Cancer-specific dose and fractionation schedules in stereotactic body radiotherapy for oligometastatic disease: An interim analysis of the EORTC-ESTRO E2-RADIatE OligoCare study.

BACKGROUND AND INTRODUCTION: Optimal dose and fractionation in stereotactic body radiotherapy (SBRT) for oligometastatic cancer patients remain unknown. In this interim analysis of OligoCare, we analyzed factors associated with SBRT dose and fractionation. MATERIALS AND METHODS: Analysis was based on the first 1,099 registered patients. SBRT doses were converted to biological effective doses (BED) using α/ß of 10 Gy for all primaries, and cancer-specific α/ß of 10 Gy for non-small cell lung and colorectal cancer (NSCLC, CRC), 2.5 Gy for breast cancer (BC), or 1.5 Gy for prostate cancer (PC). RESULTS: Of the interim analysis population of 1,099 patients, 999 (99.5 %) fulfilled inclusion criteria and received metastasis-directed SBRT for NSCLC (n = 195; 19.5 %), BC (n = 163; 16.3 %), CRC (n = 184; 18.4 %), or PC (n = 457; 47.5 %). Two thirds of patients were treated for single metastasis. Median number of fractions was 5 (IQR, 3-5) and median dose per fraction was 9.7 (IQR, 7.7-12.4) Gy. The most frequently treated sites were non-vertebral bone (22.8 %), lung (21.0 %), and distant lymph node metastases (19.0 %). On multivariate analysis, the dose varied significantly for primary cancer type (BC: 237.3 Gy BED, PC 300.6 Gy BED, and CRC 84.3 Gy BED), and metastatic sites, with higher doses for lung and liver lesions. CONCLUSION: This real-world analysis suggests that SBRT doses are adjusted to the primary cancers and oligometastasis location. Future analysis will address safety and efficacy of this site- and disease-adapted SBRT fractionation approach (NCT03818503).

Effect of iron fortification on anaemia and risk of malaria among Ghanaian pre-school children with haemoglobinopathies and different ABO blood groups.

BACKGROUND: Haemoglobinopathies such as sickle cell disorder and glucose-6-phosphate dehydrogenase (G6PD) deficiency as well as differences in ABO blood groups have been shown to influence the risk of malaria and/or anaemia in malaria-endemic areas. This study assessed the effect of adding MNP containing iron to home-made weaning meals on anaemia and the risk of malaria in Ghanaian pre-school children with haemoglobinopathies and different ABO blood groups. METHODS: This study was a double-blind, randomly clustered trial conducted within six months among infants and young children aged 6 to 35 months in rural Ghana (775 clusters, n = 860). Participants were randomly selected into clusters to receive daily semiliquid home-prepared meals mixed with either micronutrient powder without iron (noniron group) or with iron (iron group; 12.5 mg of iron daily) for 5 months. Malaria infection was detected by microscopy, blood haemoglobin (Hb) levels were measured with a HemoCue Hb analyzer, the reversed ABO blood grouping microtube assay was performed, and genotyping was performed by PCR-RFLP analysis. RESULTS: The prevalence of G6PD deficiency among the study participants was 11.2%. However, the prevalence of G6PD deficiency in hemizygous males (8.5%) was significantly higher than that in homozygous females (2.7%) (p = 0.005). The prevalence rates of sickle cell traits (HbAS and HbSC) and sickle cell disorder (HbSS) were 17.5% and 0.5%, respectively. Blood group O was dominant (41.4%), followed by blood group A (29.6%) and blood group B (23.3%), while blood group AB (5.7%) had the least frequency among the study participants. We observed that children on an iron supplement with HbAS had significantly moderate anaemia at the endline (EL) compared to the baseline level (BL) (p = 0.004). However, subjects with HbAS and HbAC and blood groups A and O in the iron group had a significantly increased number of malaria episodes at EL than at BL (p < 0.05). Furthermore, children in the iron group with HbSS (p < 0.001) and the noniron group with HbCC (p = 0.010) were significantly less likely to develop malaria. CONCLUSIONS: Iron supplementation increased anaemia in children with HbAS genotypes and provided less protection against malaria in children with HbAC and AS and blood groups A and O. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01001871 . Registered 27/10/2009. REGISTRATION NUMBER: https://clinicaltrials.gov/ct2/show/record/NCT01001871 .

Socioeconomic factors associated with the number of children ever born by married Ghanaian females: a cross-sectional analysis.

OBJECTIVE: Most studies in Ghana on determinants of children ever born (CEB) are often conducted among all females of reproductive age and do not adequately report patterns among married females. Considering the importance of marriage to fertility in the Ghanaian context, this study seeks to explore the association of socioeconomic characteristics of married Ghanaian women with CEB. DESIGN: Data from the 2017 Ghana Maternal Health Survey were used. Three separate models were considered: linear regression model using CEB and two logistic regression models. Bivariate and multivariate analyses were considered for all models. SETTING: The study was conducted in all 10 administrative regions of Ghana. PARTICIPANTS: Married females aged between 15 and 49 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Socioeconomic factors associated with married females' CEB. RESULTS: In all three models, place of residence, zone, wealth index, age, age at marriage, media exposure, level of education, number of abortions and age at first sex were all significantly (p<0.05) associated with CEB. Married females with higher education had lower odds of one or more births and lower odds of giving birth to three or more children. Also, married females from households with the highest wealth index had fewer CEB, lower odds of one or more births and lower odds of giving birth to three or more children. CONCLUSION: Socioeconomic characteristics of married females in Ghana, including education and wealth status had a significant influence on the number of CEBs. We recommend governments' intervention to help bridge the gaps in access to education and income-generating opportunities. The mass media must be used to propagate and counsel married females on the potential of high fertility and its consequences.

Thrombocytopenia limits the feasibility of salvage lomustine chemotherapy in recurrent glioblastoma: a secondary analysis of EORTC 26101.

BACKGROUND: Thrombocytopenia represents the main cause of stopping alkylating chemotherapy for toxicity. Here, we explored the incidence, and the consequences for treatment exposure and survival, of thrombocytopenia induced by lomustine in recurrent glioblastoma. METHODS: We performed a retrospective analysis of the associations of thrombocytopenia with treatment delivery and outcome in EORTC 26101, a randomised trial designed to define the role of lomustine versus bevacizumab versus their combination in recurrent glioblastoma. RESULTS: A total of 225 patients were treated with lomustine alone (median 1 cycle) (group 1) and 283 patients were treated with lomustine plus bevacizumab (median 3 lomustine cycles) (group 2). Among cycle delays and dose reductions of lomustine for toxicity, thrombocytopenia was the leading cause. Among 129 patients (57%) of group 1 and 187 patients (66%) of group 2 experiencing at least one episode of thrombocytopenia, 36 patients (16%) in group 1 and 93 (33%) in group 2 had their treatment modified because of thrombocytopenia. Lomustine was discontinued for thrombocytopenia in 16 patients (7.1%) in group 1 and in 38 patients (13.4%) in group 2. On adjusted analysis accounting for major prognostic factors, dose modification induced by thrombocytopenia was associated with inferior progression-free survival in patients with MGMT promoter-methylated tumours in groups 1 and 2. This effect was noted for overall survival, too, but only for group 2 patients. CONCLUSION: Drug-induced thrombocytopenia is a major limitation to adequate exposure to lomustine chemotherapy in recurrent glioblastoma. Mitigating thrombocytopenia to enhance lomustine exposure might improve outcome in patients with MGMT promoter-methylated tumours.

Association of antidepressant drug use with outcome of patients with glioblastoma.

Depressive symptoms are common among patients with glioblastoma, but patients are often not treated with antidepressants. There is only limited evidence on the association of antidepressant drug use with survival in glioblastoma. We performed a pooled analysis of patients treated within the CENTRIC, CORE, AVAglio and ACT-IV trials to explore the relation of antidepressant drug use with progression-free (PFS) and overall survival (OS) at baseline, at the start of maintenance therapy and at the start of maintenance cycle 4. We further assessed the association of antidepressant drugs with seizure, cognition, fatigue and a diagnosis of depression. Among more than 1700 patients, we found no significant association between the use of antidepressants at baseline or at the start of maintenance therapy and PFS or OS. However, we found OS, but not PFS, to be significantly worse in patients using antidepressants at the start of maintenance cycle 4. After adjustment for antiepileptic drug use and despite showing a trend for increased risk, seizures were not significantly associated with antidepressant drug use, nor was there a change in mini mental state examination (MMSE) scores or fatigue by antidepressant drug use at baseline. However, there was a significant positive association between antidepressant use at the start of maintenance treatment and fatigue during maintenance treatment. The association of antidepressant use at the start of maintenance cycle 4 with inferior OS of glioblastoma patients requires independent confirmation and further study. Further prospective trials should evaluate efficacy, side effects and associations with outcome of antidepressants in glioblastoma.

Effectiveness of school-based interventions for preventing tobacco smoking initiation among young people in low- and middle-income countries: a systematic review protocol.

BACKGROUND: Despite the commendable progress made globally in tobacco control, the world is falling short of achieving a 30% relative reduction in current tobacco use by 2025. The African region remains the least in the efforts in fighting the tobacco epidemic and is most exploited by the tobacco industry. Schools have been continuously used for over three decades as a setting for delivering youth smoking prevention programmes; however, the evidence of the effectiveness of those school-based interventions provides varying outcomes. Also, interventions that proved to be effective, in high-income countries (HICs), may not necessarily be effective in the African region as a result of cultural differences and other contrasting factors. An existing systematic review that explored school-based tobacco prevention programmes among the youth in African countries from 2000 to 2016 showed partial effectiveness. This review will address the gap by updating the 2016 review to examine studies in LMICs to generate findings to help target resources which have the potential to save lives by preventing smoking initiation among young people. METHODS: The JBI methodology for systematic reviews of effectiveness will guide the conduct of this review. A comprehensive strategic search will be developed to retrieve both published and unpublished studies that evaluate school-based interventions to prevent tobacco smoking initiation among in-school young people in LMICs compared to non-intervention programmes. Published studies would be from databases such as MEDLINE via Ovid, CINAHL via EBSCO, Embase, PsycINFO, PsycEXTRA, and the Cochrane Central Register of Controlled Trials. Sources of grey literature would be ProQuest Dissertations and Theses, MedNar, EBSCO Open Dissertations, Open Access Theses and Dissertations, and Trove. The databases will be searched for published studies in the English language. The processes of study selection, critical appraisal, data extraction, and data synthesis will be in accordance with the JBI approach for reviews of effectiveness with a minimum of two reviewers at each stage. The primary outcome of the review will be the non-initiation of tobacco smoking by the youth. DISCUSSION: The review will provide synthesized evidence on the effectiveness of school-based smoking initiation prevention among young people in LMICs. The findings of the review would support policymakers and programme implementers to develop targeted interventions for effective tobacco control initiatives. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021246206.

Associations of levetiracetam use with the safety and tolerability profile of chemoradiotherapy for patients with newly diagnosed glioblastoma.

Background: Levetiracetam (LEV) is one of the most frequently used antiepileptic drugs (AED) for brain tumor patients with seizures. We hypothesized that toxicity of LEV and temozolomide-based chemoradiotherapy may overlap. Methods: Using a pooled cohort of patients with newly diagnosed glioblastoma included in clinical trials prior to chemoradiotherapy (CENTRIC, CORE, AVAglio) or prior to maintenance therapy (ACT-IV), we tested associations of hematologic toxicity, nausea or emesis, fatigue, and psychiatric adverse events during concomitant and maintenance treatment with the use of LEV alone or with other AED versus other AED alone or in combination versus no AED use at the start of chemoradiotherapy and of maintenance treatment. Results: Of 1681 and 2020 patients who started concomitant chemoradiotherapy and maintenance temozolomide, respectively, 473 and 714 patients (28.1% and 35.3%) were treated with a LEV-containing regimen, 538 and 475 patients (32.0% and 23.5%) with other AED, and 670 and 831 patients (39.9% and 41.1%) had no AED. LEV was associated with higher risk of psychiatric adverse events during concomitant treatment in univariable and multivariable analyses (RR 1.86 and 1.88, P < .001) while there were no associations with hematologic toxicity, nausea or emesis, or fatigue. LEV was associated with reduced risk of nausea or emesis during maintenance treatment in multivariable analysis (HR = 0.80, P = .017) while there were no associations with hematologic toxicity, fatigue, or psychiatric adverse events. Conclusions: LEV is not associated with reduced tolerability of chemoradiotherapy in patients with glioblastoma regarding hematologic toxicity and fatigue. Antiemetic properties of LEV may be beneficial during maintenance temozolomide.

The prevalence of molecular markers of resistance to sulfadoxine-pyrimethamine among pregnant women at first antenatal clinic attendance and delivery in the forest-savannah area of Ghana.

Intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is used to prevent malaria and associated unfavorable maternal and foetal outcomes in pregnancy in moderate to high malaria transmission areas. Effectiveness of IPTp-SP is, however, threatened by mutations in the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes which confer resistance to pyrimethamine and sulfadoxine, respectively. This study determined the prevalence of molecular markers of SP resistance among pregnant women in a high malaria transmission area in the forest-savannah area of Ghana. Genomic DNA was extracted from 286 P. falciparum-positive dried blood spots obtained from pregnant women aged ≥18 years (255 at first Antenatal Care (ANC) clinic visit and 31 at delivery from 2017 to 2019) using Chelex 100. Mutations in Pfdhfr and Pfdhps genes were detected using molecular inversion probes and next generation sequencing. In the Pfdhfr gene, single nucleotide polymorphisms (SNPs) were detected in 83.1% (157/189), 92.0% (173/188) and 91.0% (171/188) at codons 51, 59, and 108 respectively in samples collected at first ANC visit, while SNPs were detected in 96.6 (28/29), 96.6% (28/29) and 96.8% (30/31) in isolates collected at delivery. The Pfdhfr triple mutant N51I, C59R and S108N (IRN) was carried by 80.5% (128/159) and 96.5% (28/29) of the typed isolates collected at ANC visit and at delivery respectively. In the Pfdhps gene, SNPs were detected in 0.6% (1/174), 76.2% (138/181), 33.2% (60/181), 1.2% (2/174), 0% (0/183), and 16.6% (27/173) at codons 431, 436, 437, 540, 581 and 613 respectively in samples collected at ANC, and 0% (0/25), 72% (18/25), 40% (10/25), 3.6% (1/25), 0% (0/29) and 7.4% (2/27) in samples collected at delivery. Quadruple mutant Pfdhfr N51I, C59R, and S108N + Pfdhps A437G (IRN-GK) was present in 25.8% (33/128) and 34.8% (8/23) of isolates at ANC and at delivery respectively. Quintuple mutant alleles Pfdhfr N51I, C59R, and S108N + Pfdhps A437G and K540E (IRN-GE) were detected in 0.8% (1/128) and 4.4% (1/23) of samples collected at ANC and at delivery respectively. No mutations were identified at Pfdhfr codons 16 or 164 or Pfdhps 581. There is a high prevalence of Pfdhfr triple mutant P. falciparum infections among pregnant women in the study area. However, prevalence of the combined Pfdhfr/Pfdhps quadruple and quintuple mutants IRN-GK and IRN-GE respectively prior to commencement of IPTp-SP were low, and no Pfdhps A581G mutant was detected, indicating that SP is still likely to be efficacious for IPTp-SP in the forest-savannah area in the middle belt of Ghana.

Demographic disparities in unimproved drinking water and sanitation in Ghana: a nationally representative cross-sectional study.

OBJECTIVE: The government of Ghana has targeted universal access to safe drinking water by 2025 and elimination of open defecation by year 2030. This study explored the use of unimproved drinking water and unimproved sanitation and assessed their association with demographic factors. DESIGN: This was a secondary data analysis of the 2017 Ghana Maternal Health Survey, a nationally representative cross-sectional survey. Open defecation households were mapped to show regional differences. Weighted logistic regression was used to assess the association of demographic variables with use of unimproved drinking water and unimproved toilet facilities. SETTING: Ghana. PARTICIPANTS: A total of 26 324 households were included in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: Use of unimproved drinking water and unimproved toilet facilities. RESULTS: Out of the 26 324 households, 8.9% used unimproved drinking water while 81.6% used unimproved sanitation. Open defecation was practised by 15.2% of Ghanaian households, with a prevalence of 58.8%, 6.7% and 12.5% in the Northern, Middle and Coastal zones, respectively. In the multivariate analysis, rural households (p<0.001), households with more than five members (p<0.001), households with heads less than 25 years (p=0.018), male-headed households (p<0.001) and household heads with no/low level of education (p<0.001) were significantly associated with drinking unimproved water. Also, rural households (p=0.002), households in the Northern zone (p<0.001), single-member households (p<0.001), households with heads less than 25 years (p<0.001) and household heads with no/low level of education (p<0.001) were significantly associated with using unimproved toilet facilities. CONCLUSION: The target of universal access to safe drinking water by 2025 and elimination of open defecation by 2030 seems impossible to be achieved if appropriate measures are not implemented. We recommend that state authorities, health partners and non-governmental organisations support local-level sanitation plans and strategies.

Prognostic significance of therapy-induced myelosuppression in newly diagnosed glioblastoma.

BACKGROUND: Myelosuppression is the major toxicity encountered during temozolomide chemoradiotherapy for newly diagnosed glioblastoma. METHODS: We assessed the association of myelosuppression (neutropenia, thrombocytopenia, anemia, and lymphopenia) during temozolomide chemoradiotherapy alone or in combination with experimental agents with progression-free survival (PFS) or overall survival (OS) in 2073 patients with newly diagnosed glioblastoma enrolled into five clinical trials: CENTRIC, CORE, EORTC 26082, AVAglio, and EORTC 26981. A landmark Cox model was used. For each primary association analysis, a significance level of 1.7% was used. RESULTS: Lower neutrophil counts at baseline were associated with better PFS (P = .011) and OS (P < .001), independently of steroid intake. Females experienced uniformly more myelotoxicity than males. Lymphopenia during concomitant chemoradiotherapy was associated with OS (P = .009): low-grade (1-2) lymphopenia might be associated with superior OS (HR 0.78, 98.3% CI 0.58-1.06), whereas high-grade (3-4) lymphopenia might be associated with inferior OS (HR 1.08, 98.3% CI 0.75-1.54). There were no associations of altered hematological parameters during concomitant chemoradiotherapy with PFS. During maintenance chemoradiotherapy, no significant association was found between any parameter of myelosuppression and PFS or OS, although exploratory analysis at 5% significance level indicated that either mild-to-moderate (HR 0.76, 95% CI 0.62-0.93) or high-grade lymphopenia (HR 0.65, 95% CI 0.46-0.92) was associated with superior OS (P = .013), but not PFS. CONCLUSIONS: The association of higher neutrophil counts at baseline with inferior PFS and OS requires further prospective evaluation. The link of therapy-induced lymphopenia to better outcome may guide the design for immunotherapy trials in newly diagnosed glioblastoma.

Corrigendum to "Prenatal household air pollutant exposure is associated with reduced size and gestational age at birth among a cohort of Ghanaian infants" [Environ. Int. 155 (2021) 106659].

[This corrects the article PMC8628363.].

Effectiveness of intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) in Ghana.

INTRODUCTION: Ghana adopted the revised WHO recommendation on intermittent preventive treatment in pregnancy using sulfadoxine-pyrimethamine (IPTp-SP) in 2012. This study has assessed the effectiveness and safety of this policy in Ghana. METHODS: A total of 1926 pregnant women enrolled at antenatal care (ANC) clinics were assessed for birth outcomes at delivery, and placental histology results for malaria infection were obtained from 1642 participants. Association of reduced placental or peripheral malaria, anaemia and low birth weight (LBW) in women who received ≥4 IPTp-SP doses compared with 3 or ≤2 doses was determined by logistic regression analysis. RESULTS: Among the 1926 participants, 5.3% (103), 19.2% (369), 33.2% (640) and 42.3% (817) of women had received ≤1, 2, 3 or ≥4 doses, respectively. There was no difference in risk of active placental malaria (PM) infection in women who received 3 doses compared with ≥4 doses (adjusted OR (aOR) 1.00, 95% CI 0.47 to 2.14). The risk of overall PM infection was 1.63 (95% CI 1.07 to 2.48) in 2 dose group and 1.06 (95% CI 0.72 to 1.57) in 3 dose group compared with ≥4 dose group. The risk of LBW was 1.55 (95% CI 0.97 to 2.47) and 1.06 (95% CI 0.68 to 1.65) for 2 and 3 dose groups, respectively, compared with the ≥4 dose group. Jaundice in babies was present in 0.16%, and 0% for women who received ≥4 doses of SP. CONCLUSION: There was no difference in the risk of PM, LBW or maternal anaemia among women receiving 3 doses compared with ≥4 doses. Receiving ≥3 IPTp-SP doses during pregnancy was associated with a lower risk of overall PM infection compared with 2 doses. As there are no safety concerns, monthly administration of IPTp-SP offers a more practical opportunity for pregnant women to receive ≥3 doses during pregnancy.

A cluster randomised trial of cookstove interventions to improve infant health in Ghana.

INTRODUCTION: Household air pollution from solid fuel combustion for cooking and heating is a leading cause of childhood morbidity and mortality worldwide. We hypothesised that clean cooking interventions delivered during pregnancy would improve child health. METHODS: We conducted a cluster randomised trial in rural Ghana to test whether providing pregnant women liquefied petroleum gas (LPG) cookstoves or improved biomass cookstoves would reduce personal carbon monoxide and fine particulate pollution exposure, increase birth weight and reduce physician-assessed severe pneumonia in the first 12 months of life, compared with control participants who continued to cook with traditional stoves. Primary analyses were intention-to-treat. The trial was registered with ClinicalTrials.gov and follow-up is complete. RESULTS: Enrolment began on 14 April 2014, and ended on 20 August 2015. We enrolled 1414 pregnant women; 361 in the LPG arm, 527 in the improved biomass cookstove arm and 526 controls. We saw no improvement in birth weight (the difference in mean birth weight for LPG arm births was 29 g lighter (95% CI -113 to 56, p=0.51) and for improved biomass arm births was 9 g heavier (95% CI -64 to 82, p=0.81), compared with control newborns) nor severe child pneumonia (the rate ratio for pneumonia in the LPG arm was 0.98 (95% CI 0.58 to 1.70; p=0.95) and for the improved biomass arm was 1.21 (95% CI 0.78 to 1.90; p=0.52), compared with the control arm). Air pollution exposures in the LPG arm remained above WHO health-based targets (LPG median particulate matter less than 2.5 microns in diameter (PM2.5) 45 µg/m³; IQR 32-65 vs control median PM2.5 67 µg/m³, IQR 46-97). CONCLUSIONS: Neither prenatally-introduced LPG nor improved biomass cookstoves improved birth weight or reduced severe pneumonia risk in the first 12 months of life. We hypothesise that this is due to lower-than-expected exposure reductions in the intervention arms. TRIAL REGISTRATION NUMBER: NCT01335490.

Impact of IgG response to malaria-specific antigens and immunity against malaria in pre-school children in Ghana. A cluster randomized, placebo-controlled trial.

BACKGROUND: Iron fortification and micronutrient initiatives, specifically, vitamin A, and zinc supplementation are the most cost-effective developmental strategies against malnutrition and health emergencies in pre-school children. Iron-deficiency among pre-school children have been documented, however, studies evaluating the impact of immunoglobulin G (IgG) isotype responses among iron-fortified pre-school children in malaria endemic communities has not been assessed. We evaluated the impact of iron fortification on the IgG responses to GLURP R0, GLURP R2 and MSP3 FVO malaria-specific antigens among pre-school children in malaria endemic areas. METHODS: This community-based, placebo-controlled, double-blinded, cluster-randomized trial study was conducted in Wenchi Municipal and Tain District of Bono Region. The trial was registered at ClinicalTrials.gov-registered trial (Identifier: NCT01001871). Ethical approval was obtained and informed consent were sought from each participant parents/guardian. For the current objective, 871 children aged 6-35 months were screened, from which 435 children received semi-liquid home-made meals mixed with 12.5 mg of iron daily (intervention group), and 436 received micronutrient powder without iron (placebo group) for 5 months. Standardized clinical and epidemiological questionnaires were administered and blood samples taken to measure IgG responses to GLURP R0, GLURP R2 and MSP3 FVO recombinant antigens using the Afro Immunoassay (AIA) protocol. RESULTS: Baseline anthropometry, malaria diagnosis, anaemia and iron status, demographic features and dietary intake were identical among the groups (p > 0.05). After the intervention, there was no significant difference in the IgG response against GLUP R0, GLUP R2 and MSP3 FVO between the iron-containing micronutrient and placebo groups (p > 0.05). The iron-containing micronutrient powder group who were iron-sufficient or iron replete had significantly higher IgG response to GLURP R0 and GLURP R2 compared to iron-deficient and iron-deficiency anaemia in the same group (p < 0.05). The IgG responses to all the three malaria specific antigens were low among children without malaria episode but high among those with two and four episodes due to exposure differences. CONCLUSION: Iron fortification did not influence antibody response against endogenous malaria specific antigens among pre-school children in malaria endemic areas, however, IgG response to malaria specific antigens were high among children with sufficient iron status.

Prenatal household air pollutant exposure is associated with reduced size and gestational age at birth among a cohort of Ghanaian infants.

BACKGROUND: Low birth weight and prematurity are important risk factors for death and disability, and may be affected by prenatal exposure to household air pollution (HAP). METHODS: We investigate associations between maternal exposure to carbon monoxide (CO) during pregnancy and birth outcomes (birth weight, birth length, head circumference, gestational age, low birth weight, small for gestational age, and preterm birth) among 1288 live-born infants in the Ghana Randomized Air Pollution and Health Study (GRAPHS). We evaluate whether evidence of malaria during pregnancy, as determined by placental histopathology, modifies these associations. RESULTS: We observed effects of CO on birth weight, birth length, and gestational age that were modified by placental malarial status. Among infants from pregnancies without evidence of placental malaria, each 1 ppm increase in CO was associated with reduced birth weight (-53.4 g [95% CI: -84.8, -21.9 g]), birth length (-0.3 cm [-0.6, -0.1 cm]), gestational age (-1.0 days [-1.8, -0.2 days]), and weight-for-age Z score (-0.08 standard deviations [-0.16, -0.01 standard deviations]). These associations were not observed in pregnancies with evidence of placental malaria. Each 1 ppm increase in maternal exposure to CO was associated with elevated odds of low birth weight (LBW, OR 1.14 [0.97, 1.33]) and small for gestational age (SGA, OR 1.14 [0.98, 1.32]) among all infants. CONCLUSIONS: Even modest reductions in exposure to HAP among pregnant women could yield substantial public health benefits, underscoring a need for interventions to effectively reduce exposure. Adverse associations with HAP were discernible only among those without evidence of placental malaria, a key driver of impaired fetal growth in this malaria-endemic area.

Determinants of the varied profiles of Plasmodium falciparum infections among infants living in Kintampo, Ghana.

BACKGROUND: Understanding why some infants tolerate infections, remaining asymptomatic while others succumb to repeated symptomatic malaria is beneficial for studies of naturally acquired immunity and can guide control interventions. This study compared demographic, host and maternal factors associated with being either parasite negative or having asymptomatic infections versus developing symptomatic malaria in the first year of life. METHODS: A birth cohort (n = 1264) was monitored longitudinally over two years for malaria infections in Kintampo, Ghana. Symptomatic and asymptomatic infections were detected actively through monthly home visits, complemented by passive case detection. Light microscopy was used to detect parasitaemia. Based on data from a minimum of eight monthly visits within the first year of life, infants were classified into one of four groups: "parasite negative", "only-asymptomatic", "only-symptomatic" or "alternating" i.e., sometimes symptomatic and other times asymptomatic. The host and maternal characteristics and demographic factors in relation to these four groups were compared. RESULTS: The parasite negative group formed 36% of the cohort, whilst the only-symptomatic were 35%. The alternating group were 22% and the only-asymptomatic were 7% of the cohort. There were significant associations between residence, socio-economic status (SES), parity, IPTp doses, delivery place of infant and having or not having malaria parasites. Maternal factors such as early commencement and frequency of ante-natal care (ANC) were significantly higher in the parasite negative group compared to all others. ITN use in pregnancy increased the odds of infant having only asymptomatic infections ("protected against disease"). Placental malaria was more common in the groups of infants with symptomatic malaria. Urban residence was significantly higher in the parasite negative group, while birth in the malaria transmission season were significantly more common in the alternating and parasite negative groups. Risk factors for infants with symptomatic malaria included low SES, birth in private maternity homes, sickle cell normal variant, lower MUAC, reported intake of anti-malarials and increased morbidity before the first microscopic infection was detected. CONCLUSION: Strengthening ANC by encouraging early and regular attendance, the use of IPTp, maternal bed nets and improving the nourishment of infants help reduce the frequency of symptomatic malaria over the first year of life.

Correction: Profiles of Plasmodium falciparum infections detected by microscopy through the first year of life in Kintampo a high transmission area of Ghana.

[This corrects the article DOI: 10.1371/journal.pone.0240814.].

Determinants of contraceptive use among sexually active unmarried adolescent girls and young women aged 15-24 years in Ghana: a nationally representative cross-sectional study.

OBJECTIVE: There is a decline in contraceptive use among sexually active unmarried young women in Ghana. This study assessed the prevalence of contraceptive knowledge and use, and the determinant of contraceptive use among sexually active unmarried young women in Ghana. DESIGN: This was a nationally representative cross-sectional survey, using data from the 2017 Ghana Maternal Health Survey. Weighted logistic regression was used to assess the association between background and obstetric characteristics of young women and contraceptive use. SETTING: Ghana. PARTICIPANTS: A total of 809 sexually active unmarried adolescent girls (15-19 years) and young women (20-24 years). PRIMARY AND SECONDARY OUTCOME MEASURES: Knowledge and use of both modern and traditional contraceptive methods. RESULTS: Knowledge of at least one modern and traditional contractive method was 99.8% and 95.0%, respectively. The prevalence of contraceptive use was 43%-with 34% modern and 9% traditional methods. From the unadjusted analyses, age (p=0.002), past pregnancy (p<0.001), abortion in the past 5 years (p=0.007) and history of childbirth (p=0.025) were independently associated with contraceptive use, whereas education (p=0.072), place of residence (p=0.702), household wealth (p=0.836) and age at first sex (p=0.924) were not independently associated with contraceptive use. In the adjusted analysis, contraceptive use was significantly higher among respondents with secondary education compared with those with primary education (OR 2.43, 95% CI 1.31 to 4.49, p=0.017), and was higher among respondents with a history of pregnancy (OR 2.13, 95% CI 1.48 to 3.06, p<0.001). CONCLUSION: There is a significant gap between knowledge and use of contraceptives among the study population. While intensifying knowledge of adolescents and young women on contraceptives, adolescent-friendly corners should be established at vantage points to increase utilisation and to prevent societal stigma on young women who access contraceptives services.

Impact of iron fortification on anaemia and iron deficiency among pre-school children living in Rural Ghana.

Anaemia in young sub-Saharan African children may be due to the double burden of malaria and iron deficiency. Primary analysis of a double-blind, cluster randomized trial of iron containing micronutrient powder supplementation in Ghanaian children aged 6 to 35 months found no difference in malaria risk between intervention and placebo groups. Here, we performed a secondary analysis of the trial data to assess the impact of long-term prophylactic iron fortificant on the risk of iron deficiency and anaemia in trial subjects. This population-based randomized-cluster trial involved 1958 children aged between 6 to 35 months, identified at home and able to eat semi-solid foods. The intervention group (n = 967) received a daily dose containing 12.5 mg elemental iron (as ferrous fumarate), vitamin A (400 µg), ascorbic acid (30 mg) and zinc (5 mg). The placebo group (n = 991) received a similar micronutrient powder but without iron. Micronutrient powder was provided daily to both groups for 5 months. At baseline and endline, health assessment questionnaires were administered and blood samples collected for analysis. The two groups had similar baseline anthropometry, anaemia, iron status, demographic characteristics, and dietary intakes (p > 0.05). Of the 1904 (97.2%) children who remained at the end of the intervention, the intervention group had significantly higher haemoglobin (p = 0.0001) and serum ferritin (p = 0.0002) levels than the placebo group. Soluble transferrin receptor levels were more saturated among children from the iron group compared to non-iron group (p = 0.012). Anaemia status in the iron group improved compared to the placebo group (p = 0.03). Continued long-term routine use of micronutrient powder containing prophylactic iron reduced anaemia, iron deficiency and iron deficiency anaemia among pre-school children living in rural Ghana's malaria endemic area.

The Influence of Apparent Temperature on Mortality in the Kintampo Health and Demographic Surveillance Area in the Middle Belt of Ghana: A Retrospective Time-Series Analysis.

Globally, studies have shown that diurnal changes in weather conditions and extreme weather events have a profound effect on mortality. Here, we assessed the effect of apparent temperature on all-cause mortality and the modifying effect of sex on the apparent temperature-mortality relationship using mortality and weather data archived over an eleven-year period. An overdispersed Poisson regression and distributed lag nonlinear models were used for this analysis. With these models, we analysed the relative risk of mortality at different temperature values over a 10-day lag period. By and large, we observed a nonlinear association between mean daily apparent temperature and all-cause mortality. An assessment of different temperature values over a 10-day lag period showed an increased risk of death at the lowest apparent temperature (18°C) from lag 2 to 4 with the highest relative risk of mortality (RR = 1.61, 95% CI: 1.2, 2.15, p value = 0.001) occurring three days after exposure. The relative risk of death also varied between males (RR = 0.31, 95% CI: 0.10, 0.94) and females (RR = 4.88, 95% CI: 1.40, 16.99) by apparent temperature and lag. On the whole, males are sensitive to both temperature extremes whilst females are more vulnerable to low temperature-related mortality. Accordingly, our findings could inform efforts at reducing temperature-related mortality in this context and other settings with similar environmental and demographic characteristics.