Sudden onset methaemoglobinaemia in a previously well Ugandan child: a case report and literature review

Methaemoglobinaemia is a rare condition of unknown prevalence. Diagnostic tests in resource limited settings are very rare but clinical signs can be a good guide. We set out to describe a case of Methaemoglobinaemia, raise awareness among practitioners in resource limited settings and to share experiences in its diagnosis and management. A previously well three and a half year old girl was admitted with central cyanosis of sudden onset. She underwent clinical, laboratory and radiological evaluation. Having been in a resource limited setting, the process of making a diagnosis was slow and difficult. After the diagnosis, the treatment was not available in the country but we managed to get it all the way from Nairobi, Kenya. A diagnosis of Methaemoglobinaemia was made using Spectrophotometry and she was successfully treated using 2 doses of intravenous Methylene blue. The cause of Methaemoglobinaemia was established to have been nitrites from food preservatives

Presentation and Outcome of Tuberculous Meningitis among Children: Experiences from a Tertiary Children’s Hospital

Background: Diagnosis of tuberculous meningitis (TBM) is complicated and outcome is poor especially in resource limited settings. Early diagnosis and prompt treatment are vital in effective treatment. We set out to describe experiences in the management and immediate outcome of TBM a tertiary-level children’s hospital in a high HIV and tuberculosis co-infection setting. Methods: This retrospective study included children who were diagnosed with TBM in the year 2009. A pre-coded questionnaire was used to extract data on presentation, diagnostics, treatment and outcome at the time of hospital discharge. Data was analyzed using STATA statistical package (StataCorp, Version 11). Results: Of the 40 children diagnosed with TBM, 6 (15%) had definitive TBM, 17 (42.5%) had probable TBM and 17 (42.5%) had possible TBM. The cerebrospinal fluid (CSF) chemistry and cells were abnormal in 39/40 (98%). Mantoux test was reactive in 16/29 (55%) and 17/30 (57%) had Chest X-rays suggestive of tuberculosis. Only 3/21 (14%) had positive sputum tuberculosis culture and 89% (32/36) had neuro-imaging abnormalities. Outcome at discharge was; 8% died, 49% improved with neurological sequelae and 43% improved without sequelae. Having TBM stage 3 at admission was associated with mortality (p=0.001). Conclusions: Most children had early diagnosis of TBM and mortality was lower than previous studies. We recommend a larger prospective study to further understand the outcome of TBM.Keywords: Tuberculous meningitis, children, presentation, outcome, AfricaAfrican Health sciences Vol 14 No. 1 March 201

Efavirenz poisoning in a 12 year old HIV negative African boy

Efavirenz is an oral antiretroviral drug in the class of non nucleoside reverse transcriptase inhibitors. Toxicity at therapeutic doses has been documented but there is scarcity of data on presentation and management of Efavirenz overdose. We describe a case of Efavirenz poisoning in a 12-year old HIV Negative African boy with a very unique presentation after ingesting 3 grams of Efavirenz as a single dose. The most prominent problems were burning sensation in the throat immediately after ingestion then visual impairment one hour later then tremors, screaming at night and motor deficits in lower limbs for 5 days before admission. His medical history, physical exam and investigations revealed no other cause of his presentation other than the EFV. Unfortunately, it was not possible to do EFV levels. He was given supportive treatment and 10 days later he was completely well.Key words: Efavirenz, poisoning, intoxication, adverse reaction, HI

Cytoadherence in paediatric malaria: ABO blood group, CD36, and ICAM1 expression and severe Plasmodium falciparum infection

As a leading cause of childhood mortality worldwide, selection pressure by Plasmodium falciparum continues to shape the human genome. Severe disturbances within the microcirculation result from the adhesion of infected erythrocytes to host receptors on monocytes, platelets, and endothelium. In this prospective study, we compared expression of all major host cytoadhesion receptors among Ugandan children presenting with uncomplicated malaria (n = 1078) versus children with severe malaria (n = 855), including cerebral malaria (n = 174), severe anaemia (n = 522), and lactic acidosis (n = 154). We report a significant survival advantage attributed to blood group O and increased monocyte expression of CD36 and ICAM1 (CD54). The high case fatality rate syndromes of cerebral malaria and lactic acidosis were associated with high platelet CD36 expression and thrombocytopenia, and severe malaria anaemia was characterized by low ICAM1 expression. In a logistic regression model of disease severity, odds ratios for the mitigating effects of blood group O, CD36, and ICAM1 phenotypes were greater than that of sickle haemoglobin. Host genetic adaptations to Plasmodium falciparum suggest new potential malaria treatment strategies

Inter-Relationships of Cardinal Features and Outcomes of Symptomatic Pediatric Plasmodium falciparum Malaria in 1,933 Children in Kampala, Uganda

Malaria remains a challenging diagnosis with variable clinical presentation and a wide spectrum of disease severity. Using a structured case report form, we prospectively assessed 1,933 children at Mulago Hospital in Kampala, Uganda with acute Plasmodium falciparum malaria. Children with uncomplicated malaria significantly differed from those with severe disease for 17 features. Among 855 children with severe disease, the case-fatality rate increased as the number of severity features increased. Logistic regression identified five factors independently associated with death: cerebral malaria, hypoxia, severe thrombocytopenia, leukocytosis, and lactic acidosis. Cluster analysis identified two groups: one combining anemia, splenomegaly, and leukocytosis; and a second group centered on death, severe thrombocytopenia, and lactic acidosis, which included cerebral malaria, hypoxia, hypoglycemia, and hyper-parasitemia. Our report updates previous clinical descriptions of severe malaria, quantifies significant clinical and laboratory inter-relationships, and will assist clinicians treating malaria and those planning or assessing future research (NCT00707200) (www.clinicaltrials.gov)

Effect of milk protein and whey permeate in large quantity lipid-based nutrient supplement on linear growth and body composition among stunted children: A randomized 2 × 2 factorial trial in Uganda

Background: Despite possible benefits for growth, milk is costly to include in foods for undernourished children. Furthermore, the relative effects of different milk components, milk protein (MP), and whey permeate (WP) are unclear. We aimed to assess the effects of MP and WP in lipid-based nutrient supplement (LNS), and of LNS itself, on linear growth and body composition among stunted children. Methods and findings: We performed a randomized, double-blind, 2 × 2 factorial trial among 12 to 59 months old stunted children in Uganda. Children were randomized to 4 formulations of LNS with MP or soy protein isolate and WP or maltodextrin (100 g/day for 12 weeks) or no supplementation. Investigators and outcome assessors were blinded; however, participants were only blinded to the ingredients in LNS. Data were analyzed based on intention-to-treat (ITT) using linear mixed-effects models adjusted for age, sex, season, and site. Primary outcomes were change in height and knee-heel length, and secondary outcomes included body composition by bioimpedance analysis (ISRCTN13093195). Between February and September 2020, we enrolled 750 children with a median age of 30 (interquartile range 23 to 41) months, with mean (± standard deviation) height-for-age z-score (HAZ) −3.02 ± 0.74 and 12.7% (95) were breastfed. The 750 children were randomized to LNS (n = 600) with or without MP (n = 299 versus n = 301) and WP (n = 301 versus n = 299), or no supplementation (n = 150); 736 (98.1%), evenly distributed between groups, completed 12-week follow-up. Eleven serious adverse events occurred in 10 (1.3%) children, mainly hospitalization with malaria and anemia, all deemed unrelated to the intervention. Unsupplemented children had 0.06 (95% confidence interval, CI [0.02, 0.10]; p = 0.015) decline in HAZ, accompanied by 0.29 (95% CI [0.20, 0.39]; p < 0.001) kg/m2 increase in fat mass index (FMI), but 0.06 (95% CI [−0.002; 0.12]; p = 0.057) kg/m2 decline in fat-free mass index (FFMI). There were no interactions between MP and WP. The main effects of MP were 0.03 (95% CI [−0.10, 0.16]; p = 0.662) cm in height and 0.2 (95% CI [−0.3, 0.7]; p = 0.389) mm in knee-heel length. The main effects of WP were −0.08 (95% CI [−0.21, 0.05]; p = 220) cm and −0.2 (95% CI [−0.7; 0.3]; p = 403) mm, respectively. Interactions were found between WP and breastfeeding with respect to linear growth (p < 0.02), due to positive effects among breastfed and negative effects among non-breastfed children. Overall, LNS resulted in 0.56 (95% CI [0.42, 0.70]; p < 0.001) cm height increase, corresponding to 0.17 (95% CI [0.13, 0.21]; p < 0.001) HAZ increase, and 0.21 (95% CI [0.14, 0.28]; p < 0.001) kg weight increase, of which 76.5% (95% CI [61.9; 91.1]) was fat-free mass. Using height-adjusted indicators, LNS increased FFMI (0.07 kg/m2, 95% CI [0.0001; 0.13]; p = 0.049), but not FMI (0.01 kg/m2, 95% CI [−0.10, 0.12]; p = 0.800). Main limitations were lack of blinding of caregivers and short study duration. Conclusions: Adding dairy to LNS has no additional effects on linear growth or body composition in stunted children aged 12 to 59 months. However, supplementation with LNS, irrespective of milk, supports linear catch-up growth and accretion of fat-free mass, but not fat mass. If left untreated, children already on a stunting trajectory gain fat at the expense of fat-free mass, thus nutrition programs to treat such children should be considered

Correlates of Iron, Cobalamin, Folate, and Vitamin A Status among Stunted Children : A Cross-Sectional Study in Uganda

Micronutrient deficiencies and stunting are prevalent. We assessed correlates of iron, cobalamin, folate, and vitamin A biomarkers in a cross-sectional study of stunted children aged 12–59 months in eastern Uganda. The biomarkers measured were serum ferritin (S-FE), soluble transferrin receptor (S-TfR), retinol binding protein (S-RBP), plasma cobalamin (P-Cob), methylmalonic acid (P-MMA), and folate (P-Fol). Using linear regression, we assessed socio-demography, stunting severity, malaria rapid test, and inflammation as correlates of micronutrient biomarkers. Of the 750 children, the mean (SD) age was 32.0 (11.7) months, and 45% were girls. Iron stores were depleted (inflammation-corrected S-FE 8.3 mg/L). P-Cob was low (0.75 µmol/L). Inflammation-corrected S-RBP was low (<0.7 µmol/L) in 21% and P-Fol (<14 nmol/L) in 1%. Age 24–59 months was associated with higher S-FE and P-Fol and lower S-TfR. Breastfeeding beyond infancy was associated with lower iron status and cobalamin status, and malaria was associated with lower cobalamin status and tissue iron deficiency (higher S-TfR) despite iron sequestration in stores (higher S-FE). In conclusion, stunted children have iron, cobalamin, and vitamin A deficiencies. Interventions addressing stunting should target co-existing micronutrient deficiencies.Peer reviewe

Adherence to Antiretroviral Therapy among HIV Infected Children Measured by Caretaker Report, Medication Return, and Drug Level in Dar Es Salaam, Tanzania.

Adherence to antiretroviral drugs in the treatment of paediatric HIV infection is complicated because of many factors including stigma and drug intake logistics. It is therefore important to identify children with non-adherence in order to intervene before they become at risk of developing treatment failure or drug resistance. The aim of this study was to determine the level of adherence to antiretroviral therapy (ART), measured by caretaker report, medication return and nevirapine plasma concentration. In addition, the association between level of adherence and patient's immune status was compared across the three methods of measuring adherence. This was a descriptive cross-sectional study involving HIV infected children aged 2-14 years, on nevirapine- based antiretroviral treatment for at least six months, attending care and treatment clinic in three municipal hospitals in Dar- Es- Salaam City. Eligible patients and their accompanying caretakers were consecutively enrolled after obtaining written informed consent. Structured questionnaires were administered to caretakers to assess patient's adherence by caretaker report and medication return whereas a single blood sample for CD4 cell count/percent and determination of nevirapine plasma concentration was taken from patients on the day of assessment. A total of 300 patients and accompanying caretakers were enrolled and the mean patient age (SD) was 8 (3) years. Caretakers' report and medication return showed good adherence (98% and 97%) respectively. However, the level of adherence assessed by nevirapine plasma concentration (85%) was significantly lower than caretaker report and medication return (p < 0.001). The agreement between nevirapine plasma concentration and medication return and between nevirapine plasma concentration and caretaker report was weak (k = 0. 131) (k = 0. 09) respectively. Nevirapine plasma concentration below 3 μg/ml was associated with immunosuppression (p = 0. 021) whereas medication return (>5% of prescribed doses) and caretaker reported missing more than one dose within 72 hours prior to interview were not associated with immunosuppression (p = 0. 474), (p = 0. 569) respectively. Lower adherence level observed using nevirapine plasma concentration and its association with immunological response supports the validity of the method and indicates that adherence data obtained from caretaker report and medication return may overestimate the true adherence in paediatric antiretroviral therapy