Grant Mackenzie

Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study

Summary Background Little information is available about the effect of pneumococcal conjugate vaccines (PCVs) in low-income countries. We measured the effect of these vaccines on invasive pneumococcal disease in The Gambia where the 7-valent vaccine (PCV7) was introduced in August, 2009, followed by the 13-valent vaccine (PCV13) in May, 2011. Methods We conducted population-based surveillance for invasive pneumococcal disease in individuals aged 2 months and older who were residents of the Basse Health and Demographic Surveillance System (BHDSS) in the Upper River Region, The Gambia, using standardised criteria to identify and investigate patients. Surveillance was done between May, 2008, and December, 2014. We compared the incidence of invasive pneumococcal disease between baseline (May 12, 2008–May 11, 2010) and after the introduction of PCV13 (Jan 1, 2013–Dec 31, 2014), adjusting for changes in case ascertainment over time. Findings We investigated 14u2008650 patients, in whom we identified 320 cases of invasive pneumococcal disease. Compared with baseline, after the introduction of the PCV programme, the incidence of invasive pneumococcal disease decreased by 55% (95% CI 30–71) in the 2–23 months age group, from 253 to 113 per 100u2008000 population. This decrease was due to an 82% (95% CI 64–91) reduction in serotypes covered by the PCV13 vaccine. In the 2–4 years age group, the incidence of invasive pneumococcal disease decreased by 56% (95% CI 25–75), from 113 to 49 cases per 100u2008000, with a 68% (95% CI 39–83) reduction in PCV13 serotypes. The incidence of non-PCV13 serotypes in children aged 2–59 months increased by 47% (−21 to 275) from 28 to 41 per 100u2008000, with a broad range of serotypes. The incidence of non-pneumococcal bacteraemia varied little over time. Interpretation The Gambian PCV programme reduced the incidence of invasive pneumococcal disease in children aged 2–59 months by around 55%. Further surveillance is needed to ascertain the maximum effect of the vaccine in the 2–4 years and older age groups, and to monitor serotype replacement. Low-income and middle-income countries that introduce PCV13 can expect substantial reductions in invasive pneumococcal disease. Funding GAVIs Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP), Bill & Melinda Gates Foundation, and the UK Medical Research Council.

Standardization of Clinical Assessment and Sample Collection Across All PERCH Study Sites

Abstract Background. Variable adherence to standardized case definitions, clinical procedures, specimen collection techniques, and laboratory methods has complicated the interpretation of previous multicenter pneumonia etiology studies. To circumvent these problems, a program of clinical standardization was embedded in the Pneumonia Etiology Research for Child Health (PERCH) study. Methods. Between March 2011 and August 2013, standardized training on the PERCH case definition, clinical procedures, and collection of laboratory specimens was delivered to 331 clinical staff at 9 study sites in 7 countries (The Gambia, Kenya, Mali, South Africa, Zambia, Thailand, and Bangladesh), through 32 on-site courses and a training website. Staff competency was assessed throughout 24 months of enrollment with multiple-choice question (MCQ) examinations, a video quiz, and checklist evaluations of practical skills. Results. MCQ evaluation was confined to 158 clinical staff members who enrolled PERCH cases and controls, with scores obtained for >86% of eligible staff at each time-point. Median scores after baseline training were ≥80%, and improved by 10 percentage points with refresher training, with no significant intersite differences. Percentage agreement with the clinical trainer on the presence or absence of clinical signs on video clips was high (≥89%), with interobserver concordance being substantial to high (AC1 statistic, 0.62–0.82) for 5 of 6 signs assessed. Staff attained median scores of >90% in checklist evaluations of practical skills. Conclusions. Satisfactory clinical standardization was achieved within and across all PERCH sites, providing reassurance that any etiological or clinical differences observed across the study sites are true differences, and not attributable to differences in application of the clinical case definition, interpretation of clinical signs, or in techniques used for clinical measurements or specimen collection.

Increased Disease due to Haemophilus influenzae Type b Population-based Surveillance in Eastern Gambia, 2008-2013

Background: In 1997, The Gambia became the first African country to introduce conjugate Haemophilus influenzae type b (Hib) vaccine with good disease control through to 2010. Methods: Culture-based surveillance for invasive bacterial disease in eastern Gambia, specifically the Basse Health and Demographic Surveillance System (BHDSS) area, was conducted from 12 May 2008 and in Fuladu West district from 12 September 2011 until 31 December 2013. In 2011, Hib serology was measured in 5–34-year-olds. Results: In all, 16,735 of 17,932 (93%) eligible patients were investigated. We detected 57 cases of invasive H. influenzae disease; 24 (42%) were type b. No cases of Hib disease were detected in the BHDSS area in 2008–2009; 1 was detected in 2010, 2 in 2011, 4 in 2012 and 7 in 2013. In 2013, the incidence of Hib disease in those aged 2–11 and 2–59 months in the BHDSS area was 88 [95% confidence interval (CI): 29–207] and 22 (95% CI: 9–45) cases per 105 person-years, respectively. In 2013, disease incidence in Fuladu West among those aged 0–59 months was 26 (95% CI: 7–67) cases per 105 person-years. Nine of 24 Hib cases were vaccine failures (2 HIV positive) and 9 were too young to have been vaccinated. The proportion of children aged 5–6 years (n = 223) with anti-Hib IgG ≥1.0 &mgr;g/mL was 67%; the antibody nadir was in 9–14-year-olds (n = 58) with 55% above threshold. Conclusions: Hib disease in eastern Gambia has increased in recent years. Surveillance in developing countries should remain alert to detect such changes.

Child Mortality after Discharge from a Health Facility following Suspected Pneumonia, Meningitis or Septicaemia in Rural Gambia: A Cohort Study.

Objective To measure mortality and its risk factors among children discharged from a health centre in rural Gambia. Methods We conducted a cohort study between 12 May 2008 and 11 May 2012. Children aged 2–59 months, admitted with suspected pneumonia, sepsis, or meningitis after presenting to primary and secondary care facilities, were followed for 180 days after discharge. We developed models associating post-discharge mortality with clinical syndrome on admission and clinical risk factors. Findings One hundred and five of 3755 (2.8%) children died, 80% within 3 months of discharge. Among children aged 2–11 and 12–59 months, there were 30 and 29 deaths per 1000 children per 180 days respectively, compared to 11 and 5 respectively in the resident population. Children with suspected pneumonia unaccompanied by clinically severe malnutrition (CSM) had the lowest risk of post-discharge mortality. Mortality increased in children with suspected meningitis or septicaemia without CSM (hazard ratio [HR] 2.6 and 2.2 respectively). The risk of mortality greatly increased with CSM on admission: CSM with suspected pneumonia (HR 8.1; 95% confidence interval (CI) 4.4 to 15), suspected sepsis (HR 18.4; 95% CI 11.3 to 30), or suspected meningitis (HR 13.7; 95% CI 4.2 to 45). Independent associations with mortality were: mid-upper arm circumference (MUAC) of 11.5–13.0 cm compared to >13.0 cm (HR 7.2; 95% CI 3.0 to 17.0), MUAC 10.5–11.4 cm (HR 24; 95% CI 9.4 to 62), and MUAC <10.5 cm (HR 44; 95% CI 18 to 108), neck stiffness (HR 10.4; 95% CI 3.1 to 34.8), non-medical discharge (HR 4.7; 95% CI 2.0 to 10.9), dry season discharge (HR 2.0; 95% CI 1.2 to 3.3), while greater haemoglobin (HR 0.82; 0.73 to 0.91), axillary temperature (HR 0.71; 95% CI 0.58 to 0.87), and oxygen saturation (HR 0.96; 95% CI 0.93 to 0.99) were associated with reduced mortality. Conclusion Gambian children experience increased mortality after discharge from primary and secondary care. Interventions should target both moderately and severely malnourished children.

Impact of the introduction of pneumococcal conjugate vaccination on pneumonia in The Gambia: population-based surveillance and case-control studies

Summary Background Pneumococcal conjugate vaccines (PCVs) are used in many low-income countries but their impact on the incidence of pneumonia is unclear. The Gambia introduced PCV7 in August, 2009, and PCV13 in May, 2011. We aimed to measure the impact of the introduction of these vaccines on pneumonia incidence. Methods We did population-based surveillance and case-control studies. The primary endpoint was WHO-defined radiological pneumonia with pulmonary consolidation. Population-based surveillance was for suspected pneumonia in children aged 2–59 months (minimum age 3 months in the case-control study) between May 12, 2008, and Dec 31, 2015. Surveillance for the impact study was limited to the Basse Health and Demographic Surveillance System (BHDSS), whereas surveillance for the case-control study included both the BHDSS and Fuladu West Health and Demographic Surveillance System. Nurses screened all outpatients and inpatients at all health facilities in the surveillance area using standardised criteria for referral to clinicians in Basse and Bansang. These clinicians recorded clinical findings and applied standardised criteria to identify patients with suspected pneumonia. We compared the incidence of pneumonia during the baseline period (May 12, 2008, to May 11, 2010) and the PCV13 period (Jan 1, 2014, to Dec 31, 2015). We also investigated the effectiveness of PCV13 using case-control methods between Sept 12, 2011, and Sept 31, 2014. Controls were aged 90 days or older, and were eligible to have received at least one dose of PCV13; cases had the same eligibility criteria with the addition of having WHO-defined radiological pneumonia. Findings We investigated 18u2008833 children with clinical pneumonia and identified 2156 cases of radiological pneumonia. Among children aged 2–11 months, the incidence of radiological pneumonia fell from 21·0 cases per 1000 person-years in the baseline period to 16·2 cases per 1000 person-years (23% decline, 95% CI 7–36) in 2014–15. In the 12–23 month age group, radiological pneumonia decreased from 15·3 to 10·9 cases per 1000 person-years (29% decline, 12–42). In children aged 2–4 years, incidence fell from 5·2 to 4·1 cases per 1000 person-years (22% decline, 1–39). Incidence of all clinical pneumonia increased by 4% (–1 to 8), but hospitalised cases declined by 8% (3–13). Pneumococcal pneumonia declined from 2·9 to 1·2 cases per 1000 person-years (58% decline, 22–77) in children aged 2–11 months and from 2·6 to 0·7 cases per 1000 person-years (75% decline, 47–88) in children aged 12–23 months. Hypoxic pneumonia fell from 13·1 to 5·7 cases per 1000 person-years (57% decline, 42–67) in children aged 2–11 months and from 6·8 to 1·9 cases per 1000 person-years (72% decline, 58–82) in children aged 12–23 months. In the case-control study, the best estimate of the effectiveness of three doses of PCV13 against radiological pneumonia was an adjusted odds ratio of 0·57 (0·30–1·08) in children aged 3–11 months and vaccine effectiveness increased with greater numbers of doses (p=0·026). The analysis in children aged 12 months and older was underpowered because there were few unvaccinated cases and controls. Interpretation The introduction of PCV in The Gambia was associated with a moderate impact on the incidence of radiological pneumonia, a small reduction in cases of hospitalised pneumonia, and substantial reductions of pneumococcal and hypoxic pneumonia in young children. Low-income countries that introduce PCV13 with reasonable coverage can expect modest reductions in hospitalised cases of pneumonia and a marked impact on the incidence of severe childhood pneumonia. Funding GAVIs Pneumococcal vaccines Accelerated Development and Introduction Plan, Bill & Melinda Gates Foundation, and UK Medical Research Council.

Pneumococcal carriage in rural Gambia prior to the introduction of pneumococcal conjugate vaccine: a population-based survey

To evaluate pneumococcal colonisation before and after the introduction of pneumococcal conjugate vaccine (PCV) in eastern Gambia.

Childhood pneumonia and crowding, bed-sharing and nutrition: a case-control study from The Gambia

SUMMARY SETTING: Greater Banjul and Upper River Regions, The Gambia. OBJECTIVE: To investigate tractable social, environmental and nutritional risk factors for childhood pneumonia. DESIGN: A case-control study examining the association of crowding, household air pollution (HAP) and nutritional factors with pneumonia was undertaken in children aged 2–59 months: 458 children with severe pneumonia, defined according to the modified WHO criteria, were compared with 322 children with non-severe pneumonia, and these groups were compared to 801 neighbourhood controls. Controls were matched by age, sex, area and season. RESULTS: Strong evidence was found of an association between bed-sharing with someone with a cough and severe pneumonia (adjusted OR [aOR] 5.1, 95%CI 3.2–8.2, P < 0.001) and non-severe pneumonia (aOR 7.3, 95%CI 4.1–13.1, P < 0.001), with 18% of severe cases estimated to be attributable to this risk factor. Malnutrition and pneumonia had clear evidence of association, which was strongest between severe malnutrition and severe pneumonia (aOR 8.7, 95%CI 4.2–17.8, P < 0.001). No association was found between pneumonia and individual carbon monoxide exposure as a measure of HAP. CONCLUSION: Bed-sharing with someone with a cough is an important risk factor for severe pneumonia, and potentially tractable to intervention, while malnutrition remains an important tractable determinant.

The large contribution of twins to neonatal and post-neonatal mortality in The Gambia, a 5-year prospective study

BackgroundA high twinning rate and an increased risk of mortality among twins contribute to the high burden of infant mortality in Africa. This study examined the contribution of twins to neonatal and post-neonatal mortality in The Gambia, and evaluated factors that contribute to the excess mortality among twins.MethodsWe analysed data from the Basse Health and Demographic Surveillance System (BHDSS) collected from January 2009 to December 2013. Demographic and epidemiological variables were assessed for their association with mortality in different age groups.ResultsWe included 32,436 singletons and 1083 twins in the analysis (twining rate 16.7/1000 deliveries). Twins represented 11.8xa0% of all neonatal deaths and 7.8xa0% of post-neonatal deaths. Mortality among twins was higher than in singletons [adjusted odds ratio (AOR) 4.33 (95 % CI: 3.09, 6.06) in the neonatal period and 2.61 (95 % CI: 1.85, 3.68) in the post-neonatal period]. Post-neonatal mortality among twins increased in girls (P for interactionu2009=u20090.064), being born during the dry season (P for interactionu2009=u20090.030) and lacking access to clean water (P for interactionu2009=u20090.042).ConclusionMortality among twins makes a significant contribution to the high burden of neonatal and post-neonatal mortality in The Gambia and preventive interventions targeting twins should be prioritized.

The definition and classification of pneumonia.

Following the publication of a volume of Pneumonia focused on diagnosis, the journal’s Editorial Board members debated the definition and classification of pneumonia and came to a consensus on the need to revise both of these. The problem with our current approach to the classification of pneumonia is twofold: (i) it results in widespread empirical, and often unnecessary, use of antimicrobials that contributes to pathogen resistance; and (ii) it contributes to heterogeneity among the groups of subjects compared in research, causing misclassification bias and mixtures of effects that threaten internal validity. After outlining the problem of classification, this commentary describes the strengths and weaknesses of a range of systems for the classification of pneumonia. The commentary then calls for debate to generate consensus classifications in the field, proposing a working definition and way forward focusing on the following three points: (i) pneumonia should be defined as an acute infection of the lung parenchyma by various pathogens, excluding the condition of bronchiolitis; (ii) defining pneumonia as a group of specific (co)infections with different characteristics is an ideal that currently has limited use, because the identification of aetiologic organisms in individuals is often not possible (however, the benefits of classifying pneumonia into specific, more homogenous phenotypes should be carefully considered when designing research studies); and (iii) investigation of more homogenous pneumonia groupings is achievable and is likely to yield more rapid advances in the field.

The economic burden of childhood pneumococcal diseases in The Gambia

BackgroundStreptococcus pneumoniae is a common cause of child death. However, the economic burden of pneumococcal disease in low-income countries is poorly described. We aimed to estimate from a societal perspective, the costs incurred by health providers and families of children with pneumococcal diseases.MethodsWe recruited children less than 5xa0years of age with outpatient pneumonia, inpatient pneumonia, pneumococcal sepsis and bacterial meningitis at facilities in rural and urban Gambia. We collected provider costs, out of pocket costs and productivity loss for the families of children. For each disease diagnostic category, costs were collected before, during, and for 1xa0week after discharge from hospital or outpatient visit.ResultsA total of 340 children were enrolled; 100 outpatient pneumonia, 175 inpatient pneumonia 36 pneumococcal sepsis, and 29 bacterial meningitis cases. The mean provider costs per patient for treating outpatient pneumonia, inpatient pneumonia, pneumococcal sepsis and meningitis were US