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Background Bloodstream infections (BSIs) are a major cause of morbidity and mortality in hospitalized neonates. Data on antibiotic resistance in neonatal BSIs and their impact on clinical outcomes in Africa are limited. Methods We conducted a prospective cohort study at 2 tertiary level neonatal intensive care units (NICUs) in Ghana. All neonates admitted to the NICUs were included from October 2017 to September 2019. We monitored BSI rates and analyzed the effect of BSI and antibiotic resistance on mortality and duration of hospitalization. Results Out of 5433 neonates included, 3514 had at least one blood culture performed and 355 had growth of a total of 368 pathogenic microorganisms. Overall incidence of BSI was 1.0 (0.9-1.1) per 100 person days. The predominant organisms were Klebsiella pneumoniae 49.7% (183/368) and Streptococcus spp. 10.6% (39/368). In addition, 512 coagulase negative Staphylococci were isolated but considered probable contaminants. Among K. pneumoniae, resistance to gentamicin and amikacin was 91.8% and 16.4%, respectively, while carbapenem resistance was 4.4%. All-cause mortality among enrolled neonates was 19.7% (1066/5416). The mortality rate was significantly higher in neonates with BSI compared with culture-negative neonates in univariate analysis (27.9%, n = 99/355 vs. 16.5%, n = 520/3148; hazard ratio 1.4, 95% confidence interval 1.07-1.70) but not in multivariate analysis. Conclusion The diversity of etiological agents and the high risk of antibiotic resistance suggest that standard empirical treatment is unlikely to improve the outcome of BSIs in low and middle income. Such improvements will depend on access to reliable clinical microbiologic services.

Background Individuals with sickle cell disease (SCD) are susceptible to infective conditions that predispose them to hemolysis and anemia. Folic acid is recommended as a preventative measure against anemia in SCD patients; however, there is scarce literature on the implications of this practice. Patients and Methods Plasma concentrations of folate were measured in acutely ill pediatric SCD patients presenting with malaria or bacteremia and compared with those of SCD patients in steady state, or acutely ill non-SCD patients with confirmed malaria. Results The proportion of individuals with high (>45.3 nmol/L) folate concentrations was 29.5% (13/44), 18.2% (8/44), 33.3% (6/18), and 0% in the SCD-malaria, SCD steady state, SCD bacteremia, and the non-SCD malaria groups, respectively. The proportion of SCD patients with high folate levels did not vary significantly at steady state and during confirmed malaria (p = 0.216), and during acute bacteremia (p = 0.20). The median (interquartile range) plasma folate levels were 34.50 (24.40-52.00 nmol/L), 33.40 (15.83-60.85 nmol/L), 30.85 (24.68-39.65 nmol/L), and 13.30 (10.03-17.18 nmol/L), respectively, in the SCD malaria, SCD bacteremia, SCD steady state, and the non-SCD malaria sub-groups. The median folate levels of SCD steady state, SCD malaria, and SCD bacteremia sub-groups differed significantly (p < 0.0001) when compared with non-SCD patients, but the levels in the SCD bacteremia and malaria groups were not significantly different from the SCD steady state group. Conclusion Elevated levels of plasma folate were found in a high proportion of pediatric SCD patients. The implications of such elevated folate levels in pediatric SCD patients are unknown but may suggest a need for review of current recommendations for prophylactic doses of folic acid in SCD patients.

Healthcare-associated infections (HAIs) remain a serious threat to patient safety worldwide, particularly in low- and middle-income countries. Reducing the burden of HAIs through the observation and enforcement of infection prevention and control (IPC) practices remains a priority. Despite growing emphasis on HAI prevention in low- and middle-income countries, limited evidence is available to improve IPC practices to reduce HAIs. This study examined the perspectives of healthcare providers (HPs) and mothers in the neonatal intensive care unit on HAIs and determined the major barriers and facilitators to promoting standard IPC practices. This study draws on data from an ethnographic study using 38 in-depth interviews, four focus group discussions and participant observation conducted among HPs and mothers in neonatal intensive care units of a secondary- and tertiary-level hospital in Ghana. The qualitative data were analysed using a grounded theory approach, and NVivo 12 to facilitate coding. HPs and mothers demonstrated a modest level of understanding about HAIs. Personal, interpersonal, community, organizational and policy-level factors interacted in complex ways to influence IPC practices. HPs sometimes considered HAI concerns to be secondary in the face of a heavy clinical workload, a lack of structured systems and the quest to protect professional authority. The positive attitudes of some HPs, and peer interactions promoted standard IPC practices. Mothers expressed interest in participation in IPC activities. It however requires systematic efforts by HPs to partner with mothers in IPC. Training and capacity building of HPs, provision of adequate resources and improving communication between HPs and mothers were recommended to improve standard IPC practices. We conclude that there is a need for institutionalizing IPC policies and strengthening strategies that acknowledge and value mothers’ roles as caregivers and partners in IPC. To ensure this, HPs should be better equipped to prioritize communication and collaboration with mothers to reduce the burden of HAIs.

Background Neonatal jaundice (NNJ) is a major cause of preventable childhood mortality and long-term impairment especially in countries with significant prevalence of the inherited condition, glucose-6-phosphate dehydrogenase (G6PD) defect. In Ghana, routine screening of pregnant women for G6PD defect is standard care. Prevention of poor health outcomes from NNJ is contingent on population health literacy and early diagnosis. As part of a project to evaluate a screening tool for NNJ, we assessed the knowledge, attitude, and perceptions of Ghanaian mothers on NNJ at baseline. Methods Using a cross-sectional design, mothers attending antenatal and postnatal clinics at 3 selected health facilities in 2 geographical regions of Ghana were interviewed. Data on mothers’ understanding, perceptions, beliefs, and actions towards NNJ were evaluated. Chi-square test was used to determine the association between selected maternal characteristics and knowledge, attitude, and perception to NNJ. Results Of the 504 mothers interviewed, 428(85.4%) had heard about NNJ, 346 (68.7%) said the earliest signs are seen in the eyes, 384(76.2%) knew NNJ may be harmful and 467(92.7%) recommended seeking healthcare for the jaundiced newborn. None of the women knew about G6PD or their G6PD status following antenatal screening. Most did not know the signs/symptoms of severe NNJ. Of the 15 mothers who had had a jaundiced neonate, cost was the most perceived (8 out of 15) barrier to accessing health care. There were significant associations (p-value ≤ 0.05) between maternal age, educational level, and knowledge of NNJ. Conclusion Despite the high level of awareness of NNJ, gaps still exit in the knowledge, attitudes and perceptions of mothers concerning NNJ. Improving education of women about the causes, symptoms/signs, and the role of G6PD in severe NNJ is recommended. Addressing barriers to accessing healthcare for the jaundiced infant may enhance timely management of NNJ and reduce the associated complications and mortality.

Background Rapid diagnostic tests (RDTs) have been extensively evaluated and play an important role in malaria diagnosis. However, the accuracy of RDTs for malaria diagnosis in patients with sickle cell disease (SCD) is unknown. Methods We compared the performance of a histidine rich protein 2 (HRP-2)-based RDT (First Response) and a lactate dehydrogenase (LDH)-based RDT (Optimal) with routine microscopy as reference standard in 445 children with SCD and an acute febrile illness in Accra, Ghana. Results The overall sensitivity, specificity, and positive and negative predictive values of the HRP-2-based RDTs were 100%, 95.7%, 73.8%, and 100%, respectively. Comparable values for the LDH-based RDTs were 91.7%, 99.5%, 95.7%, and 99.0%, respectively. A total of 423 results were true in both tests, 1 result was false in both tests, 16 results were false in the HRP-2 test only, and 5 were false in the LDH test only (McNemar test, P = .03). At follow-up, 73.7% (28/38), 52.6% (20/38), 48.6% (17/35), and 13.2% (5/38) of study participants were HRP-2 positive on days 14, 28, 35, and 42, respectively, compared with 0%, 2.6% (1/38), 2.9% (1/35), and 2.6% (1/38) for LDH. Conclusion The HRP2-based RDT fulfilled World Health Organization criteria for malaria diagnosis in patients with SCD and may provide diagnostic evidence for treatment to begin in cases in which treatment would otherwise have begun presumptively based on symptoms, whereas LDH-based RDTs may be more suitable as a confirmatory test in low-parasitemic subgroups, such as patients with SCD.

Key points Therapeutic hypothermia (HT) to 33.0–34.0°C for 72 h provides optimal therapy for infants with neonatal encephalopathy (NE) in high‐resource settings. HT is not universally implemented in low‐ and middle‐income countries as a result of both limited resources and evidence.Facilitated passive cooling, comprising infants being allowed to passively lower their body temperature in the days after birth, is an emerging practice in some West African neonatal units.In this observational study, we demonstrate that infants undergoing facilitated passive cooling in a neonatal unit in Accra, Ghana, achieve temperatures within the HT target range ∼20% of the 72 h. Depth of HT fluctuates and can be excessive, as well as not maintained, especially after 24 h.Sustained and deeper passive cooling was evident for severe NE and for those that died.It is important to prevent excessive cooling, to understand that severe NE babies cool more and to be aware of facilitated passive cooling with respect to the design of clinical trials in low‐ and mid‐resource settings. Abstract Neonatal encephalopathy (NE) is a significant worldwide problem with the greatest burden in sub‐Saharan Africa. Therapeutic hypothermia (HT), comprising the standard of care for infants with moderate‐to‐severe NE in settings with sophisticated intensive care, is not available to infants in many sub‐Saharan African countries, including Ghana. We prospectively assessed the temperature response in relation to outcome in the 80 h after birth in a cohort of babies with NE undergoing ‘facilitated passive cooling’ at Korle Bu Teaching Hospital, Accra, Ghana. We hypothesized that NE infants demonstrate passive cooling. Thirteen infants (69% male) ≥36 weeks with moderate‐to‐severe NE were enrolled. Ambient mean ± SD temperature was 28.3 ± 0.7°C. Infant core temperature was 34.2 ± 1.2°C over the first 24 h and 35.0 ± 1.0°C over 80 h. Nadir mean temperature occurred at 15 h. Temperatures were within target range for HT with respect to 18 ± 14% of measurements within the first 72 h. Axillary temperature was 0.5 ± 0.2°C below core. Three infants died before discharge. Core temperature over 80 h for surviving infants was 35.3 ± 0.9°C and 33.96 ± 0.7°C for those that died (P = 0.043). Temperature profile negatively correlated with Thompson NE score on day 4 (r 2 = 0.66): infants with a Thompson score of 0–6 had higher temperatures than those with a score of 7–15 (P = 0.021) and a score of 16+/deceased (P = 0.007). More severe NE was associated with lower core temperatures. Passive cooling is a physiological response after hypoxia–ischaemia; however, the potential neuroprotective effect of facilitated passive cooling is unknown. An awareness of facilitated passive cooling in babies with NE is important for the design of clinical trials of neuroprotection in low and mid resource settings., Key points Therapeutic hypothermia (HT) to 33.0–34.0°C for 72 h provides optimal therapy for infants with neonatal encephalopathy (NE) in high‐resource settings. HT is not universally implemented in low‐ and middle‐income countries as a result of both limited resources and evidence.Facilitated passive cooling, comprising infants being allowed to passively lower their body temperature in the days after birth, is an emerging practice in some West African neonatal units.In this observational study, we demonstrate that infants undergoing facilitated passive cooling in a neonatal unit in Accra, Ghana, achieve temperatures within the HT target range ∼20% of the 72 h. Depth of HT fluctuates and can be excessive, as well as not maintained, especially after 24 h.Sustained and deeper passive cooling was evident for severe NE and for those that died.It is important to prevent excessive cooling, to understand that severe NE babies cool more and to be aware of facilitated passive cooling with respect to the design of clinical trials in low‐ and mid‐resource settings.

Background: Neonatal mortality has been decreasing slowly in Ghana despite investments in maternal-newborn services. Although community-based interventions are effective in reducing newborn deaths, hospital-based services provide better health outcomes.Objective: To examine the process and cost of hospital-based services for perinatal asphyxia and low birth weight/preterm at a district and a regional level referral hospital in Ghana.Methods: A cross-sectional study was conducted at 2 hospitals in Greater Accra Region during May-July 2016. Term infants with perinatal asphyxia and low birth weight/preterm infants referred for special care within 24hours after birth were eligible. Time-driven activity-based costing (TDABC) approach was used to examine the process and cost of all activities in the full cycle of care from admission until discharge or death. Costs were analysed from health provider’s perspective.Results: Sixty-two newborns (perinatal asphyxia 27, low-birth-weight/preterm 35) were enrolled. Cost of care was proportionately related to length-of-stay. Personnel costs constituted over 95% of direct costs, and all resources including personnel, equipment and supplies were overstretched.Conclusion: TDABC analysis revealed gaps in the organization, process and financing of neonatal services that undermined the quality of care for hospitalized newborns. The study provides baseline cost data for future cost-effectiveness studies on neonatal services in Ghana.Keywords: perinatal asphyxia; low-birth-weight; time-driven activity-based costing; process of careFunding: Authors received no external funding for the study

Background: There is limited information on the safety or efficacy of currently recommended antimalarial drugs in patients with sickle cell disease (SCD), a population predisposed to worse outcomes if affected by acute malaria. Artesunate-amodiaquine (ASAQ) is the first-line treatment for uncomplicated malaria (UM) in many malaria-endemic countries and is also used for treatment of UM in SCD patients. There is, however, no information to date, on the pharmacokinetics (PK) of amodiaquine or artesunate or the metabolites of these drugs in SCD patients. Objectives: This study sought to determine the PK of desethylamodiaquine (DEAQ), the main active metabolite of amodiaquine, among paediatric SCD patients with UM treated with artesunate-amodiaquine (ASAQ). Methods: Plasma concentration-time data (median DEAQ levels) of SCD children (n = 16) was initially compared with those of concurrently recruited non-SCD paediatric patients with acute UM (n = 13). A population PK modelling approach was then used to analyze plasma DEAQ concentrations obtained between 64 and 169 hours after oral administration of ASAQ in paediatric SCD patients with acute UM (n = 16). To improve PK modeling, DEAQ concentration-time data (n = 21) from SCD was merged with DEAQ concentration-time data (n = 169) of a historical paediatric population treated with ASAQ (n = 103) from the same study setting. Results: The median DEAQ concentrations on days 3 and 7 were comparatively lower in the SCD patients compared to the non-SCD patients. A two-compartment model best described the plasma DEAQ concentration-time data of the merged data (current SCD data and historical data). The estimated population clearance of DEAQ was higher in the SCD patients (67 L/h, 21% relative standard error (RSE) compared with the non-SCD population (15.5 L/h, 32% RSE). The central volume of distribution was larger in the SCD patients compared with the non-SCD patients (4400 L, 43% RSE vs. 368 L, 34% RSE). Conclusions: The data shows a tendency towards lower DEAQ concentration in SCD patients and the exploratory population PK estimates suggest altered DEAQ disposition in SCD patients with acute UM. These findings, which if confirmed, may reflect pathophysiological changes associated with SCD on DEAQ disposition, have implications for therapeutic response to amodiaquine in SCD patients. The limited number of recruited SCD patients and sparse sampling approach however, limits extrapolation of the data, and calls for further studies in a larger population. Key words: Clearance, Desethylamodiaquine, Sickle cell disease

Understanding the epidemiology of human norovirus infection in children within Ghana and the entire sub-Saharan African region, where future norovirus vaccines would have the greatest impact, is essential. We analyzed 1337 diarrheic stool samples collected from children &lt, 5 years from January 2008 to December 2017 and found 485 (36.2%) shedding the virus. GII.4 (54.1%), GII.3 (7.7%), GII.6 (5.3%), GII.17 (4.7%), and GII.5 (4.7%) were the most common norovirus genotypes. Although norovirus GII.4 remained the predominant capsid genotype throughout the study period, an increase in GII.6 and GII.3 capsid genotypes was observed in 2013 and 2014, respectively. The severity of clinical illness in children infected with GII.4 norovirus strains was similar to illness caused by non-GII.4 strains. Since the epidemiology of norovirus changes rapidly, establishment of systematic surveillance within sentinel sites across the country would enhance the monitoring of circulating norovirus strains and allow continuous understanding of norovirus infection in Ghana.

Background Carriage of multidrug resistant (MDR) Gram-negative bacteria (GN) in hospitalized neonates may increase the risk of difficult-to-treat invasive infections at neonatal intensive care units (NICUs). Data on MDRGN carriage among hospitalized newborns in Africa are limited. Methods We conducted a cross-sectional study at the NICUs of 2 tertiary hospitals in Ghana. Swabs from the axilla, groin, perianal region, and the environment were cultured, GN were identified, and antibiotic susceptibility was tested. We obtained blood culture isolates from neonates with sepsis. Whole-genome sequencing was used to characterize carbapenemase-producing Klebsiella pneumoniae. Typing was done by multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis. Results A total of 276 GN were isolated from 228 screened neonates. Pathogenic GN were cultured in 76.8% (175 of 228) of neonates. Klebsiella spp (41.7%; 115 of 276) and Escherichia coli (26.4%; 73 of 276) were the commonest organisms. Carriage rates of MDRGN and third-generation cephalosporin resistant organisms were 49.6% (113 of 228) and 46.1% (105 of 228), respectively. Among Klebsiella spp, 75.6% (87 of 115) phenotypically expressed extended-spectrum β-lactamase activity, whereas 15.6% expressed carbapenemase and harbored bla-OXA-181 and bla-CTX-M-15. Overall, 7.0% (16 of 228) of neonates developed GN bloodstream infection. In 2 of 11 neonates, sequencing showed the same identity between carriage and the bloodstream isolate. Length of stay before specimen collection and antibiotic use were independently associated with carriage rates, which increased from 13% at admission to 42% by day 2 and reached a plateau at 91% by day 15. Conclusions High carriage rates of MDRGN, including carbapenemase-producing enterobacterales may be an emerging problem in NICUs in Africa., We show carriage rate of MDR enterobacterales among neonates in 2 NICUs in Ghana. MDR carriage is associated with duration of stay and antibiotic use. We also report OXA-181 carbapenemase-producing organism from Ghana. WGS showed identity between carriage and BSI.

We sequenced 29 carbapenemase-producing Klebsiella pneumoniae isolates from a neonatal intensive care unit in Ghana. Twenty-eight isolates were sequence type 17 with blaOXA-181 and differed by 0-32 single-nucleotide polymorphisms. Improved surveillance and infection control are needed to characterize and curb the spread of multidrug-resistant organisms in sub-Saharan Africa.

Ghana introduced the monovalent rotavirus vaccine (Rotarix) into its national paediatric vaccination programme in May2012. Vaccine introduction was initiated nationwide and achieved85% coverage within a few months. Rotavirus strain distribution pre- and post-RV vaccine introduction is reported.Stool samples were collected from diarrhoeic children5 years of age hospitalized between 2009 and 2016 at sentinel sites across Ghana and analyzed for the presence of group A rotavirus by enzyme immunoassay. Rotavirus strains were characterized by RT-PCR and sequencing.A total of 1363 rotavirus EIA-positive samples were subjected to molecular characterization. These were made up of 823 (60.4%) and 540 (39.6%) samples from the pre- and post-vaccine periods respectively. Rotavirus VP7 genotypes G1, G2 and G3, and VP4 genotypes P[6] and P[8] constituted more than 65% of circulating G and P types in the pre-vaccine period. The common strains detected were G1P[8] (20%), G3P[6] (9.2%) and G2P[6] (4.9%). During the post-vaccine period, G12, G1 and G10 genotypes, constituted more than 65% of the VP7 genotypes whilst P[6] and P[8] made up more than 75% of the VP4 genotypes. The predominant circulating strains were G12P[8] (26%), G10P[6] (10%) G3P[6] (8.1%) and G1P[8] (8.0%). We also observed the emergence of the unusual rotavirus strain G9P[4] during this period.Rotavirus G1P[8], the major strain in circulation during the pre-vaccination era, was replaced by G12P[8] as the most predominant strain after vaccine introduction. This strain replacement could be temporary and unrelated to vaccine introduction since an increase in G12 was observed in countries yet to introduce the rotavirus vaccine in West Africa. A continuous surveillance programme in the post-vaccine era is necessary for the monitoring of circulating rotavirus strains and the detection of unusual/emerging genotypes.

The West African subregion has the highest burden of neonatal mortality globally and the neonatal mortality rate is decreasing very slowly. A high proportion of newborn deaths are preventable and improved quality of care can reduce long-term morbidity in survivors. Perinatal asphyxia is the major cause of death and disability in term infants in the subregion. Neonatal resuscitation training programs have reduced stillbirths and early neonatal mortality but the overall effect on survival to discharge, population-based perinatal mortality, and long-term impairment is uncertain. Gaps in the health system and quality of postresuscitation care for affected newborns may defeat gains from global efforts to improve care around the time of birth. The aim of this review is to discuss the current situation of postresuscitation care of term infants with presumed birth-associated neonatal encephalopathy in West Africa. Limitations in diagnosing and treating affected infants and feasible interventions to improve acute and postdischarge care are discussed.

A smartphone app to screen for neonatal jaundice has a large potential impact in reducing neonatal death and disability. Our app, neoSCB, uses a colour measurement of the sclera to make a screening decision. Although there are numerous benefits of a smartphone-based approach, smartphone colour measurement that is accurate and repeatable is a challenge. Using data from a clinical setting in Ghana, we compare sclera colour measurement using an ambient subtraction method to sclera colour measurement using a standard colour card method, and find they are comparable provided the subtracted signal-to-noise ratio (SSNR) is sufficient. Calculating a screening decision metric via the colour card method gave 100% sensitivity and 69% specificity (n=87), while applying the ambient subtraction method gave 100% sensitivity and 78% specificity (SSNR>3.5; n=50).

In 2010, the rare OP354-like P[8]b rotavirus subtype was detected in children less than 2 years old in Ghana. In this follow-up study, to provide insight into the evolutionary history of the genome of Ghanaian P[8]b strains RVA/Human-wt/GHA/GHDC949/2010/G9P[8] and RVA/Human-wt/GHA/GHM0094/2010/G9P[8] detected in an infant and a 7-month old child hospitalised for acute gastroenteritis, we sequenced the complete genome using both Sanger sequencing and Illumina MiSeq technology followed by phylogenetic analysis of the near-full length sequences. Both strains possessed the Wa-like/genotype 1 constellation G9P[8]b-I1-R1-C1-M1-A1-N1-T1-E1-H1. Sequence comparison and phylogenetic inference showed that both strains were identical at the lineage level throughout the 11 genome segments. Their VP7 sequences belonged to the major sub-lineage of the G9-lineage III whereas their VP4 sequences belonged to P[8]b cluster I. The VP7 and VP4 genes of the study strains were closely related to a Senegalese G9P[8]b strain detected in 2009. In the remaining nine genome segments, both strains consistently clustered together with Wa-like RVA strains possessing either P[8]a or P[8]b mostly of African RVA origin. The introduction of a P[8]b subtype VP4 gene into the stable Wa-like strain backbone may result in strains that might propagate easily in the human population, with a potential to become an important public health concern, especially because it is not certain if the monovalent rotavirus vaccine (Rotarix) used in Ghana will be efficacious against such strains. Our analysis of the full genomes of GHM0094 and GHDC949 adds to knowledge of the genetic make-up and evolutionary dynamics of P[8]b rotavirus strains.

Introduction: We aimed to investigate whether the provision of water, sanitation, and hand hygiene (WASH) interventions were associated with changes in hand hygiene compliance and perceptions of healthcare workers towards infection control. Methodology: The study was conducted from June 2017 through February 2018 among healthcare workers in two Northern districts of Ghana. Using a pretest-posttest design, we performed hand hygiene observations and perception surveys at baseline (before the start of WASH interventions) and post-intervention (midline and endline). We assessed adherence to hand hygiene practice using the WHO direct observation tool. The perception study was conducted using the WHO perception survey for healthcare workers. Study outcomes were compared between baseline, midline and endline assessments. Results: The hand hygiene compliance significantly improved from 28.8% at baseline through 51.7% at midline (n = 726/1404; 95% CI: 49.1-54.2%) to 67.9% at endline (n = 1000/1471; 95% CI: 65.6-70.3%). The highest increase in compliance was to the WHO hand hygiene moment 5 after touching patients surrounding (relative increase, 205%; relative rate, 3.05; 95% CI: 2.23-4.04; p < 0.0001). Post-intervention, the top three policies deemed most effective at improving hand hygiene practice were: provision of water source (rated mean score, n = 6.1 ± 1.4), participation in educational activities (rated mean score 6.0 ± 1.5); and hand hygiene promotional campaign (6.0 ± 1.3). Conclusion: Hand hygiene compliance significantly improved post-intervention. Sustaining good hand hygiene practices in low resource settings should include education, the provision of essential supplies, and regular hand hygiene audits and feedback.

We used the dideoxynucleotide chain termination method to determine the strains of nine non-typeable rotavirus enzyme immunoassay-positive samples, which were identified as G2. We detected nucleotide changes in the primer-binding region and amino acid substitutions within the VP7 protein of the G2 rotavirus strains. Genotyping primers need to be updated regularly.

Background: Each year an estimated 2.6 million newborns die, mainly from complications of prematurity, neonatal infections, and intrapartum events. Reducing these deaths requires high coverage of good quality care at birth, and inpatient care for small and sick newborns. In low- and middle-income countries, standardised measurement of the readiness of facilities to provide emergency obstetric care has improved tracking of readiness to provide care at birth in recent years. However, the focus has been mainly on obstetric care; service readiness for providing inpatient care of small and sick newborns is still not consistently measured or tracked. Methods: We reviewed existing international guidelines and resources to create a matrix of the structural characteristics (infrastructure, equipment, drugs, providers and guidelines) for service readiness to deliver a package of inpatient care interventions for small and sick newborns. To identify gaps in existing measurement systems, we reviewed three multi-country health facility survey tools (the Service Availability and Readiness Assessment, the Service Provision Assessment and the Emergency Obstetric and Newborn Care Assessment) against our service readiness matrix. Findings: For service readiness to provide inpatient care for small and sick newborns, our matrix detailed over 600 structural characteristics. Our review of the SPA, the SARA and the EmONC assessment tools identified several measurement omissions to capture information on key intervention areas, such as thermoregulation, feeding and respiratory support, treatment of specific complications (seizures, jaundice), and screening and follow up services, as well as specialised staff and service infrastructure. Conclusions: Our review delineates the required inputs to ensure readiness to provide inpatient care for small and sick newborns. Based on these findings, we detail where questions need to be added to existing tools and describe how measurement systems can be adapted to reflect small and sick newborns interventions. Such work can inform investments in health systems to end preventable newborn death and disability as part of the Every Newborn Action Plan.

Summary Background There is a paucity of data describing hospital-acquired infections (HAIs) in Africa. Objective To describe the prevalence and distribution of HAIs in acute care hospitals in Ghana. Methods Between September and December 2016, point-prevalence surveys were conducted in participating hospitals using protocols of the European Centre for Disease Prevention and Control. Medical records of eligible inpatients at or before 8am on the survey date were reviewed to identify HAIs present at the time of the survey. Findings Ten hospitals were surveyed, representing 32.9% of all acute care beds in government hospitals. Of 2107 inpatients surveyed, 184 HAIs were identified among 172 patients, corresponding to an overall prevalence of 8.2%. The prevalence values in hospitals ranged from 3.5% to 14.4%, with higher proportions of infections in secondary and tertiary care facilities. The most common HAIs were surgical site infections (32.6%), bloodstream infections (19.5%), urinary tract infections (18.5%) and respiratory tract infections (16.3%). Device-associated infections accounted for 7.1% of HAIs. For 12.5% of HAIs, a micro-organism was reported; the most commonly isolated micro-organism was Escherichia coli. Approximately 61% of all patients surveyed were on antibiotics; 89.5% of patients with an HAI received at least one antimicrobial agent on the survey date. The strongest independent predictors for HAI were the presence of an invasive device before onset of infection and duration of hospital stay. Conclusion A low HAI burden was found compared with findings from other low- and middle-income countries.

INTRODUCTION: Ghana introduced monovalent rotavirus vaccine in April 2012. We sought to determine the long-term impact of routine rotavirus vaccination on rotavirus gastroenteritis hospitalizations in Ghana during the first 4 years following rotavirus vaccine introduction. METHODS: Active sentinel surveillance for acute gastroenteritis hospitalizations among children

The major causes of newborn deaths in sub-Saharan Africa are well-known and countries are gradually implementing evidence-based interventions and strategies to reduce these deaths. Facility-based care provides the best outcome for sick and or small babies; however, little is known about the cost and burden of hospital-based neonatal services on parents in West Africa, the sub-region with the highest global neonatal death burden. To estimate the actual costs borne by parents of newborns hospitalised with birth-associated brain injury (perinatal asphyxia) and preterm/low birth weight, this study examined economic costs using micro-costing bottom-up approach in two referral hospitals operating under the nationwide social health insurance scheme in an urban setting in Ghana. We prospectively assessed the process of care and parental economic costs for 25 out of 159 cases of perinatal asphyxia and 33 out of 337 cases of preterm/low birth weight admitted to hospital on the day of birth over a 3 month period. Results showed that medical-related costs accounted for 66.1% (IQR 49% - 81%) of out-of-pocket payments irrespective of health insurance status. On average, families spent 8.1% and 9.1% of their annual income on acute care for preterm/LBW and perinatal asphyxia respectively. The mean out-of-pocket expenditure for preterm/LBW was $147.6 (median $101.8) and for perinatal asphyxia was $132.3 (median $124). The study revealed important gaps in the financing and organization of health service delivery that may impact the quality of care for hospitalised newborns. It also provides information for reviewing complementary health financing options for newborn services and further economic evaluations.

Introduction: Symptoms of sepsis are non-specific among neonates and diagnosis requires a high index of suspicion. The study sought to evaluate the utility of procalcitonin (PCT) versus C-reactive protein (CRP) in diagnosing early-onset neonatal sepsis.Methods: This was a crosssectional study in which neonates admitted to the neonatal intensive care unit, with signs suggesting sepsis were categorized according to an adapted criteria from Tollner's sepsis score and case definition of bloodstream infection as: ''highly probable'', ''probable'' and ''less probable''. Laboratory investigations including blood culture, complete blood count, PCT and CRP levels were done before first antimicrobial drug administration.Results: A total of 62 neonates less than 12 hours postnatal age (0.16-9.82 hours) were recruited. Proportion of neonates with PCT>2 ng/mL was 91% (20/22) in the ''highly probable'' group compared to 31.6% (6/19) in the ''probable group'' (p5 mg/L was 54.4% (12/22) in the ''highly probable'' group compared to 26.3% (5/19) in the ''probable group'' (p = 0.07). The receiver operator characteristics for PCT and CRP were; sensitivity (87.5% vrs 50%), specificity (63.0% vrs 72.2%), positive predictive value (44.1% vrs 37.5%) and negative predictive value (93.8% vrs 81.3%), respectively.Conclusion: PCT was a better predictive marker for neonatal sepsis within the first 12 hours of life than CRP in this setting, however, its low specificity relative to CRP suggests that neonates without patent infection are more likely to be incorrectly diagnosed with sepsis using this test.Keywords: Diagnostic marker, neonatal sepsis, predictive value, sensitivity, specificity

The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction.We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children5 years of age during 2013-2014 from 16 countries. We used previously developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs).Rotavirus remained the leading etiology (overall weighted AF, 40.3% [95% confidence interval {CI}, 37.6%-44.3%]), though the AF was substantially lower in the Americas (AF, 12.2 [95% CI, 8.9-15.6]), based on samples from a country with universal rotavirus vaccination. Norovirus GII (AF, 6.2 [95% CI, 2.8-9.2]), Cryptosporidium (AF, 5.8 [95% CI, 4.0-7.6]), Shigella (AF, 4.7 [95% CI, 2.8-6.9]), heat-stable enterotoxin-producing Escherichia coli (ST-ETEC) (AF, 4.2 [95% CI, 2.0-6.1]), and adenovirus 40/41 (AF, 4.2 [95% CI, 2.9-5.5]) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% CI, 48.3%-61.5%) in rotavirus vaccine age-ineligible children to 20.0% (95% CI, 12.4%-30.4%) in age-eligible children.Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of rotavirus vaccine introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea.

BACKGROUND: Amikacin exhibits marked pharmacokinetic (PK) variability and is commonly used in combination with other drugs in the treatment of neonatal sepsis. There is a paucity of amikacin PK information in neonates from low-resource settings.OBJECTIVES: To determine the PK parameters of amikacin, and explore the influence of selected covariates, including coadministration with aminophylline, on amikacin disposition in neonates of African origin.METHODS: Neonates with suspected sepsis admitted to an intensive care unit in Accra, Ghana, and treated with amikacin (15 mg/kg loading followed by 7.5 mg/kg every 12 hours), were recruited. Serum amikacin concentration was measured at specified times after treatment initiation and analyzed using a population PK modeling approach.RESULTS: A total of 419 serum concentrations were available for 247 neonates. Mean (SD) trough amikacin concentration (from samples collected 30 minutes before the fourth dose) among term (n = 25), and preterm (CONCLUSIONS: The V and half-life of amikacin in this cohort varied from that reported in non-African populations, and the high trough and low peak amikacin concentrations in both term and preterm neonates suggest strategies to optimize amikacin dosing are required in this population.

The World Health Organisation rotavirus surveillance networks have documented and shown eclectic geographic and temporal diversity in circulating G- and P- genotypes identified in children

Background Diagnosis of bloodstream infections (BSI) in neonates is usually difficult due to minimal symptoms at presentation; thus early empirical therapy guided by local antibiotic susceptibility profile is necessary to improve therapeutic outcomes. Methods A review of neonatal blood cultures submitted to the microbiology department of the Korle-Bu Teaching Hospital was conducted from January 2010 through December 2013. We assessed the prevalence of bacteria and fungi involved in BSI and the susceptibility coverage of recommended empiric antibiotics by Ghana Standard Treatment guidelines and the WHO recommendations for managing neonatal sepsis. The national and WHO treatment guidelines recommend either ampicillin plus gentamicin or ampicillin plus cefotaxime for empiric treatment of neonatal BSI. The WHO recommendations also include cloxacillin plus gentamicin. We described the resistance profile over a 28-day neonatal period using multivariable logistic regression analysis with linear or restricted cubic splines. Results A total of 8,025 neonatal blood culture reports were reviewed over the four-year period. Total blood culture positivity was 21.9 %. Gram positive organisms accounted for most positive cultures, with coagulase negative staphylococci (CoNS) being the most frequently isolated pathogen in early onset infections (EOS) (59.1 %) and late onset infections (LOS) (52.8 %). Susceptibility coverage of early onset bacterial isolates were 20.7 % to ampicillin plus cefotaxime, 32.2 % to the combination of ampicillin and gentamicin, and 71.7 % to cloxacillin plus gentamicin. For LOS, coverage was 24.6 % to ampicillin plus cefotaxime, 36.2 % to the combination ampicillin and gentamicin and 63.6 % to cloxacillin plus gentamicin. Cloxacillin plus gentamicin remained the most active regimen for EOS and LOS after exclusion of BSI caused by CoNS. For this regimen, the adjusted odds of resistance decreased between 12-34 % per day from birth to day 3 followed by the slowest rate of resistance increase, compared to the other antibiotic regimen, thereafter until day 28. The trend in resistance remained generally unchanged after excluding data from CoNS. Multidrug resistant isolates were significantly (p-value

BACKGROUND: Ghana was among the first African nations to introduce monovalent rotavirus vaccine (RV1) into its childhood immunization schedule in April 2012. We aimed to assess the impact of vaccine introduction on rotavirus and acute gastroenteritis (AGE) hospitalizations and to estimate vaccine effectiveness (VE). METHODS: Using data from 2 teaching hospitals monthly AGE and rotavirus admissions by age were examined 40 months before and 31 months after RV1 introduction using interrupted time-series analyses. From January 2013 we enrolled children

Introduction: though giardiasis is an important public health problem in Ghana, several aspects of its epidemiology, particularly the molecular epidemiology has not been investigated adequately. This could be a major hindrance to effective surveillance and control of giardiasis in the country. The study was carried out to determine the prevalence, risk factors and genotypes of Giardia lamblia infecting children at a paediatric hospital in Ghana. Methods: a total of 485 patients including 365 diarrhoea and 120 non-diarrhoea children were enrolled into the study. Stool samples were collected and analysed for parasite presence using microscopy, ELISA and PCR. Positive samples were subsequently characterized into assemblages by PCR-RFLP, and further confirmed with sequencing of the glutamate dehydrogenase (gdh) gene. Epidemiological data on demographic, clinical and behavioral features of the study subjects were also collected. Results: prevalence of G. lamblia infections in diarrhea and non-diarrhea children were 5.8% and 5% respectively (P>0.5). Sequence data confirmed Giardia lamblia assemblage B as the predominant genotype in both diarrhoea and non-diarrhoea cases. There was no significant association of G. lamblia infection with any of the epidemiological variables investigated. Conclusion: our findings suggest that assemblage B could be the predominant genotype causing giardiasis in children. Increased public health education focusing on good sanitary practices, particularly among mothers and children, could decrease the risk of G. lamblia infection.The Pan African Medical Journal 2016;24

Logistic regression models using linear or restricted cubic spline function (with the lowest AIC) of neonatesâ age. Table S2. Changes in the odds of antibiotic resistance with age of neonates to various antibiotic combinations using multivariable logistic regression models with linear spline function. (DOCX 19 kb)

Malnutrition in preterm low birth weight infants has adverse long-term metabolic, growth, and neurodevelopmental effects. In the past 3 decades, parenteral nutrition, enriched preterm formula, and fortification of human milk have been used to alleviate these adverse effects. Unfortified human breast milk does not provide sufficient nutrients for the growth and development of preterm infants at the volumes recommended; however, it is usually the only source of nutrition available for such infants in low-resource countries. Many newborns, including very low birth weight infants, are surviving in these countries because of concerted efforts to achieve the fourth millennium development goal. These efforts have not addressed the nutrition needs of sick preterm very low birth weight infants. The authors report 3 cases of severe acute malnutrition in very low birth weight newborns and suggest possible interventions.

Introduction: Vaccination is the most effective preventive strategy against rotavirus disease. Regional differences in prevalent rotavirus genotypes may affect vaccine efficacy. Pre-vaccine surveillance for burden of rotavirus disease, prevalent rotavirus genotypes, and association between rotavirus disease and intussusceptions helps in monitoring the impact of vaccination. Methodology: A prospective study was conducted from January 2008 to December 2009 in children younger than five years hospitalized for longer than 24 hours with acute gastroenteritis. Data on confirmed cases of intussusception were collected retrospectively. Stools were tested by enzyme immunoassay, reverse-transcriptase polymerase chain reaction and nucleotide sequencing. Results: Acute gastroenteritis (AGE) caused 13.1% (2,147/16,348) of hospitalizations among children under five years. Stools were tested for 50.2% (1077/2147) of AGE cases. Of these, 49% (528/1077) were rotavirus positive. Rotavirus gastroenteritis, non-rotavirus gastroenteritis, and intussusceptions were most prevalent in children under 15 months [80.3%, 74% and 91% respectively]. Rotavirus was detected from more than 60% of acute gastroenteritis cases during peak months. The prevalence of intussusception showed no seasonal pattern. The peak ages of six to twelve months for acute gastroenteritis and five to eight months for intussusception overlapped. G1, G2 and mixed G/P genotypes were common in the isolated rotaviruses. Conclusion: Rotavirus gastroenteritis causes significant morbidity in children younger than five years of age in Ghana. Although the peak age of rotavirus gastroenteritis and intussusceptions overlapped, there was no seasonal correlation between them. The high prevalence of mixed G/P genotypes in Ghanaian children may affect the effectiveness of vaccination.

Each year 3.6 million infants are estimated to die in the first 4 weeks of life (neonatal period)--but the majority continue to die at home, uncounted. This article reviews progress for newborn health globally, with a focus on the countries in which most deaths occur--what data do we have to guide accelerated efforts? All regions are advancing, but the level of decrease in neonatal mortality differs by region, country, and within countries. Progress also differs by the main causes of neonatal death. Three major causes of neonatal deaths (infections, complications of preterm birth, and intrapartum-related neonatal deaths or "birth asphyxia") account for more than 80% of all neonatal deaths globally. The most rapid reductions have been made in reducing neonatal tetanus, and there has been apparent progress towards reducing neonatal infections. Limited, if any, reduction has been made in reducing global deaths from preterm birth and for intrapartum-related neonatal deaths. High-impact, feasible interventions to address these 3 causes are summarized in this article, along with estimates of potential for lives saved. A major gap is reaching mothers and babies at birth and in the early postnatal period. There are promising community-based service delivery models that have been tested mainly in research studies in Asia that are now being adapted and evaluated at scale and also being tested through a network of African implementation research trials. To meet Millennium Development Goal 4, more can and must be done to address neonatal deaths. A critical step is improving the quantity, quality and use of data to select and implement the most effective interventions and strengthen existing programs, especially at district level.

Severe rotavirus diarrhea in children

Purpose TO determine the magnitude and pattern of ocular manifestations in sickle cell disease at Korlebu Hospital, Accra, Ghana. Methods Hospital-based cross-sectional study including all patients with sickle cell disease reporting for routine follow-up at the Sickle Cell Clinic at Korlebu Hospital, Accra, Ghana. Results A total of 201 patients with sickle cell disease (67 male and 134 female) were enrolled, comprising 114 subjects with genotype HbSS, aged 6–58 years, mean 19.26 (SD 11.70), and 87 with genotype HbSC, aged 6–65 years, mean 31.4 (SD 16.76). Visual impairment was found in 5.6% of eyes examined. Causes were cataract, proliferative sickle retinopathy (PSR), optic atrophy, phthisis bulbi, and central retinal artery occlusion. Common anterior segment signs of sickle cell disease, which were more common in HbSC patients, were tortuous corkscrew conjunctival vessels, iris atrophy, and cataract. Eyes with iris atrophy or depigmentation were 1.8 times more at risk of PSR than eyes without. Overall, PSR was found in 12.9% of subjects examined (3.5% of HbSS, 25.3% of HbSC; 15.9% of males and 11.2% of females). The prevalence of proliferative sickle retinopathy increased with age and increased systemic severity of sickle cell disease; sex did not have an influence. Conclusions There is a high prevalence of ocular morbidity in sickle cell disease patients at Korlebu Hospital. Prevalence increased with age, systemic severity of sickle cell disease, and HbSC genotype.

The annual toll of losses resulting from poor pregnancy outcomes include half a million maternal deaths, more than three million stillbirths, of whom at least one million die during labour and 3.8 million neonatal deaths--up to half on the first day of life. Neonatal deaths account for an increasing proportion of child deaths (now 41%) and must be reduced to achieve Millennium Development Goal (MDG) 4 for child survival. Newborn survival is also related to MDG 5 for maternal health as the interventions are closely linked. This article reviews current progress for newborn health globally, with a focus on the countries where most deaths occur. Three major causes of neonatal deaths (infections, complications of preterm birth, intrapartum-related neonatal deaths) account for almost 90% of all neonatal deaths. The highest impact interventions to address these causes of neonatal death are summarised with estimates of potential for lives saved. Two priority opportunities to address newborn deaths through existing maternal health programmes are highlighted. First, antenatal steroids are high impact, feasible and yet under-used in low resource settings. Second, with increasing investment to scale up skilled attendance and emergency obstetric care, it is important to include skills and equipment for simple immediate newborn care and neonatal resuscitation. A major gap is care during the early postnatal period for mothers and babies. There are promising models that have been tested mainly in research studies in Asia that are now being adapted and evaluated at scale including through a network of African implementation research trials.

BACKGROUND: The Every Newborn Action Plan (ENAP), launched in 2014, aims to end preventable newborn deaths and stillbirths, with national targets of ≤12 neonatal deaths per 1000 live births and ≤12 stillbirths per 1000 total births by 2030. This requires ambitious improvement of the data on care at birth and of small and sick newborns, particularly to track coverage, quality and equity. METHODS: In a multistage process, a matrix of 70 indicators were assessed by the Every Newborn steering group. Indicators were graded based on their availability and importance to ENAP, resulting in 10 core and 10 additional indicators. A consultation process was undertaken to assess the status of each ENAP core indicator definition, data availability and measurement feasibility. Coverage indicators for the specific ENAP treatment interventions were assigned task teams and given priority as they were identified as requiring the most technical work. Consultations were held throughout. RESULTS: ENAP published 10 core indicators plus 10 additional indicators. Three core impact indicators (neonatal mortality rate, maternal mortality ratio, stillbirth rate) are well defined, with future efforts needed to focus on improving data quantity and quality. Three core indicators on coverage of care for all mothers and newborns (intrapartum/skilled birth attendance, early postnatal care, essential newborn care) have defined contact points, but gaps exist in measuring content and quality of the interventions. Four core (antenatal corticosteroids, neonatal resuscitation, treatment of serious neonatal infections, kangaroo mother care) and one additional coverage indicator for newborns at risk or with complications (chlorhexidine cord cleansing) lack indicator definitions or data, especially for denominators (population in need). To address these gaps, feasible coverage indicator definitions are presented for validity testing. Measurable process indicators to help monitor health service readiness are also presented. A major measurement gap exists to monitor care of small and sick babies, yet signal functions could be tracked similarly to emergency obstetric care. CONCLUSIONS: The ENAP Measurement Improvement Roadmap (2015-2020) outlines tools to be developed (e.g., improved birth and death registration, audit, and minimum perinatal dataset) and actions to test, validate and institutionalise proposed coverage indicators. The roadmap presents a unique opportunity to strengthen routine health information systems, crosslinking these data with civil registration and vital statistics and population-based surveys. Real measurement change requires intentional transfer of leadership to countries with the greatest disease burden and will be achieved by working with centres of excellence and existing networks.