Previous analyses derived the relative risk ( RR ) of dying as a result of low weight-for-age and calculated the proportion of child deaths worldwide attributable to underweight . OBJECTIVES The objectives were to examine whether the risk of dying because of underweight varies by cause of death and to estimate the fraction of deaths by cause attributable to underweight . DESIGN Data were obtained from investigators of 10 cohort studies with both weight-for-age category ( < -3 SDs , -3 to < -2 SDs , -2 to < -1 SD , and > -1 SD ) and cause of death information . All 10 studies contributed information on weight-for-age and risk of diarrhea , pneumonia , and all-cause mortality ; however , only 6 studies contributed information on deaths because of measles , and only 3 studies contributed information on deaths because of malaria or fever . With use of weighted r and om effects models , we related the log mortality rate by cause and anthropometric status in each study to derive cause-specific RRs of dying because of undernutrition . Prevalences of each weight-for-age category were obtained from analyses of 310 national nutrition surveys . With use of the RR and prevalence information , we then calculated the fraction of deaths by cause attributable to undernutrition . RESULTS The RR of mortality because of low weight-for-age was elevated for each cause of death and for all-cause mortality . Overall , 52.5 % of all deaths in young children were attributable to undernutrition , varying from 44.8 % for deaths because of measles to 60.7 % for deaths because of diarrhea . CONCLUSION A significant proportion of deaths in young children worldwide is attributable to low weight-for-age , and efforts to reduce malnutrition should be a policy priority Objective : To examine the relation of circulating appetite neuropeptides , CCK-8 sulphate ( CCK-8s ) and β-endorphin , and the tumour necrosis factor-alpha ( TNF-α ) and soluble TNF receptors ( sTNFR ) to the anorexia and wasting associated with HIV-infection . Design : Cross-sectional analysis . Setting : A university-based HIV/AIDS ambulatory clinic in Madrid , Spain . Participants : Thirty-six r and omly selected AIDS patients without concomitant diseases or secondary infections were classified into two groups : 19 patients with wasting and 17 with normal body weight , and 18 healthy controls . Measurements : Nutritional status was evaluated by anthropometry , laboratory parameters and  self-report of appetite . Plasma levels of TNF-α and sTNFR proteins p55 ( sTNFR-p55 )  and p75 ( sTNFR-p75 ) were determined by enzyme immunoassay , whereas CCK-8s and β-endorphin levels were measured by radioimmunoassay . Results : AIDS patients with wasting had significantly higher plasma concentrations of CCK-8s , but lower levels of β-endorphin when compared to well-nourished AIDS patients ( P < 0.01 ) or controls ( P < 0.001 ) . Mean levels of TNF-α , and sTNFR-p55 and sTNFR-p75 were greater in AIDS patients with wasting than in asymptomatic AIDS patients or in controls . No significant association was observed between any of these circulating peptides and the parameters of malnutrition . Conclusions : An activation of the TNF system , together with reciprocal changes in plasma concentrations of two neuropeptides with opposing appetite regulation , that is increased concentrations of CCK-8s but lower levels of β-endorphin , are associated with the presence of HIV wasting . We hypothesize that these changes may contribute to the development of HIV wasting by producing a pathological inhibition of appetite BACKGROUND Children 's development is affected by the interplay of internal and external factors and changes in one factor can precipitate changes in multiple developmental domains . AIMS The aim of this study was to test a theoretical model of children 's development using structural equation modeling . STUDY DESIGN This was design ed as a sub study of a r and omized , placebo-controlled , 2 × 2 factorial trial of the effects of daily supplementation with iron ( 12.5 mg ) + folic acid ( 50 μg ) ( FeFA ) with or without zinc ( 10 mg ) ( Zn ) on child mortality . SUBJECTS Zanzibari children aged 5 - 9 mo ( n = 106 ) and 10 - 14 mo ( n = 141 ) at baseline were included in this sub study . OUTCOME MEASURES Longitudinal data on children 's hemoglobin , growth , malaria infection , motor development , motor activity , and language development and caregiver behavior were used to test the fit of the theoretical model for two age groups and to examine the direct and indirect relationships among the variables in the model . RESULTS The theoretical models were a good fit to the data for both age groups and revealed that FeFA with or without Zn had positive effects on motor development . FeFA alone had negative effects on language development in both age groups and Zn alone had negative effects on language development in children aged 10 - 14 mo . The incidence of malaria had negative effects on the majority of health and development outcomes in children aged 5 - 9 mo , and on motor development and hemoglobin in children aged 10 - 14 mo . CONCLUSIONS These findings illustrate how nutrition and health factors can affect different domains of development and how these changes can precipitate changes in other domains . More work is needed to better underst and the multiple impacts of internal and external factors on children 's development and how changes in developmental domains interact with each other over time to determine children 's overall developmental trajectory . The r and omized , placebo-controlled study was registered as an International St and ard R and omized Controlled Trial , number IS RCT N59549825 BACKGROUND Previous studies on the association of malaria and stunted growth  delivered inconsistent results . These conflicting results may be due to different levels of confounding and to considerable difficulties in elucidating a causal relationship . R and omized experiments are impractical and previous observational studies have not fully controlled for potential confounding including nutritional deficiencies , breastfeeding habits , other infectious diseases and socioeconomic status . METHODS This study aims to estimate the causal effect between malaria episodes and stunted growth by applying a combination of Mendelian r and omization , using the sickle cell trait , and matching . We demonstrate the method on a cohort of children in the Ashanti Region , Ghana . RESULTS We found that the risk of stunting increases by 0.32 ( P-value : 0.004 , 95 % CI : 0.09 , 1.0 ) for every malaria episode . The risk estimate based on Mendelian r and omization substantially differs from the multiple regression estimate of 0.02 ( P-value : 0.02 , 95 % CI : 0.003 , 0.03 ) . In addition , based on the sensitivity analysis , our results were reasonably insensitive to unmeasured confounders . CONCLUSIONS The method applied in this study indicates a causal relationship between malaria  and stunting in young children in an area of high endemicity and demonstrates the usefulness of the sickle cell trait as an instrument for the analysis of conditions that might be causally related to malaria Negative consequences of malaria might account for seasonality in nutritional status in children in the Sahel . We report the impact of a r and omized , double-blind , placebo-controlled trial of seasonal intermittent preventive anti-malarial treatment on growth and nutritional status in 1,063 Senegalese preschool children .  A combination of artesunate and sulfadoxine-pyrimethamine was given monthly from September to November . In the intervention arm , mean weight gain was significantly greater ( 122.9 + /- 340 versus 42.9 + /- 344 [ SD ] g/mo , P < 0.0001 ) and losses in triceps and subscapular skinfold measurements were less ( -0.39 + /- 1.01 versus -0.66 + /- 1.01 mm/mo , and -0.15 + /- 0.64 versus -0.36 + /- 0.62 mm/mo , respectively , P < 0.0001 for both ) . There was no difference in height increments . The prevalence of wasting increased significantly in the control arm ( 4.6 % before versus 9.5 % after , P < 0.0001 ) , but remained constant in intervention children : 5.6 % versus 7.0 % ( P = 0.62 ) . The prevention of malaria would improve child nutritional status in areas with seasonal transmission BACKGROUND The mechanisms of severe malarial anemia and cerebral malaria , which are extreme manifestations of Plasmodium falciparum malaria , are not fully understood . METHODS Children aged < 6 years from southern Zambia presenting to the hospital with severe malarial anemia ( n = 72 ) , cerebral malaria ( n = 28 ) , or uncomplicated malaria ( n = 66 ) were studied prospect ively . Children with overlapping severe anemia and cerebral malaria were excluded . RESULTS Low interleukin 10 concentrations had the strongest association with severe anemia ( st and ard β = .61 ; P < .001 ) followed by high tumor necrosis factor α and sFas concentrations , low weight-for-age z scores , presence of stool parasites , and splenomegaly ( st and ard β = .15-.25 ; P ≤ .031 ) ; most of these factors were also associated with lower reticulocytes . Greater parasitemia was associated with higher interleukin 10 and tumor necrosis factor α concentrations , whereas sulfadoxizole/pyrimethamine therapy and lower weight-for-age z scores were associated with lower interleukin 10 levels . Thrombocytopenia and elevated tissue plasminogen activator inhibitor 1 levels had the strongest associations with cerebral malaria ( st and ard β = .37 or .36 ; P < .0001 ) , followed by exposure to traditional herbal medicine and hemoglobinuria ( st and ard β = .21-.31 ; P ≤ .006 ) . CONCLUSIONS Predictors of severe malarial anemia ( altered immune responses 
    Output:
    