title: Indicators of fatal outcome in paediatric cerebral malaria: a study of 134 comatose Papua New Guinean children. Malaria and nutritional status in children living on the coast of Kenya. Undernutrition as an underlying cause of child deaths associated with diarrhea, pneumonia, malaria, and measles. Altered concentrations of appetite regulators may contribute to the development and maintenance of HIV‐associated wasting Developmental effects of micronutrient supplementation and malaria in Zanzibari children. The causal effect of malaria on stunting: a Mendelian randomization and matching approach. Impact of intermittent preventive anti-malarial treatment on the growth and nutritional status of preschool children in rural Senegal (west Africa). Distinct clinical and immunologic profiles in severe malarial anemia and cerebral malaria in Zambia. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. REFEEDING-MALARIA AND HYPERFERRÆMIA Influence of nutritional status on child mortality in rural Zaire Effects of acute Plasmodium falciparum malaria on body weight in children in an endemic area Factors associated with growth patterns from birth to 18 months in a Beninese cohort of children.
abstract: 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 , poor nutrition , intestinal parasites , and impaired erythropoiesis ) differed from those of cerebral malaria ( thrombocytopenia , herbal medicine , and intravascular hemolysis ) . Improved preventive and therapeutic measures may need to consider these differences OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity During the Central African ( Sahelian ) drought , attacks of falciparum malaria were common in patients and their relatives shortly after their arrival in a hospital in Eastern Niger . A prospect i ve study of 72 adult patients not admitted for malaria and 109 accompanying relatives was undertaken to investigate this observation . 23 attacks occurred in patients and 51 in relatives , with a peak frequency five days after arrival . On arrival , parasitaemia was low but reached a maximum by five days . Serum-iron and percentage saturation of transferrin were moderately increased initially , rose dramatically within forty-eight hours with near maximum saturation , and were falling by the fifth day . It is suggested that the early hyperferraemia , apparently related to refeeding , led to rapid multiplication of existing parasites and attacks of malaria . The results of experimental malarial infection of Wistar rats , half of which had been given intramuscular iron , supported this hypothesis Although the association between nutritional status and mortality risk is obvious for extreme malnutrition , the issue is not so clear for mild to moderate undernutrition . We have investigated this association in children of 0 - 5 years in the rural area of Bwam and a , Zaire , where an integrated development project , with good medical facilities , has operated for 20 years . A r and om cluster sample of 5167 children was taken ; newborn infants and immigrants were included at six quarterly survey rounds from October , 1989 , until February , 1991 . All surveys included clinical and anthropometric assessment of nutritional status . Deaths were recorded up to April , 1992 ; there were 246 deaths . Marasmus , kwashiorkor , and other causes of death were defined by the verbal autopsy method and checked against medical records kept at the central hospital and the peripheral dispensaries . As expected , we found an increased risk of death in severe malnutrition . When deaths directly attributed to marasmus or kwashiorkor were excluded , mild to moderate stunting or wasting were not associated with higher mortality in the short term ( within 3 months of the previous study round ) or in the long term ( from 3 - 30 months after study entry ) . The commonest causes of death were malaria and anaemia . Extreme marasmus and kwashiorkor caused 16 % of deaths , and are important causes of death even in this favoured area with an integrated development project . Nutritional interventions should be targeted more selectively so that children with moderate malnutrition can be protected from progression to marasmus or kwashiorkor The impacts of acute falciparum malaria  on body weight and the host and parasite factors predictive of change in body weight were characterized in 465 prospect ively studied children in an endemic area of southwest Nigeria . Pre-treatment weights were significantly lower than the 14 to 28-day post-treatment weights ( P = 0.0001 ) . In 187 children , fractional fall in body weight ( FFBW ) exceeded 4.9 % . FFBW correlated negatively with age and body weight ( P = 0.014 and 0.0001 , respectively ) , but not with enrolment parasitaemia . In a multiple regression model , an age ≤5 years ( AOR = 2.03 , 95 % CI 1.2–3.2 , P = 0.003 ) , a hematocrit ≤29 % ( AOR = 1.6 , 95 % CI 1.0–2.3 , P = 0.037 ) , and a body weight ≤9.6 kg ( AOR = 5.4 , 95 % CI 1.7–20 , P = 0.003 ) were independent predictors of FFBW ≥5 % at presentation . Children who , after initial clearance , had recurrence of their parasitaemia within 28 days had a significantly higher propensity not to gain weight than children who were aparasitaemic after treatment ( log-rank statistic 6.76 , df = 1 , P = 0.009 ) . These results indicate that acute malaria contribute to sub-optimal growth in young children and may have implication s for malaria control efforts in sub-Saharan Africa The aim of this study was to analyze factors influencing the growth pattern of children from birth to 18 months . A longitudinal prospect i ve study was conducted in three maternity wards in Southern Benin . Inclusion took place between June 2007 and July 2008 ; children were followed-up until 18 months of age . Height-for-age and weight-for-height Z-scores were computed using the newborn 's anthropometric measurements taken at delivery , every month up to 6 months and then quarterly . Infant and young child feeding ( IYCF ) practice s and malarial morbidity were recorded . Gestational age was estimated using the Ballard method ; William 's sex-specific reference curve of birth weight-for-gestational-age was used to determine intrauterine growth retardation ( IUGR ) . Analyses were performed on 520 children using a linear mixed model . Low birth weight ( coef=-0.43 ; p=0.002 ) , IUGR ( coef=-0.49 ; p<0.001 ) , maternal short stature ( coef=-0.25 ; p=0.001 ) and maternal low weight status ( coef=-0.19 ; p=0.006 ) were significantly associated with growth impairment . Only LBW ( coef=-0.28 ; p=0.05 ) and maternal low weight status ( coef=-0.23 ; p=0.004 ) were associated with wasting . A good IYCF score was positively associated with weight gain ( coef=0.14 ; p<0.001 ) whereas we found a paradoxical association with length ( coef=-0.18 ; p<0.001 ) . Malaria morbidity was not associated with growth . LBW , IUGR and maternal low weight status and height were important determinants of children 's growth . These results reinforce and justify continuing public health initiatives to fight IUGR and LBW and break the intergenerational cycle of malnutrition
target: 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 .
background: Background Multiple studies in various parts of the world have analysed the association of nutritional status on malaria using anthropometric measures , but results differ due to the heterogeneity of the study population , species of the parasite , and other factors involved in the host and parasite relationship .
  The aim of this study was to perform a systematic review on the inter-relationship of nutritional status based on anthropometry and malarial infection .