Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis.

BACKGROUND: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. METHODS: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. FINDINGS: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92). INTERPRETATION: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. FUNDING: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

Contribution of Food from Market Purchases and Home Production to Child Nutrient Intake: Evidence from the EFFECTS Study Baseline Data.

BACKGROUND: Child undernutrition is prevalent in Tanzania, and households rely primarily on local markets and home production as food sources. However, little is known about the contribution of food market purchases to nutrient intakes among children consuming complementary foods. OBJECTIVES: To quantify the relationships between diversity of foods purchased and produced by households and adequate child nutrient intake in Mara, Tanzania. METHODS: Cross-sectional baseline dietary and household food source data from the Engaging Fathers for Effective Child Nutrition and Development in Tanzania study were collected from mothers of 586 children aged 9-23 mo clustered in 80 villages in Mara, Tanzania. We conducted mixed effects linear regressions to quantify the association between the diversity of foods consumed at home, from market purchases and home production, and nutrient intake adequacy (based on 24-h food recalls). RESULTS: Children had inadequate diets, with fewer than half of children consuming adequate amounts of vitamin A, vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B9 (folate), calcium, iron, and zinc. Breastfeeding was associated with higher overall mean adequacy (b = 0.15-0.19 across models, P < 0.001). Diversity of foods purchased was positively associated with the intake of vitamin B12 and calcium (both P < 0.001); this effect was attenuated among breastfed children. Among nonbreastfed children, production diversity was positively associated with vitamin A intake (b=0.04; P < .05) but not with intake of other nutrients. CONCLUSIONS: Both household food purchase and food production diversities were positively associated with children's nutrient intake in rural Mara, Tanzania. Nutrition programming should consider the role of food markets in addition to home food production to improve child diets. This trial was registered at clinicaltrials.gov as NCT03759821, https://clinicaltrials.gov/study/NCT03759821.

Effects of engaging fathers and bundling parenting and nutrition interventions on early child development and maternal and paternal parenting in Mara, Tanzania: a factorial cluster-randomized controlled trial.

BACKGROUND: Multicomponent interventions are needed to address the various co-occurring risks that compromise early child nutrition and development. We compared the independent and combined effects of engaging fathers and bundling parenting components into a nutrition intervention on early child development (ECD) and parenting outcomes. METHODS: We conducted a 2×2 factorial cluster-randomized controlled trial across 80 villages in Mara Region, Tanzania, also known as EFFECTS (Engaging Fathers for Effective Child Nutrition and Development in Tanzania; ClinicalTrials.gov, NCT03759821). Households with children under 18 months of age residing with their mother and father were enrolled. Villages were randomly assigned to one of five groups: a nutrition intervention for mothers, a nutrition intervention for couples, a bundled nutrition and parenting intervention for mothers, a bundled intervention for couples, and a standard-of-care control. Interventions were delivered by trained community health workers through peer groups and home visits over 12 months. Mothers, fathers, and children were assessed at baseline, midline, and endline or postintervention. We used a difference-in-difference approach with intention-to-treat analysis to estimate intervention effects on ECD (Bayley Scales of Infant and Toddler Development, third edition) and maternal and paternal parenting and psychosocial well-being. RESULTS: Between October 29, 2018, and May 24, 2019, 960 households were enrolled (n = 192 per arm). Compared to nutrition interventions, bundled interventions improved children's cognitive (ß = .18 [95% CI: 0.01, 0.36]) and receptive language development (ß = .23 [0.04, 0.41]). There were no differences between interventions for other ECD domains. Compared to nutrition interventions, bundled interventions achieved additional benefits on maternal stimulation (ß = .21 [0.04, 0.38]) and availability of home learning materials (ß = .25 [0.07-0.43]) and reduced paternal parenting distress (ß = -.34 [-0.55, -0.12]). Compared to interventions with mothers only, interventions that engaged fathers improved paternal stimulation (ß = .45 [0.27, 0.63]). CONCLUSIONS: Jointly bundling parenting components into nutrition interventions while also engaging both mothers and fathers is most effective for improving maternal and paternal parenting and ECD outcomes.

Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis.

BACKGROUND: Since the World Health Organization recommended single low-dose (0.25 mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant Plasmodium falciparum, several single-site studies have been conducted to assess efficacy. METHODS: An individual patient meta-analysis to assess gametocytocidal and transmission-blocking efficacy of PQ in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (1) gametocyte carriage in the first 2 weeks post treatment; and (2) the probability of infecting at least 1 mosquito or of a mosquito becoming infected. RESULTS: In 2574 participants from 14 studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytemia on day 0 (odds ratio [OR], 0.22; 95% confidence interval [CI], .17-.28 and OR, 0.12; 95% CI, .08-.16, respectively). Rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (P = .010 for day 7). Addition of 0.25 mg/kg PQ was associated with near complete prevention of transmission to mosquitoes. CONCLUSIONS: Transmission blocking is achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.

Exploring drivers of food choice among PLHIV and their families in a peri-urban Dar es Salaam, Tanzania.

BACKGROUND: A nutritious diet is critical to minimizing disease progression of human immunodeficiency virus (HIV) and maximizing treatment efficacy. In low resource settings, meeting the food preference needs of people living with the HIV (PLHIV) can be achieved with a supportive food environment when HIV status is disclosed. However, less is known about family-level strategies related to building a supportive food environment. The Diet, Environment, and Choices of positive living (DECIDE), a mixed-methods observational study conducted in peri-urban Dar es Salaam, Tanzania, explored food preferences as influenced by the personal, family, and external food domains. METHODS: We completed a qualitative analysis of data generated from 40 interviews (n = 20 PLHIV and n = 20 family members) aimed at exploring the dynamics of food choice for using a family perspective. We expanded on Turner's food environment framework and drew on Giddens' structuration theory to guide our data collection and analysis. Interviews were audio recorded, transcribed, translated from Kiswahili to English, coded, and organized into themes. RESULTS: We found PLHIV personal food preferences were influenced by organoleptic properties, medications, disease stage, and gender norms. Family members were knowledgeable about the importance of nutritious food for HIV treatment and prioritized these needs to avoid HIV-related stigma and fulfill family obligations. With high prices of nutritious foods (animal source foods, fruits), family members strategized to secure preferred foods for the PLHIV by, 1) forgoing their own food preferences; 2) reallocating food within the household; 3)making food substitutions; and 4) leveraging external networks. These strategies were increasingly employed as the disease progressed. CONCLUSION: The use of this expanded framework that included a family perspective on PLHIV food choice illuminated the various households decision-making dynamics that took place in this low resource community. Family members of PLHIV tried to buffer the limitations imposed by the external food environment, especially as the disease progressed. In the context of HIV status disclosure, integrating a family perspective into HIV nutrition interventions and programs has the potential to influence health outcomes and slow disease progression.

Are home gardening programs a sustainable way to improve nutrition? Lessons from a cluster-randomized controlled trial in Rufiji, Tanzania.

Homestead food production (HFP) programs may improve diet and nutrition outcomes by increasing availability of nutrient dense foods such as vegetables and supporting livelihoods. We conducted a pair-matched cluster-randomized controlled trial to investigate whether vegetable home gardens could improve women's dietary diversity, household food security, maternal and child iron status, and the probability of women consuming nutrient-rich food groups. We enrolled 1,006 women of reproductive age (18-49 years) in ten villages in Pwani Region, Eastern Tanzania, matched the villages into pairs according to village characteristics, and randomly allocated villages to intervention or control. Households in the intervention villages received agricultural training, inputs to promote home production of nutritious crops, and nutrition and health education. Data were collected in 2016, 2017, and 2019 and analyzed using linear regression models with propensity score weighting adjusting for individual-level confounders, differential loss to follow-up, and fixed effects for village pairs to accommodate the pair-matched design. Results after one year of the intervention (previously published) found significant improvements in dietary diversity. However, three years after the start of the intervention the difference in dietary diversity disappeared, even though the number of women who grew at least one crop was significantly higher (75 percentage points, 95% CI: 72, 81) in treatment households compared to controls. Barriers to maintaining a home garden, including lack of irrigation opportunities and fencing materials, and social disruption may have precluded sustained impacts from home gardening in this context. Future home garden programs should carefully consider mechanisms and investments needed for sustained impact over time.

Food Crop Diversity, Women's Income-Earning Activities, and Distance to Markets in Relation to Maternal Dietary Quality in Tanzania.

BACKGROUND: Women's dietary diversity and quality are limited in low- and middle-income countries (LMICs). Nutrition-sensitive interventions that promote food crop diversity and women's access to income could improve diets and address the double burden of malnutrition in LMICs. OBJECTIVES: We examined the associations among food crop diversity and women's income-earning activities with women's diet quality, as well as effect modification by access to markets, in the context of small-holder food production in rural Tanzania. METHODS: Data from a cross-sectional study of 880 women from Rufiji, Tanzania, were analyzed. Women's dietary intake was assessed using a food frequency questionnaire. The prime diet quality score (PDQS; 21 food groups; range, 0-42), a unique diet-quality metric for women that captures the healthy and unhealthy aspects of diet, was computed. Generalized estimating equation linear models were used to evaluate the associations of food crop diversity and women's income-earning activities with PDQS, while controlling for socio-economic factors. RESULTS: Maternal overweight (24.3%) and obesity (13.1%) were high. The median PDQS was 19 (IQR, 17-21). Households produced 2.0 food crops (SD ± 1.0) yearly. Food crop diversity was positively associated with PDQS (P < 0.001), but the association was strengthened by proximity to markets (P for interaction = 0.02). For women living close (<1.1 km) to markets, producing 1 additional food crop was associated with a 0.67 (95% CI, 0.22-1.12) increase in PDQS, versus a 0.40 (95% CI, 0.24-0.57) increase for women living farther away. The PDQS increased with women's salaried employment (estimate, 0.96; 95% CI, 0.26-1.67). CONCLUSIONS: Household food production may interact with access to markets for sales and purchases, while nonfarm income also improves women's diet quality in rural Tanzania. Programs to improve women's diet quality should consider improving market access and women's access to income (source of empowerment), in addition to diversifying production.

Safety monitoring experience of single-low dose primaquine co-administered with artemether-lumefantrine among providers and patients in routine healthcare practice: a qualitative study in Eastern Tanzania.

BACKGROUND: Primaquine is a gametocytocidal drug recommended by the World Health Organization (WHO) in a single-low dose combined with artemisinin-based combination therapy (ACT) for the treatment and prevention of Plasmodium falciparum malaria transmission. Safety monitoring concerns and the lack of a universal validated and approved primaquine pharmacovigilance tool is a challenge for a national rollout in many countries. This study aimed to explore the acceptance, reliability and perceived effectiveness of the primaquine roll out monitoring pharmacovigilance tool (PROMPT). METHODS: This study was conducted in three dispensaries in the Coastal region of Eastern Tanzania. The study held six in-depth interviews with healthcare providers and six participatory focus group discussions with malaria patients (3) and parents/guardians of sick children (3). Participants were purposively sampled. Thematic analysis was conducted with the aid of NVivo qualitative analysis software. RESULTS: The respondents' general acceptance and perceived effectiveness of the single-low dose primaquine and PROMPT was good. Screening procedure for treatment eligibility and explaining to patients about the possible adverse events was considered very useful for safety reasons. Crushing and dissolving of primaquine tablet to get the appropriate dose, particularly in children, was reported by all providers to be challenging. Transport costs and poor access to the health facility were the main reasons for a patient failing to return to the clinic for a scheduled follow-up visit. Treatment was perceived to be safe by both providers and patients and reported no case of a severe adverse event. Some providers were concerned with the haemoglobin drop observed on day 7. CONCLUSION: Single-low dose primaquine was perceived to be safe and acceptable among providers and patients. PROMPT demonstrated to be a reliable and user-friendly tool among providers. Further validation of the tool by involving the National Malaria Control Programme is pivotal to addressing key challenges and facilitating primaquine adoption in the national policy.

Health priority-setting for official development assistance in low-income and middle-income countries: a Best Fit Framework Synthesis study with primary data from Ethiopia, Nigeria and Tanzania.

BACKGROUND: Decision making process for Official Development Assistance (ODA) for healthcare sector in low-income and middle-income countries involves multiple agencies, each with their unique power, priorities and funding mechanisms. This process at country level has not been well studied. METHODS: This paper developed and applied a new framework to analyze decision-making process for priority setting in Ethiopia, Nigeria, and Tanzania, and collected primary data to validate and refine the model. The framework was developed following a scoping review of published literature. Interviews were then conducted using a pre-determined interview guide developed by the research team. Transcripts were reviewed and coded based on the framework to identify what principles, players, processes, and products were considered during priority setting. Those elements were further used to identify where the potential capacity of local decision-makers could be harnessed. RESULTS: A framework was developed based on 40 articles selected from 6860 distinct search records. Twenty-one interviews were conducted in three case countries from 12 institutions. Transcripts or meeting notes were analyzed to identify common practices and specific challenges faced by each country. We found that multiple stakeholders working around one national plan was the preferred approach used for priority setting in the countries studied. CONCLUSIONS: Priority setting process can be further strengthened through better use of analytical tools, such as the one described in our study, to enhance local ownership of priority setting for ODA and improve aid effectiveness.

Home gardening improves dietary diversity, a cluster-randomized controlled trial among Tanzanian women.

Homestead food production (HFP) programmes improve the availability of vegetables by providing training in growing nutrient-dense crops. In rural Tanzania, most foods consumed are carbohydrate-rich staples with low micronutrient concentrations. This cluster-randomized controlled trial investigated whether women growing home gardens have higher dietary diversity, household food security or probability of consuming nutrient-rich food groups than women in a control group. We enrolled 1,006 women of reproductive age in 10 villages in Pwani Region in eastern Tanzania, split between intervention (INT) and control (CON) groups. INT received (a) agricultural training and inputs to promote HFP and dietary diversity and (b) nutrition and public health counselling from agricultural extension workers and community health workers. CON received standard services provided by agriculture and health workers. Results were analysed using linear regression models with propensity weighting adjusting for individual-level confounders and differential loss to follow up. Women in INT consumed 0.50 (95% CI [0.20, 0.80], p = 0.001) more food groups per day than women in CON. Women in INT were also 14 percentage points (95% CI [6, 22], p = 0.001) more likely to consume at least five food groups per day, and INT households were 6 percentage points (95% CI [-13, 0], p = 0.059) less likely to experience moderate-to-severe food insecurity compared with CON. This home gardening intervention had positive effects on diet quality and food security after 1 year. Future research should explore whether impact is sustained over time as well as the effects of home garden interventions on additional measures of nutritional status.

Pregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.

BACKGROUND: Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection. METHODS: A systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted. The risks of stillbirth (pregnancy loss at ≥ 28.0 weeks of gestation), moderate to late preterm birth (PTB, live birth between 32.0 and < 37.0 weeks), small for gestational age (SGA, birthweight of < 10th percentile), and placental malaria (defined as deposition of malaria pigment in the placenta with or without parasites) after different treatments of uncomplicated falciparum malaria were assessed by mixed-effects logistic regression, using artemether-lumefantrine, the most used antimalarial, as the reference standard. Registration PROSPERO: CRD42018104013. RESULTS: Of the 22 eligible studies (n = 5015), IPD from16 studies were shared, representing 95.0% (n = 4765) of the women enrolled in literature. Malaria treatment in this pooled analysis mostly occurred in the second (68.4%, 3064/4501) or third trimester (31.6%, 1421/4501), with gestational age confirmed by ultrasound in 91.5% (4120/4503). Quinine (n = 184) and five commonly used artemisinin-based combination therapies (ACTs) were included: artemether-lumefantrine (n = 1087), artesunate-amodiaquine (n = 775), artesunate-mefloquine (n = 965), and dihydroartemisinin-piperaquine (n = 837). The overall pooled proportion of stillbirth was 1.1% (84/4361), PTB 10.0% (619/4131), SGA 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of SGA (adjusted odds ratio [aOR] 1.14 per 10-fold increase, 95% confidence interval [CI] 1.03 to 1.26, p = 0.009) and deposition of malaria pigment in the placenta (aOR 1.67 per 10-fold increase, 95% CI 1.42 to 1.96, p < 0.001). CONCLUSIONS: The risks of stillbirth, PTB, SGA, and placental malaria were not different between the commonly used ACTs. The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs. Reduction of malaria-associated adverse birth outcomes requires effective prevention in pregnant women.

Prevalence and risk factors associated with malnutrition among adolescents in rural Tanzania.

OBJECTIVE: To determine the prevalence and risk factors associated with malnutrition among adolescents in a rural Tanzanian community. METHODS: Cross-sectional survey of 1226 randomly selected adolescents from the Dodoma Health and Demographic Surveillance System (HDSS) in the Chamwino district in the Dodoma region. Anthropometric measurements for weight and height were collected. Height-for-age-z-scores (HAZs) and body mass index (BMI)-for-age-z-scores (BAZs) were computed. Descriptive estimates were documented in graphs and tables, and weighted linear regression models were used to examine predictors of malnutrition. RESULTS: Stunting prevalence was 18%, and thinness prevalence was 14%. Overweight and obesity affected 5.23% of participants. Girls had higher HAZs (ß: 0.46, 95% CI 0.33, 0.59, P < 0.0001) and BAZs (ß: 0.20, 95% CI 0.05, 0.35, P = 0.0098) than boys. Age was inversely associated with HAZs (ß: -0.13, 95% CI -0.17, -0.08, P < 0.0001) and BAZs (ß: -0.05, 95% CI -0.10, -0.004, P = 0.0327). Wealth score (ß: 0.10, 95% CI 0.04, 0.16, P = 0.0009) and dietary diversity score (ß: 0.04, 95% CI 0.01, 0.07, P = 0.0080) were positively associated with HAZs and BAZs. Out-of-school adolescents had higher HAZs (ß: -0.49, 95% CI -0.75, -0.23, P = 0.0003) and BAZs (ß: -0.68, 95% CI -0.99, -0.37, P < 0.0001) than adolescents who attended school. CONCLUSION: There are substantial variations of HAZs and BAZs across gender, age, education and wealth, with an emerging burden of overweight and obesity among adolescents in this rural population. Interventions are urgently required to curb both ends of the malnutrition spectrum.

OBJECTIF: Déterminer la prévalence et les facteurs de risque associés à la malnutrition chez les adolescents d'une communauté rurale en Tanzanie. MÉTHODES: Enquête transversale auprès de 1.226 adolescents choisis au hasard dans le Système de Surveillance Démographique et de Santé (SSDS) de Dodoma dans le district de Chamwino, dans la région de Dodoma. Des mesures anthropométriques du poids et de la taille ont été recueillies. Les scores z de la taille pour l'âge (HAZ) et les scores z d'indice de masse corporelle (IMC) pour l'âge (BAZ) ont été calculés. Des estimations descriptives ont été documentées dans des graphiques et des tableaux, et des modèles de régression linéaire pondérés ont été utilisés pour analyser les prédicteurs de la malnutrition. RÉSULTATS: La prévalence du retard de croissance était de 18% et la prévalence de la maigreur était de 14%. Le surpoids et l'obésité touchaient 5,23% des participants. Les filles avaient des scores HAZ (ß: 0,46, IC95%: 0,33-0,59 ; P < 0,0001) et des scores BAZ (ß: 0,20 ; IC95%: 0,05-0,35 ; P = 0,0098) plus élevés que les garçons. L'âge était inversement associé au score HAZ (ß: −0,13, IC95%: −0,17, −0,08, P < 0,0001) et au score BAZ (ß: −0,05 ; IC95%: −0,104, −0,004 ; P = 0,0327). Le score de richesse (ß: 0,10 ; IC95%: 0,04-0,16; P = 0,0009) et le score de diversité alimentaire (ß: 0,04 ; IC95%: 0,01-0,07 ; P = 0,0080) étaient positivement associés aux scores HAZ et BAZ. Les adolescents non scolarisés présentaient des scores HAZ (ß: −0,49 ; IC95%: −0,75, −0,23 ; P = 0,0003) et des scores BAZ plus élevés (ß: −0,68 ; IC95%: −0,99 −0,37 ; P < 0,0001) que les adolescents qui fréquentaient l'école. CONCLUSION: Il existe des variations substantielles dans les scores HAZ et BAZ selon le sexe, l'âge, l'éducation et la richesse, avec une charge émergente de surpoids et d'obésité chez les adolescents dans la population rurale. Des interventions urgentes sont nécessaires pour réduire les deux extrémités du spectre de la malnutrition.

Optimal timing of primaquine to reduce Plasmodium falciparum gametocyte carriage when co-administered with artemether-lumefantrine.

BACKGROUND: Primaquine is an important gametocytocidal drug that is combined with conventional malaria treatment for prevention of Plasmodium falciparum malaria transmission. Primaquine has been administered together on the first or the last day of conventional treatment but the impact of primaquine timing has never been examined. This study aimed to assess safety, efficacy and optimal timing of single full-dose (0.75 mg/kg) primaquine when added to a standard 6-dose regimen of artemether-lumefantrine (AL). METHODS: In an individual-level randomized controlled trial, enrolled participants who were G6PD normal and had uncomplicated P. falciparum malaria were randomly assigned to receive: AL only; AL and a single 0.75 mg/kg primaquine dose on the first day of AL (day 1); or AL and single 0.75 mg//kg primaquine on the last day of AL (day 3). On days 2, 3, 4, 8, 11 and 15, gametocytes were assessed and quantified by microscope and quantitative nuclear acid sequence based quantification (QT-NASBA). RESULTS: Overall, 111 participants aged between 3 and 17 years were randomly allocated to receive AL only (36) or combined with primaquine on day 1 (38), or primaquine on day 3 (37). Day 4 gametocyte prevalence in AL + day 1 primaquine was half the level seen in either AL + day 3 primaquine or AL only arm (11% [4/35] vs 26% [8/31] and 27% [8/30], respectively) albeit not statistically significant. A similar trend of lower gametocyte in the AL + day 1 primaquine verses AL + day 3 primaquine or AL only arm was observed in mean gametocyte density. Mean (sd) haemoglobin level in AL + day 3 primaquine arm recovered from -0.42(1.2) g/dl on day 2 to 0.35 (1.5) g/dl on day 15 of follow up. This was not the case in AL only and AL + day 1 primaquine arms during the same follow-up period, although the difference was not statistically significant (p = 318). No serious adverse events reported in the study. Across arms, 23% (26/111) of participants reported a total of 31 mild adverse events and the difference was not statistically significant (p = 0.477). CONCLUSION: Primaquine administration on the first day of AL is well tolerated and as safe as later administration. Whilst the World Health Organization currently recommends a lower dose of primaquine (0.25 mg/kg), the findings are supportive of early primaquine administration when combined with artemisinin-combination therapy. ClinicalTrials.gov Registration NCT01906788.

Neighbour home gardening predicts dietary diversity among rural Tanzanian women.

OBJECTIVE: The present study's aim was to assess the impact of a nutrition-sensitive intervention on dietary diversity and home gardening among non-participants residing within intervention communities. DESIGN: The study was a cross-sectional risk factor analysis using linear and logistic multivariate models. SETTING: In Tanzania, women and children often consume monotonous diets of poor nutritional value primarily because of physical or financial inaccessibility or low awareness of healthy foods.ParticipantsParticipants were women of reproductive age (18-49 years) in rural Tanzania. RESULTS: Mean dietary diversity was low with women consuming three out of ten possible food groups. Only 23·4 % of respondents achieved the recommended minimum dietary diversity of five or more food groups out of ten per day. Compared with those who did not, respondents who had a neighbour who grew crops in their home garden were 2·71 times more likely to achieve minimum dietary diversity (95 % CI 1·60, 4·59; P=0·0004) and 1·91 times more likely to grow a home garden themselves (95 % CI 1·10, 3·33; P=0·02). Other significant predictors of higher dietary diversity were respondent age, education and wealth, and number of crops grown. CONCLUSIONS: These results suggest that there are substantial positive externalities of home garden interventions beyond those attained by the people who own and grow the vegetables. Cost-effectiveness assessments of nutrition-sensitive agriculture, including home garden interventions, should factor in the effects on the community, and not just on the individual households receiving the intervention.

Appropriateness of malaria diagnosis and treatment for fever episodes according to patient history and anti-malarial blood measurement: a cross-sectional survey from Tanzania.

BACKGROUND: Monitoring the impact of case management strategies at large scale is essential to evaluate the public health benefit they confer. The use of methodologies relying on objective and standardized endpoints, such as drug levels in the blood, should be encouraged. Population drug use, diagnosis and treatment appropriateness in case of fever according to patient history and anti-malarials blood concentration was evaluated. METHODS: A cross-sectional survey took place between May and August 2015 in three regions of Tanzania with different levels of malaria endemicity. Interviews were conducted and blood samples were collected by dried blood spots through household surveys for further anti-malarial measurements. Appropriate testing when individuals attended care was defined as a patient with history of fever being tested for malaria and appropriate treatment as (i) having anti-malarial in the blood if the test result was positive (ii) having anti-malarial in the blood if the person was not tested, and (iii) no anti-malarial in the blood when the test result was negative. RESULTS: Amongst 6391 participants included in the anti-malarial analysis, 20.8% (1330/6391) had anti-malarial drug detected in the blood. Only 28.0% (372/1330) of the individuals with anti-malarials in their blood reported the use of anti-malarials within the previous month. Amongst all participants, 16.0% (1021/6391) reported having had a fever in the previous 2 weeks and 37.5% of them (383/1021) had detectable levels of anti-malarials in the blood. Of the individuals who sought care in health facilities, 69.4% (172/248) were tested and 52.0% (129/248) appropriately treated. When other providers were sought, 6% (23/382) of the persons were appropriately tested and 44.2% (169/382) appropriately treated. Overall, the proportion of individuals treated was larger than that being tested [47.3% (298/630) treated, 31.0% (195/630) tested]. CONCLUSION: This study showed high prevalence of circulating anti-malarial drug in the sampled population. Efforts should be made to increase rapid diagnostic tests use at all levels of health care and improve compliance to test result in order to target febrile patients that are sick with malaria and reduce drug pressure. Objective drug measurements collected at community level represent a reliable tool to evaluate overall impact of case management strategies on population drug pressure.

First-trimester artemisinin derivatives and quinine treatments and the risk of adverse pregnancy outcomes in Africa and Asia: A meta-analysis of observational studies.

BACKGROUND: Animal embryotoxicity data, and the scarcity of safety data in human pregnancies, have prevented artemisinin derivatives from being recommended for malaria treatment in the first trimester except in lifesaving circumstances. We conducted a meta-analysis of prospective observational studies comparing the risk of miscarriage, stillbirth, and major congenital anomaly (primary outcomes) among first-trimester pregnancies treated with artemisinin derivatives versus quinine or no antimalarial treatment. METHODS AND FINDINGS: Electronic databases including Medline, Embase, and Malaria in Pregnancy Library were searched, and investigators contacted. Five studies involving 30,618 pregnancies were included; four from sub-Saharan Africa (n = 6,666 pregnancies, six sites) and one from Thailand (n = 23,952). Antimalarial exposures were ascertained by self-report or active detection and confirmed by prescriptions, clinic cards, and outpatient registers. Cox proportional hazards models, accounting for time under observation and gestational age at enrollment, were used to calculate hazard ratios. Individual participant data (IPD) meta-analysis was used to combine the African studies, and the results were then combined with those from Thailand using aggregated data meta-analysis with a random effects model. There was no difference in the risk of miscarriage associated with the use of artemisinins anytime during the first trimester (n = 37/671) compared with quinine (n = 96/945; adjusted hazard ratio [aHR] = 0.73 [95% CI 0.44, 1.21], I2 = 0%, p = 0.228), in the risk of stillbirth (artemisinins, n = 10/654; quinine, n = 11/615; aHR = 0.29 [95% CI 0.08-1.02], p = 0.053), or in the risk of miscarriage and stillbirth combined (pregnancy loss) (aHR = 0.58 [95% CI 0.36-1.02], p = 0.099). The corresponding risks of miscarriage, stillbirth, and pregnancy loss in a sensitivity analysis restricted to artemisinin exposures during the embryo sensitive period (6-12 wk gestation) were as follows: aHR = 1.04 (95% CI 0.54-2.01), I2 = 0%, p = 0.910; aHR = 0.73 (95% CI 0.26-2.06), p = 0.551; and aHR = 0.98 (95% CI 0.52-2.04), p = 0.603. The prevalence of major congenital anomalies was similar for first-trimester artemisinin (1.5% [95% CI 0.6%-3.5%]) and quinine exposures (1.2% [95% CI 0.6%-2.4%]). Key limitations of the study include the inability to control for confounding by indication in the African studies, the paucity of data on potential confounders, the limited statistical power to detect differences in congenital anomalies, and the lack of assessment of cardiovascular defects in newborns. CONCLUSIONS: Compared to quinine, artemisinin treatment in the first trimester was not associated with an increased risk of miscarriage or stillbirth. While the data are limited, they indicate no difference in the prevalence of major congenital anomalies between treatment groups. The benefits of 3-d artemisinin combination therapy regimens to treat malaria in early pregnancy are likely to outweigh the adverse outcomes of partially treated malaria, which can occur with oral quinine because of the known poor adherence to 7-d regimens. REVIEW REGISTRATION: PROSPERO CRD42015032371.

Dietary iron and calcium intakes during pregnancy are associated with lower risk of prematurity, stillbirth and neonatal mortality among women in Tanzania.

OBJECTIVE: Prematurity, stillbirth and other adverse birth outcomes remain major concerns in resource-limited settings. Poor dietary intake of micronutrients during pregnancy has been associated with increased risk of adverse outcomes. We determined the relationships between dietary Fe and Ca intakes during pregnancy and risks of adverse birth outcomes among HIV-negative women. DESIGN: Women's diet was assessed through repeated 24 h diet recalls in pregnancy. Mean intakes of total Fe, Fe from animal sources and Ca during pregnancy were examined in relation to adverse birth outcomes and neonatal mortality. Women were prescribed daily Fe supplements as per standard perinatal care. SETTING: Dar es Salaam, Tanzania. SUBJECTS: A cohort of 7634 pregnant women. RESULTS: Median (interquartile range) daily dietary intake of total Fe, animal Fe and Ca was 11·9 (9·3-14·7), 0·5 (0-1·1) and 383·9 (187·4-741·2) mg, respectively. Total Fe intake was significantly associated with reduced risk of stillbirth (trend over quartiles, P=0·010). Animal Fe intake was significantly associated with reduced risk of preterm birth and extreme preterm birth. Animal Fe intake was inversely related to neonatal mortality risk; compared with women in the lowest intake quartile, those in the top quartile were 0·51 times as likely to have neonatal death (95 % CI 0·33, 0·77). Higher Ca intake was associated with reduced risk of preterm birth (relative risk; 95 % CI: 0·76; 0·65, 0·88) and extreme preterm birth (0·63; 0·47, 0·86). Women in the highest Ca intake quartile had reduced risk of neonatal mortality (0·59; 0·37, 0·92). CONCLUSIONS: Daily dietary Fe and Ca intakes among pregnant women are very low. Improvement of women's diet quality during gestation is likely to improve the risks of adverse birth outcomes.

Population pharmacokinetics and clinical response for artemether-lumefantrine in pregnant and nonpregnant women with uncomplicated Plasmodium falciparum malaria in Tanzania.

Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated malaria in the second and third trimesters of pregnancy. Its efficacy during pregnancy has recently been challenged due to altered pharmacokinetic (PK) properties in this vulnerable group. The aim of this study was to determine the PK profile of AL in pregnant and nonpregnant women and assess their therapeutic outcome. Thirty-three pregnant women and 22 nonpregnant women with malaria were treated with AL (80/480 mg) twice daily for 3 days. All patients provided five venous plasma samples for drug quantification at random times over 7 days. Inter- and intraindividual variability was assessed, and the effects of covariates were quantified using a nonlinear mixed-effects modeling approach (NONMEM). A one-compartment model with first-order absorption and elimination with linear metabolism from drug to metabolite fitted the data best for both arthemether (AM) and lumefantrine (LF) and their metabolites. Pregnancy status and diarrhea showed a significant influence on LF PK. The relative bioavailability of lumefantrine and its metabolism rate into desmethyl-lumefantrine were, respectively, 34% lower and 78% higher in pregnant women than in nonpregnant patients. The overall PCR-uncorrected treatment failure rates were 18% in pregnant women and 5% in nonpregnant women (odds ratio [OR] = 4.04; P value of 0.22). A high median day 7 lumefantrine concentration was significantly associated with adequate clinical and parasitological response (P = 0.03). The observed reduction in the relative bioavailability of lumefantrine in pregnant women may explain the higher treatment failure in this group, mostly due to lower posttreatment prophylaxis. Hence, a modified treatment regimen of malaria in pregnancy should be considered.

Effectiveness of intermittent preventive treatment with sulfadoxine-pyrimethamine during pregnancy on placental malaria, maternal anaemia and birthweight in areas with high and low malaria transmission intensity in Tanzania.

OBJECTIVE: To assess the effectiveness of IPTp in two areas with different malaria transmission intensities. METHODS: Prospective observational study recruiting pregnant women in two health facilities in areas with high and low malaria transmission intensities. A structured questionnaire was used for interview. Maternal clinic cards and medical logs were assessed to determine drug intake. Placental parasitaemia was screened using both light microscopy and real-time quantitative PCR. RESULTS: Of 350 pregnant women were recruited and screened for placental parasitaemia, 175 from each area. Prevalence of placental parasitaemia was 16.6% (CI 11.4-22.9) in the high transmission area and 2.3% (CI 0.6-5.7) in the low transmission area. Being primigravida and residing in a high transmission area were significant risk factors for placental malaria (OR 2.4; CI 1.1-5.0; P = 0.025) and (OR 9.4; CI 3.2-27.7; P < 0.001), respectively. IPTp was associated with a lower risk of placental malaria (OR 0.3; CI 0.1-1.0; P = 0.044); the effect was more pronounced in the high transmission area (OR 0.2; CI 0.06-0.7; P = 0.015) than in the low transmission area (OR 0.4; CI 0.04-4.5; P = 0.478). IPTp use was not associated with reduced risk of maternal anaemia or low birthweight, regardless of transmission intensity. The number needed to treat (NNT) was four (CI 2-6) women in the high transmission area and 33 (20-50) in the low transmission area to prevent one case of placental malaria. CONCLUSION: IPTp may have an effect on lowering the risk of placental malaria in areas of high transmission, but this effect did not translate into a benefit on risks of maternal anaemia or low birthweight. The NNT needs to be considered, and weighted against that of other protective measures, eventually targeting areas which are above a certain threshold of malaria transmission to maximise the benefit.

Safety of artemether-lumefantrine exposure in first trimester of pregnancy: an observational cohort.

BACKGROUND: There is limited data available regarding safety profile of artemisinins in early pregnancy. They are, therefore, not recommended by WHO as a first-line treatment for malaria in first trimester due to associated embryo-foetal toxicity in animal studies. The study assessed birth outcome among pregnant women inadvertently exposed to artemether-lumefantrine (AL) during first trimester in comparison to those of women exposed to other anti-malarial drugs or no drug at all during the same period of pregnancy. METHODS: Pregnant women with gestational age <20 weeks were recruited from Maternal Health clinics or from monthly house visits (demographic surveillance), and followed prospectively until delivery. RESULTS: 2167 pregnant women were recruited and 1783 (82.3%) completed the study until delivery. 319 (17.9%) used anti-malarials in first trimester, of whom 172 (53.9%) used (AL), 78 (24.4%) quinine, 66 (20.7%) sulphadoxine-pyrimethamine (SP) and 11 (3.4%) amodiaquine. Quinine exposure in first trimester was associated with an increased risk of miscarriage/stillbirth (OR 2.5; 1.3-5.1) and premature birth (OR 2.6; 1.3-5.3) as opposed to AL with (OR 1.4; 0.8-2.5) for miscarriage/stillbirth and (OR 0.9; 0.5-1.8) for preterm birth. Congenital anomalies were identified in 4 exposure groups namely AL only (1/164[0.6%]), quinine only (1/70[1.4%]), SP (2/66[3.0%]), and non-anti-malarial exposure group (19/1464[1.3%]). CONCLUSION: Exposure to AL in first trimester was more common than to any other anti-malarial drugs. Quinine exposure was associated with adverse pregnancy outcomes which was not the case following other anti-malarial intake. Since AL and quinine were used according to their availability rather than to disease severity, it is likely that the effect observed was related to the drug and not to the disease itself. Even with this caveat, a change of policy from quinine to AL for the treatment of uncomplicated malaria during the whole pregnancy period could be already envisaged.