Flaviah B. Namiiro

Objectives: Several recent studies highlight the high prevalence of resistance to multiple antibiotic classes used in current treatment regimens for neonatal sepsis and new treatment options are urgently needed. We aimed to identify potential new combination antibiotic treatment regimens by investigating the drug-resistance and genetic profiles of the most frequently isolated Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries (LMICs) in the NeoOBS study. Material and methods: Gram-negative bacteria isolated from neonates with culture-confirmed sepsis from 13 clinical sites in nine countries, mainly LMICs, were analyzed. Culture-based identification was followed by whole-genome sequencing (WGS). Minimal inhibitory concentrations (MICs) for 8 antibiotics were determined for a representative subset of 108 isolates. Results: Five bacterial species, Klebsiella pneumoniae (n=135), Acinetobacter baumannii (n=80), Escherichia coli (n=34), Serratia marcescens (n=33) and Enterobacter cloacae complex (ECC) (n=27) accounted for most Gram-negative bacterial isolates received (309/420, 74%). Extended-spectrum β-lactamases (ESBL) genes mostly belonging to CTX-M-15 were found in 107 (79%) K. pneumoniae isolates and 13 (38%) E. coli , as well as in 6 (18%) and 10 (37%) S. marcescens and ECC isolates, respectively. Carbapenem resistance genes were present in 41 (30%) K. pneumoniae, while 73 (91%) of A. baumannii isolates were predicted to be MDR based on carbapenem resistance genes. Apart from A. baumannii, in which two major pandemic lineages predominated, a wide genetic diversity occurred at the intraspecies level with different MDR clones occurring at the different sites. Phenotypic testing showed resistance to the WHO first- and second- line recommended treatment regimens: 74% of K. pneumoniae isolates were resistant to gentamicin and 85% to cefotaxime; E. coli isolates showed resistance to ampicillin, gentamicin and cefotaxime in 90%, 38% and 47%, respectively. For the novel antibiotic regimens involving different combinations of flomoxef, fosfomycin and amikacin, the overall predicted MIC-determined susceptibility for Enterobacterales isolates was 71% (n=77) to flomoxef-amikacin, 76% (n=82) to flomoxef-fosfomycin and 79% (n=85) to fosfomycin-amikacin combinations, compared to 31% and 22% isolates susceptible to ampicillin-gentamicin and cefotaxime, respectively. ESBL-producing Enterobacterales isolates were 100% susceptible both to flomoxef-fosfomycin and flomoxef-amikacin and 92% to fosfomycin-amikacin. Conclusion: Enterobacterales carried multiple resistance genes to cephalosporins, carbapenems and aminoglycosides. ESBL-producing K. pneumoniae and E. coli isolates were highly susceptible to the three new antibiotic combination regimens planned to be evaluated in the currently recruiting GARDP-sponsored NeoSep1 trial.

Objective: Every year, an estimated 20 million babies are born with low birthweight and this number is increasing globally. Survivors are at risk of lifelong morbidities like undernutrition. We assessed the growth and nutritional status for children born with low birthweight at Mulago Hospital, Uganda. Methods: We conducted a cross sectional study to describe the nutritional status of children aged between 22 and 38 months and born weighing ≤ 2000 g. Anthropometric measurements; weight for height, height for age and weight for age z-scores were generated based on the World Health Organization standards to define wasting, stunting and underweight respectively. Data was collected using a structured questionnaire and analysis was done using STATA version 14. Results: Of the 251 children, 129 (51.4%) were male, mean age was 29.7 months SD 4.5) and maternal mean age was 29.9 (SD 5.3). A total of 101(40.2%) had normal nutritional status. The prevalence of wasting, underweight and stunting were: 8 (3.2%), 36 (14.4%) and 106 (42.2%) respectively. Conclusion: Six of ten children born with low birthweight were at risk of undernutrition in early childhood: underweight and stunting were higher than the national prevalence. Targeted interventions are needed for children with very low birth weight.

Background: Preterm birth is associated with life-long cost implications on the infant, family, health system, and society at large. The costs related to lost productivity at contributions at work during care of preterm infants are difficult to measure. We aimed to explore and document the unpriced costs parents incur following birth of a preterm infant in the first year of life in a low resource setting. Methods: Thirty-nine mothers and five fathers of preterm infants who had ever attended the preterm follow-up clinic after discharge from Mulago National Referral Hospital, were included in a qualitative study between November 2019 and February 2020. Participants were purposively selected, and data were collected using four focused group discussions with mothers and in-depth interviews with the fathers lasting 30–70 minutes each. These were audio-recorded, transcribed and translated. The data were manually analysed using the thematic approach. Findings: Three themes were generated: i) complex nature of the infant, ii) time to care for the infant, iii) mother as the predominant caregiver. The parents perceived preterm infants as delicate, complicated and their care more costly compared to those born at term. Expressions of need for time to care for their infants, frequent hospital visits and readmission were raised. Availability of the mother as the predominant caregiver some of whose roles cannot be delegated and their experiences following return to work after birth of a preterm were cited by the participants. Conclusion: The results highlight the unpriced costs incurred by the parents through disruption of the work pattern due to the actual and perceived needs of a preterm infant and time to care in a low resource setting. We recommend guidance on financial planning, development of policies and programs on social and financial support for parents and future studies on indirect costs of preterm care.

Objectives We sought to understand the facilitators and barriers impacting utilisation of follow-up services for children born preterm as perceived by parents in a low-resource setting.Methods We conducted a qualitative study at Mulago Hospital, Uganda, with parents of children born preterm and aged 22-38 months at the time of the study. We collected data using five in-depth interviews and four focus group discussions. Data were analysed using thematic analysis informed by the social-ecological model.Results Ten subthemes emerged that could be grouped into three main themes: (1) Individual: parents' knowledge, parenting skills, perception of follow-up and infant's condition; (2) Relationship: support for the mother and information sharing; (3) Institution: facility setup, cost of care, available personnel and distance from the facility. Parents of preterm infants perceived receiving timely information, better understanding of prematurity and its complications, support from spouses, availability of free services and encouragement from health workers as facilitators for utilisation of follow-up services. Limited male involvement, parents' negative perception of follow-up, stable condition of infant, health facility challenges especially congestion at the hospital, distance and care costs were key barriers.Conclusion An interplay of facilitators and barriers at individual, interpersonal and health system levels encourage or deter parents from taking their preterm children for follow-up services. Improving utilisation of services will require educating parents on the importance of follow-up even when children are not sick, eliciting maternal support from spouses and peers and addressing health system gaps that make follow-up unattractive and costly.

Introduction Advances in neonatal care have led to the increasing survival of preterm/low birth weight infants worldwide. However, there is limited data on growth outcomes following preterm births especially in low and middle income countries. We assessed the catch-up growth, nutritional status and associated factors of Ugandan children who were born preterm/ low birth weight at Mulago National Referral Hospital.Methods: We enrolled children aged 22-38 months who had been born as preterm with low birth weight and their mothers. Participants were identified and recruited from the follow up clinic for preterm babies discharged from the neonatal unit of Mulago Hospital. Anthropometric measurements for mothers and children were taken. The children’s weight for height z-scores, height for age z-scores, weight for age z-scores, head circumference and mid upper arm circumference (MUAC) were taken and the mothers’ body mass index were generated based on the World Health Organization standards. Results: Of the 251 children and mother pairs recruited, 129 children (51.4%) were male, the mean age was 29.7 months (SD±4.5) and the mean maternal age was 29.9 (SD±5.3). 101(40.1%) of the children enrolled had attained catch up growth on the normal anthropometric measurements for their age. Among the participants, the prevalence of wasting, underweight and stunting was: 8 (3.2%), 36 (14.4%) and 106 (42.2%) respectively. Factors associated with stunting were male sex (AOR 2.36, 95% CI 1.42 to 3.95); p=0.001), maternal age ≤ 25years: AOR 2.27 (95%CI 1.13, 4.52); p= 0.020, and maternal height 0.002. Associations with underweight in the children were; birth weight ≤1500 gms: AOR 2.38(95%CI 1.14, 4.95); p=0.020 and post-natal hospitalization of more than 14 days: AOR 5.93(95%CI 1.96, 17.90); p=0.002. For 246 (98.8%) participants, MUAC was normal (≥ 12.5 cm) and for 216 (86.8%) the head circumference was within normal range for age.Conclusion: Of the children born preterm/LBW 40.1% of the participants had attained the expected catch up growth at 2 to 3 years of age, 42.2% were observed to be stunted while 14.4% were underweight both higher than the national levels. Targeted interventions are specifically needed for children born with very low birth weight, those requiring long postnatal hospitalization, males and those born to short or young mothers.

Background: Follow up after hospital discharge is a recommended and common medical practice for high risk infants like those born with low birthweight and at preterm, this however is rare in LIC. Premature babies are at risk of long term disabilities and require continued care both at home and in designated facilities. We sought to determine the attendance of scheduled follow up clinic visits for preterm infants post hospital discharge. Methods: A review of records for all infants seen in the preterm clinic at Mulago National Referral Hospital between January and December 2015 was done. After discharge from the SCBU, infants are followed up in the Kangaroo Mother Care clinic every fortnight until they weigh 2500 grams. They then transition to the Preterm Care Clinic where they are followed up every two to three months until 18 months of corrected age. Findings: Between September 2014 and December 2015, 7224 neonates were admitted to the SCU of Mulago Hospital. Of these, 3537 (49 %) weighed less or equal to 2500 grams, thus majority were eligible for follow up in the special clinics after discharge. Of the 590 babies registered in the PTC during 2016; 423 (71.7%) were included for analysis and 167 (28.3) % were excluded due to missing or incomplete data. Majority of the infants weighed 1501-2000gms (50%), only 3% weighed less than 1000gms, 14% more than 2000gms and 5% record of birth weight was missing. Almost 90% of the visits during KMC clinic were on schedule as compared to 64% during PTC visits. The average number of visits in the KMC clinic were three per baby; 105 babies had between 4-5 visits and 15% of all the participants were still attending the clinic by one year of age. Many babies were not seen in the clinic after the age of 6 months. Conclusion: Scheduled follow up clinic attendance for low birth weight preterm infants is suboptimal with only one out of four were followed up after one year. There is need to strengthen utilization of available services, community support and devise means to improve the long term follow up.

Prolonged second stage of labour is a major cause of perinatal and maternal morbidity and mortality in low-income countries. Vacuum extraction is a proven effective intervention, hardly used in Africa. Many authors and organisations recommend (re)introduction of vacuum extraction, but successful implementation has not been reported. In 2012, a program to increase the use of vacuum extraction was implemented in Mulago Hospital, Uganda. The program consisted of development of a vacuum extraction guideline, supply of equipment and training of staff. The objective of this study was to investigate the impact of the program. Audit of a quality improvement intervention with before and after measurement of outcome parameters. Setting: Mulago Hospital, the national referral hospital for Uganda with approximately 33 000 deliveries per year. It is the university teaching hospital for Makerere University and most of the countries doctors and midwives are trained here. Data was collected from hospital registers and medical files for a period of two years. Main outcome measures were vacuum extraction rate, intrapartum stillbirth, neonatal death, uterine rupture, maternal death and decision to delivery interval. Mode of delivery and outcome of 12 143 deliveries before and 34 894 deliveries after implementation of the program were analysed. The vacuum extraction rate increased from 0.6 – 2.4 % of deliveries (p < 0.01) and was still rising after 18 months. There was a decline in intrapartum stillbirths from 34 to 26 per 1000 births (-23.6 %, p < 0.01) and women with uterine rupture from 1.1 – 0.8 per 100 births (-25.5 %, p < 0.01). Decision to delivery interval for vacuum extraction was four hours shorter than for caesarean section. A program to increase the use of vacuum extraction was successful in a high-volume university hospital in sub-Saharan Africa. The use of vacuum extraction increased. An association with improved maternal and perinatal outcome is strongly suggested. We recommend broad implementation of vacuum extraction, whereby university hospitals like Mulago Hospital can play an important role.To support implementation, we recommend further research into outcome of vacuum extraction and into vacuum extraction devices for low-income countries. Such studies are now in progress at Mulago Hospital.

Healthy infants typically regain their birth weight by 21 days of age; however, failure to do so may be due to medical, nutritional or environmental factors. Globally, the incidence of low birth weight deliveries is high, but few studies have assessed the postnatal weight changes in this category of infants, especially in Africa. The aim was to determine what proportion of LBW infants had not regained their birth weight by 21 days of age after discharge from the Special Care Unit of Mulago hospital, Kampala.