Journal Article > ResearchFull Text
PLOS Med. 2024 September 12; Volume 21 (Issue 9); e1004428.; DOI:10.1371/journal.pmed.1004428
Schilling WHK, Mukaka M, Callery JJ, Llewelyn MJ, Cruz CV, et al.
PLOS Med. 2024 September 12; Volume 21 (Issue 9); e1004428.; DOI:10.1371/journal.pmed.1004428
BACKGROUND
Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use.
METHODS AND FINDINGS
Healthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention. HCQ was evaluated in Europe and Africa, and chloroquine (CQ) was evaluated in Asia, (both base equivalent of 155 mg once daily). The primary endpoint was symptomatic COVID-19, confirmed by PCR or seroconversion during the 3-month follow-up period. The secondary and tertiary endpoints were: asymptomatic laboratory-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection; severity of COVID-19 symptoms; all-cause PCR-confirmed symptomatic acute respiratory illness (including SARS-CoV-2 infection); participant reported number of workdays lost; genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity (not reported here); and health economic analyses of HCQ and CQ prophylaxis on costs and quality of life measures (not reported here). The primary and safety analyses were conducted in the intention-to-treat (ITT) population. Recruitment of 40,000 (20,000 HCQ arm, 20,000 CQ arm) participants was planned but was not possible because of protracted delays resulting from controversies over efficacy and adverse events with HCQ use, vaccine rollout in some countries, and other factors. Between 29 April 2020 and 10 March 2022, 4,652 participants (46% females) were enrolled (HCQ/CQ n = 2,320; placebo n = 2,332). The median (IQR) age was 29 (23 to 39) years. SARS-CoV-2 infections (symptomatic and asymptomatic) occurred in 1,071 (23%) participants. For the primary endpoint the incidence of symptomatic COVID-19 was 240/2,320 in the HCQ/CQ versus 284/2,332 in the placebo arms (risk ratio (RR) 0.85 [95% confidence interval, 0.72 to 1.00; p = 0.05]). For the secondary and tertiary outcomes asymptomatic SARS-CoV-2 infections occurred in 11.5% of HCQ/CQ recipients and 12.0% of placebo recipients: RR: 0.96 (95% CI, 0.82 to 1.12; p = 0.6). There were no differences in the severity of symptoms between the groups and no severe illnesses. HCQ/CQ chemoprevention was associated with fewer PCR-confirmed all-cause respiratory infections (predominantly SARS-CoV-2): RR 0.61 (95% CI, 0.42 to 0.88; p = 0.009) and fewer days lost to work because of illness: 104 days per 1,000 participants over 90 days (95% CI, 12 to 199 days; p < 0.001). The prespecified meta-analysis of all published pre-exposure RCTs indicates that HCQ/CQ prophylaxis provided a moderate protective benefit against symptomatic COVID-19: RR 0.80 (95% CI, 0.71 to 0.91). Both drugs were well tolerated with no drug-related serious adverse events (SAEs). Study limitations include the smaller than planned study size, the relatively low number of PCR-confirmed infections, and the lower comparative accuracy of serology endpoints (in particular, the adapted dried blood spot method) compared to the PCR endpoint. The COPCOV trial was registered with ClinicalTrials.gov; number NCT04303507.
INTERPRETATION
In this large placebo-controlled, double-blind randomised trial, HCQ and CQ were safe and well tolerated in COVID-19 chemoprevention, and there was evidence of moderate protective benefit in a meta-analysis including this trial and similar RCTs.
Journal Article > CommentaryFull Text
Am J Trop Med Hyg. 2023 September 6; Volume 109 (Issue 3); 511-514.; DOI:10.4269/ajtmh.22-0606
Kabore Y, Vatrinet R, Guindo O, Moussa SH, Schilling WHK, et al.
Am J Trop Med Hyg. 2023 September 6; Volume 109 (Issue 3); 511-514.; DOI:10.4269/ajtmh.22-0606
In 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a rapidly emerging virus causing the coronavirus disease 2019 (COVID-19) pandemic, had no known effective prophylaxis and no widely available proven effective antiviral treatment. Hydroxychloroquine/Chloroquine was identified as an early potential therapeutic candidate drawing on evidence from reports of both in vitro and in vivo testing. A multicountry placebo-controlled randomized trial was set to evaluate the use of hydroxychloroquine/chloroquine to prevent infection in healthcare workers and staff working in a health facility involved in COVID-19 management. One of the sites of this trial was in Niger. In Niger, of the 240 persons who were provided information about the study and with whom participation was discussed, only five participants provided their informed consent. In this article, we describe the key difficulties encountered in the conduct of this trial from the perspective of the site study team. Among the difficulties, we recognize that the epidemic context, controversy surrounding hydroxychloroquine, vaccine rollout, participants’ perspectives, and trial design had a major impact on participation.
Journal Article > ResearchFull Text
Antimicrob Resist Infect Control. 2023 July 11; Volume 12 (Issue 1); 67.; DOI:10.1186/s13756-023-01271-7
Mambula G, Nanjebe D, Munene A, Guindo O, Salifou A, et al.
Antimicrob Resist Infect Control. 2023 July 11; Volume 12 (Issue 1); 67.; DOI:10.1186/s13756-023-01271-7
BACKGROUND
Antibiotic resistance is a significant public health problem and is responsible for high mortality in children and new-borns. Strengthening the rational use of antibiotics and improving the quality and access to existing antibiotics are important factors in the fight against antibiotic resistance. This study aims to provide knowledge on the use of antibiotics in children in resource-limited countries in order to identify problems and possible avenues for improvement of antibiotics use.
METHODS
We conducted a retrospective study in July 2020 and collected quantitative clinical and therapeutic data on antibiotic prescriptions between January and December 2019 in 4 hospitals or health centres in both Uganda and Niger, respectively from January to December 2019. Semi-structured interviews and focus groups were conducted among healthcare personnel and carers for children under 17 years of age, respectively.
RESULTS
A total of 1,622 children in Uganda and 660 children in Niger (mean age of 3.9 years (SD 4.43)) who received at least one antibiotic were included in the study. In hospital settings, 98.4 to 100% of children prescribed at least one antibiotic received at least one injectable antibiotic. Most hospitalized children received more than one antibiotic in both Uganda (52.1%) and Niger (71.1%). According to the WHO-AWaRe index, the proportion of prescriptions of antibiotics belonging to the Watch category was 21.8% (432/1982) in Uganda and 32.0% (371/1158) in Niger. No antibiotics from the Reserve category were prescribed. Health care provider’s prescribing practices are rarely guided by microbiological analyses. Prescribers are faced with numerous constraints, such as lack of standard national guidelines, unavailability of essential antibiotics at the level of hospital pharmacies, the limited financial means of the families, and pressure to prescribe antibiotics from caregivers as well as from drug company representatives. The quality of some antibiotics provided by the National Medical Stores to the public and private hospitals has been questioned by some health professionals. Self-medication is a widespread practice for the antibiotic treatment of children for economic and access reasons.
CONCLUSION
The study findings indicate that an intersection of policy, institutional norms and practices including individual caregiver or health provider factors, influence antibiotic prescription, administration and dispensing practices.
Antibiotic resistance is a significant public health problem and is responsible for high mortality in children and new-borns. Strengthening the rational use of antibiotics and improving the quality and access to existing antibiotics are important factors in the fight against antibiotic resistance. This study aims to provide knowledge on the use of antibiotics in children in resource-limited countries in order to identify problems and possible avenues for improvement of antibiotics use.
METHODS
We conducted a retrospective study in July 2020 and collected quantitative clinical and therapeutic data on antibiotic prescriptions between January and December 2019 in 4 hospitals or health centres in both Uganda and Niger, respectively from January to December 2019. Semi-structured interviews and focus groups were conducted among healthcare personnel and carers for children under 17 years of age, respectively.
RESULTS
A total of 1,622 children in Uganda and 660 children in Niger (mean age of 3.9 years (SD 4.43)) who received at least one antibiotic were included in the study. In hospital settings, 98.4 to 100% of children prescribed at least one antibiotic received at least one injectable antibiotic. Most hospitalized children received more than one antibiotic in both Uganda (52.1%) and Niger (71.1%). According to the WHO-AWaRe index, the proportion of prescriptions of antibiotics belonging to the Watch category was 21.8% (432/1982) in Uganda and 32.0% (371/1158) in Niger. No antibiotics from the Reserve category were prescribed. Health care provider’s prescribing practices are rarely guided by microbiological analyses. Prescribers are faced with numerous constraints, such as lack of standard national guidelines, unavailability of essential antibiotics at the level of hospital pharmacies, the limited financial means of the families, and pressure to prescribe antibiotics from caregivers as well as from drug company representatives. The quality of some antibiotics provided by the National Medical Stores to the public and private hospitals has been questioned by some health professionals. Self-medication is a widespread practice for the antibiotic treatment of children for economic and access reasons.
CONCLUSION
The study findings indicate that an intersection of policy, institutional norms and practices including individual caregiver or health provider factors, influence antibiotic prescription, administration and dispensing practices.
Journal Article > ResearchAbstract Only
J. Infect.. 2023 June 25; Volume S0163-4453 (Issue 23); 00336-5.; DOI:10.1016/j.jinf.2023.06.015
Jacquier H, Assao B, Chau F, Guindo O, Condamine B, et al.
J. Infect.. 2023 June 25; Volume S0163-4453 (Issue 23); 00336-5.; DOI:10.1016/j.jinf.2023.06.015
OBJECTIVE
Whole genome sequencing (WGS) of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. coli faecal isolates in rural Southern Niger.
METHODS
Stools of 383 healthy participants were collected among which 92.4% were ESBL-Enterobacterales carriers. A subset of 90 ESBL-E. coli containing stools (109 ESBL-E. coli isolates) were further analysed by WGS, using short- and long-reads.
RESULTS
Most isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. The blaCTX-M-15 gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne, blaCTX-M-15 was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis of blaCTX-M-15 in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome.
CONCLUSIONS
Massive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration of blaCTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.
Whole genome sequencing (WGS) of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. coli faecal isolates in rural Southern Niger.
METHODS
Stools of 383 healthy participants were collected among which 92.4% were ESBL-Enterobacterales carriers. A subset of 90 ESBL-E. coli containing stools (109 ESBL-E. coli isolates) were further analysed by WGS, using short- and long-reads.
RESULTS
Most isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. The blaCTX-M-15 gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne, blaCTX-M-15 was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis of blaCTX-M-15 in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome.
CONCLUSIONS
Massive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration of blaCTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.
Conference Material > Abstract
Idrissa AA, Atti S, Wasaulua RK, Kazadi S, Guindo O, et al.
MSF Scientific Day International 2023. 2023 June 7; DOI:10.57740/wg9g-dq47
INTRODUCTION
MSF supported Niger’s Ministry of Health (MoH) in responding to a serogroup C meningococcal meningitis epidemic in Magaria and Dungass Districts in 2022. WHO’s global roadmap for defeating meningitis by 2030 emphasises appropriate care for meningitis sequelae, but this is not yet part of standard epidemic response. Meningitis sequelae in the African meningitis belt are poorly described, hampering access to rehabilitation services. To better orient future care for sequelae, we performed a follow-up survey of survivors 9 months after the 2022 epidemic.
METHODS
WHO case definitions were used during the epidemic. Patient-level line-lists detailing village of origin were obtained from authorities, and results of polymerase chain reaction testing on cerebrospinal fluid were integrated. Guided by village leaders, study nurses attempted to visit cases at home to assess for sequelae. Nurses administered questionnaires asking about history including seizures and subjective vision and hearing loss; and carried out physical examinations assessing anosmia, weakness, and paralysis. Data were collected tablets using REDCap software. Prevalence of sequelae among survivors was calculated.
ETHICS
This study was approved by the MSF Ethics Review Board and by the National Ethics Committee for Health Research of Niger.
RESULTS
1001 suspected cases and 50 deaths (case fatality rate, CFR, 5.0%) originating in 230 villages were recorded on the line-lists. 469 cases (47%) had lumbar puncture, and 220 (47%) had a causative agent identified, including 192 cases of Neisseria meningitidis serogroup C (NmC) and 22 Streptococcus pneumoniae. After excluding 82 cases living in villages difficult to access, we attempted to trace 919 cases, of whom 570 (62%) were found and consented to interview. Among these cases, 49 had died (CFR 8.6%). Among the cases visited, 151 had confirmed NmC and 10 S. pneumoniae. Among the 521 surviving cases evaluated, 62 (12%) had sequelae; the most common were hearing loss (29), paralysis (16), epilepsy (9), and developmental regression (6). Among the 138 surviving confirmed cases of NmC, 25 (18%) had one or more sequelae.
CONCLUSION
We documented a higher CFR than reported during the epidemic, and a high burden of sequelae among survivors, particularly among those with confirmed NmC infection. To our knowledge, this is the second time that meningitis sequelae have been documented in Niger; these findings help identify priorities for integrating meningitis after-care into epidemic responses. MSF and the MoH should work to ensure linkages to long-term care and support for meningitis survivors and their caregivers. We were unable to find all cases, so the true prevalence of sequelae among survivors may differ. This follow-up survey used simple methods adapted for in-home evaluation, and formal audiometry may have led to detection of more subtle hearing loss.
CONFLICTS OF INTEREST
None declared
MSF supported Niger’s Ministry of Health (MoH) in responding to a serogroup C meningococcal meningitis epidemic in Magaria and Dungass Districts in 2022. WHO’s global roadmap for defeating meningitis by 2030 emphasises appropriate care for meningitis sequelae, but this is not yet part of standard epidemic response. Meningitis sequelae in the African meningitis belt are poorly described, hampering access to rehabilitation services. To better orient future care for sequelae, we performed a follow-up survey of survivors 9 months after the 2022 epidemic.
METHODS
WHO case definitions were used during the epidemic. Patient-level line-lists detailing village of origin were obtained from authorities, and results of polymerase chain reaction testing on cerebrospinal fluid were integrated. Guided by village leaders, study nurses attempted to visit cases at home to assess for sequelae. Nurses administered questionnaires asking about history including seizures and subjective vision and hearing loss; and carried out physical examinations assessing anosmia, weakness, and paralysis. Data were collected tablets using REDCap software. Prevalence of sequelae among survivors was calculated.
ETHICS
This study was approved by the MSF Ethics Review Board and by the National Ethics Committee for Health Research of Niger.
RESULTS
1001 suspected cases and 50 deaths (case fatality rate, CFR, 5.0%) originating in 230 villages were recorded on the line-lists. 469 cases (47%) had lumbar puncture, and 220 (47%) had a causative agent identified, including 192 cases of Neisseria meningitidis serogroup C (NmC) and 22 Streptococcus pneumoniae. After excluding 82 cases living in villages difficult to access, we attempted to trace 919 cases, of whom 570 (62%) were found and consented to interview. Among these cases, 49 had died (CFR 8.6%). Among the cases visited, 151 had confirmed NmC and 10 S. pneumoniae. Among the 521 surviving cases evaluated, 62 (12%) had sequelae; the most common were hearing loss (29), paralysis (16), epilepsy (9), and developmental regression (6). Among the 138 surviving confirmed cases of NmC, 25 (18%) had one or more sequelae.
CONCLUSION
We documented a higher CFR than reported during the epidemic, and a high burden of sequelae among survivors, particularly among those with confirmed NmC infection. To our knowledge, this is the second time that meningitis sequelae have been documented in Niger; these findings help identify priorities for integrating meningitis after-care into epidemic responses. MSF and the MoH should work to ensure linkages to long-term care and support for meningitis survivors and their caregivers. We were unable to find all cases, so the true prevalence of sequelae among survivors may differ. This follow-up survey used simple methods adapted for in-home evaluation, and formal audiometry may have led to detection of more subtle hearing loss.
CONFLICTS OF INTEREST
None declared
Conference Material > Slide Presentation
Idrissa AA, Atti S, Wasaulua RK, Kazadi S, Guindo O, et al.
MSF Scientific Day International 2023. 2023 June 7; DOI:10.57740/0c2k-z823
Journal Article > ResearchFull Text
BMJ Open. 2022 October 5; Volume 12 (Issue 10); e061673.; DOI:10.1136/bmjopen-2022-061673
Debellut F, Tang K, Clark A, Pecenka C, Assao B, et al.
BMJ Open. 2022 October 5; Volume 12 (Issue 10); e061673.; DOI:10.1136/bmjopen-2022-061673
OBJECTIVES
To evaluate the cost-effectiveness of alternative rotavirus vaccines in Niger, using UNIVAC, a proportionate outcomes model.
SETTING
The study leverages global, regional and local data to inform cost-effectiveness modelling. Local data were collected as part of a clinical trial taking place in the Madarounfa district, Maradi region, Niger.
PARTICIPANTS
The study models impact of infants vaccination on rotavirus gastroenteritis in children under 5 years of age.
INTERVENTIONS
We compared the use of ROTARIX (GlaxoSmithKline, Belgium), ROTAVAC (Bharat Biotech, India) and ROTASIIL (Serum Institute, India) to no vaccination and to each other over a 10-year period starting in 2021.
RESULTS
We estimated that ROTARIX, ROTAVAC and ROTASIIL would each prevent 13 million cases and 20 000 deaths of children under 5 years over a 10-year period in Niger. Compared with no vaccination, the cost to avert a disability-adjusted life-year was US$146 with ROTARIX, US$107 with ROTASIIL and US$76 with ROTAVAC from the government perspective. ROTAVAC dominated ROTARIX and ROTASIIL (eg, provided similar or higher benefits at a lower cost) and had 90% chance to be cost-effective at a US$100 willingness-to-pay threshold.
CONCLUSIONS
This study can inform decision-making around rotavirus vaccination policy in Niger, demonstrating that ROTAVAC is likely the most cost-effective option. Alternative products (ROTASIIL and ROTARIX) may also be considered by decision-makers if they are priced more competitively, or if their cold chain requirements could bring additional economic benefits.
To evaluate the cost-effectiveness of alternative rotavirus vaccines in Niger, using UNIVAC, a proportionate outcomes model.
SETTING
The study leverages global, regional and local data to inform cost-effectiveness modelling. Local data were collected as part of a clinical trial taking place in the Madarounfa district, Maradi region, Niger.
PARTICIPANTS
The study models impact of infants vaccination on rotavirus gastroenteritis in children under 5 years of age.
INTERVENTIONS
We compared the use of ROTARIX (GlaxoSmithKline, Belgium), ROTAVAC (Bharat Biotech, India) and ROTASIIL (Serum Institute, India) to no vaccination and to each other over a 10-year period starting in 2021.
RESULTS
We estimated that ROTARIX, ROTAVAC and ROTASIIL would each prevent 13 million cases and 20 000 deaths of children under 5 years over a 10-year period in Niger. Compared with no vaccination, the cost to avert a disability-adjusted life-year was US$146 with ROTARIX, US$107 with ROTASIIL and US$76 with ROTAVAC from the government perspective. ROTAVAC dominated ROTARIX and ROTASIIL (eg, provided similar or higher benefits at a lower cost) and had 90% chance to be cost-effective at a US$100 willingness-to-pay threshold.
CONCLUSIONS
This study can inform decision-making around rotavirus vaccination policy in Niger, demonstrating that ROTAVAC is likely the most cost-effective option. Alternative products (ROTASIIL and ROTARIX) may also be considered by decision-makers if they are priced more competitively, or if their cold chain requirements could bring additional economic benefits.
Journal Article > ResearchFull Text
PLOS Med. 2022 May 2; Volume 19 (Issue 5); e1003984.; DOI:10.1371/journal.pmed.1003984
Sudfeld CR, Bliznashka L, Salifou A, Guindo O, Soumana I, et al.
PLOS Med. 2022 May 2; Volume 19 (Issue 5); e1003984.; DOI:10.1371/journal.pmed.1003984
BACKGROUND
It is estimated that over 250 million children under 5 years of age in low- and middle-income countries (LMICs) do not reach their full developmental potential. Poor maternal diet, anemia, and micronutrient deficiencies during pregnancy are associated with suboptimal neurodevelopmental outcomes in children. However, the effect of prenatal macronutrient and micronutrient supplementation on child development in LMIC settings remains unclear due to limited evidence from randomized trials.
METHODS AND FINDINGS
We conducted a 3-arm cluster-randomized trial (n = 53 clusters) that evaluated the efficacy of (1) prenatal multiple micronutrient supplementation (MMS; n = 18 clusters) and (2) lipid-based nutrient supplementation (LNS; n = 18 clusters) as compared to (3) routine iron-folic acid (IFA) supplementation (n = 17 clusters) among pregnant women in the rural district of Madarounfa, Niger, from March 2015 to August 2019 (ClinicalTrials.gov identifier NCT02145000). Children were followed until 2 years of age, and the Bayley Scales of Infant and Toddler Development III (BSID-III) were administered to children every 3 months from 6 to 24 months of age. Maternal report of WHO gross motor milestone achievement was assessed monthly from 3 to 24 months of age. An intention-to-treat analysis was followed. Child BSID-III data were available for 559, 492, and 581 singleton children in the MMS, LNS, and IFA groups, respectively. Child WHO motor milestone data were available for 691, 781, and 753 singleton children in the MMS, LNS, and IFA groups, respectively. Prenatal MMS had no effect on child BSID-III cognitive (standardized mean difference [SMD]: 0.21; 95% CI: −0.20, 0.62; p = 0.32), language (SMD: 0.16; 95% CI: −0.30, 0.61; p = 0.50) or motor scores (SMD: 0.18; 95% CI: −0.39, 0.74; p = 0.54) or on time to achievement of the WHO gross motor milestones as compared to IFA. Prenatal LNS had no effect on child BSID-III cognitive (SMD: 0.17; 95% CI: −0.15, 0.49; p = 0.29), language (SMD: 0.11; 95% CI: −0.22, 0.44; p = 0.53) or motor scores (SMD: −0.04; 95% CI: −0.46, 0.37; p = 0.85) at the 24-month endline visit as compared to IFA. However, the trajectory of BSID-III cognitive scores during the first 2 years of life differed between the groups with children in the LNS group having higher cognitive scores at 18 and 21 months (approximately 0.35 SD) as compared to the IFA group (p-value for difference in trajectory <0.001). Children whose mothers received LNS also had earlier achievement of sitting alone (hazard ratio [HR]: 1.57; 95% CI: 1.10 to 2.24; p = 0.01) and walking alone (1.52; 95% CI: 1.14 to 2.03; p = 0.004) as compared to IFA, but there was no effect on time to achievement of other motor milestones. A limitation of our study is that we assessed child development up to 2 years of age, and, therefore, we may have not captured effects that are easier to detect or emerge at older ages.
CONCLUSIONS
There was no benefit of prenatal MMS on child development outcomes up to 2 years of age as compared to IFA. There was evidence of an apparent positive effect of prenatal LNS on cognitive development trajectory and time to achievement of selected gross motor milestones.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02145000
It is estimated that over 250 million children under 5 years of age in low- and middle-income countries (LMICs) do not reach their full developmental potential. Poor maternal diet, anemia, and micronutrient deficiencies during pregnancy are associated with suboptimal neurodevelopmental outcomes in children. However, the effect of prenatal macronutrient and micronutrient supplementation on child development in LMIC settings remains unclear due to limited evidence from randomized trials.
METHODS AND FINDINGS
We conducted a 3-arm cluster-randomized trial (n = 53 clusters) that evaluated the efficacy of (1) prenatal multiple micronutrient supplementation (MMS; n = 18 clusters) and (2) lipid-based nutrient supplementation (LNS; n = 18 clusters) as compared to (3) routine iron-folic acid (IFA) supplementation (n = 17 clusters) among pregnant women in the rural district of Madarounfa, Niger, from March 2015 to August 2019 (ClinicalTrials.gov identifier NCT02145000). Children were followed until 2 years of age, and the Bayley Scales of Infant and Toddler Development III (BSID-III) were administered to children every 3 months from 6 to 24 months of age. Maternal report of WHO gross motor milestone achievement was assessed monthly from 3 to 24 months of age. An intention-to-treat analysis was followed. Child BSID-III data were available for 559, 492, and 581 singleton children in the MMS, LNS, and IFA groups, respectively. Child WHO motor milestone data were available for 691, 781, and 753 singleton children in the MMS, LNS, and IFA groups, respectively. Prenatal MMS had no effect on child BSID-III cognitive (standardized mean difference [SMD]: 0.21; 95% CI: −0.20, 0.62; p = 0.32), language (SMD: 0.16; 95% CI: −0.30, 0.61; p = 0.50) or motor scores (SMD: 0.18; 95% CI: −0.39, 0.74; p = 0.54) or on time to achievement of the WHO gross motor milestones as compared to IFA. Prenatal LNS had no effect on child BSID-III cognitive (SMD: 0.17; 95% CI: −0.15, 0.49; p = 0.29), language (SMD: 0.11; 95% CI: −0.22, 0.44; p = 0.53) or motor scores (SMD: −0.04; 95% CI: −0.46, 0.37; p = 0.85) at the 24-month endline visit as compared to IFA. However, the trajectory of BSID-III cognitive scores during the first 2 years of life differed between the groups with children in the LNS group having higher cognitive scores at 18 and 21 months (approximately 0.35 SD) as compared to the IFA group (p-value for difference in trajectory <0.001). Children whose mothers received LNS also had earlier achievement of sitting alone (hazard ratio [HR]: 1.57; 95% CI: 1.10 to 2.24; p = 0.01) and walking alone (1.52; 95% CI: 1.14 to 2.03; p = 0.004) as compared to IFA, but there was no effect on time to achievement of other motor milestones. A limitation of our study is that we assessed child development up to 2 years of age, and, therefore, we may have not captured effects that are easier to detect or emerge at older ages.
CONCLUSIONS
There was no benefit of prenatal MMS on child development outcomes up to 2 years of age as compared to IFA. There was evidence of an apparent positive effect of prenatal LNS on cognitive development trajectory and time to achievement of selected gross motor milestones.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02145000
Journal Article > ResearchFull Text
BMC Nutr. 2019 July 1; Volume 5; DOI:10.1186/s40795-019-0298-3
Isanaka S, Kodish SR, Mamaty AA, Guindo O, Zeilani M, et al.
BMC Nutr. 2019 July 1; Volume 5; DOI:10.1186/s40795-019-0298-3
Background
In food insecure settings, it may be difficult for pregnant women to meet increased nutritional needs through traditional diets. A promising new strategy to fill nutrient gaps in pregnancy involves the provision of lipid-based nutrient supplements (LNS). We aimed to assess the acceptability and utilization of a 40 g LNS formulation (Epi-E) with increased micronutrient content relative to the recommended daily allowance among pregnant women in rural Niger.
Methods
We conducted a two-part, multi-methods study among pregnant women presenting to antenatal care in Madarounfa, Niger during two periods (Ramadan and non-Ramadan). Part 1 included two LNS test meals provided at the health center, and Part 2 included a 14-day home trial to simulate more realistic conditions outside of the health center. Open- and closed-ended questions were used to assess organoleptic properties of Epi-E using a 5-point hedonic scale after the test meals, as well as utilization and willingness to pay for Epi-E after the 14-day home trial.
Results
Participants consumed more than 90% of the test meal in both periods. Epi-E was rated highly in terms of overall liking, color, taste and smell during test meals in both periods (median 5/5 for all); only time, mode and frequency of consumption varied between Ramadan and non-Ramadan periods in observance of daily fasting during the holy month.
Conclusion
Epi- E, a 40 g LNS formulation with increased micronutrient content, was highly acceptable among pregnant women in rural Niger, and utilization was guided by household and individual considerations that varied by time period. This formulation can be further tested as a potential strategy to improve the nutritional status of pregnant women in this context.
In food insecure settings, it may be difficult for pregnant women to meet increased nutritional needs through traditional diets. A promising new strategy to fill nutrient gaps in pregnancy involves the provision of lipid-based nutrient supplements (LNS). We aimed to assess the acceptability and utilization of a 40 g LNS formulation (Epi-E) with increased micronutrient content relative to the recommended daily allowance among pregnant women in rural Niger.
Methods
We conducted a two-part, multi-methods study among pregnant women presenting to antenatal care in Madarounfa, Niger during two periods (Ramadan and non-Ramadan). Part 1 included two LNS test meals provided at the health center, and Part 2 included a 14-day home trial to simulate more realistic conditions outside of the health center. Open- and closed-ended questions were used to assess organoleptic properties of Epi-E using a 5-point hedonic scale after the test meals, as well as utilization and willingness to pay for Epi-E after the 14-day home trial.
Results
Participants consumed more than 90% of the test meal in both periods. Epi-E was rated highly in terms of overall liking, color, taste and smell during test meals in both periods (median 5/5 for all); only time, mode and frequency of consumption varied between Ramadan and non-Ramadan periods in observance of daily fasting during the holy month.
Conclusion
Epi- E, a 40 g LNS formulation with increased micronutrient content, was highly acceptable among pregnant women in rural Niger, and utilization was guided by household and individual considerations that varied by time period. This formulation can be further tested as a potential strategy to improve the nutritional status of pregnant women in this context.
Journal Article > ResearchFull Text
Clin Pharmacol Ther
Clinical Pharmacology and Therapeutics. 2019 June 1
Chotsiri P, Denoeud-Ndam L, Baudin E, Guindo O, Diawara H, et al.
Clin Pharmacol Ther
Clinical Pharmacology and Therapeutics. 2019 June 1
Severe acute malnutrition (SAM) has been reported to be associated with increased malaria morbidity in Sub‐Saharan African children and may affect the pharmacology of antimalarial drugs. This population pharmacokinetic‐pharmacodynamic study included 131 SAM and 266 non‐SAM children administered artemether‐lumefantrine twice daily for 3 days. Lumefantrine capillary plasma concentrations were adequately described by two transit‐absorption compartments followed by two distribution compartments. Allometrically scaled body weight and an enzymatic maturation effect were included in the pharmacokinetic model. Mid‐upper arm circumference (MUAC) was associated with decreased absorption of lumefantrine (25.4% decrease per 1 cm reduction). Risk of recurrent malaria episodes (i.e. reinfection) were characterised by an interval‐censored time‐to‐event model with a sigmoid EMAX‐model describing the effect of lumefantrine. SAM children were at risk of under‐exposure to lumefantrine and an increased risk of malaria reinfection compared to well‐nourished children. Research on optimised regimens should be considered for malaria treatment in malnourished children.