Effect of 10-valent pneumococcal conjugate vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children: an interrupted time-series analysis.

BACKGROUND: Pneumococcal conjugate vaccines (PCV) are highly protective against invasive pneumococcal disease caused by vaccine serotypes, but the burden of pneumococcal disease in low-income and middle-income countries is dominated by pneumonia, most of which is non-bacteraemic. We examined the effect of 10-valent PCV on the incidence of pneumonia in Kenya. METHODS: We linked prospective hospital surveillance for clinically-defined WHO severe or very severe pneumonia at Kilifi County Hospital, Kenya, from 2002 to 2015, to population surveillance at Kilifi Health and Demographic Surveillance System, comprising 45 000 children younger than 5 years. Chest radiographs were read according to a WHO standard. A 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PCV10) was introduced in Kenya in January, 2011. In Kilifi, there was a three-dose catch-up campaign for infants (aged <1 year) and a two-dose catch-up campaign for children aged 1-4 years, between January and March, 2011. We estimated the effect of PCV10 on the incidence of clinically-defined and radiologically-confirmed pneumonia through interrupted time-series analysis, accounting for seasonal and temporal trends. FINDINGS: Between May 1, 2002 and March 31, 2015, 44 771 children aged 2-143 months were admitted to Kilifi County Hospital. We excluded 810 admissions between January and March, 2011, and 182 admissions during nurses' strikes. In 2002-03, the incidence of admission with clinically-defined pneumonia was 2170 per 100 000 in children aged 2-59 months. By the end of the catch-up campaign in 2011, 4997 (61·1%) of 8181 children aged 2-11 months had received at least two doses of PCV10 and 23 298 (62·3%) of 37 416 children aged 12-59 months had received at least one dose. Across the 13 years of surveillance, the incidence of clinically-defined pneumonia declined by 0·5% per month, independent of vaccine introduction. There was no secular trend in the incidence of radiologically-confirmed pneumonia over 8 years of study. After adjustment for secular trend and season, incidence rate ratios for admission with radiologically-confirmed pneumonia, clinically-defined pneumonia, and diarrhoea (control condition), associated temporally with PCV10 introduction and the catch-up campaign, were 0·52 (95% CI 0·32-0·86), 0·73 (0·54-0·97), and 0·63 (0·31-1·26), respectively. Immediately before PCV10 was introduced, the annual incidence of clinically-defined pneumonia was 1220 per 100 000; this value was reduced by 329 per 100 000 at the point of PCV10 introduction. INTERPRETATION: Over 13 years, admissions to Kilifi County Hospital for clinically-defined pneumonia decreased sharply (by 27%) in association with the introduction of PCV10, as did the incidence of radiologically-confirmed pneumonia (by 48%). The burden of hospital admissions for childhood pneumonia in Kilifi, Kenya, has been reduced substantially by the introduction of PCV10. FUNDING: Gavi, The Vaccine Alliance and Wellcome Trust.

Diarrhoea complicating severe acute malnutrition in Kenyan children: a prospective descriptive study of risk factors and outcome.

BACKGROUND: Severe acute malnutrition (SAM) accounts for two million deaths worldwide annually. In those hospitalised with SAM, concomitant infections and diarrhoea are frequent complications resulting in adverse outcome. We examined the clinical and laboratory features on admission and outcome of children with SAM and diarrhoea at a Kenyan district hospital. METHODS: A 4-year prospective descriptive study involving 1,206 children aged 6 months to 12 years, hospitalized with SAM and managed in accordance with WHO guidelines. Data on clinical features, haematological, biochemical and microbiological findings for children with diarrhoea (≥ 3 watery stools/day) were systematically collected and analyzed to identify risk factors associated with poor outcome. RESULTS: At admission 592 children (49%) had diarrhoea of which 122 (21%) died compared to 72/614 (12%) deaths in those without diarrhoea at admission (Χ(2) = 17.6 p<0.001). A further 187 (16%) children developed diarrhoea after 48 hours of admission and 33 died (18%). Any diarrhoea during admission resulted in a significantly higher mortality 161/852 (19%) than those uncomplicated by diarrhoea 33/351 (9%) (Χ(2) = 16.6 p<0.001). Features associated with a fatal outcome in children presenting with diarrhoea included bacteraemia, hyponatraemia, low mid-upper arm circumference <10 cm, hypoxia, hypokalaemia and oedema. Bacteraemia had the highest risk of death (adjusted OR 6.1; 95% C.I 2.3, 16.3 p<0.001); and complicated 24 (20%) of fatalities. Positive HIV antibody status was more frequent in cases with diarrhoea at admission (23%) than those without (15%, Χ(2) = 12.0 p = 0.001) but did not increase the risk of death in diarrhoea cases. CONCLUSION: Children with SAM complicated by diarrhoea had a higher risk of death than those who did not have diarrhoea during their hospital stay. Further operational and clinical research is needed to reduce mortality in children with SAM in the given setting.

Hypothermia in children with severe malnutrition: low prevalence on the tropical coast of Kenya.

Hypothermia is stated as a common complication of severe malnutrition although there are little primary data to support this. We performed a prospective study of children with severe acute malnutrition (SAM) admitted to a district hospital in Kenya. We documented the prevalence of hypothermia and examined its association with outcome and ambient temperature. During a 2-year period 667 children were recruited. Hypothermia was recorded in only 12 out of 15 191 (0.08%) temperature observations and as a single event in 12 children (2% of cases). There was no correlation with ambient temperature. Although mortality rates were higher in children with hypothermia (4/12, 33%) than those without (121/655, 18%), the timing of hypothermia did not coincide with clinical deterioration. Hypothermia was a rare marker of severity in our setting. We recommend that other observations be highlighted to identify high risk groups and that routine temperature observations be reduced wherever staff are few.

Emergency triage assessment for hypoxaemia in neonates and young children in a Kenyan hospital: an observational study.

OBJECTIVE: To describe the prevalence of hypoxaemia in children admitted to a hospital in Kenya for the purpose of identifying clinical signs of hypoxaemia for emergency triage assessment, and to test the hypothesis that such signs lead to correct identification of hypoxaemia in children, irrespective of their diagnosis. METHODS: From 2002 to 2005 we prospectively collected clinical data and pulse oximetry measurements for all paediatric admissions to Kilifi District Hospital, Kenya, irrespective of diagnosis, and assessed the prevalence of hypoxaemia in relation to the WHO clinical syndromes of 'pneumonia' on admission and the final diagnoses made at discharge. We used the data collected over the first three years to derive signs predictive of hypoxaemia, and data from the fourth year to validate those signs. FINDINGS: Hypoxemia was found in 977 of 15 289 (6.4%) of all admissions (5% to 19% depending on age group) and was strongly associated with inpatient mortality (age-adjusted risk ratio: 4.5; 95% confidence interval, CI: 3.8-5.3). Although most hypoxaemic children aged > 60 days met the WHO criteria for a syndrome of 'pneumonia' on admission, only 215 of the 693 (31%) such children had a final diagnosis of lower respiratory tract infection (LRTI). The most predictive signs for hypoxaemia included shock, a heart rate < 80 beats per minute, irregular breathing, a respiratory rate > 60 breaths per minute and impaired consciousness. However, 5-15% of the children who had hypoxaemia on admission were missed, and 18% of the children were incorrectly identified as hypoxaemic. CONCLUSION: The syndromes of pneumonia make it possible to identify most hypoxaemic children, including those without LRTI. Shock, bradycardia and irregular breathing are important predictive signs, and severe malaria with respiratory distress is a common cause of hypoxaemia. Overall, however, clinical signs are poor predictors of hypoxaemia, and using pulse oximetry in resource-poor health facilities to target oxygen therapy is likely to save costs.

Population pharmacokinetics of a single daily intramuscular dose of gentamicin in children with severe malnutrition.

OBJECTIVES: The World Health Organization recommends that all children admitted with severe malnutrition should routinely receive parenteral ampicillin and gentamicin; despite this, mortality remains high. Since this population group is at risk of altered volume of distribution, we aimed to study the population pharmacokinetics of once daily gentamicin (7.5 mg/kg) in children with severe malnutrition and to evaluate clinical factors affecting pharmacokinetic parameters. METHODS: Thirty-four children aged 0.5-10 years were studied. One hundred and thirty-two gentamicin concentrations (median of four per patient), drawn 0.4-24.6 h after administration of the intramuscular dose, were analysed. The data were fitted by a two-compartment model using the population package NONMEM. RESULTS: Gentamicin was rapidly absorbed and all concentrations measured within the first 2 h after administration were > 8 mg/L (indicating that satisfactory peak concentrations were achieved). Ninety-eight percent of samples measured more than 20 h after the dose were < 1 mg/L. The best model included weight, and it was found that high base deficit, high creatinine concentration and low temperature (all markers of hypovolaemic shock) reduced clearance (CL/F). Weight influenced volume of the central (V1/F) and peripheral (V2/F) compartments, and high base deficit reduced V2/F and intercompartmental CL (Q/F). Interindividual variability in CL was 26%, in V1/F 33% and in V2/F and Q/F was 52%. Individual estimates of CL/F ranged from 0.02 to 0.16 (median 0.10) L/h/kg and those of Vss/F from 0.26 to 1.31 (median 0.67) L/kg. Initial half-lives had a median of 1.4 h and elimination half-lives and a median of 14.9 h. Excessive concentrations were observed in one patient who had signs of renal impairment and shock. CONCLUSIONS: Although a daily dose of 7.5 mg/kg achieves satisfactory gentamicin concentrations in the majority of patients, patients with renal impairment and shock may be at risk of accumulation with 24 hourly dosing. Further studies of gentamicin pharmacokinetics in this group are now needed to inform future international guideline recommendations.