Reproductive Concerns and Associated Factors Among Adolescent and Young Adult Cancer Survivors in Uganda: A Hospital-Based Cross-Sectional Study.

Purpose: Reproductive health (RH) is a critical issue among cancer survivors worldwide. However, in developing countries where RH services for patients with cancer are often lacking, reproductive concerns among adolescent and young adult (AYA) survivors remain uncertain. In this study, we assessed the reproductive concerns of AYA cancer survivors in a resource-limited context of Uganda. Methods: We collected data from AYA cancer survivors at two facilities in Uganda using an interviewer-administered questionnaire. Descriptive statistics were calculated, one-way analysis of variance was used for intergroup comparisons, and multiple regressions were used to test for predictors of reproductive concerns. Results: A total of 110 AYA cancer survivors, with a median age of 20 years (interquartile range [IQR], 18-22), were interviewed. More than half (53.6%) of the respondents were males. The median time since cancer diagnosis was 19 months (IQR, 13.0-35.0). Almost all (91.8%) respondents had a future desire to have children, but only 15.5% received reproductive counseling. The mean total score for the reproductive concern subscales was highest for the fertility concern, followed by the information-seeking and health-related concerns. Reproductive counseling, desire to have children, and respondents' age were the factors influencing reproductive concern. Conclusions: The study shows a strong desire for biological parenthood with very low reproductive counseling among AYA cancer survivors, who remain concerned about their fertility, information needs, and health. This outcome underscores the need to integrate RH services into resource-limited cancer care settings.

Utilization of antiretroviral therapy services and associated factors among adolescents living with HIV in northern Uganda: A cross-sectional study.

BACKGROUND: Suboptimal utilization of antiretroviral therapy (ART) services remains a problem among adolescents in low- and middle-income countries, which has a negative impact on their response to treatment and increases the risk of developing resistance. Optimal use is essential to enhancing treatment efficacy. We investigated the optimal use of ART service and predictors among adolescents living with HIV (ALHIV) in northern Uganda. METHODS: We used a cross-sectional study design to collect quantitative data from 293 ALHIV at three health facilities in Lira municipality, northern Uganda. We used an interviewer-administered questionnaire and data abstraction form. Data were analysed using SPSS version 23 software. Descriptive analysis and logistic regressions were performed to determine the relationship between the predictor and outcome variables. Statistical significance was determined at P-value<0.05 and the adjusted odds ratio with a 95% confidence interval was used. RESULTS: The level of utilization of ART services was suboptimal among 27.6% (81/293) of the participants, and only 63.1% (185/293) were virally suppressed. Of the participants who were optimally utilizing ART services, the majority 86.8% (184/212) were virally suppressed. Age 10-14 years (aOR = 3.34), the presence of both parents (aOR = 1.85), parental and peer reminders (aOR = 2.91) and (aOR = 0.49) respectively, and being on ART for five years or less were the characteristics related with optimal utilization of ART services. CONCLUSIONS AND RECOMMENDATIONS: Not all ALHIV used ART services to their full potential. However, factors such as participants' age, the presence of both parents, reminders from parents and peers, and being on ART for some time were all related to the optimal use of ART services. There is a need for developing strategies to increase family and peer support with a focus on older adolescents if the 95-95-95 goal is to be achieved in this age group.

Anti-malarial drug use, appropriateness and associated factors among children under-five with febrile illnesses presenting to a tertiary health facility: a cross sectional study.

BACKGROUND: Malaria is endemic in 95% of Uganda and constitutes the country's most significant public health problem-being the leading cause of morbidity and mortality, especially among children under five years of age. The current national malaria treatment policy is to use artemisinin-based combination therapy (ACT) as first-line treatment, and recommends parasitological confirmation of malaria before therapy. Adherence to this policy, however, remains suboptimal, with the self-initiated home-based therapy being common-posing undue exposures to, and pressure on the current artemisinin-based combinations, with the danger of emergence of drug resistance. The study evaluated the anti-malarial use and its appropriateness among febrile children under five presenting to a tertiary health facility in northern Uganda in light of the current malaria treatment policy. METHODS: This was a cross-sectional study in a tertiary health facility in northern Uganda between March and September 2021. Children aged 6-59 months with fever were selected using systematic random sampling. A pretested interviewer-administered questionnaire was used to collect clinical data from the caregivers. Data were analysed using SPSS version 23. Descriptive statistics and multiple logistic regression models were applied. P-value < 0.05 was considered for statistical significance. RESULTS: Seventy-two (34.3%) of the 210 children with fever in this study used anti-malarials prior to the hospital visit, 29.2% (21/72) of which were on a self-medication basis, 22.2% (16/72) were empiric prescriptions-all of which inappropriate, and only 48.6% (35/72) were prescribed based on a parasitological diagnosis of malaria. The most commonly used anti-malarials were artemether-lumefantrine 60/72 (88.3%), while a lesser proportion of quinine 7/72 (9.7%), artesunate 3/72 (4.2%) and dihydroartemisinin-piperaquine 2/72 (2.8%) were used. The factors independently associated with anti-malarial use among the children with febrile illnesses were duration of fever (p = 0.001); level of the nearest facility (p = 0.027), distance from the nearest health facility (p = 0.025), and caregivers' age (p = 0.038). CONCLUSIONS: Inappropriate use of anti-malarials for childhood febrile illnesses is prevalent in the study setting, facilitated by the ease of over-the-counter access, empiric prescription and use of leftover anti-malarials. This calls for a need to address communities' health-seeking behaviour and the health providers' practice alike.

The clinicopathological profile and value of multidisciplinary management of pediatric brain tumors in a low-income setting.

Brain tumors are the most common solid tumors in children and a leading cause of cancer-related mortality in children worldwide. Data on the epidemiology and management of pediatric brain tumors in Uganda are limited. We aimed to assess the clinicopathological profile and management of pediatric brain tumors at the national oncology center in Uganda since the inception of weekly multidisciplinary meetings. Records of children younger than19 years diagnosed with primary brain tumors at Uganda Cancer Institute between 2017 and 2021 were retrospectively reviewed. Patient and tumor characteristics were collected with multidisciplinary team management treatment plans for analysis. There were 35 patients evaluated, most of whom were males (57.1%). Craniopharyngioma (n = 9, 25.7%) was the most common brain tumor, followed by astrocytoma (n = 5, 14.2%) and medulloblastoma (n = 4, 11.4%). Management included surgical resection in 28.5% of patients, chemotherapy (28.6%), radiotherapy (17.1%) and palliative care (20.0%). Over the last five years, there were increasing trends in the number of cases discussed in the multidisciplinary team and the number for whom the multidisciplinary management decisions were implemented. The majority (n = 18, 51.4%) of the children with brain tumors were alive and active in care, 34.2% abandoned treatment/lost to follow-up, and 8.6% died. The relative distribution of pediatric brain tumors types in Uganda Cancer Institute differs slightly from international reports, and there has been a notable increase in the number of cases over the years. Implementing multidisciplinary management decisions benefited patients and decreased abandonment and patient loss to follow-up.

Multidisciplinary team management for pediatric neuro-oncology is a sustainable resource for improved patient care and outcome in resource-limited settings.Pediatric neuro-oncology patients have lower rates of treatment abandonment and loss to follow-up when managed according to multidisciplinary team meetings.

Oral-visceral iatrogenic Kaposi sarcoma following treatment for acute lymphoblastic leukemia: a case report and review of the literature.

BACKGROUND: There have hardly been any reported cases of children presenting with Kaposi sarcoma as a second malignancy following treatment for acute lymphoblastic leukemia outside a transplant setting. CASE PRESENTATION: We report a case of a 5-year-old boy of Bantu origin, which, to our knowledge, could be only the second reported case of oral-visceral Kaposi sarcoma after acute lymphoblastic leukemia treatment. The patient presented with a 1-month history of progressive, non-painful, soft tissue oral mass, 1 month after completing treatment for high-risk acute lymphoblastic leukemia. He was successfully treated for Kaposi sarcoma on a two-drug regimen (bleomycin and vincristine) with good clinical response. CONCLUSION: Visceral Kaposi sarcoma as a second malignancy may occur after pediatric acute lymphoblastic leukemia treatment, but its rarity makes it unlikely to raise suspicion among clinicians, thus precluding early diagnosis and treatment. We recommend routine evaluation for Kaposi sarcoma lesions in children undergoing long-term surveillance following treatment for childhood acute leukemia.

Pre-hospital exposures to antibiotics among children presenting with fever in northern Uganda: a facility-based cross-sectional study.

BACKGROUND: The rise in the indiscriminate use of antibiotics has become a major global public health problem and presents the biggest global health challenge in the twenty-first century. In developing countries, caregivers initiate treatment with antibiotics at home before presentation to a health facility. However, there is a paucity of evolving data towards surveillance of this trend in low-income countries. We investigated antibiotic use among febrile children presenting to a tertiary health facility in northern Uganda. METHODS: We conducted a cross-sectional study in a tertiary health facility in northern Uganda between March and September 2021. Children aged 6-59 months with fever were selected using systematic random sampling. A pre-tested interviewer-administered questionnaire was used the collect clinical data from the caregivers. Data were analyzed using SPSS version 23. Descriptive statistics and multiple logistic regression models were applied. P-value < 0.05 was considered for statistical significance. RESULTS: Eighty-three (39.5%) of the 210 children with fever in this study used antibiotics prior to the hospital visit, 55.4% of which were on a self-medication basis, while 44.6% were empiric prescriptions. The most commonly used antibiotics were amoxicillin 33/83 (39.8%), erythromycin 18 (21.7%), metronidazole 14 (16.9%), ciprofloxacin 13 (15.7%) and ampicillin 6 (7.2%). The main sources of the antibiotics included buying from drug shops 30/83 (36.1%), issuance from clinics (33.7%), remnants at home (12.0%), picking from a neighbour (7.2%) and others (10.8%). The factors associated with antibiotic use among the febrile children were residence (p < 0.001); distance from the nearest health facility (p = 0.005); caregivers' gender (p = 0.043); cough (p = 0.012); diarrhoea (p = 0.007); duration of fever (p = 0.002); perceived convulsion complicating fever (p = 0.026), and caregivers' perception that fever (p = 0.001), cough (p = 0.003), diarrhoea (p < 0.001) and any infection (p < 0.001) are indications for antibiotics. CONCLUSIONS: Inappropriate use of antibiotics for childhood febrile illnesses is prevalent in the study setting, facilitated by the ease of access and use of leftover antibiotics. There is a need to address communities' health-seeking behaviour and the health providers' practice alike.

Care Burden and Coping Strategies among Caregivers of Paediatric HIV/AIDS in Northern Uganda: A Cross-Sectional Mixed-Method Study.

BACKGROUND: Family caregivers provide the bulk of care to children living with HIV. This places an enormous demand and care burden on the caregivers who often struggle to cope in various ways, some of which may be maladaptive. This may adversely affect their quality of care. Very little literature exists in resource-limited contexts on the burden of care experienced by caregivers on whom children living with HIV/AIDS depend for their long-term care. We assessed care burden and coping strategies among the caregivers of paediatric HIV/AIDS patients in Lira district, northern Uganda. METHODS: A mixed-method cross-sectional study was conducted among 113 caregivers of paediatric HIV patients attending the ART clinic at a tertiary healthcare facility in Lira district, northern Uganda. A consecutive sampling method was used to select participants for the quantitative study, while 15 respondents were purposively sampled for the qualitative data. Quantitative data were collected using standard interviewer-administered questionnaires, while in-depth interview guides were used to collect qualitative data. Data were entered, cleaned, and analysed using SPSS version 23. Qualitative data were analysed thematically. RESULTS: The majority of the caregivers, 65.5% (74), experienced mild-to-moderate burden. The mean burden scores significantly differed by caregivers' age (P=0.017), marital status (P=0.017), average monthly income (P=0.035), and child's school attendance (P=0.039). Accepting social support, seeking spiritual support, and reframing were the three most commonly used strategies for coping. Marital status and occupation were, respectively, positively and negatively correlated with information-seeking as a coping strategy, while monthly income was positively correlated with psychosocial support as a strategy. Seeking community support was negatively correlated with the duration of the child's care. CONCLUSIONS: Our findings show that care burden is a common problem among the caregivers of children living with HIV in the study context.

HIV-free survival among breastfed infants born to HIV-positive women in northern Uganda: a facility-based retrospective study.

INTRODUCTION: the HIV-free survival rate is the gold-standard measure of the effectiveness of interventions towards prevention of mother-to-child transmission of HIV in any setting. However, data on HIV-free survival among the HIV-exposed infants followed up in most low-resource settings are lacking. We determined the HIV-free survival among breastfed infants in two tertiary facilities in a resource-poor setting in northern Uganda. METHODS: we conducted a retrospective cohort study in May 2019 and retrospectively reviewed records of HIV-exposed infants registered in 2014 through 2016 at two tertiary facilities in northern Uganda. We analyzed data using SPSS v16 software package. The chi-square and Student t-tests were used to compare factors among infant groups. Multivariate logistic regression analysis was used to determine factors independently associated with HIV-free survival. P-value <0.05 was considered for statistical significance. RESULTS: majority of the infants were males 55.6% (203/365) and 98.6% (360/365) received nevirapine prophylaxis. A total of 345 (94.5%) infants were exclusively breastfed, only 100/345 (29.0%) of whom were exclusively breastfed for at least 6 months, while the breastfeeding status of 44/345 (12.8 %) infants could not be ascertained. The overall HIV-free survival rate was 93.7% (342/365), while 2.7% (10/365) were HIV-infected and 3.6% (13/365) died. Infants´ age at enrolment in care (aOR 5.20, p=0.008) and treatment facility (aOR 3.76, p=0.027) were the independent determinants of HIV-free survival. CONCLUSION: the HIV-free survival rate among the breastfed infants in the study setting marginally falls short of the recommended standard, thus calling for more efforts to improve survival.

Mortality risk over time after early fluid resuscitation in African children.

BACKGROUND: African children hospitalised with severe febrile illness have a high risk of mortality. The Fluid Expansion As Supportive Therapy (FEAST) trial (ISCRTN 69856593) demonstrated increased mortality risk associated with fluid boluses, but the temporal relationship to bolus therapy and underlying mechanism remains unclear. METHODS: In a post hoc retrospective analysis, flexible parametric models were used to compare change in mortality risk post-randomisation in children allocated to bolus therapy with 20-40 ml/kg 5% albumin or 0.9% saline over 1-2 h or no bolus (control, 4 ml/kg/hour maintenance), overall and for different terminal clinical events (cardiogenic, neurological, respiratory, or unknown/other). RESULTS: Two thousand ninety-seven and 1041 children were randomised to bolus vs no bolus, of whom 254 (12%) and 91 (9%) respectively died within 28 days. Median (IQR) bolus fluid in the bolus groups received by 4 h was 20 (20, 40) ml/kg and was the same at 8 h; total fluids received in bolus groups at 4 h and 8 h were 38 (28, 43) ml/kg and 40 (30, 50) ml/kg, respectively. Total fluid volumes received in the control group by 4 h and 8 h were median (IQR) 10 (6, 15) ml/kg and 10 (10, 26) ml/kg, respectively. Mortality risk was greatest 30 min post-randomisation in both groups, declining sharply to 4 h and then more slowly to 28 days. Maximum mortality risk was similar in bolus and no bolus groups; however, the risk declined more slowly in the bolus group, with significantly higher mortality risk compared to the no bolus group from 1.6 to 101 h (4 days) post-randomisation. The delay in decline in mortality risk in the bolus groups was most pronounced for cardiogenic modes of death. CONCLUSIONS: The increased risk from bolus therapy was not due to a mechanism occurring immediately after bolus administration. Excess mortality risk in the bolus group resulted from slower decrease in mortality risk over the ensuing 4 days. Thus, administration of modest bolus volumes appeared to prevent mortality risk declining at the same rate that it would have done without a bolus, rather than harm associated with bolus resulting from a concurrent increased risk of death peri-bolus administration. TRIAL REGISTRATION: ISRCTN69856593. Date of registration 15 December 2008.

Lactate clearance as a prognostic marker of mortality in severely ill febrile children in East Africa.

BACKGROUND: Hyperlactataemia (HL) is a biomarker of disease severity that predicts mortality in patients with sepsis and malaria. Lactate clearance (LC) during resuscitation has been shown to be a prognostic factor of survival in critically ill adults, but little data exist for African children living in malaria-endemic areas. METHODS: In a secondary data analysis of severely ill febrile children included in the Fluid Expansion as Supportive Therapy (FEAST) resuscitation trial, we assessed the association between lactate levels at admission and LC at 8 h with all-cause mortality at 72 h (d72). LC was defined as a relative lactate decline ≥ 40% and/or lactate normalisation (lactate < 2.5 mmol/L). RESULTS: Of 3170 children in the FEAST trial, including 1719 children (57%) with Plasmodium falciparum malaria, 3008 (95%) had a baseline lactate measurement, 2127 (71%) had HL (lactate ≥ 2.5 mmol/L), and 1179 (39%) had severe HL (≥ 5 mmol/L). Within 72 h, 309 children (10.3%) died, of whom 284 (92%) had baseline HL. After adjustment for potential confounders, severe HL was strongly associated with mortality (Odds Ratio (OR) 6.96; 95% CI 3.52, 13.76, p < 0.001). This association was not modified by malaria status, despite children with malaria having a higher baseline lactate (median 4.6 mmol/L vs 3 mmol/L; p < 0.001) and a lower mortality rate (OR = 0.42; p < 0.001) compared to non-malarial cases. Sensitivity and specificity analysis identified a higher lactate on admission cut-off value predictive of d72 for children with malaria (5.2 mmol/L) than for those with other febrile illnesses (3.4 mmol/L). At 8 h, 2748/3008 survivors (91%) had a lactate measured, 1906 (63%) of whom had HL on admission, of whom 1014 (53%) fulfilled pre-defined LC criteria. After adjustment for confounders, LC independently predicted survival after 8 h (OR 0.24; 95% CI 0.14, 0.42; p < 0.001). Absence of LC (< 10%) at 8 h was strongly associated with death at 72 h (OR 4.62; 95% CI 2.7, 8.0; p < 0.001). CONCLUSIONS: Independently of the underlying diagnosis, HL is a strong risk factor for death at 72 h in children admitted with severe febrile illnesses in Africa. Children able to clear lactate within 8 h had an improved chance of survival. These findings prompt the more widespread use of lactate and LC to identify children with severe disease and monitor response to treatment. TRIAL REGISTRATION: ISRCTN69856593 Registered 21 January 2009.

High Frequency of Blackwater Fever Among Children Presenting to Hospital With Severe Febrile Illnesses in Eastern Uganda.

BACKGROUND: In the Fluid Expansion as a Supportive Treatment (FEAST) trial, an unexpectedly high proportion of participants from eastern Uganda presented with blackwater fever (BWF). METHODS: We describe the prevalence and outcome of BWF among trial participants and compare the prevalence of 3 malaria-protective red blood cell polymorphisms in BWF cases vs both trial (non-BWF) and population controls. RESULTS: Of 3170 trial participants, 394 (12.4%) had BWF. The majority (318 [81.0%]) presented in eastern Uganda and were the subjects of further analysis. BWF cases typically presented with both clinical jaundice (254/318 [80%]) and severe anemia (hemoglobin level <5 g/dL) (238/310 [77%]). Plasmodium falciparum parasitemia was less frequent than in non-BWF controls, but a higher proportion were positive for P. falciparum histidine rich protein 2 (192/246 [78.0%]) vs 811/1154 [70.3%]; P = .014), suggesting recent antimalarial treatment. Overall, 282 of 318 (88.7%) received transfusions, with 94 of 282 (33.3%) and 9 of 282 (3.4%) receiving 2 or 3 transfusions, respectively. By day 28, 39 of 318 (12.3%) BWF cases and 154 of 1554 (9.9%) non-BWF controls had died (P = .21), and 7 of 255 (3.0%) vs 13/1212 (1%), respectively, had severe anemia (P = .036). We found no association with G6PD deficiency. The prevalence of both the sickle cell trait (10/218 [4.6%]) and homozygous α+thalassemia (8/216 [3.7%]) were significantly lower among cases than among population controls (334/2123 [15.7%] and 141/2114 [6.6%], respectively), providing further support for the role of malaria. CONCLUSIONS: We report the emergence of BWF in eastern Uganda, a condition that, according to local investigators, was rare until the last 7 years. We speculate that this might relate to the introduction of artemisinin-based combination therapies. Further studies investigating this possibility are urgently required.

Prevalence and factors associated with use of herbal medicines during pregnancy among women attending postnatal clinics in Gulu district, Northern Uganda.

BACKGROUND: According to World Health Organization (WHO) estimates, 80 % of the population living in rural areas in developing countries depends on traditional medicine for their health needs, including use during pregnancy. Despite the fact that knowledge of potential side effects of many herbal medicines in pregnancy is limited and that some herbal products may be teratogenic, data on the extent of use of herbal medicines by women during pregnancy in the study setting is largely unknown. We determined the prevalence and factors associated with herbal medicine use during pregnancy among women attending postnatal clinics in Gulu district, Northern Uganda. METHODS: This was a descriptive cross-sectional study which involved 383 women attending postnatal care across four sites in Gulu district using quantitative and qualitative methods of data collection. A structured questionnaire was used to collect quantitative data while qualitative data were obtained using focus group discussions and key informant interviews. The selection of the study participants was by systematic sampling and the main outcome variable was the proportion of mothers who used herbal medicine. Quantitative data was coded and entered into a computerized database using Epidata 3.1. Analysis was done using Statistical Package for Social Scientists version 13, while thematic analysis was used for qualitative data. RESULTS: The prevalence of herbal medicines use during the current pregnancy was 20 % (78/383), and was commonly used in the second 23 % (18/78) and third 21 % (16/78) trimesters. The factors significantly associated with use of herbal medicines during pregnancy were perception (OR 2.18, CI 1.02-4.66), and having ever used herbal medicines during previous pregnancy (OR 2.51, CI 1.21-5.19) and for other reasons (OR 3.87, CI 1.46-10.25). CONCLUSIONS: The use of herbal medicines during pregnancy among women in Gulu district is common, which may be an indicator for poor access to conventional western healthcare. Perception that herbal medicines are effective and having ever used herbal medicines during previous pregnancy were associated with use of herbal medicines during current pregnancy. This therefore calls for community sensitization drives on the dangers of indiscriminate use of herbal medicine in pregnancy, as well as integration of trained traditional herbalists and all those community persons who influence the process in addressing the varied health needs of pregnant women.

Predicting mortality in sick African children: the FEAST Paediatric Emergency Triage (PET) Score.

BACKGROUND: Mortality in paediatric emergency care units in Africa often occurs within the first 24 h of admission and remains high. Alongside effective triage systems, a practical clinical bedside risk score to identify those at greatest risk could contribute to reducing mortality. METHODS: Data collected during the Fluid As Expansive Supportive Therapy (FEAST) trial, a multi-centre trial involving 3,170 severely ill African children, were analysed to identify clinical and laboratory prognostic factors for mortality. Multivariable Cox regression was used to build a model in this derivation dataset based on clinical parameters that could be quickly and easily assessed at the bedside. A score developed from the model coefficients was externally validated in two admissions datasets from Kilifi District Hospital, Kenya, and compared to published risk scores using Area Under the Receiver Operating Curve (AUROC) and Hosmer-Lemeshow tests. The Net Reclassification Index (NRI) was used to identify additional laboratory prognostic factors. RESULTS: A risk score using 8 clinical variables (temperature, heart rate, capillary refill time, conscious level, severe pallor, respiratory distress, lung crepitations, and weak pulse volume) was developed. The score ranged from 0-10 and had an AUROC of 0.82 (95 % CI, 0.77-0.87) in the FEAST trial derivation set. In the independent validation datasets, the score had an AUROC of 0.77 (95 % CI, 0.72-0.82) amongst admissions to a paediatric high dependency ward and 0.86 (95 % CI, 0.82-0.89) amongst general paediatric admissions. This discriminative ability was similar to, or better than other risk scores in the validation datasets. NRI identified lactate, blood urea nitrogen, and pH to be important prognostic laboratory variables that could add information to the clinical score. CONCLUSIONS: Eight clinical prognostic factors that could be rapidly assessed by healthcare staff for triage were combined to create the FEAST Paediatric Emergency Triage (PET) score and externally validated. The score discriminated those at highest risk of fatal outcome at the point of hospital admission and compared well to other published risk scores. Further laboratory tests were also identified as prognostic factors which could be added if resources were available or as indices of severity for comparison between centres in future research studies.

Anaemia and blood transfusion in African children presenting to hospital with severe febrile illness.

BACKGROUND: Severe anaemia in children is a leading cause of hospital admission and a major cause of mortality in sub-Saharan Africa, yet there are limited published data on blood transfusion in this vulnerable group. METHODS: We present data from a large controlled trial of fluid resuscitation (Fluid Expansion As Supportive Therapy (FEAST) trial) on the prevalence, clinical features, and transfusion management of anaemia in children presenting to hospitals in three East African countries with serious febrile illness (predominantly malaria and/or sepsis) and impaired peripheral perfusion. RESULTS: Of 3,170 children in the FEAST trial, 3,082 (97%) had baseline haemoglobin (Hb) measurement, 2,346/3,082 (76%) were anaemic (Hb <10 g/dL), and 33% severely anaemic (Hb <5 g/dL). Prevalence of severe anaemia varied from 12% in Kenya to 41% in eastern Uganda. 1,387/3,082 (45%) children were transfused (81% within 8 hours). Adherence to WHO transfusion guidelines was poor. Among severely anaemic children who were not transfused, 52% (54/103) died within 8 hours, and 90% of these deaths occurred within 2.5 hours of randomisation. By 24 hours, 128/1,002 (13%) severely anaemic children had died, compared to 36/501 (7%) and 71/843 (8%) of those with moderate and mild anaemia, respectively. Among children without severe hypotension who were randomised to receive fluid boluses of 0.9% saline or albumin, mortality was increased (10.6% and 10.5%, respectively) compared to controls (7.2%), regardless of admission Hb level. Repeat transfusion varied from ≤2% in Kenya/Tanzania to 6 to 13% at the four Ugandan centres. Adverse reactions to blood were rare (0.4%). CONCLUSIONS: Severe anaemia complicates one third of childhood admissions with serious febrile illness to hospitals in East Africa, and is associated with increased mortality. A high proportion of deaths occurred within 2.5 hours of admission, emphasizing the need for rapid recognition and prompt blood transfusion. Adherence to current WHO transfusion guidelines was poor. The high rates of re-transfusion suggest that 20 mL/kg whole blood or 10 mL/kg packed cells may undertreat a significant proportion of anaemic children. Future evaluation of the impact of a larger volume of transfused blood and optimum transfusion management of children with Hb of <6 g/dL is warranted.

Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial.

BACKGROUND: Early rapid fluid resuscitation (boluses) in African children with severe febrile illnesses increases the 48-hour mortality by 3.3% compared with controls (no bolus). We explored the effect of boluses on 48-hour all-cause mortality by clinical presentation at enrolment, hemodynamic changes over the first hour, and on different modes of death, according to terminal clinical events. We hypothesize that boluses may cause excess deaths from neurological or respiratory events relating to fluid overload. METHODS: Pre-defined presentation syndromes (PS; severe acidosis or severe shock, respiratory, neurological) and predominant terminal clinical events (cardiovascular collapse, respiratory, neurological) were described by randomized arm (bolus versus control) in 3,141 severely ill febrile children with shock enrolled in the Fluid Expansion as Supportive Therapy (FEAST) trial. Landmark analyses were used to compare early mortality in treatment groups, conditional on changes in shock and hypoxia parameters. Competing risks methods were used to estimate cumulative incidence curves and sub-hazard ratios to compare treatment groups in terms of terminal clinical events. RESULTS: Of 2,396 out of 3,141 (76%) classifiable participants, 1,647 (69%) had a severe metabolic acidosis or severe shock PS, 625 (26%) had a respiratory PS and 976 (41%) had a neurological PS, either alone or in combination. Mortality was greatest among children fulfilling criteria for all three PS (28% bolus, 21% control) and lowest for lone respiratory (2% bolus, 5% control) or neurological (3% bolus, 0% control) presentations. Excess mortality in bolus arms versus control was apparent for all three PS, including all their component features. By one hour, shock had resolved (responders) more frequently in bolus versus control groups (43% versus 32%, P <0.001), but excess mortality with boluses was evident in responders (relative risk 1.98, 95% confidence interval 0.94 to 4.17, P = 0.06) and 'non-responders' (relative risk 1.67, 95% confidence interval 1.23 to 2.28, P = 0.001), with no evidence of heterogeneity (P = 0.68). The major difference between bolus and control arms was the higher proportion of cardiogenic or shock terminal clinical events in bolus arms (n = 123; 4.6% versus 2.6%, P = 0.008) rather than respiratory (n = 61; 2.2% versus 1.3%, P = 0.09) or neurological (n = 63, 2.1% versus 1.8%, P = 0.6) terminal clinical events. CONCLUSIONS: Excess mortality from boluses occurred in all subgroups of children. Contrary to expectation, cardiovascular collapse rather than fluid overload appeared to contribute most to excess deaths with rapid fluid resuscitation. These results should prompt a re-evaluation of evidence on fluid resuscitation for shock and a re-appraisal of the rate, composition and volume of resuscitation fluids. TRIAL REGISTRATION: ISRCTN69856593.

Mortality after fluid bolus in African children with severe infection.

BACKGROUND: The role of fluid resuscitation in the treatment of children with shock and life-threatening infections who live in resource-limited settings is not established. METHODS: We randomly assigned children with severe febrile illness and impaired perfusion to receive boluses of 20 to 40 ml of 5% albumin solution (albumin-bolus group) or 0.9% saline solution (saline-bolus group) per kilogram of body weight or no bolus (control group) at the time of admission to a hospital in Uganda, Kenya, or Tanzania (stratum A); children with severe hypotension were randomly assigned to one of the bolus groups only (stratum B). All children received appropriate antimicrobial treatment, intravenous maintenance fluids, and supportive care, according to guidelines. Children with malnutrition or gastroenteritis were excluded. The primary end point was 48-hour mortality; secondary end points included pulmonary edema, increased intracranial pressure, and mortality or neurologic sequelae at 4 weeks. RESULTS: The data and safety monitoring committee recommended halting recruitment after 3141 of the projected 3600 children in stratum A were enrolled. Malaria status (57% overall) and clinical severity were similar across groups. The 48-hour mortality was 10.6% (111 of 1050 children), 10.5% (110 of 1047 children), and 7.3% (76 of 1044 children) in the albumin-bolus, saline-bolus, and control groups, respectively (relative risk for saline bolus vs. control, 1.44; 95% confidence interval [CI], 1.09 to 1.90; P=0.01; relative risk for albumin bolus vs. saline bolus, 1.01; 95% CI, 0.78 to 1.29; P=0.96; and relative risk for any bolus vs. control, 1.45; 95% CI, 1.13 to 1.86; P=0.003). The 4-week mortality was 12.2%, 12.0%, and 8.7% in the three groups, respectively (P=0.004 for the comparison of bolus with control). Neurologic sequelae occurred in 2.2%, 1.9%, and 2.0% of the children in the respective groups (P=0.92), and pulmonary edema or increased intracranial pressure occurred in 2.6%, 2.2%, and 1.7% (P=0.17), respectively. In stratum B, 69% of the children (9 of 13) in the albumin-bolus group and 56% (9 of 16) in the saline-bolus group died (P=0.45). The results were consistent across centers and across subgroups according to the severity of shock and status with respect to malaria, coma, sepsis, acidosis, and severe anemia. CONCLUSIONS: Fluid boluses significantly increased 48-hour mortality in critically ill children with impaired perfusion in these resource-limited settings in Africa. (Funded by the Medical Research Council, United Kingdom; FEAST Current Controlled Trials number, ISRCTN69856593.).

Lactose intolerance among severely malnourished children with diarrhoea admitted to the nutrition unit, Mulago hospital, Uganda.

BACKGROUND: Lactose intolerance is a common complication of diarrhoea in infants with malnutrition and a cause of treatment failure. A combination of nutritional injury and infectious insults in severe protein energy malnutrition reduces the capacity of the intestinal mucosa to produce lactase enzyme necessary for the digestion of lactose. The standard management of severe malnutrition involves nutritional rehabilitation with lactose-based high energy formula milk. However, some of these children may be lactose intolerant, possibly contributing to the high rate of unfavorable treatment outcomes. This study was therefore designed to establish the prevalence of lactose intolerance and associated factors in this population. METHODS: A descriptive cross sectional study involving 196 severely malnourished children with diarrhoea aged 3-60 months was done in Mwanamugimu Nutrition Unit (MNU), Mulago hospital between October 2006 and February 2007. RESULTS: During the study period, 196 severely malnourished children with diarrhoea were recruited, 50 (25.5%) of whom had evidence of lactose intolerance (stool reducing substance >or= 1 + [0.5%] and stool pH < 5.5) and it occurred more commonly in children with kwashiorkor 27/75 (36.0%) than marasmic-kwashiorkor 6/25 (24.0%) and marasmus 17/96 (17.7%). Oedematous malnutrition (p = 0.032), perianal skin erosion (p = 0.044), high mean stool frequency (p = < 0.001) and having >or=2 diarrhoea episodes in the previous 3 months (p = 0.007) were the independent predictors of lactose intolerance. Other factors that were significantly associated with lactose intolerance on bi-variate analysis included: young age of 3-12 months; lack of up to-date immunization; persistent diarrhoea; vomiting; dehydration, and abdominal distension. Exclusive breastfeeding for less than 4 months and worsening of diarrhoea on initiation of therapeutic milk were the other factors. CONCLUSIONS: The prevalence of lactose intolerance in this study setting of 25.5% is relatively high. Routine screening by stool pH and reducing substances should be performed especially in the severely malnourished children with diarrhoea presenting with oedematous malnutrition, perianal skin erosion, higher mean stool frequency and having had >or=2 diarrhoea episodes in the previous 3 months. Use of lactose-free diets such as yoghurt should be considered for children found to have evidence of lactose intolerance and whose response on standard therapeutic milk formula is poor.