Cardiovascular abnormalities in chest radiographs of children with pneumonia, Uganda.

Objective: To describe chest radiograph findings among children hospitalized with clinically diagnosed severe pneumonia and hypoxaemia at three tertiary facilities in Uganda. Methods: The study involved clinical and radiograph data on a random sample of 375 children aged 28 days to 12 years enrolled in the Children's Oxygen Administration Strategies Trial in 2017. Children were hospitalized with a history of respiratory illness and respiratory distress complicated by hypoxaemia, defined as a peripheral oxygen saturation (SpO2) < 92%. Radiologists blinded to clinical findings interpreted chest radiographs using standardized World Health Organization method for paediatric chest radiograph reporting. We report clinical and chest radiograph findings using descriptive statistics. Findings: Overall, 45.9% (172/375) of children had radiological pneumonia, 36.3% (136/375) had a normal chest radiograph and 32.8% (123/375) had other radiograph abnormalities, with or without pneumonia. In addition, 28.3% (106/375) had a cardiovascular abnormality, including 14.9% (56/375) with both pneumonia and another abnormality. There was no significant difference in the prevalence of radiological pneumonia or of cardiovascular abnormalities or in 28-day mortality between children with severe hypoxaemia (SpO2: < 80%) and those with mild hypoxaemia (SpO2: 80 to < 92%). Conclusion: Cardiovascular abnormalities were relatively common among children hospitalized with severe pneumonia in Uganda. The standard clinical criteria used to identify pneumonia among children in resource-poor settings were sensitive but lacked specificity. Chest radiographs should be performed routinely for all children with clinical signs of severe pneumonia because it provides useful information on both cardiovascular and respiratory systems.

Reducing preterm mortality in eastern Uganda: the impact of introducing low-cost bubble CPAP on neonates <1500 g.

BACKGROUND: Complications of prematurity are the leading cause of deaths in children under the age of five. The predominant reason for these preterm deaths is respiratory distress syndrome (RDS). In low-income countries (LICs) there are limited treatment options for RDS. Due to their simplicity and affordability, low-cost bubble continuous positive airway pressure (bCPAP) devices have been introduced in neonatal units in LICs to treat RDS. This study is the first observational study from a LIC to compare outcomes of very-low-birth-weight (VLBW) neonates in pre- and post-CPAP periods. METHODS: This was a retrospective study of VLBW neonates (weight < 1500 g) in Mbale Regional Referral Hospital Neonatal Unit (MRRH-NNU), a government hospital in eastern Uganda. It aimed to measure the outcome of VLBW neonates in two distinct study periods: A 14-month period beginning at the opening of MRRH-NNU and covering the period until bCPAP was introduced (pre-bCPAP) and an 18-month period following the introduction of bCPAP (post-bCPAP). After the introduction of bCPAP, it was applied to preterm neonates with RDS when clinically indicated and if a device was available. Clinical features and outcomes of all neonates < 1500 g were compared before and after the introduction of bCPAP. RESULTS: The admission records of 377 VLBW neonates < 1500 g were obtained. One hundred fifty-eight were admitted in the pre-bCPAP period and 219 in the post-bCPAP period. The mortality rate in the pre- bCPAP period was 39.2% (62/158) compared with 26.5% (58/219, P = 0.012) in the post-bCPAP period. Overall, there was a 44% reduction in mortality (OR 0.56, 95%CI 0.36-0.86, P = 0.01). There were no differences in birthweight, sex, presence of signs of respiratory distress or apnoea between the two groups. CONCLUSION: Specialized and resource-appropriate neonatal care, that appropriately addresses the challenges of healthcare provision in LICs, has the potential to reduce neonatal deaths. The use of a low-cost bCPAP to treat RDS in VLBW neonates resulted in a significant improvement in their survival in a neonatal unit in eastern Uganda. Since RDS is one of the leading causes of neonatal mortality, it is possible that this relatively simple and affordable intervention could have a huge impact on global neonatal mortality.

Preventing neonatal sepsis in rural Uganda: a cross-over study comparing the tolerance and acceptability of three alcohol-based hand rub formulations.

BACKGROUND: Neonatal sepsis causes 0.5 million deaths annually, mostly in low resource settings. Babies born in African rural homes without running water or toilet facilities are especially vulnerable. Alcohol-based hand rub (ABHR) may be used by mothers and carers as an alternative to hand washing with soap to prevent neonatal infection. However, no definite study has established the preferred formulation of hand rub for the mothers. This study aimed to assess the effects of addition of bitterants and perfume towards the acceptability of the alcohol-based hand rubs by the mothers in their homes after childbirth. METHODS: This was a 3-way blinded cross-over study design. Mothers with children aged ≤3 months were recruited from immunisation clinics at 3 local health facilities in rural eastern Uganda and received 3-different ABHR formulations (in the order plain, bitterant and perfumed) packed in 100 ml bottles. Each ABHR was used for 5 consecutive days followed by a 2-day 'washout' period (evaluation period). Overall satisfaction with each hand rub was evaluated at the end of each week using a 7-point Likert scale. RESULTS: A total of 43 women were recruited, whose ages ranged from 16 to 45 years (mean 26.2 years old). None of the participants normally used a hand protective lotion/cream. The three formulations were used for a mean of 5 (range 3-7) days. A significantly greater volume of the "bitterant" and "perfumed" formulations (mean 91 and 83 ml respectively) were used in comparison to the "plain" formulation (mean 64 ml). Overall satisfaction was high with all the hand rubs, but the perfumed formulation had a significantly higher overall satisfaction score [mean 6.7, range 4-7] compared with the plain [6.4, 3-7] and bitterant [6.2, 2-7] formulations. CONCLUSIONS: All the 3 ABHR formulations were well accepted with little to choose between them. The ABHR with added perfume scored highest on overall satisfaction and was used significantly more often than plain ABHR. ABHR with bitterant additive did, however, score highly and may be a preferable choice to those with concern over alcohol misuse. TRIAL REGISTRATION: ISRCTN67852437 , prospectively registered on 18/03/2018.

Randomised controlled trial of oxygen therapy and high-flow nasal therapy in African children with pneumonia.

PURPOSE: The life-saving role of oxygen therapy in African children with severe pneumonia is not yet established. METHODS: The open-label fractional-factorial COAST trial randomised eligible Ugandan and Kenyan children aged > 28 days with severe pneumonia and severe hypoxaemia stratum (SpO2 < 80%) to high-flow nasal therapy (HFNT) or low-flow oxygen (LFO: standard care) and hypoxaemia stratum (SpO2 80-91%) to HFNT or LFO (liberal strategies) or permissive hypoxaemia (ratio 1:1:2). Children with cyanotic heart disease, chronic lung disease or > 3 h receipt of oxygen were excluded. The primary endpoint was 48 h mortality; secondary endpoints included mortality or neurocognitive sequelae at 28 days. RESULTS: The trial was stopped early after enrolling 1852/4200 children, including 388 in the severe hypoxaemia stratum (median 7 months; median SpO2 75%) randomised to HFNT (n = 194) or LFO (n = 194) and 1454 in the hypoxaemia stratum (median 9 months; median SpO2 88%) randomised to HFNT (n = 363) vs LFO (n = 364) vs permissive hypoxaemia (n = 727). Per-protocol 15% of patients in the permissive hypoxaemia group received oxygen (when SpO2 < 80%). In the severe hypoxaemia stratum, 48-h mortality was 9.3% for HFNT vs. 13.4% for LFO groups. In the hypoxaemia stratum, 48-h mortality was 1.1% for HFNT vs. 2.5% LFO and 1.4% for permissive hypoxaemia. In the hypoxaemia stratum, adjusted odds ratio for 48-h mortality in liberal vs permissive comparison was 1.16 (0.49-2.74; p = 0.73); HFNT vs LFO comparison was 0.60 (0.33-1.06; p = 0.08). Strata-specific 28 day mortality rates were, respectively: 18.6, 23.4 and 3.3, 4.1, 3.9%. Neurocognitive sequelae were rare. CONCLUSIONS: Respiratory support with HFNT showing potential benefit should prompt further trials.

In search of a primary outcome for community-based newborn infection trials in Eastern Uganda: a nested cohort study within the BabyGel pilot trial.

BACKGROUND: Due to their immature immune system, neonates are at high risk of infection. This vulnerability when combined with limited resources and health education in developing countries can lead to sepsis, resulting in high global neonatal mortality rates. Many of these deaths are preventable. The BabyGel pilot trial tested the feasibility of conducting the main randomised trial, with the provision of alcohol handgel to postpartum mothers for prevention of neonatal infective morbidity in the rural community. This secondary analysis sought to evaluate the methods of detecting infections in babies up to 3 months of age. METHODS: The pilot two-arm cluster randomised controlled trial took place in 10 villages around Mbale, Eastern Uganda. Women were eligible and recruited antenatally if their gestation was ≥ 34 weeks. All infants of mothers participating in the BabyGel pilot trial were followed up for the first 3 months of life. Evidence for infant infection was collected using five different methods: clinician diagnosed infection, microbiologically confirmed infection, maternally reported infection, a positive infection screen using the World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) screening criteria, and reported antibiotic use identified during home and clinic visits. These methods were assessed quantitatively regarding the detection rates of suspected infections and qualitatively by exploring the challenges collecting data in the rural community setting. RESULTS: A total of 103 eligible women participated in the BabyGel pilot trial, with 1 woman delivering twins. Of the 99 mother-infant pairs who consented to participate in the study, 55 infants were identified with infection in total. Maternal report of illness provided the highest estimate, with mothers reporting suspected illness for 45 infants (81.8% of the total suspected infections identified). The WHO IMCI screening criteria identified 30 infants with suspected infection (54.5%), and evidence for antibiotic use was established in 22 infants (40%). Finally, clinician-diagnosed infection identified 19 cases (34.5%), which were also microbiologically confirmed in 5 cases (9.1%). Data collection in the rural setting was hindered by poor communication between mothers and the research team, limited staff awareness of the study in health centres resulting in reduced safeguarding of clinical notes, and widespread use of antibiotics prior to notification and clinical review. Furthermore, identification of suspected infection may not have been limited to severe infections, with ambiguity and no official clinical diagnosis being given to those identified solely by maternal report of infection. CONCLUSIONS: A high rate of suspected infection was identified spanning the five sources of data collection, but no ideal method was found for detection of community neonatal infection. Although maternal self-reports of infant infection provided the highest detection rate, data collection via each source was limited and may have identified minor rather than major infections. Future studies could utilise the IMCI screening tool to detect severe community infection leading to referral for clinical confirmation. This should be combined with weekly contact with mothers to detect maternally suspected illness. Obtaining more details of the symptoms and timescale will improve the accuracy when detecting the total burden of suspected disease, and advising participants to retain medication packaging and prescriptions will improve identification of antibiotic use. TRIAL REGISTRATION: Babygel pilot trial - trial registration: ISCRCTN 67852437. Registered 02/03/2015.

BabyGel pilot: a pilot cluster randomised trial of the provision of alcohol handgel to postpartum mothers to prevent neonatal and young infant infection-related morbidity in the community.

BACKGROUND: Alcohol-based hand rub (ABHR) is widely used in both health and social facilities to prevent infection, but it is not known whether supplying it for regular perinatal use can prevent newborn sepsis in African rural homes. Our study piloted a cluster randomised trial of providing ABHR to postpartum mothers to prevent neonatal infection-related morbidity in the communities. METHODS: We conducted a pilot parallel cluster randomised controlled trial across ten villages (clusters) in rural Eastern Uganda. Pregnant women of over 34 weeks' gestation were recruited over a period of 3 months. Both clusters received the standard of care of antenatal health education, Maama Kit, and clinic appointments. In addition, women in the intervention villages received ABHR, instructions on ABHR use, a poster on the 'three moments of hand hygiene', and training. We followed up each mother-baby pair for 3 months after birth and measured rates of consent, recruitment, and follow-up (our target rate was more than 80%). Other measures included ABHR use (the acceptable use was more than four times a day) and its mode of distribution (village health workers (VHWs) or pharmacy), acceptability of study protocol and electronic data capture, and the use of WHO Integrated Management of Childhood Illness (IMCI) tool to screen for newborn infection. RESULTS: We selected 36% (10/28) of villages for randomisation to either intervention or control. Over 12 weeks, 176 pregnant women were screened and 58.5% (103/176) were eligible. All, 100% (103/103), eligible women gave consent and were enrolled into the trial (55 intervention and 48 control). After birth, 94.5% (52/55) of mothers in the intervention and 100% (48/48) of mothers in the control villages were followed up within 72 h. Most, 90.9% (50/55), of the mothers in the intervention villages (96.2% of live births) and 95.8% (46/48) of mothers in the control villages (95.9% of live births) were followed up at 3 months. In intervention villages, the average hand rub use was 6.6 times per day. VHWs accounted for all ABHR stock, compared to the pharmacy that could not account for 5 l of ABHR. The screening tool was positive for infection among a third of babies, i.e. 29.2% (14/48) in the intervention villages versus 31.4% (16/51) in the control villages.VHWs completed the first four questions of IMCI screening tool with ease and accuracy. There were no adverse reactions with the ABHR. CONCLUSION: It is feasible to conduct a cluster-randomised controlled trial (cRCT) of the provision of ABHR to postpartum mothers to prevent neonatal infection-related morbidity in the community in resource-poor settings. Our results indicate that home recruitment promotes excellent follow-up and retention of participants in community trials. The intervention was safe. This pilot study informed the substantial changes necessary in the larger cRCT, including a change in the primary outcome to a composite outcome considering multiple methods of infection detection. A large BabyGel cluster randomised controlled trial is now required. TRIAL REGISTRATION: ISRCTN67852437, registered March 02, 2015. TRIAL FUNDING: Medical Research Council/WellcomeTrust/DfID (Global Health Trials Scheme).

Optimising informed consent for participants in a randomised controlled trial in rural Uganda: a comparative prospective cohort mixed-methods study.

BACKGROUND: Poor participant understanding of research information can be a problem in community interventional studies with rural African women, whose levels of illiteracy are high. This study aimed to improve the informed consent process for women living in rural eastern Uganda. We assessed the impact of alternative consent models on participants' understanding of clinical trial information and their contribution to the informed consent process in rural Uganda. METHODS: The study applied a parallel mixed-methods design for a prospective comparative cohort, nested within a pilot study on the community distribution of an alcohol-based hand rub to prevent neonatal sepsis (BabyGel pilot trial). Women of at least 34 weeks' pregnancy, suitable for inclusion in the BabyGel pilot trial, were recruited into this study from their homes in 13 villages in Mbale District. As part of the informed consent process, information about the trial was presented using one of three consent methods: standard researcher-read information, a slide show using illustrated text on a flip chart or a video showing the patient information being read as if by a newsreader in either English or the local language. In addition, all women received the patient information sheet in their preferred language. Each information-giving method was used in recruitment for 1 week. Two days after recruitment, women's understanding of the clinical trial was evaluated using the modified Quality of Informed Consent (QuIC) tool. They were also shown the other two methods and their preference assessed using a 5-point Likert scale. Semi-structured interviews were administered to each participant. The interviews were audio-recorded, transcribed and translated verbatim, and thematically analysed. RESULTS: A total of 30 pregnant women in their homes participated in this study. Their recall of the trial information within the planned 48 h was assessed for the majority (90%, 27/30). For all three consent models, women demonstrated a high understanding of the study. There was no statistically significant difference between the slide-show message (mean 4.7; standard deviation, SD 0.47; range 4-5), video message (mean 4.9; SD 0.33; range 4-5) and standard method (mean 4.5; SD 0.53; range 4-5; all one-way ANOVA, p = 0.190). The slide-show message resulted in the most objective understanding of question items with the highest average QuIC score of 100 points. For women who had been recruited using any of the three models, the slide show was the most popular method, with a mean score for all items of not less than 4.2 (mean 4.8; SD 0.6; range 4-5). Most women (63%, 19/30) preferred the slide-show message, compared with 17% (5/30) and 20% (6/30) for the standard and video messages, respectively. The reasons given included the benefits of having pictures to aid understanding and the logical progression of the information. CONCLUSION: Our results from this small study suggest that slide-show messages may be an effective and popular alternative way of presenting trial information to women in rural Uganda, many of whom have little or no literacy. TRIAL REGISTRATION: ISRCTN, ISRCTN67852437 . Registered on 18 March 2018.