The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The Effect of Intensive Phototherapy on Management of Hyperbilirubinemia in Neonates with the Gestational Age of 34 Weeks and More

Background: Neonatal hyperbilirubinemia is one of the most common causes of neonatal morbidity and a global health priority. This study aimed to evaluate the effect of intensive phototherapy on management of hyperbilirubinemia with different etiologies. Methods: This retrospective cohort study was conducted on 219 neonates with indirect hyperbilirubinemia, who had the indication for phototherapy, admitted to neonatal intensive care unit of Akbar-abadi Hospital, Tehran, Iran, during 2014-2016. The levels of total bilirubin, hemoglobin, reticulocyte, and glucose 6-phosphate dehydrogenase (G6PD) enzyme were examined and direct Coombs test was performed during hospital stay. The participants were assigned to four groups based on the etiology of hyperbilirubinemia and underwent intensive phototherapy.Finally, the level of total bilirubin was compared among the groups to assess the effect of intensive phototherapy. Results: According to the results of this study, nonhemolytic jaundice was the most frequent cause of hyperbilirubinemia (82.19%). The mean bilirubin levels after 6 and 24 hours of intensive phototherapy were 4 and 6.2 mg/dl, respectively. Intensive phototherapy after 6 hours led to more significant reduction in the total bilirubin level of the neonates with total bilirubin level of higher than 14 mg/dl in comparison to those with the total bilirubin level of 14 mg/dl or less. The total bilirubin level was significantly decreased in all the groups after 6 and 24 hours of intensive phototherapy. Comparison of the rate of decrement of the total bilirubin level among the groups demonstrated that the neonates with ABO incompatibility showed the greatest decline after 6 and 24 hours of treatment (the rate of bilirubin decline: -5.16;

Standard Multiple and Single Daily Dosing of Amikacin in Premature Infants

Background: Bacterial sepsis is highly prevalent among premature infants. Amikacin is an antibiotic widely recommended for the treatment of neonatal sepsis, one of the consequences of which might be nephrotoxicity. The present study aimed to compare the efficacy and nephrotoxicity of multiple daily dosing (MDD) and once-daily dosing (ODD) of amikacin in preterm infants suspected of sepsis. Methods: This triple-blind, randomized, controlled clinical trial was conducted on 40 premature infants suspected of sepsis, who were randomly divided into two groups. In addition to ampicillin, one group was administered with the standard daily dose, and the other group received an ODD of intravenous amikacin. Maximum and minimum serum levels of amikacin and urine neutrophil gelatinase-associated lipocalin (NGAL) were measured in both groups. Data were extracted and analyzed based on the research hypothesis and literature review. Results: No significant differences were observed between the study groups in terms of gender, gestational age, mode of delivery, birth weight, and Apgar score. After the intervention, mean plasma creatinine reduced in both groups, while the mean reduction was significantly higher in the group administered with the ODD of amikacin (P=0.0001). However, mean changes in the urine NGAL had no significant difference between the groups (P=0.635). Minimum and maximum serum levels of amikacin in the study groups indicated a more significant reduction in mean level of the infants administered with the ODD of amikacin compared to the MDD group (P=0.0001). Conclusion: Considering the higher maximum and lower minimum levels of amikacin in the neonates receiving the daily dosage regimen, it seems that this regimen is more effective in the treatment of sepsis in preterm infants. Moreover, no significant difference was observed in the efficacy and nephrotoxicity of the daily amikacin dosing in the premature infants suspected of sepsis compared to those treated by multiple doses of amikacin

Effect of Protein Supplementation on the Growth of Infants Weighing Less than 1,000 Grams Hospitalized on the Neonatal Intensive Care Unit of Akbar Abadi Hospital in Tehran, Iran (2015-2016)

Background: Breast milk provides adequate protein to facilitate growth for term infants. Appropriate nutrition is necessary for the growth of preterm infants. Extremely-low-birth-weight (ELBW) infants require higher protein intakes to achieve adequate growth. The present study aimed to evaluate the effect of protein supplements on the physical growth of infants weighing less than 1,000 grams through the serial measurement of their anthropometric indices (weight, height, and head circumference) during admission at the neonatal intensive care unit (NICU). Methods: This triple-blind, randomized clinical trial was conducted on 64 infants weighing less than 1,000 grams, who were admitted to the NICU of Akbar Abadi Hospital in Tehran, Iran during 2015-2016. Data on the daily nutritional intake of the subjects were recorded until discharge from the hospital. Data analysis was performed in SPSS version 24. Results: In total, 63 infants were enrolled in the study. Mean daily weight gain of the infants was 55.92±36.90 and 30.80±13.91 grams in the case and control groups, respectively (P=0.001). Mean weekly linear growth in the case and control groups was 0.77±0.67 and 0.76±0.29 centimeter, respectively (P=0.939). Mean weekly head circumference growth in the case and control groups was 0.51±0.10 and 0.34±0.16 centimeter, respectively (

Evaluation of Cortisol Level in Premature Neonates: Are There any Correlations between Prevalence of Patent Ductus Arteriosus and Prenatal Administration of Betamethasone?

Background: The results of previous studies suggested that there is an increased risk of patent ductus arteriosus (PDA) in the neonates with lower serum cortisol levels. This study aimed to assess the association between serum cortisol values and PDA and investigate if there is an association between PDA and the antenatal administration of betamethasone. Methods: The present study was carried out on the neonates with gestational age between 28 to 35 weeks. The prenatal administration of betamethasone to the mothers was extracted from the records. A pediatric cardiologist performed an echocardiographic assessment on the second day of life (DOL) and fifth DOL and the infants were evaluated for the presence of PDA. The blood samples were obtained on the second and fifth DOL and serum cortisol levels were measured. We evaluated the association between serum cortisol levels and PDA. Also, the correlation between PDA and the antenatal administration of betamethasone was assessed. Results: The mean scores of serum cortisol levels on the second DOL in the neonates with and without PDA were 4.99±2.69 (μg/dl) and 7.23±2.87 (μg/dl), respectively that were significantly lower in the first group, compared to those of the second group. However, the mean levels of serum cortisol in the neonates with and without the prenatal administration of betamethasone were not significant (P=0.522). Conclusion: We have concluded that lower serum cortisol level was associated with the increase in the risk of PDA and the prenatal administration of glucocorticoids may not reduce the occurrence of PDA

Comparison of the effect of entonox gas and Sufentanil epidural anesthesia in labor pain on the umbilical cord blood gas analysis and neonatal apgar score

Background: Today, the health of mothers and babies is of particular importance in health systems. So far, various interventions have been implemented to improve the health of pregnant mothers. The present study aimed to compare the effect of Entonox gas and Sufentanil epidural anesthesia in labor pain on the umbilical cord blood gas analysis and neonatal Apgar score. Methods: The present study is a clinical trial on 800 pregnant women It was done in April 2020 to January 2022 at Shahid Akbarabadi Hospital. Mothers were divided into two groups: spinal anesthesia and the group receiving Entonox gas. To measure the effectiveness, Apgar scores were measured at 1 and 5 minutes along with BE, HCO3, and PCO2 parameters. Two independent sample t-tests and ANOVA were used in SPSS version 22 software to analyze the data. Results: The results of the study showed that the average age of mothers participating in the study was 27 years, and the average Apgar score of 1 and 5 minutes in the group of mothers receiving Entonox gas and spinal anesthesia was 9.9 and 8.6, respectively. Also, the average Apgar score at minutes 1 and 5 in the group of mothers with spinal anesthesia was 9.8 and 8.2, respectively. The results of the analysis and comparison of the parameters obtained from the arterial gases of the umbilical cord of newborns were not significantly different between both groups of mothers. Also, no significant difference was found in Apgar scores between both groups of mothers. Conclusion: There is no significant difference between the effectiveness of using Entonox gas with spinal analgesia in the painless delivery of mothers; Therefore, considering the cost of each intervention along with their effect may cause a difference in the two interventions. This means that although both of the interventions have the same clinical and diagnostic effects, the one which costs less, will be more preferable from the point of view of the health system

Does Adding Intravenous Phosphorus to Parenteral Nutrition Has Any Effects on Calcium and Phosphorus Metabolism and Bone Mineral Content in Preterm Neonates?

The use of parenteral nutritional supplementation of phosphorus may lead to exhibit higher plasma phosphate concentrations and less radiological features in premature neonates susceptible to osteopenia. The present study aimed to assess the beneficial effects of adding intravenous phosphorus to total parenteral nutrition (TPN) on calcium and phosphorus metabolism in preterm neonates by measuring bone mineral content. This open-labeled randomized clinical trial was conducted on premature neonates who were hospitalized at NICU. The neonates were randomly assigned to two groups received TPN with intravenous sodium glycerophosphate or Glycophos (1.5 mmol/kg/day) or TPN without sodium glycerophosphate. At the end of the four weeks of treatment, the presence of osteopenia was examined using DEXA Scan. After completing treatment protocols, the group received TPN with intravenous Glycophos had significantly lower serum alkaline phosphatase (360±60 versus 762±71, P<0.001), as well as higher serum calcium to creatinine ratio (1.6±0.3 versus 0.44±0.13, P<0.001) compared to the control group received TPN without Glycophos. Those who received TPN with intravenous Glycophos experienced more increase in bone mineral density than those in control group (0.13±0.01 versus 0.10±0.02, P<0.001). There was no significant difference in serum calcium and serum vitamin D between the case and control groups. Adding intravenous sodium glycerophosphate to TPN in premature neonates can compensate the lack of bone mineral content and help to prevent osteopenia

A global point prevalence survey of antimicrobial use in neonatal intensive care units : The no-more-antibiotics and resistance (NO-MAS-R) study

Background: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. Methods: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. Findings: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received &gt;= 1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0.02). Interpretation: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide