Delayed Presentation and Mortality in Children With Sepsis in a Public Tertiary Care Hospital in Tanzania.

Background: Over 40% of the global burden of sepsis occurs in children under 5 years of age, making pediatric sepsis the top cause of death for this age group. Prior studies have shown that outcomes in children with sepsis improve by minimizing the time between symptom onset and treatment. This is a challenge in resource-limited settings where access to definitive care is limited. Methods: A secondary analysis was performed on data from 1,803 patients (28 days-14 years old) who presented to the emergency department (ED) at Muhimbili National Hospital (MNH) from July 1, 2016 to June 30, 2017 with a suspected infection and ≥2 clinical systemic inflammatory response syndrome criteria. The objective of this study was to determine the relationship between delayed presentation to definitive care (>48 h between fever onset and presentation to the ED) and mortality, as well as the association between socioeconomic status (SES) and delayed presentation. Multivariable logistic regression models tested the two relationships of interest. We report both unadjusted and adjusted odds ratios and 95% confidence intervals. Results: During the study period, 11.3% (n = 203) of children who presented to MNH with sepsis died inhospital. Delayed presentation was more common in non-survivors (n = 90/151, 60%) compared to survivors (n = 614/1,353, 45%) (p ≤ 0.01). Children who had delayed presentation to definitive care, compared to those who did not, had an adjusted odds ratio for mortality of 1.85 (95% CI: 1.17-3.00). Conclusions: Delayed presentation was an independent risk factor for mortality in this cohort, emphasizing the importance of timely presentation to care for pediatric sepsis patients. Potential interventions include more efficient referral networks and emergency transportation systems to MNH. Additional clinics or hospitals with pediatric critical care may reduce pediatric sepsis mortality in Tanzania, as well as parental education programs for recognizing pediatric sepsis.

Functional Outcomes and Morbidity in Pediatric Sepsis Survivors: A Tanzanian Experience.

Pediatric sepsis remains a significant cause of childhood morbidity and mortality, disproportionately affecting resource-limited settings. As more patients survive, it is paramount that we improve our understanding of post-sepsis morbidity and its impact on functional outcomes. The functional status scale (FSS) is a pediatric validated outcome measure quantifying functional impairment, previously demonstrating decreased function following critical illnesses, including sepsis, in resource-rich settings. However, functional outcomes utilizing the FSS in pediatric sepsis survivors have never been studied in resource-limited settings or in non-critically ill septic children. In a Tanzanian cohort of pediatric sepsis patients, we aimed to evaluate morbidity associated with an acute septic episode using the FSS modified for resource-limited settings. This was a prospective cohort study at an urban referral hospital in Tanzania, including children with sepsis aged 28 days to 14 years old over a 12-month period. The FSS was adapted to the site's available resources. Functional status scale scores were obtained by interviewing guardians both at the time of presentation to determine the child's baseline and at 28-day follow-up. The primary outcome was "decline in functional status," as defined by a change in FSS score of at least 3. In this cohort, 4.3% of the 1,359 surviving children completing 28-day follow-up had a "decline in functional status." Conversely, 13.8% of guardians reported that their child was not yet back to their pre-illness state. Three-quarters of children reported as not fully recovered were not identified via the FSS as having a decline in functional status. In our cohort of pediatric sepsis patients, we identified a low rate of decline in functional status when using the FSS adapted for resource-limited settings. A higher proportion of children were subjectively identified as not being recovered to baseline. This suggests that the FSS has limitations in this population, despite being adapted for resource-limited settings. Next steps include developing and validating a further revised FSS to better capture patients identified as not recovered but missed by the current FSS.

A 14-day follow-up of adult non-malarial fever patients seen by mobile clinics in rural Malawi.

Background: While health providers consistently use malaria rapid diagnostic tests to rule out malaria, they often lack tools to guide treatment for those febrile patients who test negative. Without the tools to provide an alternative diagnosis, providers may prescribe unnecessary antibiotics or miss a more serious condition, potentially contributing to antibiotic resistance and/or poor patient outcomes. Methods: This study ascertained which diagnoses and treatments might be associated with poor outcomes in adults who test negative for malaria. Adult patients for rapid diagnostic test of malaria seen in mobile health clinics in Mulanje and Phalombe districts were followed for 14 days. Participants were interviewed on sociodemographic characteristics, health-seeking behaviour, diagnosis, treatment and access to care. Mobile clinic medical charts were reviewed. Two weeks (±2 days) following clinic visit, follow-up interviews were conducted to assess whether symptoms had resolved. Results: Initially, 115 adult patients were enrolled and 1 (0.88%) was lost to follow-up. Of the 114 adult patients remaining in the study, 55 (48%) were seen during the dry season and 59 (52%) during the wet season. Symptoms resolved in 90 (80%) patients at the 14-day follow-up visit (n=90) with the rest (n=24) reporting no change in symptoms. None of the patients in the study died or were referred for further care. Almost all patients received some type of medication during their clinic visit (98.2%). Antibiotics were given to 38.6% of patients, and virtually all patients received pain or fever relief (96.5%). However, no anti-malarials were prescribed. Conclusions: Mobile clinics provide important health care where access to care is limited. Although rapid tests have guided appropriate treatment, challenges remain when a patient's presenting complaint is less well defined. In rural areas of southern Malawi, simple diagnostics are needed to guide treatment decisions.

Characterizing Pediatric Non-Malarial Fever and Identifying the At-Risk Child in Rural Malawi.

Objective. To characterize children with non-malarial fever at risk of nonrecovery or worsening in rural Malawi. Methods. This is a subgroup analysis of patients ≤14 years of age from a prospective cohort study in non-malarial fever subjects (temperature ≥37.5°C, or fever within 48 hours, and malaria negative) in southern Malawi cared for at a mobile clinic during the 2016 dry (August to September) or wet (November to December) season. Data collection included chart review and questionnaires; 14-day follow-up was conducted. We conducted univariate descriptive statistics on cohort characteristics, bivariate analyses to examine associations between characteristics and outcomes, and multivariate logistic regressions to explore factors associated with nonrecovery. Results. A total of 2893 patients were screened, 401 were enrolled, 286 of these were children, and 280 children completed follow-up. Eighty-seven percent reported symptom resolution, 12.9% reported no improvement, and there were no deaths or hospitalizations. No improvement was associated with dry season presentation (42.6% vs 75.0%, P < .0003), >2 days of symptoms (51.6% vs 72.2%, P = .03), and food insecurity (62.3% vs 86.1%, P = .007). Dry season subjects had a 4.35 times greater likelihood of nonimprovement (95% confidence interval [CI] = 1.96-11.11). Household food insecurity and being >2 hours from a permanent clinic were associated with no improvement (adjusted odds ratio [AOR] = 4.61, 95% CI = 1.81-14.29; and AOR = 2.38, 95% CI = 1.11-5.36, respectively). Conclusion. Outcomes were generally excellent in this rural, outpatient pediatric cohort, though risk factors for nonrecovery included food insecurity, access to a standing clinic, and seasonality. Ideally, this study will inform clinic- and policy-level changes aimed at ameliorating the modifiable risk factors in Malawi and throughout rural Africa.

Bubble continuous positive airway pressure in the treatment of severe paediatric pneumonia in Malawi: a cost-effectiveness analysis.

OBJECTIVES: Pneumonia is the largest infectious cause of death in children under 5 years globally, and limited resource settings bear an overwhelming proportion of this disease burden. Bubble continuous positive airway pressure (bCPAP), an accepted supportive therapy, is often thought of as cost-prohibitive in these settings. We hypothesise that bCPAP is a cost-effective intervention in a limited resource setting and this study aims to determine the cost-effectiveness of bCPAP, using Malawi as an example. DESIGN: Cost-effectiveness analysis. SETTING: District and central hospitals in Malawi. PARTICIPANTS: Children aged 1 month-5 years with severe pneumonia, as defined by WHO criteria. INTERVENTIONS: Using a decision tree analysis, we compared standard of care (including low-flow oxygen and antibiotics) to standard of care plus bCPAP. PRIMARY AND SECONDARY OUTCOME MEASURES: For each treatment arm, we determined the costs, clinical outcomes and averted disability-adjusted life years (DALYs). We assigned input values from a review of the literature, including applicable clinical trials, and calculated an incremental cost-effectiveness ratio (ICER). RESULTS: In the base case analysis, the cost of bCPAP per patient was $15 per day and $41 per hospitalisation, with an incremental net cost of $64 per pneumonia episode. bCPAP averts 5.0 DALYs per child treated, with an ICER of $12.88 per DALY averted compared with standard of care. In one-way sensitivity analyses, the most influential uncertainties were case fatality rates (ICER range $9-32 per DALY averted). In a multi-way sensitivity analysis, the median ICER was $12.97 per DALY averted (90% CI, $12.77 to $12.99). CONCLUSION: bCPAP is a cost-effective intervention for severe paediatric pneumonia in Malawi. These results may be used to inform policy decisions, including support for widespread use of bCPAP in similar settings.

Clinical outcomes and mortality before and after implementation of a pediatric sepsis protocol in a limited resource setting: A retrospective cohort study in Bangladesh.

BACKGROUND: Pediatric sepsis has a high mortality rate in limited resource settings. Sepsis protocols have been shown to be a cost-effective strategy to improve morbidity and mortality in a variety of populations and settings. At Dhaka Hospital in Bangladesh, mortality from pediatric sepsis in high-risk children previously approached 60%, which prompted the implementation of an evidenced-based protocol in 2010. The clinical effectiveness of this protocol had not been measured. We hypothesized that implementation of a pediatric sepsis protocol improved clinical outcomes, including reducing mortality and length of hospital stay. MATERIALS AND METHODS: This was a retrospective cohort study of children 1-59 months old with a diagnosis of sepsis, severe sepsis or septic shock admitted to Dhaka Hospital from 10/25/2009-10/25/2011. The primary outcome was inpatient mortality pre- and post-protocol implementation. Secondary outcomes included fluid overload, heart failure, respiratory insufficiency, length of hospital stay, and protocol compliance, as measured by antibiotic and fluid bolus administration within 60 minutes of hospital presentation. RESULTS: 404 patients were identified by a key-word search of the electronic medical record; 328 patients with a primary diagnosis of sepsis, severe sepsis, or septic shock were included (143 pre- and185 post-protocol) in the analysis. Pre- and post-protocol mortality were similar and not statistically significant (32.17% vs. 34.59%, p = 0.72). The adjusted odds ratio (AOR) for post-protocol mortality was 1.55 (95% CI, 0.88-2.71). The odds for developing fluid overload were significantly higher post-protocol (AOR 3.45, 95% CI, 2.04-5.85), as were the odds of developing heart failure (AOR 4.52, 95% CI, 1.43-14.29) and having a longer median length of stay (AOR 1.81, 95% CI 1.10-2.96). There was no statistically significant difference in respiratory insufficiency (pre- 65.7% vs. post- 70.3%, p = 0.4) or antibiotic administration between the cohorts (pre- 16.08% vs. post- 12.43%, p = 0.42). CONCLUSIONS: Implementation of a pediatric sepsis protocol did not improve all-cause mortality or length of stay and may have been associated with increased fluid overload and heart failure during the study period in a large, non-governmental hospital in Bangladesh. Similar rates of early antibiotic administration may indicate poor protocol compliance. Though evidenced-based protocols are a potential cost-effective strategy to improve outcomes, future studies should focus on optimal implementation of context-relevant sepsis protocols in limited resource settings.

Challenges and Priorities for Pediatric Critical Care Clinician-Researchers in Low- and Middle-Income Countries.

INTRODUCTION: There is need for more data on critical care outcomes and interventions from low- and middle-income countries (LMIC). Global research collaborations could help improve health-care delivery for critically ill children in LMIC where child mortality rates remain high. MATERIALS AND METHODS: To inform the role of collaborative research in health-care delivery for critically ill children in LMIC, an anonymous online survey of pediatric critical care (PCC) physicians from LMIC was conducted to assess priorities, major challenges, and potential solutions to PCC research. A convenience sample of 56 clinician-researchers taking care of critically ill children in LMIC was targeted. In addition, the survey was made available on a Latin American PCC website. Descriptive statistics were used for data analysis. RESULTS: The majority of the 47 survey respondents worked at urban, public teaching hospitals in LMIC. Respondents stated their primary PCC research motivations were to improve clinical care and establish guidelines to standardize care. Top challenges to conducting research were lack of funding, high clinical workload, and limited research support staff. Respondent-proposed solutions to these challenges included increasing research funding options for LMIC, better access to mentors from high-income countries, research training and networks, and higher quality medical record documentation. CONCLUSION: LMIC clinician-researchers must be better empowered and resourced to lead and influence the local and global health research agenda for critically ill children. Increased funding options, access to training and mentorship in research methodology, and improved data collection systems for LMIC PCC researchers were recognized as key needs for success.

Clinical Presentation and Outcomes among Children with Sepsis Presenting to a Public Tertiary Hospital in Tanzania.

BACKGROUND: Pediatric sepsis causes significant global morbidity and mortality and low- and middle-income countries (LMICs) bear the bulk of the burden. International sepsis guidelines may not be relevant in LMICs, especially in sub-Saharan Africa (SSA), due to resource constraints and population differences. There is a critical lack of pediatric sepsis data from SSA, without which accurate risk stratification tools and context-appropriate, evidence-based protocols cannot be developed. The study's objectives were to characterize pediatric sepsis presentations, interventions, and outcomes in a public Emergency Medicine Department (EMD) in Tanzania. METHODS: Prospective descriptive study of children (28 days to 14 years) with sepsis [suspected infection with ≥2 clinical systemic inflammatory response syndrome (SIRS) criteria] presenting to a tertiary EMD in Dar es Salaam, Tanzania (July 1 to September 30, 2016). Outcomes included: in-hospital mortality (primary), EMD mortality, and hospital length of stay. We report descriptive statistics using means and SDs, medians and interquartile ranges, and counts and percentages as appropriate. Predictive abilities of SIRS criteria, the Alert-Verbal-Painful-Unresponsive (AVPU) score and the Lambaréné Organ Dysfunction Score (LODS) for in-hospital, early and late mortality were tested. RESULTS: Of the 2,232 children screened, 433 (19.4%) met inclusion criteria, and 405 were enrolled. There were 247 (61%) subjects referred from an outside facility. Approximately half (54.1%) received antibiotics in the EMD, and some form of microbiologic culture was collected in 35.8% (n = 145) of subjects. In-hospital and EMD mortality were 14.2 and 1.5%, respectively, median time to death was 3 days (IQR 1-6), and median length of stay was 6 days (IQR 1-12). SIRS criteria, the AVPU score, and the LODS had low positive (17-27.1, 33.3-43.9, 18.3-55.6%, respectively) and high negative predictive values (88.6-89.8, 86.5-91.2, 86.8-90.5%, respectively) for in-hospital mortality. CONCLUSION: This pediatric sepsis cohort had high and early in-hospital mortality. Current criteria and tested clinical scores were inadequate for risk-stratification and mortality prediction in this population and setting. Pediatric sepsis management must take into account the local patient population, etiologies of sepsis, healthcare system, and resource availability. Only through studies such as this that generate regional data in LMICs can accurate risk stratification tools and context-appropriate, evidence-based guidelines be developed.