Growth and micronutrient status parameters of Nigerian preterm infants consuming preterm formula or breastmilk.

BACKGROUND: Moderate-to-late preterm infants (32-34 weeks GA) have increased risk of neonatal morbidities compared to term infants, however dedicated nutritional guidelines are lacking. METHODS: Moderate-to-late preterm infants received a preterm formula (n = 17) or breastmilk (n = 24) from age 2-10 weeks in a non-randomized, open-label observational study. Anthropometric measurements were assessed bi-weekly. Blood concentrations of hemoglobin, ferritin, serum retinol, and 25-hydroxy-vitamin D (25OHD) were analyzed at age 2 and 10 weeks. RESULT: Average growth per day was 14.7 g/kg BW/day in formula-fed and 12.8 g/kg BW/day in breastmilk-fed infants but not different from each other. Length and head circumference in both groups were in line with the median reference values of the Fenton growth chart. At 10 weeks of age, hemoglobin tended to be higher in the formula-fed group (10.2 g/dL vs. 9.6 g/dL, p = 0.053). 25OHD increased in formula- and breastmilk-fed infants from 73.8 to 180.9 nmol/L and from 70.7 to 97.6 nmol/L, respectively. Serum retinol only increased in the formula-fed group (0.63 to 1.02 µmol/L, p < 0.001). CONCLUSION: Breastfeeding resulted in adequate growth in moderate-late preterm infants but was limiting in some micronutrients. The preterm formula provided adequate micronutrients, but weight gain velocity was higher than the Fenton reference value. IMPACT STATEMENT: Unfortified breastmilk resulted in adequate growth in weight, length and head circumference in Nigerian moderate to late preterm infants during an study period of 8 weeks, but status of vitamin D, vitamin A and iron needs to be monitored. The high-energy formula, developed for very preterm infants, resulted in higher growth in body weight in moderate to late preterm infants than the median of the Fenton preterm growth chart. This study supports the necessity of dedicated nutritional guidelines, and regular monitoring of growth and nutritional status of moderate to late preterm infants.

The burden, prevention and care of infants and children with congenital anomalies in sub-Saharan Africa: A scoping review.

The aim of this scoping review was to determine the scope, objectives and methodology of contemporary published research on congenital anomalies (CAs) in sub-Saharan Africa (SSA), to inform activities of the newly established sub-Saharan African Congenital Anomaly Network (sSCAN). MEDLINE was searched for CA-related articles published between January 2016 and June 2021. Articles were classified into four main areas (public health burden, surveillance, prevention, care) and their objectives and methodologies summarized. Of the 532 articles identified, 255 were included. The articles originated from 22 of the 49 SSA countries, with four countries contributing 60% of the articles: Nigeria (22.0%), Ethiopia (14.1%), Uganda (11.7%) and South Africa (11.7%). Only 5.5% of studies involved multiple countries within the region. Most articles included CA as their primary focus (85%), investigated a single CA (88%), focused on CA burden (56.9%) and care (54.1%), with less coverage of surveillance (3.5%) and prevention (13.3%). The most common study designs were case studies/case series (26.6%), followed by cross-sectional surveys (17.6%), retrospective record reviews (17.3%), and cohort studies (17.2%). Studies were mainly derived from single hospitals (60.4%), with only 9% being population-based studies. Most data were obtained from retrospective review of clinical records (56.1%) or via caregiver interviews (34.9%). Few papers included stillbirths (7.5%), prenatally diagnosed CAs (3.5%) or terminations of pregnancy for CA (2.4%).This first-of-a-kind-scoping review on CA in SSA demonstrated an increasing level of awareness and recognition among researchers in SSA of the contribution of CAs to under-5 mortality and morbidity in the region. The review also highlighted the need to address diagnosis, prevention, surveillance and care to meet Sustainable Development Goals 3.2 and 3.8. The SSA sub-region faces unique challenges, including fragmentation of efforts that we hope to surmount through sSCAN via a multidisciplinary and multi-stakeholder approach.

An open randomized clinical trial in comparing two artesunate-based combination treatments on Plasmodium falciparum malaria in Nigerian children: artesunate/sulphamethoxypyrazine/pyrimethamine (fixed dose over 24 hours) versus artesunate/amodiaquine (fixed dose over 48 hours).

BACKGROUND: Several studies have demonstrated the efficacy of artemisinin-combination therapy (ACT) across malaria zones of the world. Fixed dose ACT with shorter courses and fewer tablets may be key determinants to ease of administration and compliance. METHODS: Children aged one year to 13 years presenting with uncomplicated Plasmodium falciparum malaria were recruited in Ibadan, south-western Nigeria. A total of 250 children each were randomly assigned to receive three doses of artesunate/sulphamethoxypyrazine/pyrimethamine (AS + SMP) (12 hourly doses over 24 hours) or three doses of artesunate/amodiaquine (AS + AQ) (daily doses over 48 hours). Efficacy and safety of the two drugs were assessed using a 28-day follow-up and the primary outcome was PCR- corrected parasitological cure rate and clinical response. RESULTS: There were two (0.4%) early treatment failures, one in each treatment arm. The PCR corrected cure rates for day 28 was 97.9% in the AS + AQ arm and 95.6% in the AS + SMP arm (p = 0.15). The re-infection rate was 1.7% in the AS + AQ arm and 5.7% in the AS + SMP arm (p = 0.021). The fever clearance time was similar in the two treatment groups: 1 - 2 days for both AS + SMP and AS + AQ (p = 0.271). The parasite clearance time was also similar in the two treatment groups with 1 - 7 days for AS + SMP and 1 - 4 days for AS + AQ (p = 0.941). The proportion of children with gametocytes over the follow-up period was similar in both treatment groups. Serious Adverse Events were not reported in any of the patients and in all children, laboratory values (packed cell volume, liver enzymes, bilirubin) remained within normal levels during the follow-up period but the packed cell volume was significantly lower in the AS + SMP group. CONCLUSIONS: This study demonstrates that AS + SMP FDC given as three doses over 24 hours (12-hour intervals) has similar efficacy as AS + AQ FDC given as three doses over 48 hours (24-hour interval) for the treatment of uncomplicated Plasmodium falciparum malaria in children in Nigeria. Both drugs also proved to be safe. Therefore, AS + SMP could be an alternative to currently recommended first-line ACT with continuous resistance surveillance.

Cellular responses to modified Plasmodium falciparum MSP119 antigens in individuals previously exposed to natural malaria infection.

BACKGROUND: MSP1 processing-inhibitory antibodies bind to epitopes on the 19 kDa C-terminal region of the Plasmodium falciparum merozoite surface protein 1 (MSP1(19)), inhibiting erythrocyte invasion. Blocking antibodies also bind to this antigen but prevent inhibitory antibodies binding, allowing invasion to proceed. Recombinant MSP1(19) had been modified previously to allow inhibitory but not blocking antibodies to continue to bind. Immunization with these modified proteins, therefore, has the potential to induce more effective protective antibodies. However, it was unclear whether the modification of MSP1(19) would affect critical T-cell responses to epitopes in this antigen. METHODS: The cellular responses to wild-type MSP1(19) and a panel of modified MSP1(19) antigens were measured using an in-vitro assay for two groups of individuals: the first were malaria-naïve and the second had been naturally exposed to Plasmodium falciparum infection. The cellular responses to the modified proteins were examined using cells from malaria-exposed infants and adults. RESULTS: Interestingly, stimulation indices (SI) for responses induced by some of the modified proteins were at least two-fold higher than those elicited by the wild-type MSP1(19). A protein with four amino acid substitutions (Glu27-->Tyr, Leu31-->Arg, Tyr34-->Ser and Glu43-->Leu) had the highest stimulation index (SI up to 360) and induced large responses in 64% of the samples that had significant cellular responses to the modified proteins. CONCLUSION: This study suggests that specific MSP1(19) variants that have been engineered to improve their antigenicity for inhibitory antibodies, retain T-cell epitopes and the ability to induce cellular responses. These proteins are candidates for the development of MSP1-based malaria vaccines.

Cytokine profiles and antibody responses to Plasmodium falciparum malaria infection in individuals living in Ibadan, southwest Nigeria.

BACKGROUND: The ability of the host immune system to efficiently clear Plasmodium falciparum parasites during a malaria infection depends on the type of immune response mounted by the host. STUDY DESIGN: In a cross-sectional study, we investigated the cellular-and antibody responses in individuals with P. falciparum infection, in an attempt to identify immunological signs indicative of the development of natural immunity against malaria in Ibadan, Nigeria. Levels of IL-10, IL-12(p70), IFN-gamma, and IgM, IgG and IgG1-4 subclasses in the serum of 36 symptomatic children with microscopically confirmed malaria parasitaemia and 54 asymptomatic controls were analysed by ELISA. RESULTS: IFN-gamma and IL-10 were significantly higher in the symptomatic children (p=0.009, p=0.025 respectively) than in the asymptomatic controls but no differences were seen for IL-12(p70). Estimated higher ratios of IFN-gamma/IL-10 and IFN-gamma/IL-12 were also observed in the symptomatic children while the asymptomatic controls had higher IL-12/IL-10 ratio. The mean concentration levels of anti-P. falciparum IgG1, IgG2, IgG3 antibodies were statistically significantly higher in the individuals >5 years of age than <5 years while anti-P. falciparum IgG3 antibodies were notably low in <5 years category. Children <5 years had higher IgM antibodies than IgG and the expression of IgG subclasses increased with age. CONCLUSION: Taken together, malaria infection is on a delicate balance of pro- and anti-inflammatory cytokines. The higher levels of IFN-gamma seen in the symptomatic children (<6 months) may be instrumental in immune-protection against malaria by limiting parasite replication. The observed variations in immunoglobulin subclass levels were age-dependent and exposure-related.

Dihydroartemisinin suppository in moderately severe malaria: comparative efficacy of dihydroartemisinin suppository versus intramuscular artemeter followed by oral sulfadoxine-pyrimethamine in the management of moderately severe malaria in Nigerian children.

We compared two dose forms of artemisinin derivatives, dihydroartemisinin suppository (DHA) and intramuscular artemether (ART), in children 6 months to 10 years of age with moderately severe malaria for which oral therapy was not appropriate. Children were randomly allocated to receive three daily doses of DHA or ART followed by a single oral dose of sulfadoxine-pyrimethamine on the third day of both treatment regimens and were monitored for parasitologic and clinical response for 14 days. At enrollment, parasite density was 1,640-523,333/microL (geometric mean parasite density [GMPD] = 58,129/microL) in patients treated with DHA, whereas that for children who received ART was 1,440-559,400/microL (GMPD = 60,387/microL). Mean parasite and fever clearance times were similar in both groups. Days 14 and 28 parasitologic cure rates were 100% (34 of 34) and 96.2% (25 of 26) versus 96.2% (25 of 26) and 91.7% (22 of 24) for children treated with DHA and ART, respectively. In conclusion, both treatment regimens were efficacious and well tolerated.