Blood pressure and electrocardiographic profile of children with sickle cell anaemia in steady-state and vaso-occlusive crisis.

Objective: To compare the cardiovascular features of patients with sickle cell anaemia (SCA) in steady-state with those in vaso-occlusive crisis (VOC) at the Wesley Guild Hospital (WGH). Design: A descriptive cross-sectional, matched, case-control study among children with SCA at the WGH, a tertiary health facility in southwest Nigeria. Setting: The participants were recruited from the children's emergency unit and paediatric haematology clinic of the WGH. Participants: Consisted of 93 children with VOC (cases) and 93 age and sex-matched in steady state (controls), aged 5 - 15 years. Main outcome measures: Cardiovascular parameters, including pulse rate, blood pressure, and electrocardiographic profile, were assessed and compared using the appropriate statistical tests. Results: The mean (SD) age of the cases and controls were 8.8 (3.2) years and 9.0 (3.1) years, respectively (p= 0.106). There was no significant difference in the mean height of the groups. The mean pulse rate, diastolic, systolic, and mean arterial pressures were significantly higher in the cases than in the controls. A significantly higher proportion of the cases than the controls also had a higher frequency of heart blocks, prolonged QTc interval, ST elevation or depression, and T wave abnormality (p = 0.018, 0.039, 0.041, 0.009, respectively). The prevalence of chamber enlargements was not significantly different between the two groups. Conclusion: Cardiovascular dysfunction is worse during VOC when compared with steady state. Physicians should look for these dysfunctions in SCA children with VOC to reduce mortality from the disease. Funding: None declared.

Incidence of Catastrophic Health Expenditures Amongst Hospitalized Neonates in Ekiti, Southwest Nigeria.

Background: Neonatal illnesses require huge spending due to prolonged hospital stay. The management of these illnesses is usually financed by individual families which in most instances are living below the poverty line. This healthcare financing method can readily push families into catastrophic spending on health. Aim: To ascertain the average cost of managing common neonatal illnesses and the financial burden, it constitutes to families in Ekiti State, southwest Nigeria. Methods: We conducted a cross-sectional study on the out-of-pocket spending involved in managing neonates admitted into and discharged from the SCBU of the Ekiti State University Teaching Hospital, Ado-Ekiti, southwest Nigeria. Data collected included the monthly family income, the money spent on drugs, laboratory investigations and the hospital bill using a purposely designed structured questionnaire. Healthcare spending greater than 10% of the overall family income was described as catastrophic health spending (CHS). Results: The medical bills for most (95%) of the 119 study participants were paid through the out-of-pocket means and 81.5% of the families spent more than 10% of their monthly earnings (CHS) to settle medical bills. Close to 50% of the families belonged to the lower social economic class. The median (IQR) duration of hospital stay was 2.75 days (3.0-8.0). The median (IQR) total expenditure was N24,500.00 (N13,615.00-N41,487.50). The median (IQR) expenditure for the treatment of prematurity was highest at N55,075.00 (USD 133.10) [N27,350.00 (USD 66.10)-N105,737.50 (USD 255.53)] and more than 60.5% of the expenses was on hospital utilities and consumables. The length of hospital stay showed a robust positive correlation with the total hospital bill (r = 0.576, P < 0.001). Conclusion: Neonatal illnesses put many households at risk of catastrophic health spending. There is need for increased government investment in health and extension of the health insurance scheme to all the citizens of the country.

Relationship between ultrasound-measured spleen, liver and anthropometry of children living in a rural community in southwest Nigeria: a cross-sectional study.

BACKGROUND: Ultrasonography is noninvasive, relatively inexpensive and useful for resource-poor settings. US spleen and liver sizes have been observed to differ among populations, so there is a need for reference values for different geographic populations. OBJECTIVE: To describe the sizes of the spleen and liver of children living in a rural community in southwest Nigeria and assess the relationship between these measurements and the children's anthropometry. MATERIALS AND METHODS: We conducted a community-based cross-sectional study among 358 apparently healthy children ages 1-14 years. We obtained the participants' weights, heights, body mass index and body surface area. They underwent US imaging to obtain longitudinal measurements of their spleen and liver. We used independent t-test to compare means, and linear regression analysis to assess relationships between continuous data. The significance level was set as P < 0.05. RESULTS: There were more girls (181; 50.6%). Most children were ages 1-5 years (172; 48.0%). The body surface area had significantly strong positive relationships with US spleen size (r = 0.769; R2 = 0.592; P < 0.0001) and US liver size (r = 0.819; R2 = 0.671; P < 0.0001) but body mass index had weak positive relationships. CONCLUSION: This study contributes to data on US spleen and liver sizes of Nigerian children. The findings buttress observations that body surface area strongly correlates with US spleen and liver measurements. It is recommended that more studies be conducted among Nigerian children to generate a robust pool of data that are useful for creating homogeneous formulae to ease interpretation of US measurements of these intraabdominal organs.

Towards malaria control in Nigeria: implications of the malaria parasite rate and spleen rate among children living in a rural community in southwest Nigeria.

BACKGROUND: The World Health Organization prioritizes malaria surveillance for accurate tracking of progress of intervention programmes. The malaria parasite rate (PR) and spleen rate (SR) are economical surveillance tools. There has been a global decline in the burden of malaria over the last decade, but most African countries, like Nigeria, have a slow rate of decline. There is a need for adequate malaria surveillance to guide malaria control strategies and policymaking. METHODS: A community-based cross-sectional study was conducted among 363 children ages 1-15 y in rural southwest Nigeria. The participants' PR was determined by microscopy and the SR was determined by palpation and ultrasonography. The associations between PR and SR and other covariates were assessed. RESULTS: The PR was 26.7% and the SR was 12.9%. There was no significant association between PR or SR across age groups, but low social class was significantly associated with PR (55 [33.5%], p=0.004) and SR (29 [17.3%], p=0.013). The odds of having splenomegaly doubled with malaria parasitaemia (odds ratio 2.03 [95% confidence interval 1.06 to 3.88). CONCLUSIONS: The PR and SR suggest that the study area is meso-endemic. The PR in the study area was almost equal across age groups; our findings suggest there may be a need for policy review to plan malaria intervention programmes and include older children, not just children <5 y of age. Routine malaria surveillance using simple tools such as the PR and SR are necessary for reviewing malaria control programmes in the community.

Immunogenicity of pneumococcal conjugate vaccine formulations containing pneumococcal proteins, and immunogenicity and reactogenicity of co-administered routine vaccines - A phase II, randomised, observer-blind study in Gambian infants.

BACKGROUND: Two conserved pneumococcal proteins, pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD), combined with 10 polysaccharide conjugates from the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) in two investigational pneumococcal vaccine (PHiD-CV/dPly/PhtD) formulations were immunogenic and well-tolerated when administered to Gambian children. Here, we report immunogenicity of the polysaccharide conjugates, and immunogenicity and reactogenicity of co-administered routine vaccines. METHODS: In this phase II, controlled, observer-blind, single-centre study, healthy infants aged 8-10 weeks were randomised (1:1:1:1:1:1) to six groups. Four groups received 3+0 schedule (2-3-4 months [M]) of PHiD-CV/dPly/PhtD (10 or 30 µg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine; and two groups received 2+1 schedule (2-4-9 M) of PHiD-CV/dPly/PhtD (30 µg of each protein) or PHiD-CV. All infants received diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HBV/Hib) and oral trivalent polio vaccines (OPV) at 2-3-4 M, and measles, yellow fever, and OPV vaccines at 9 M. We evaluated immune responses at 2-5-9-12 M; and reactogenicity 0-3 days post-vaccination. RESULTS: 1200 infants were enrolled between June 2011 and May 2012; 1152 completed the study. 1 M post-primary vaccination, for each PHiD-CV serotype except 6B and 23F, ≥97.4% (3+0 schedule) and ≥96.4% (2+1 schedule) of infants had antibody concentrations ≥0.2 µg/mL. Immune responses were comparable between groups within the same vaccination schedules. Observed antibody geometric mean concentrations (GMCs) increased by 1 M post-primary vaccination compared to pre-vaccination. In the following months, GMCs and opsonophagocytic activity titres waned, with an increase post-booster for the 2+1 schedule. Immune responses to protein D and, DTPw-HBV/Hib, OPV, measles, and yellow fever vaccines were not altered by co-administration with pneumococcal proteins. Reactogenicity of co-administered vaccines was comparable between groups and did not raise concerns. CONCLUSION: Immune responses to the 10 PHiD-CV polysaccharide conjugates and co-administered vaccines were not altered by addition of dPly and PhtD. ClinicalTrials.gov identifier NCT01262872.

Efficacy of a novel, protein-based pneumococcal vaccine against nasopharyngeal carriage of Streptococcus pneumoniae in infants: A phase 2, randomized, controlled, observer-blind study.

BACKGROUND: Conserved pneumococcal proteins are potential candidates for inclusion in vaccines against pneumococcal diseases. In the first part of a two-part study, an investigational vaccine (PHiD-CV/dPly/PhtD-30) containing 10 pneumococcal serotype-specific polysaccharide conjugates (10VT) combined with pneumolysin toxoid and pneumococcal histidine triad protein D (30µg each) was well tolerated by Gambian children. Part two, presented here, assessed the efficacy of two PHiD-CV/dPly/PhtD formulations against pneumococcal nasopharyngeal carriage (NPC) prevalence in infants. METHODS: In this phase 2, randomized, controlled, observer-blind trial, healthy infants aged 8-10weeks, recruited from a peri-urban health center, were randomized (1:1:1:1:1:1) into six groups. Four groups received PHiD-CV/dPly/PhtD (10 or 30µg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine at ages 2-3-4months (3+0 infant schedule) and two groups PHiD-CV/dPly/PhtD-30 or PHiD-CV at 2-4-9months (2+1 infant schedule). The primary objective was impact on non-10VT NPC at ages 5-9-12months. Secondary objectives included confirmatory analysis of protein dose superiority and safety/reactogenicity. Impact on pneumococcal NPC acquisition, bacterial load, and ply and phtD gene sequencing were explored. RESULTS: 1200 infants were enrolled between June 2011 and May 2012. Prevalences of pneumococcal (60-67%) and non-10VT (55-61%) NPC were high at baseline. Across all post-vaccination time points, efficacy of PHiD-CV/dPly/PhtD-10 and PHiD-CV/dPly/PhtD-30 against non-10VT NPC (3+0 schedule) was 1.1% (95% CI -21.5, 19.5) and 2.1% (-20.3, 20.3), respectively; efficacy of PHiD-CV/dPly/PhtD-30 (2+1 schedule) was 0.5% (-22.1, 18.9) versus PHiD-CV. No differences were observed in pneumococcal NPC acquisition, clearance, or bacterial load. Both protein-based vaccines elicited immune responses to pneumococcal proteins. CONCLUSIONS: In this high carriage prevalence setting, inclusion of pneumococcal proteins in the PHiD-CV/dPly/PhtD investigational vaccine had no impact on pneumococcal NPC in infants, regardless of protein dose or schedule. Future evaluations will assess its impact against pneumococcal disease endpoints. FUNDING: PATH, GlaxoSmithKline Biologicals SA. ClinicalTrials.gov identifier NCT01262872.

Risk factors for delay in age-appropriate vaccinations among Gambian children.

BACKGROUND: Vaccination has been shown to reduce mortality and morbidity due to vaccine-preventable diseases. However, these diseases are still responsible for majority of childhood deaths worldwide especially in the developing countries. This may be due to low vaccine coverage or delay in receipt of age-appropriate vaccines. We studied the timeliness of routine vaccinations among children aged 12-59 months attending infant welfare clinics in semi-urban areas of The Gambia, a country with high vaccine coverage. METHODS: A cross-sectional survey was conducted in four health centres in the Western Region of the Gambia. Vaccination dates were obtained from health cards and timeliness assessed based on the recommended age ranges for BCG (birth-8 weeks), Diphtheria-Pertussis-Tetanus (6 weeks-4 months; 10 weeks-5 months; 14 weeks-6 months) and measles vaccines (38 weeks-12 months). Risk factors for delay in age-appropriate vaccinations were determined using logistic regression. Analysis was limited to BCG, third dose of Diphtheria-Pertussis -Tetanus (DPT3) and measles vaccines. RESULTS: Vaccination records of 1154 children were studied. Overall, 63.3% (95 % CI 60.6-66.1%) of the children had a delay in the recommended time to receiving at least one of the studied vaccines. The proportion of children with delayed vaccinations increased from BCG [5.8% (95 % CI 4.5-7.0%)] to DPT3 [60.4% (95 % CI 57.9%-63.0%)] but was comparatively low for the measles vaccine [10.8% (95 % CI 9.1%-12.5%)]. Mothers of affected children gave reasons for the delay, and their profile correlated with type of occupation, place of birth and mode of transportation to the health facilities. CONCLUSION: Despite high vaccination coverage reported in The Gambia, a significant proportion of the children's vaccines were delayed for reasons related to health services as well as profile of mothers. These findings are likely to obtain in several countries and should be addressed by programme managers in order to improve and optimize the impact of the immunization coverage rates.

Invasive bacteria isolates from children with severe infections in a Nigerian hospital.

BACKGROUND: Little information is available about the aetiology and epidemiology of serious bacterial infections in Nigeria. This study determined bacterial isolates from blood and cerebrospinal fluid (CSF) of children presenting in the emergency room of a teaching hospital in Nigeria. METHOD: From October 2005 to December 2006, children aged two to 60 months presenting with signs of acute systemic infections were recruited. Blood culture and CSF specimens were collected and processed using standard microbiological protocols. Data were analysed using SPSS version 11 software. RESULTS: Two hundred and two blood and 69 CSF samples were cultured. Fifty-five (27%) of the blood cultures yielded Gram-negative bacilli and Gram-positive cocci in almost equal proportions. The most common isolates from the blood cultures were Staphylococcus aureus, 26 (12.9%) and atypical coliforms, 13 (6.5%). Others are Klebsiella spp, 3 (1.5%); Klebsiella pneumonia, 2 (1.0%); Escherichia coli, 3 (1.5%); Enterobacter agglomerans, 2 (1.1%); Proteus mirabilis, 2(1%); Pseudomonas spp, 2 (1.0%); Haemophilus influenza, 1 (1.0%); and Coagulase-negative Staphylococcus, 1 (1.0%). Fourteen out of 67 (20.9%) of the CSF samples yielded bacterial isolates: Streptococcus pneumonia, 3 (4.5%); Haemophilus influenza, 8 (11.9%); Hemophilus spp, 1 (1.5%); E. Coli, 1 (1.5%); and atypical coliform, 1 (1.5%). Gram-negative coliform isolates were predominantly resistant to penicillin based antibiotics and co-trimoxazole but sensitive to third-generation cephalosporins and quinolones. A high percentage of S. aureus isolates were multi-drug resistant. CONCLUSIONS: Bacterial infections contribute to the significant morbidity among children in our environment. S. aureus was more frequently isolated in sepsis while H. influenzae appears to play a major role in meningitis. Appropriate use of antibiotics is needed to manage affected children effectively. We also recommend improved vaccine coverage of children under the age of five years.