Impact of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease and pneumonia in The Gambia: 10 years of population-based surveillance.

BACKGROUND: The Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV7) in August 2009, followed by PCV13 in May, 2011, using a schedule of three primary doses without a booster dose or catch-up immunisation. We aimed to assess the long-term impact of PCV on disease incidence. METHODS: We did 10 years of population-based surveillance for invasive pneumococcal disease (IPD) and WHO defined radiological pneumonia with consolidation in rural Gambia. The surveillance population included all Basse Health and Demographic Surveillance System residents aged 2 months or older. Nurses screened all outpatients and inpatients at all health facilities using standardised criteria for referral. Clinicians then applied criteria for patient investigation. We defined IPD as a compatible illness with isolation of Streptococcus pneumoniae from a normally sterile site (cerebrospinal fluid, blood, or pleural fluid). We compared disease incidence between baseline (May 12, 2008-May 11, 2010) and post-vaccine years (2016-2017), in children aged 2 months to 14 years, adjusting for changes in case ascertainment over time. FINDINGS: We identified 22 728 patients for investigation and detected 342 cases of IPD and 2623 cases of radiological pneumonia. Among children aged 2-59 months, IPD incidence declined from 184 cases per 100 000 person-years to 38 cases per 100 000 person-years, an 80% reduction (95% CI 69-87). Non-pneumococcal bacteraemia incidence did not change significantly over time (incidence rate ratio 0·88; 95% CI, 0·64-1·21). We detected zero cases of vaccine-type IPD in the 2-11 month age group in 2016-17. Incidence of radiological pneumonia decreased by 33% (95% CI 24-40), from 10·5 to 7·0 per 1000 person-years in the 2-59 month age group, while pneumonia hospitalisations declined by 27% (95% CI 22-31). In the 5-14 year age group, IPD incidence declined by 69% (95% CI -28 to 91) and radiological pneumonia by 27% (95% CI -5 to 49). INTERPRETATION: Routine introduction of PCV13 substantially reduced the incidence of childhood IPD and pneumonia in rural Gambia, including elimination of vaccine-type IPD in infants. Other low-income countries can expect substantial impact from the introduction of PCV13 using a schedule of three primary doses. FUNDING: Gavi, The Vaccine Alliance; Bill & Melinda Gates Foundation; UK Medical Research Council; Pfizer Ltd.

Preliminary report from the World Health Organisation Chest Radiography in Epidemiological Studies project.

Childhood pneumonia is among the leading infectious causes of mortality in children younger than 5 years of age globally. Streptococcus pneumoniae (pneumococcus) is the leading infectious cause of childhood bacterial pneumonia. The diagnosis of childhood pneumonia remains a critical epidemiological task for monitoring vaccine and treatment program effectiveness. The chest radiograph remains the most readily available and common imaging modality to assess childhood pneumonia. In 1997, the World Health Organization Radiology Working Group was established to provide a consensus method for the standardized definition for the interpretation of pediatric frontal chest radiographs, for use in bacterial vaccine efficacy trials in children. The definition was not designed for use in individual patient clinical management because of its emphasis on specificity at the expense of sensitivity. These definitions and endpoint conclusions were published in 2001 and an analysis of observer variation for these conclusions using a reference library of chest radiographs was published in 2005. In response to the technical needs identified through subsequent meetings, the World Health Organization Chest Radiography in Epidemiological Studies (CRES) project was initiated and is designed to be a continuation of the World Health Organization Radiology Working Group. The aims of the World Health Organization CRES project are to clarify the definitions used in the World Health Organization defined standardized interpretation of pediatric chest radiographs in bacterial vaccine impact and pneumonia epidemiological studies, reinforce the focus on reproducible chest radiograph readings, provide training and support with World Health Organization defined standardized interpretation of chest radiographs and develop guidelines and tools for investigators and site staff to assist in obtaining high-quality chest radiographs.

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

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 18 833 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: GAVI's Pneumococcal vaccines Accelerated Development and Introduction Plan, Bill & Melinda Gates Foundation, and UK Medical Research Council.

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

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 14 650 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 100 000 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 100 000, 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 100 000, 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: GAVI's Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP), Bill & Melinda Gates Foundation, and the UK Medical Research Council.

Chronic rhinosinusitis: correlation of symptoms with computed tomography scan findings.

INTRODUCTION: Symptomatology, nasal endoscopy and Computerised Tomographic (CT) scan have been used to diagnose chronic rhinosinusitis. The value of disease severity score in the assessment of chronic rhinosinusitis has not been well investigated. Hence, this study aims to correlate the pre-operative symptom severity score as well as overall disease severity score of patients with chronic rhinosinusitis with CT scan scores. METHODS: This is a prospective study of 60 patients diagnosed clinically with chronic rhinosinusitis. Each patients ubjectively assessed his/her presenting symptoms and severity of disease on a visual analogue scale. The patients had CT scan of the paranasal sinuses which were graded and scored using Lund-Mackay grading system. The correlation study between severity of symptoms/disease severity and CT scores was performed. The level of statistical significance was considered at p<0.05 and confidence interval at 95%. RESULTS: All patients had more than one symptom with mean symptom severity scores highest for nasal discharge and nasal obstruction. There was a significant correlation between CT scores and nasal discharge (r=-0.132; p=0.03)and nasal obstruction (r=0.193; p=0.049). No correlation with other symptoms. There was no correlation between the overall disease severity scores and the Lund-Mackay CT scores (r=0.195; p=0.6). CONCLUSION: This study showed that CT scan scores can help clinicians to predict severity of symptom for nasal obstruction and discharge but not for other symptoms of chronic rhinosinusitis. However, there was no association of CT score with the overall disease severity score.

Stroke risk factors, subtypes, and 30-day case fatality in Abuja, Nigeria.

BACKGROUND: Stroke is the second leading cause of death and the leading cause of adult disability worldwide. A better understanding of stroke risk factors and outcome may help guide efforts at reducing the community burden of stroke. This study aimed to understand stroke risk factors, imaging subtypes, and 30-day outcomes among adult Nigerians. MATERIALS AND METHODS: We prospectively recruited all patients presenting with acute stroke at the National Hospital Abuja between January 2010 and June 2012. We assessed clinical and laboratory variables, as well as brain computerized tomography, magnetic resonance imaging, and carotid Doppler ultrasound scans. We also assessed case fatality and functional outcome at 30 days after stroke. RESULTS: Of 272 patients studied, 168 (61.8%) were males. Age at presentation (mean ± standard deviation) was 56.4 ± 12.7 years in males and 52.9 ± 14.8 years in females (P = 0.039). Neuroimaging was obtained in 96.7% patients, revealing cerebral infarction (61.8%), intracerebral hemorrhage (ICH) (34.8%), and subarachnoid hemorrhage (SAH) (3.4%). Carotid plaques or stenosis ≥50% were detected in 53.2% patients with cerebral infarction. Stroke risk factors included hypertension (82.7%), obesity (32.6%), diabetes (23.5%), hyperlipidemia (18.4%), atrial fibrillation (9.2%), and cigarette smoking (7.7%). At 30 days after stroke, case-fatality rate was 18.8%, whereas modified Rankin Scale (mRS) scores for cerebral infarction, ICH, and SAH were 3.71, 4.21, and 4.56, respectively. Atrial fibrillation, a previous stroke, and age older than 50 years were all associated with worse mRS scores at 30 days. CONCLUSION: Although hypertension, obesity, diabetes mellitus, and atrial fibrillation were important stroke risk factors, in many patients, these were detected only after a stroke. While the commonest stroke subtype was cerebral infarction, observed in almost two-third of patients, SAH was associated with the highest case-fatality rate at 30 days of 44.4%. Larger population-based studies may provide additional data on stroke incidence and outcome among Nigerians.

Aetiological differences in demographical, clinical and pathological characteristics of hepatocellular carcinoma in The Gambia.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a high burden in West Africa. Data evaluating aetiological differences in HCC presentation from this region are limited. AIMS: The aim of this study was to describe the demographical, clinical and pathological characteristics of HCC by aetiology (hepatitis B or C infection, aflatoxin associated). METHODS: One hundred and ninty-three cases of HCC diagnosed between 1997 and 2001 in The Gambia were analysed. Characteristics were compared by aetiology using χ(2)-tests, student t-test and Wilcoxon's rank sum tests as appropriate. RESULTS: The prevalence of hepatitis B surface antigen, hepatitis C antibody and aflatoxin-associated 249(ser) TP53 mutations among HCC patients was 60, 20 and 38% respectively. The typical HCC patient was a 49-year-old male positive for hepatitis B surface antigen presenting with hepatomegaly (93%), abdominal pain (94%) and weight loss (95%) 8 weeks after symptom onset. Most patients had multifocal lesions with background cirrhosis. The median largest tumour was 10.3 cm and the median α-fetoprotein level was 500 ng/ml. Eighty-four per cent of patients had advanced HCC (patients not meeting the Milan criteria) at presentation. CONCLUSIONS: Irrespective of aetiological agent, HCC among West Africans presents at very advanced stages. Few clinical or pathological differences exist by aetiology. More studies are needed to understand the mechanisms of hepatocarcinogenesis among these patients as well as identify high-risk populations in which early detection through screening will be beneficial.

Aflatoxin exposure and viral hepatitis in the etiology of liver cirrhosis in the Gambia, West Africa.

BACKGROUND: Cirrhosis of the liver is thought to be a major cause of morbidity and mortality in sub-Saharan Africa, but few controlled studies on the etiology of cirrhosis have been conducted in this region. OBJECTIVES: We aimed to elucidate the association between environmental and infectious exposures and cirrhosis in The Gambia. METHODS: Ninety-seven individuals were diagnosed with cirrhosis using a validated ultrasound scoring system and were compared with 397 controls. Participants reported demographic and food frequency information. Blood samples were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis C virus (HCV) antibody, HCV RNA, and the aflatoxin-associated 249(ser) TP53 mutation. RESULTS: HBsAg seropositivity was associated with a significant increase in risk of cirrhosis [odds ratio (OR) = 8.0; 95% confidence interval (CI), 4.4-14.7] as was the presence of HBeAg (OR = 10.3; 95% CI, 2.0-53.9) and HCV infection (OR = 3.3; 95% CI, 1.2-9.5). We present novel data that exposure to aflatoxin, as assessed both by high lifetime groundnut (peanut) intake and by the presence of the 249(ser) TP53 mutation in plasma, is associated with a significant increase in the risk for cirrhosis (OR = 2.8; 95% CI, 1.1-7.7 and OR = 3.8; 95% CI, 1.5-9.6, respectively). Additionally, aflatoxin and hepatitis B virus exposure appeared to interact synergistically to substantially increase the risk of cirrhosis, although this was not statistically significant. CONCLUSIONS: Our results suggest that the spectrum of morbidity associated with aflatoxin exposure could include cirrhosis.

The Gambia Liver Cancer Study: Infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa.

Hepatocellular carcinoma (HCC) is the most common cancer in The Gambia. Hepatitis B virus (HBV) infection is endemic, with 15% to 20% of the population being chronic carriers, whereas hepatitis C virus (HCV) prevalence is low. We recruited 216 incident cases of HCC and 408 controls from three sites. HBV carriage was present in 61% (129/211) of HCC patients and 16% (64/402) of controls, whereas 19% (36/191) of HCC patients were HCV seropositive compared with 3% (11/382) of controls. HCC patients with HCV were notably older and were more likely to be female than those with HBV. Increased HCC risk was strongly associated with chronic HBV (odds ratio, 16.7; 95% CI, 9.7-28.7), HCV (16.7; 6.9-40.1), and dual infection (35.3; 3.9-323). We interpret the additive nature of risk with coinfection as representative of HBV and HCV acting primarily through shared steps in the multistage process of hepatocarcinogenesis. HCV infection was not observed among younger participants, suggesting a possible cohort effect. Reasons for the striking age and gender differences in HCC associated with HBV compared with HCV are unclear, but transmission patterns and age at exposure may be factors. In conclusion, in a standardized evaluation of well-characterized study participants from The Gambia, most cases of HCC are attributable to HBV (57%), but HCV adds a significant fraction (20%), especially among older patients and females. If HCV transmission is not perpetuated in future cohorts, focusing available resources on HB vaccination efforts could greatly ameliorate a major cause of cancer death in sub-Saharan Africa.