The Associations of Malaria and Linear Growth Faltering in Infants and Young Children in Malawi

Kasvun hidastumisen (ikäisekseen lyhyt) ja malarian maantieteellinen päällekkäisyys viittaa siihen, että ne olisivat yhteydessä toisiinsa, mutta tästä ei toistaiseksi ole selvää näyttöä. Kasvun hidastumista pyritään estämään mm. parantamalla kotona annettavaa täydennysravintoa. Tähän käytetään esimerkiksi rasvapohjaisia ravintolisiä (lipid-based nutrient supplements, LNS). On kuitenkin oltu huolissaan siitä, että rautaa sisältävät LNS-valmisteet voivat lisätä lasten malariariskiä. Siksi pitää selvittää, onko kasvun hidastumisen ja malarian välillä syy-yhteys ja voiko LNS-valmisteiden käyttö estämään kasvun hidastumista lisätä malarian riskiä. Tämän tutkimuksen tavoitteena oli siksi selvittää, voiko pituuskasvun häiriö ennustaa malariariskiä, aiheuttaako malaria pituuskasvun häiriöitä, hidastaako se lapsen kehitystä, ja lisääkö LNS-valmisteiden käyttö malariariskiä. Näitä selvitettiin käyttäen kansainväliseen iLiNS-projektin (International Lipid-based Nutrient Supplements Project) tutkimuksiin (iLiNS-DOSE ja iLiNS-DYAD-M) Malawin maaseudulla vuosina 2009–2015 osallistuneiden lasten tietoja. Tutkimuksiin otettiin kaikkiaan 2 725 kuuden kuukauden ikäistä lasta, joiden sairastuvuutta seurattiin viikoittain kotikäynneillä, joilla syntyi malariaepäily. Malariasta kerättiin lisätietoa klinikkakäynneillä. Antropometrisia tietoja kerättiin 6 kuukauden ja 18 kuukauden klinikkakäynneillä, joilla määritettiin LAZ-pistemäärä (length-for-age z), joka kuvaa pituutta ikään nähden. Kasvun hidastumisesta katsottiin olevan kyse, jos LAZ-pistemäärä oli < -2. Kehitystä (hieno- ja karkeamotoriikkaa, kielen kehitystä sekä sosiaalisen ja emotionaalisen kehityksen profiilia [Profile of Social and Emotional Development, PSED]) kuvaavat pistemäärät arvioitiin 18 kuukauden klinikkakäynnillä. Täydelliset sairastuvuustiedot saatiin 18 kuukauden iässä 2 561 lapselta (94 %), ja heillä ilmoitettiin olleen 28 032 sairausjaksoa, joista 9,7 % oli oletettavasti malariaa. Kaikkien sairauksien esiintyvyyden keskiarvo (SD) oli 16,2 (13,1) jaksoa lapsivuotta kohti, ja näistä 1,1 (1,6) oli oletettavasti malariaa. Lapset kävivät sairauden vuoksi keskimäärin 5,5 kertaa sairaalassa, ja näistä käynneistä 1,7 johtui malariasta. Mikroskoopilla varmistetun malarian esiintyvyys kasvoi 4,7 prosentista 6 kuukauden iässä 9,6 prosenttiin 18 kuukauden iässä. LAZ-pistemäärä 6 kuukauden iässä ei ollut yhteydessä oletetun malarian ilmaantuvuuteen 12 kuukauden iässä (ilmaantumistiheyksien suhde [IRR] = 1,03, 95 %:n luottamusväli = 0,98–1,09, p = 0,394) eikä malarialoisen esiintyvyyteen veressä 18 kuukauden iässä (vallitsevuussuhde [PR] = 1,11, 95 %:n luottamusväli = 0,93–1,33, p = 0,259). Kuuden ja 18 kuukauden iän välillä keskimääräinen (SD) LAZ-pistemäärän muutos oli -0,44 (0,77) ja kasvun hidastumisen esiintyvyys lisääntyi 26,7 prosentista 41,2 prosenttiin. 18 kuukauden iässä pistemäärien keskiarvot (SD) olivat seuraavat: hienomotoriikka 20,9 (2,2), karkeamotoriikka 17,3 (2,6), kielen kehitys 26,2 (5,0) ja PSED 16,2 (5,4). Oletetun malarian ilmaantuvuuden ja LAZ- pistemäärän muutoksen välillä ei ollut tilastollisesti merkitsevää yhteyttä (B = -0,02, 95 %:n luottamusväli = -0,04–0,01, p = 0,069). Oletetun malarian ilmaantuvuus oli merkitsevästi yhteydessä niiden lasten lisääntyneeseen osuuteen, joiden kasvu oli hidastunut 18 kuukauden iässä (riskisuhde = 1,04, 95 prosentin luottamusväli = 1,01–1,07, p = 0,023). Yhteys oletetun malarian ilmaantuvuuden ja lapsen kehityksen välillä 18 kuukauden iässä oli merkitsevä PSED-pistemäärien osalta (B = -0,21, 95 prosentin luottamusväli = 0,39 – -0,03; p = 0,041) mutta ei muilla lapsen kehityksen osa-alueilla. LNS-valmisteiden turvallisuudesta todettiin, että oletetun, kliinisen tai varmistetun malarian ilmaantuvuudessa ei ollut eroa erisuuruisia LNS-annoksia käyttäneillä. Verrokkiryhmään verrattuna niin oletetun, kliinisen kuin varmistetunkin malarian IRR-arvojen 95 prosentin luottamusvälit olivat alle 1,20 (mikä tarkoittaa vertailukelpoisuutta [non-inferiority]) kaikissa interventioryhmissä, paitsi 40 g/vrk LNS-valmistetta saaneessa ryhmässä, jossa varmistetun malarian ilmaantuvuus oli 21 % suurempi kuin verrokkiryhmässä. Yhteenvetona voidaan sanoa, että malawilaisessa maalaisväestössä sekä kasvun hidastuminen että malaria ovat yleisiä, mutta jos lapsia seurataan aktiivisesti ja infektiot hoidetaan hyvissä ajoin, pituuskasvun häiriö 6 kuukauden iässä ei ennusta malarian ilmaantuvuutta 6–18 kuukauden iässä. Tässä populaatiossa malaria ei liity LAZ-arvon muutokseen mutta voi lisätä kasvun hidastumisen riskiä ja heikentää sosioemotionaalista kehitystä. Lopuksi rautaa sisältävien LNS-valmisteiden pitkäaikainen käyttö tietyn suuruisina annoksina ei lisää malarian riskiä tässä populaatiossa, jossa raudanpuute ja moskiittoverkon käyttö sängyn ympärillä ovat yleisiä. Näistä löydöksistä saattaa olla hyötyä suunniteltaessa vauvojen ja pikkulasten kasvun edistämiseen ja malarian hallintaan tähtääviä toimenpiteitä malarian endeemisillä alueilla.The geographic overlap between stunting (small length for age) and malaria suggests there is a relationship between the two conditions, but current evidence is inconclusive. Interventions aimed to prevent stunting include improving the quality of complementary foods through home fortification with products such as lipid- based nutrient supplements (LNS). However, there are concerns that LNS, which contains iron, can increase the risk of malaria in children. Hence the need to establish whether a causal relationship exists between stunting and malaria; and whether LNS provision to prevent stunting can increase the risk of malaria. The present study was therefore designed to determine: whether linear growth faltering can predict the risk of malaria; whether malaria causes linear growth faltering and poor child development; and whether LNS provision does not increase the risk of malaria. These aims were addressed using data from children enrolled in the International Lipid-based Nutrient Supplements Project (iLiNS) trials (iLiNS- DOSE and iLiNS-DYAD-M), conducted in rural Malawi between 2009 and 2015. A total of 2,725 six-month old children were enrolled and followed during weekly morbidity home visits, where a diagnosis of presumed malaria was made. Additional malaria data were collected at clinic visits. Anthropometry data were collected at 6 months’ and 18 months’ clinic visits where length-for-age z scores [LAZ] were obtained. Stunting was defined as LAZ <-2. Developmental outcomes (fine motor scores, gross motor scores, language scores and Profile of Social and Emotional Development [PSED] scores) were assessed at 18 months’ clinic visit. At 18 months, 2,561 (94%) children had complete morbidity data and reported 28,032 morbidity episodes, 9.7% of which were episodes of presumed malaria. The mean (SD) incidence of all illnesses combined was 16.2 (13.1) episodes per child year, of which 1.1 (1.6) were episodes of presumed malaria. On average, the children made 5.5 visits to the hospital due to illness, of which 1.7 were due to malaria. The prevalence of malaria confirmed by microscopy increased from 4.7% to 9.6% between 6 months and 18 months. There was no association of LAZ at 6 months with subsequent 12-month incidence of presumed malaria (incidence rate ratio [IRR] = 1.03; 95% CI = 0.98 to 1.09; p =0.394) or prevalence of malaria parasitaemia at 18 months (prevalence ratio = 1.11; 95% CI = 0.93 to 1.33; p = 0.259). Between 6 months and 18 months, the mean (SD) change in LAZ was -0.44 (0.77) and the prevalence of stunting increased from 26.7% to 41.2%. At 18 months, the mean (SD) for fine motor, gross motor, language and PSED scores were 20.9 (2.2), 17.3 (2.6), 26.2 (5.0) and 16.2 (5.4) respectively. There was no statistically significant association of presumed malaria incidence with change in LAZ (B = -0.02, 95% CI = -0.04 to 0.01, p = 0.069). Presumed malaria incidence was significantly associated with increased proportion of children with stunting at 18 months (risk ratio = 1.04, 95% CI = 1.01 to 1.07, p = 0.023). The association of presumed malaria incidence with child development at 18 months was significant for PSED scores (B = -0.21; 95% CI = 0.39 to -0.03; p = 0.041), but not for the other domains of child development. Regarding the safety of LNS, there were no significant differences in the incidence of presumed malaria, clinical malaria nor confirmed malaria across the different doses of LNS. Compared to the control group, the 95% CIs of the IRRs for presumed malaria, clinical malaria, and confirmed malaria were entirely below 1.20 (suggestive of non-inferiority) in all the intervention groups, except for the 40 g/d LNS where the incidence of confirmed malaria was 21% higher in this group than the control. In conclusion, in a rural Malawian population, where both stunting and malaria are common, but with active surveillance and early treatment of infections, linear growth faltering at 6 months does not predict malaria incidence from 6 months to 18 months. In this population, malaria is not associated with change in LAZ but may increase the risk of stunting and reduce socio-emotional development. Finally, long term provision of iron-containing LNS at certain doses does not increase the risk of malaria in this population where iron deficiency and mosquito bed net utilization is high. These findings could be useful when designing growth promotion and malaria control interventions for infants and young children in malaria-endemic areas

Predictors and pathways of language and motor development in four prospective cohorts of young children in Ghana, Malawi, and Burkina Faso

BackgroundPrevious reviews have identified 44 risk factors for poor early child development (ECD) in low- and middle-income countries. Further understanding of their relative influence and pathways is needed to inform the design of interventions targeting ECD.MethodsWe conducted path analyses of factors associated with 18-month language and motor development in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements (iLiNS) Project in Ghana (n&nbsp;=&nbsp;1,023), Malawi (n&nbsp;=&nbsp;675 and 1,385), and Burkina Faso (n&nbsp;=&nbsp;1,122). In two cohorts, women were enrolled during pregnancy. In two cohorts, infants were enrolled at 6 or 9&nbsp;months. In multiple linear regression and structural equation&nbsp;models (SEM), we examined 22 out of 44 factors identified in previous reviews, plus 12 additional factors expected to be associated with ECD.ResultsOut of 42 indicators of the 34 factors examined, 6 were associated with 18-month language and/or motor development in 3 or 4 cohorts: child linear and ponderal growth, variety of play materials, activities with caregivers, dietary diversity, and child hemoglobin/iron status. Factors that were not associated with child development were indicators of maternal Hb/iron status, maternal illness and inflammation during pregnancy, maternal perceived stress and depression, exclusive breastfeeding during 6&nbsp;months postpartum, and child diarrhea, fever, malaria, and acute respiratory infections. Associations between socioeconomic status and language development were consistently mediated to a greater extent by caregiving practices than by maternal or child biomedical conditions, while this pattern for motor development was not consistent across cohorts.ConclusionsKey elements of interventions to ensure quality ECD are likely to be promotion of caregiver activities with children, a variety of play materials, and a diverse diet, and prevention of faltering in linear and ponderal growth and improvement in child hemoglobin/iron status

Infections and systemic inflammation are associated with lower plasma concentration of insulin-like growth factor I among Malawian children

Background: Insulin-like growth factor I (IGF-I) is the most important hormonal promoter of linear growth in infants and young children. Objectives: The objectives of this study were to compare plasma IGF-I concentration in a low- compared with a high-income country and characterize biological pathways leading to reduced IGF-I concentration in children in a low-income setting. Methods: We analyzed plasma IGF-I concentration from 716 Malawian and 80 Finnish children at 6-36 mo of age. In the Malawian children, we studied the association between IGF-I concentration and their environmental exposures; nutritional status; systemic and intestinal inflammation; malaria parasitemia and viral, bacterial, and parasitic enteric infections; as well as growth at 18 mo of age. We then conducted a pathway analysis to identify direct and indirect associations between these predictors and IGF-I concentration. Results: The mean IGF-I concentrations were similar in Malawi and Finland among 6-mo-old infants. At age 18 mo. the mean +/- SD concentration was almost double among the Finns compared with the Malawians [24.2 +/- 11.3 compared with 12.5 +/- 7.7 ng/mL., age- and sex-adjusted difference in mean (95% CI): 11.8 (9.9. 13.7) ng/mL; P <0.01]. Among 18-mo-old Malawians, plasma IGF-I concentration was inversely associated with systemic inflammation, malaria parasitemia, and intestinal Shigella. Campylobacter, and enterovirus infection and positively associated with the children's weight-for-length z score (WLZ), female sex, maternal height, mother's education, and dry season. Seasonally, mean plasma IGF-I concentration was highest in June and July and lowest in December and January, coinciding with changes in children's length gain and preceded by similar to 2 mo by the changes in their WLZ. Conclusions: The mean plasma IGF-I concentrations are similar in Malawi and Finland among 6-mo-old infants. Thereafter, mean concentrations rise markedly in Finland but not in Malawi. Systemic inflammation and clinically nonapparent infections are strongly associated with lower plasma IGF-I concentrations in Malawi through direct and indirect pathways.Peer reviewe

Path Analyses of Risk Factors for Linear Growth Faltering in Four Prospective Cohorts of Young Children in Ghana, Malawi and Burkina Faso

Stunting prevalence is an indicator of a country’s progress towards United Nations’ Sustainable Development Goal 2, which is to end hunger and achieve improved nutrition. Accelerating progress towards reducing stunting requires a deeper understanding of the factors that contribute to linear growth faltering. We conducted path analyses of factors associated with 18-month length-for-age z-score (LAZ) in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements Project in Ghana (n=1039), Malawi (n=684 and 1504) and Burkina Faso (n=2619). In two cohorts, women were enrolled during pregnancy. In two other cohorts, infants were enrolled at 6 or 9 months. We examined the association of 42 indicators of environmental, maternal, caregiving and child factors with 18-month LAZ. Using structural equation modelling, we examined direct and indirect associations through hypothesised mediators in each cohort. Out of 42 indicators, 2 were associated with 18-month LAZ in three or four cohorts: maternal height and body mass index (BMI). Six factors were associated with 18-month LAZ in two cohorts: length for gestational age z-score (LGAZ) at birth, pregnancy duration, improved household water, child dietary diversity, diarrhoea incidence and 6-month or 9-month haemoglobin concentration. Direct associations were more prevalent than indirect associations, but 30%–62% of the associations of maternal height and BMI with 18-month LAZ were mediated by LGAZ at birth. Factors that were not associated with LAZ were maternal iron status, illness and inflammation during pregnancy, maternal stress and depression, exclusive breast feeding during 6 months post partum, feeding frequency and child fever, malaria and acute respiratory infections. These findings may help in identifying interventions to accelerate progress towards reducing stunting; however, much of the variance in linear growth status remained unaccounted for by these 42 individual-level factors, suggesting that community-level changes may be needed to achieve substantial progress

Association between asymptomatic infections and linear growth in 18–24-month-old Malawian children

Inadequate diet and frequent symptomatic infections are considered major causes of growth stunting in low-income countries, but interventions targeting these risk factors have achieved limited success. Asymptomatic infections can restrict growth, but little is known about their role in global stunting prevalence. We investigated factors related to length-for-age Z-score (LAZ) at 24 months by constructing an interconnected network of various infections, biomarkers of inflammation (as assessed by alpha-1-acid glycoprotein [AGP]), and growth (insulin-like growth factor 1 [IGF-1] and collagen X biomarker [CXM]) at 18 months, as well as other children, maternal, and household level factors. Among 604 children, there was a continuous decline in mean LAZ and increased mean length deficit from birth to 24 months. At 18 months of age, the percentage of asymptomatic children who carried each pathogen was: 84.5% enterovirus, 15.5% parechovirus, 7.7% norovirus, 4.6% rhinovirus, 0.6% rotavirus, 69.6% Campylobacter, 53.8% Giardia lamblia, 11.9% malaria parasites, 10.2% Shigella, and 2.7% Cryptosporidium. The mean plasma IGF-1 concentration was 12.5 ng/ml and 68% of the children had systemic inflammation (plasma AGP concentration >1 g/L). Shigella infection was associated with lower LAZ at 24 months through both direct and indirect pathways, whereas enterovirus, norovirus, Campylobacter, Cryptosporidium, and malaria infections were associated with lower LAZ at 24 months indirectly, predominantly through increased systemic inflammation and reduced plasma IGF-1 and CXM concentration at 18 months.publishedVersionPeer reviewe

The Associations of Malaria and Linear Growth Faltering in Infants and Young Children in Malawi

Kasvun hidastumisen (ikäisekseen lyhyt) ja malarian maantieteellinen päällekkäisyys viittaa siihen, että ne olisivat yhteydessä toisiinsa, mutta tästä ei toistaiseksi ole selvää näyttöä. Kasvun hidastumista pyritään estämään mm. parantamalla kotona annettavaa täydennysravintoa. Tähän käytetään esimerkiksi rasvapohjaisia ravintolisiä (lipid-based nutrient supplements, LNS). On kuitenkin oltu huolissaan siitä, että rautaa sisältävät LNS-valmisteet voivat lisätä lasten malariariskiä. Siksi pitää selvittää, onko kasvun hidastumisen ja malarian välillä syy-yhteys ja voiko LNS-valmisteiden käyttö estämään kasvun hidastumista lisätä malarian riskiä. Tämän tutkimuksen tavoitteena oli siksi selvittää, voiko pituuskasvun häiriö ennustaa malariariskiä, aiheuttaako malaria pituuskasvun häiriöitä, hidastaako se lapsen kehitystä, ja lisääkö LNS-valmisteiden käyttö malariariskiä. Näitä selvitettiin käyttäen kansainväliseen iLiNS-projektin (International Lipid-based Nutrient Supplements Project) tutkimuksiin (iLiNS-DOSE ja iLiNS-DYAD-M) Malawin maaseudulla vuosina 2009–2015 osallistuneiden lasten tietoja. Tutkimuksiin otettiin kaikkiaan 2 725 kuuden kuukauden ikäistä lasta, joiden sairastuvuutta seurattiin viikoittain kotikäynneillä, joilla syntyi malariaepäily. Malariasta kerättiin lisätietoa klinikkakäynneillä. Antropometrisia tietoja kerättiin 6 kuukauden ja 18 kuukauden klinikkakäynneillä, joilla määritettiin LAZ-pistemäärä (length-for-age z), joka kuvaa pituutta ikään nähden. Kasvun hidastumisesta katsottiin olevan kyse, jos LAZ-pistemäärä oli < -2. Kehitystä (hieno- ja karkeamotoriikkaa, kielen kehitystä sekä sosiaalisen ja emotionaalisen kehityksen profiilia [Profile of Social and Emotional Development, PSED]) kuvaavat pistemäärät arvioitiin 18 kuukauden klinikkakäynnillä. Täydelliset sairastuvuustiedot saatiin 18 kuukauden iässä 2 561 lapselta (94 %), ja heillä ilmoitettiin olleen 28 032 sairausjaksoa, joista 9,7 % oli oletettavasti malariaa. Kaikkien sairauksien esiintyvyyden keskiarvo (SD) oli 16,2 (13,1) jaksoa lapsivuotta kohti, ja näistä 1,1 (1,6) oli oletettavasti malariaa. Lapset kävivät sairauden vuoksi keskimäärin 5,5 kertaa sairaalassa, ja näistä käynneistä 1,7 johtui malariasta. Mikroskoopilla varmistetun malarian esiintyvyys kasvoi 4,7 prosentista 6 kuukauden iässä 9,6 prosenttiin 18 kuukauden iässä. LAZ-pistemäärä 6 kuukauden iässä ei ollut yhteydessä oletetun malarian ilmaantuvuuteen 12 kuukauden iässä (ilmaantumistiheyksien suhde [IRR] = 1,03, 95 %:n luottamusväli = 0,98–1,09, p = 0,394) eikä malarialoisen esiintyvyyteen veressä 18 kuukauden iässä (vallitsevuussuhde [PR] = 1,11, 95 %:n luottamusväli = 0,93–1,33, p = 0,259). Kuuden ja 18 kuukauden iän välillä keskimääräinen (SD) LAZ-pistemäärän muutos oli -0,44 (0,77) ja kasvun hidastumisen esiintyvyys lisääntyi 26,7 prosentista 41,2 prosenttiin. 18 kuukauden iässä pistemäärien keskiarvot (SD) olivat seuraavat: hienomotoriikka 20,9 (2,2), karkeamotoriikka 17,3 (2,6), kielen kehitys 26,2 (5,0) ja PSED 16,2 (5,4). Oletetun malarian ilmaantuvuuden ja LAZ- pistemäärän muutoksen välillä ei ollut tilastollisesti merkitsevää yhteyttä (B = -0,02, 95 %:n luottamusväli = -0,04–0,01, p = 0,069). Oletetun malarian ilmaantuvuus oli merkitsevästi yhteydessä niiden lasten lisääntyneeseen osuuteen, joiden kasvu oli hidastunut 18 kuukauden iässä (riskisuhde = 1,04, 95 prosentin luottamusväli = 1,01–1,07, p = 0,023). Yhteys oletetun malarian ilmaantuvuuden ja lapsen kehityksen välillä 18 kuukauden iässä oli merkitsevä PSED-pistemäärien osalta (B = -0,21, 95 prosentin luottamusväli = 0,39 – -0,03; p = 0,041) mutta ei muilla lapsen kehityksen osa-alueilla. LNS-valmisteiden turvallisuudesta todettiin, että oletetun, kliinisen tai varmistetun malarian ilmaantuvuudessa ei ollut eroa erisuuruisia LNS-annoksia käyttäneillä. Verrokkiryhmään verrattuna niin oletetun, kliinisen kuin varmistetunkin malarian IRR-arvojen 95 prosentin luottamusvälit olivat alle 1,20 (mikä tarkoittaa vertailukelpoisuutta [non-inferiority]) kaikissa interventioryhmissä, paitsi 40 g/vrk LNS-valmistetta saaneessa ryhmässä, jossa varmistetun malarian ilmaantuvuus oli 21 % suurempi kuin verrokkiryhmässä. Yhteenvetona voidaan sanoa, että malawilaisessa maalaisväestössä sekä kasvun hidastuminen että malaria ovat yleisiä, mutta jos lapsia seurataan aktiivisesti ja infektiot hoidetaan hyvissä ajoin, pituuskasvun häiriö 6 kuukauden iässä ei ennusta malarian ilmaantuvuutta 6–18 kuukauden iässä. Tässä populaatiossa malaria ei liity LAZ-arvon muutokseen mutta voi lisätä kasvun hidastumisen riskiä ja heikentää sosioemotionaalista kehitystä. Lopuksi rautaa sisältävien LNS-valmisteiden pitkäaikainen käyttö tietyn suuruisina annoksina ei lisää malarian riskiä tässä populaatiossa, jossa raudanpuute ja moskiittoverkon käyttö sängyn ympärillä ovat yleisiä. Näistä löydöksistä saattaa olla hyötyä suunniteltaessa vauvojen ja pikkulasten kasvun edistämiseen ja malarian hallintaan tähtääviä toimenpiteitä malarian endeemisillä alueilla.The geographic overlap between stunting (small length for age) and malaria suggests there is a relationship between the two conditions, but current evidence is inconclusive. Interventions aimed to prevent stunting include improving the quality of complementary foods through home fortification with products such as lipid- based nutrient supplements (LNS). However, there are concerns that LNS, which contains iron, can increase the risk of malaria in children. Hence the need to establish whether a causal relationship exists between stunting and malaria; and whether LNS provision to prevent stunting can increase the risk of malaria. The present study was therefore designed to determine: whether linear growth faltering can predict the risk of malaria; whether malaria causes linear growth faltering and poor child development; and whether LNS provision does not increase the risk of malaria. These aims were addressed using data from children enrolled in the International Lipid-based Nutrient Supplements Project (iLiNS) trials (iLiNS- DOSE and iLiNS-DYAD-M), conducted in rural Malawi between 2009 and 2015. A total of 2,725 six-month old children were enrolled and followed during weekly morbidity home visits, where a diagnosis of presumed malaria was made. Additional malaria data were collected at clinic visits. Anthropometry data were collected at 6 months’ and 18 months’ clinic visits where length-for-age z scores [LAZ] were obtained. Stunting was defined as LAZ <-2. Developmental outcomes (fine motor scores, gross motor scores, language scores and Profile of Social and Emotional Development [PSED] scores) were assessed at 18 months’ clinic visit. At 18 months, 2,561 (94%) children had complete morbidity data and reported 28,032 morbidity episodes, 9.7% of which were episodes of presumed malaria. The mean (SD) incidence of all illnesses combined was 16.2 (13.1) episodes per child year, of which 1.1 (1.6) were episodes of presumed malaria. On average, the children made 5.5 visits to the hospital due to illness, of which 1.7 were due to malaria. The prevalence of malaria confirmed by microscopy increased from 4.7% to 9.6% between 6 months and 18 months. There was no association of LAZ at 6 months with subsequent 12-month incidence of presumed malaria (incidence rate ratio [IRR] = 1.03; 95% CI = 0.98 to 1.09; p =0.394) or prevalence of malaria parasitaemia at 18 months (prevalence ratio = 1.11; 95% CI = 0.93 to 1.33; p = 0.259). Between 6 months and 18 months, the mean (SD) change in LAZ was -0.44 (0.77) and the prevalence of stunting increased from 26.7% to 41.2%. At 18 months, the mean (SD) for fine motor, gross motor, language and PSED scores were 20.9 (2.2), 17.3 (2.6), 26.2 (5.0) and 16.2 (5.4) respectively. There was no statistically significant association of presumed malaria incidence with change in LAZ (B = -0.02, 95% CI = -0.04 to 0.01, p = 0.069). Presumed malaria incidence was significantly associated with increased proportion of children with stunting at 18 months (risk ratio = 1.04, 95% CI = 1.01 to 1.07, p = 0.023). The association of presumed malaria incidence with child development at 18 months was significant for PSED scores (B = -0.21; 95% CI = 0.39 to -0.03; p = 0.041), but not for the other domains of child development. Regarding the safety of LNS, there were no significant differences in the incidence of presumed malaria, clinical malaria nor confirmed malaria across the different doses of LNS. Compared to the control group, the 95% CIs of the IRRs for presumed malaria, clinical malaria, and confirmed malaria were entirely below 1.20 (suggestive of non-inferiority) in all the intervention groups, except for the 40 g/d LNS where the incidence of confirmed malaria was 21% higher in this group than the control. In conclusion, in a rural Malawian population, where both stunting and malaria are common, but with active surveillance and early treatment of infections, linear growth faltering at 6 months does not predict malaria incidence from 6 months to 18 months. In this population, malaria is not associated with change in LAZ but may increase the risk of stunting and reduce socio-emotional development. Finally, long term provision of iron-containing LNS at certain doses does not increase the risk of malaria in this population where iron deficiency and mosquito bed net utilization is high. These findings could be useful when designing growth promotion and malaria control interventions for infants and young children in malaria-endemic areas

The Provider Role and Perspective in the Denial of Family Planning Services to Women in Malawi: A Mixed-Methods Study

Family planning (FP) has been a global health priority for decades, yet barriers persist, including women being turned away from facilities without receiving services. This study assessed the provider role and perspective in client turnaway in three districts of Malawi. In 2019, data collectors surveyed 57 FP providers from 30 health facilities. All reported being comfortable providing FP to married women with children and married adolescents under 18 years old with children, whereas 12% of the providers expressed discomfort providing such services to married adolescents under 18 without children. Sixty percent of the providers required clients desiring FP and wishing to initiate oral contraceptives or injectables to be currently menstruating. Data collectors later conducted in-depth interviews (IDIs) with 8 of the 57 providers about client turnaway. During IDIs, providers&rsquo; most frequently mentioned reasons for turnaway was client pregnancy or suspicion of pregnancy. Providers expressed fears that initiating FP with a pregnant woman could cause community mistrust in the efficacy of modern contraception. Provider support for FP waned for nulliparous clients, regardless of age or marital status. To improve FP services in Malawi, providers need continuous education on all available methods of FP, a reduction in stockouts and programs to further sensitize the community to how contraception works. Understanding how Malawi has helped providers overcome social and cultural norms regarding provision of FP to adolescents might help other countries to make improvements

Does anthropometric status at 6&nbsp;months predict the over-dispersion of malaria infections in children aged 6-18&nbsp;months? A prospective cohort study.

BackgroundIn malaria-endemic settings, a small proportion of children suffer repeated malaria infections, contributing to most of the malaria cases, yet underlying factors are not fully understood. This study was aimed to determine whether undernutrition predicts this over-dispersion of malaria infections in children aged 6-18&nbsp;months in settings of high malaria and undernutrition prevalence.MethodsProspective cohort study, conducted in Mangochi, Malawi. Six-months-old infants were enrolled and had length-for-age z-scores (LAZ), weight-for-age z-scores (WAZ), and weight-for-length z-scores (WLZ) assessed. Data were collected for 'presumed', clinical, and rapid diagnostic test (RDT)-confirmed malaria until 18&nbsp;months. Malaria microscopy was done at 6 and 18&nbsp;months. Negative binomial regression was used for malaria incidence and modified Poisson regression for malaria prevalence.ResultsOf the 2723 children enrolled, 2561 (94%) had anthropometry and malaria data. The mean (standard deviation [SD]) of LAZ, WAZ, and WLZ at 6&nbsp;months were - 1.4 (1.1), - 0.7 (1.2), and 0.3 (1.1), respectively. The mean (SD) incidences of 'presumed', clinical, and RDT-confirmed malaria from 6 to 18&nbsp;months were: 1.1 (1.6), 0.4 (0.8), and 1.3 (2.0) episodes/year, respectively. Prevalence of malaria parasitaemia was 4.8% at 6&nbsp;months and 9.6% at 18&nbsp;months. Higher WLZ at 6&nbsp;months was associated with lower prevalence of malaria parasitaemia at 18&nbsp;months (prevalence ratio [PR] = 0.80, 95% confidence interval [CI] 0.67 to 0.94, p = 0.007), but not with incidences of 'presumed' malaria (incidence rate ratio [IRR] = 0.97, 95% CI 0.92 to 1.02, p = 0.190), clinical malaria (IRR = 1.03, 95% CI 0.94 to 1.12, p = 0.571), RDT-confirmed malaria (IRR = 1.00, 95% CI 0.94 to 1.06, p = 0.950). LAZ and WAZ at 6&nbsp;months were not associated with malaria outcomes. Household assets, maternal education, and food insecurity were significantly associated with malaria. There were significant variations in hospital-diagnosed malaria by study site.ConclusionIn children aged 6-18&nbsp;months living in malaria-endemic settings, LAZ, WAZ, and WLZ do not predict malaria incidence. However, WLZ may be associated with prevalence of malaria. Socio-economic and micro-geographic factors may explain the variations in malaria, but these require further study. Trial registration NCT00945698. Registered July 24, 2009, https://clinicaltrials.gov/ct2/show/NCT00945698 , NCT01239693. Registered Nov 11, 2010, https://clinicaltrials.gov/ct2/show/NCT01239693