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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.

•Average monthly EPI attendance reduced by 13.4% during the COVID interrupted period.•Average monthly immunizations were reduced by 38.3% during the interruption period.•Highest decline was observed in vaccines given early in infancy.•Reduced EPI attendance during the pandemic interruption period lasted only 3 months.•Mothers were comfortable to re-start EPI attendance with older than younger infants. The COVID-19 pandemic has affected the delivery of essential health services, such as routine immunization. We assessed the impact of the pandemic on the uptake of routine immunization in rural Gambia. We collected real-time vaccine administration data in the Basse and Fuladu West Health & Demographic Surveillance Systems from September 01, 2019, to December 31, 2020. We assessed the monthly number of Expanded Program on Immunization (EPI) clinic attendances and vaccines administered, comparing data during the baseline period (September 01, 2019–March 31, 2020), COVID-19 interruption period (April 01–June 30, 2020), initial recovery period (Jul 01–September 30, 2020) and the late recovery period (October 01–December 31, 2020). Compared to the baseline period, there was an overall average monthly decline of 13.4% in EPI attendance and 38.3% reduction in average monthly immunizations during the interruption period. This decrease was particularly noticeable for Bacille Calmette-Guérin (BCG) (47.2%), birth dose hepatitis B (Hep B) (46.9%), 1st dose pentavalent (Penta1) (43.1%), 1st dose pneumococcal conjugate vaccine (PCV1) (42.4%), and measles vaccines (15.5%). Comparing the late recovery to baseline period, average monthly EPI attendance was 5.3% higher, with 1.9% increase in average monthly immunizations. Monthly immunizations for BCG were 3.0% greater, 2.5% greater for Hep B, 22.7% greater for oral polio vaccine (OPV1), 2.0% less for Penta1, 19.2% less for Penta2, and 2.6% less for PCV1. The reduced EPI attendance during the pandemic interruption period lasted only 3 months. Significant recovery in EPI attendance occurred during the late recovery period, while rates of monthly immunization returned to pre-pandemic levels for most antigens. EPI programmes should implement strategies to deliver missed antigens when infants do present to EPI clinics, aware that missed doses may be age dependent.

The introduction in many countries of conjugate vaccines against Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis has led to significant reductions in acute bacterial meningitis (ABM) in children. However, recent population-based data on ABM in sub-Saharan Africa are limited. Population-based surveillance for meningitis was carried out in a rural area of The Gambia under demographic surveillance from 2008 to 2017, using standardised criteria for referral, diagnosis and investigation. We calculated incidence using population denominators. We diagnosed 1,666 patients with suspected meningitis and collected cerebrospinal fluid (n = 1,121) and/or blood (n = 1,070) from 1,427 (88%) of cases. We identified 169 cases of ABM, 209 cases of suspected non-bacterial meningitis (SNBM) and 1,049 cases of clinically suspected meningitis (CSM). The estimated average annual incidence of ABM was high at 145 per 100,000 population in the <2-month age group, 56 per 100,000 in the 2-23-month age group, but lower at 5 per 100,000 in the 5-14-year age group. The most common causes of ABM were Streptococcus pneumoniae (n = 44), Neisseria meningitidis (n = 42), and Gram-negative coliform bacteria (n = 26). Eighteen of 22 cases caused by pneumococcal serotypes included in PCV13 occurred prior to vaccine introduction and four afterwards. The overall case fatality ratio for ABM was 29% (49/169) and was highest in the <2-month age group 37% (10/27). The case fatality ratio was 8.6% (18/209) for suspected non-bacterial meningitis and 12.8% (134/1049) for clinically suspected meningitis cases. Gambian children continue to experience substantial morbidity and mortality associated with suspected meningitis, especially acute bacterial meningitis. Such severely ill children in sub-Saharan Africa require improved diagnostics and clinical care.

Cryptosporidium is a major pathogen associated with diarrheal disease in young children. We studied Cryptosporidium diarrhea in children enrolled in the Global Enteric Multicenter Study (GEMS) in rural Gambia. We recruited children <5 years of age with moderate-to-severe diarrhea (MSD) for 3 years (2008-2010), and children with either MSD or less severe diarrhea (LSD) for one year (November 2011-November 2012) at sentinel health centers. One or more randomly selected controls were matched to each case. Stool samples were tested to identify Cryptosporidium by immunoassay. A subset of randomly selected case-controls pairs were tested for Cryptosporidium species. We investigated the epidemiology of, and evaluated possible risk factors for, Cryptosporidium-positive diarrhea. We enrolled 1938 cases (1381 MSD, 557 LSD) and 2969 matched controls; 231/1929 (12.0%) of diarrhea cases and 141/2962 (4.8%) of controls were positive for Cryptosporidium. Most Cryptosporidium diarrhea cases (85.7%, 198/231) were aged 6-23 months, and most (81.4%, 188/231) occurred during the rainy season. Cryptosporidium hominis (C. hominis) was the predominant (82.6%) species. We found associations between increased risk of Cryptosporidium-positive MSD or LSD, or both, with consumption of stored drinking water and certain animals living in the compound-cow, cat (MSD only) and rodents (LSD only). Larger households, fowl living in the compound, and the presence of Giardia infection were associated with decreased risk of Cryptosporidium MSD and LSD. Cryptosporidium-positive diarrhea is prevalent in this setting, especially at 6-23 months of age. The preponderance of Cryptosporidium infection in the rainy season and increased risk of Cryptosporidium-positive diarrhea with consumption of stored drinking water suggest water-borne transmission. Further investigation is needed to clarify the role of animals and contamination of stored drinking water in Cryptosporidium transmission.

Sub-Saharan Africa has a high burden of pneumococcal diseases. Pneumococcal carriage precedes invasive disease and transmission. The introduction of pneumococcal conjugate vaccines (PCVs) has significantly reduced global vaccine-type (VT) pneumococcal disease, but data on PCVs' long-term impact on VT serotypes in Africa are limited. We aimed to evaluate PCV13's long-term effect on pneumococcal carriage in rural Gambia. From January to November 2022, we conducted a population-based, cross-sectional pneumococcal carriage survey in Central and Upper River Regions of The Gambia. We collected data on demographic characteristics, clinical history, risk factors, and PCV status. Nasopharyngeal swabs were taken from randomly selected household members of all ages. Streptococcus pneumoniae was isolated and serotyped using standard methods. We measured the prevalence of pneumococcal carriage by specific age groups, PCV13 vaccination status, and the proportions of different pneumococcal outcomes among carriers. We performed multivariable logistic regression to examine factors associated with VT carriage. Overall, 4087 participants were enrolled; the prevalence of pneumococcal carriage was 32.1% (95% CI: 29.34% – 35.03%). The estimated prevalence of PCV13 VT carriage was 6.4% (95% CI: 5.48% - 7.47%). Children aged 5–9 years had the highest VT carriage prevalence at 13.6% (95% CI: 10.34% - 17.56%). Among fully PCV-vaccinated children under 10, the odds of VT carriage in 5–9-year-olds were 1.60 times higher than in infants aged 0–11 months [AOR = 1.60, 95% CI:1.06–2.41]. The prevalence of VT carriage was similar among fully PCV-vaccinated and unvaccinated children under 10 years of age. Serotypes 19F, 3 and 6A were the most abundant VTs; 19F and 3 were the most prevalent among <5 and 5–14-year-old children, respectively. Ten years after the introduction of PCV13 in the Gambia, residual VT carriage persists, particularly in age groups in whom direct protection from immunization in infancy has waned. A booster dose or catch-up vaccinations could aid control of VT circulation. •Substantial reductions in VT carriage were observed in children, with significant indirect effects on unvaccinated adults.•Residual carriage of vaccine-type pneumococci persists, especially among fully PCV-vaccinated children under 10 years of age.•Children aged 5–9 years were identified as primary reservoirs of VT carriage.•The prevalence of VT carriage was similar in fully PCV-vaccinated and unvaccinated children under 10 years of age.•Serotypes 3 and 19F were the most common VT serotypes among children aged 5–14 and those aged 0–4, respectively.

Background Close contact between an infectious and susceptible person is an important factor in respiratory disease transmission. Information on social contacts and mixing patterns in a population is crucial to understanding transmission patterns and informing transmission models of respiratory infections. Although West Africa has one of the highest burdens of respiratory infections, there is a lack of data on interpersonal contact and mixing patterns in this region. Methods Between January and November 2022, we conducted a cross-sectional, social contact survey within the population of the Central and Upper River Regions of The Gambia. Selected participants completed a questionnaire about their travel history and social contacts, detailing the number, intensity, location, frequency, duration, and age of contacts. We calculated age-standardized contact matrices to determine contact patterns in the population. Results Overall, individuals made an average of 12.7 (95% CI: 12.4–13.0) contacts per day. Contact patterns were mostly age-assortative and 84.5% of all contacts were physical. School-aged children (5–14 years) had the highest mean number of physical contacts (11.3, 95% CI: 10.9–11.8) while the < 1-year age group had the fewest contacts (9.4, 95% CI: 9.1–9.8). A large proportion of contacts (78%) occurred at home. Daily number of contacts increased with household size. While we did not observe any effect of gender on contact patterns, there were seasonal variations in contact type. Non-physical contacts were higher during the dry season compared to the rainy season. In contrast, there were more physical contacts in the rainy season compared to the dry season. Conclusions In rural Gambia, social contact patterns were primarily driven by household mixing. Most contacts were physical and mostly age-assortative, particularly among school-aged children. Our data can improve infectious disease transmission models of respiratory pathogens in high-transmission settings, which are valuable for optimizing the delivery of different interventions.

Rationale The effectiveness of universal immunisation with pneumococcal conjugate vaccine (PCV) has been evident in many countries. However, the global impact of PCV is limited by its cost, which has prevented its introduction in several countries. Reducing the cost of PCV programmes may facilitate vaccine introduction in some countries and improve the sustainability of PCV in EPIs in low-income countries when they transition away from subsidised vaccine supply. Methods and design PVS is a real-world field trial of an alternative schedule of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months (i.e. the alternative ‘1+1’ schedule) compared to the standard schedule of three primary doses scheduled at 6, 10, and 14 weeks of age (i.e. the standard ‘3+0’ schedule). Delivery of the interventions began in late 2019 in 68 geographic clusters and will continue for 4 years. The primary endpoint is the prevalence of nasopharyngeal vaccine-type pneumococcal carriage in children aged 2–260 weeks with clinical pneumonia in year 4. Secondary endpoints are the prevalence of vaccine-type pneumococcal carriage among all ages in year 4 and the incidence of radiological pneumonia in children enrolled to receive the interventions. Additional disease and carriage endpoints are included. Purpose This statistical analysis plan (SAP) describes the cohorts and populations, and follow-up criteria, to be used in different analyses. The SAP defines the endpoints and describes how adherence to the interventions will be presented. We describe how analyses will account for the effect of clustering and stratified randomisation. The SAP defines the approach to non-inferiority and other analyses. Defining the SAP early in the trial will avoid bias in analyses that may arise from prior knowledge of trial findings.

To measure mortality and its risk factors among children discharged from a health centre in rural Gambia. 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. 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. Gambian children experience increased mortality after discharge from primary and secondary care. Interventions should target both moderately and severely malnourished children.

In low-resource settings, it is challenging to ascertain the burden and causes of under-5 mortality as many deaths occur outside health facilities. We aimed to determine the causes of childhood deaths in rural Gambia using verbal autopsies (VA). We used WHO VA questionnaires to conduct VAs for deaths under-5 years of age in the Basse and Fuladu West Health and Demographic Surveillance Systems (HDSS) in rural Gambia between September 01, 2019, and December 31, 2021. Using a standardized cause of death list, two physicians assigned causes of death and discordant diagnoses were resolved by consensus. VAs were conducted for 89% (647/727) of deaths. Of these deaths, 49.5% (n = 319) occurred at home, 50.1% (n = 324) in females, and 32.3% (n = 209) in neonates. Acute respiratory infection including pneumonia (ARIP) (33.7%, n = 137) and diarrhoeal diseases (23.3%, n = 95) were the commonest primary causes of death in the post-neonatal period. In the neonatal period, unspecified perinatal causes of death (34.0%, n = 71) and deaths due to birth asphyxia (27.3%, n = 57) were the commonest causes of death. Severe malnutrition (28.6%, n = 185) was the commonest underlying cause of death. In the neonatal period, deaths due to birth asphyxia (p-value<0.001) and severe anaemia (p-value = 0.03) were more likely to occur at hospitals while unspecified perinatal deaths (p-value = 0.01) were more likely to occur at home. In the post-neonatal period, deaths due to ARIP (p-value = 0.04) and diarrhoeal disease (p-value = 0.001) were more likely to occur among children aged 1-11 months and 12-23 months respectively. According to VA analysis of deaths identified within two HDSS in rural Gambia, half of deaths amongst children under-5 in rural Gambia occur at home. ARIP and diarrhoea, and the underlying cause of severe malnutrition remain the predominant causes of child mortality. Improved health care and health-seeking behaviour may reduce childhood deaths in rural Gambia.

•Vaccine-type pneumococcal carriage in young and older children declined significantly following routine use of PCV in The Gambia.•Significant residual vaccine-type carriage in children.•Non-vaccine-type carriage increased in all age groups.•Significant pneumococcal transmission continues in the population. The introduction of pneumococcal conjugate vaccines (PCV) has reduced carriage of vaccine-type (VT) pneumococci in many settings. We determined the impact of The Gambia’s national PCV programme on carriage of VT pneumococci in the population. Seven-valent PCV (PCV7) was introduced in August 2009 without catch-up and with doses scheduled at 2, 3, 4 months of age; it was replaced by PCV13 in May 2011. We did cross-sectional carriage surveys in 2009, 2015, and 2017 in age-stratified, population-based samples. Nasopharyngeal specimens were collected and processed according to WHO guidelines. We calculated observed and adjusted prevalence ratios (PR) of VT carriage before and after PCV introduction. We enrolled 2988, 3162, and 2709 participants in 2009, 2015, and 2017 respectively. The baseline (2009) prevalence of VT pneumococcal carriage among children aged 0–4 years was 42.6 %, which declined to 14.9 % and 17.5 % in 2015 and 2017 respectively (adjPR 0.32 [95 % CI 0.27, 0.38] and 0.38 [0.31, 0.46] respectively). VT prevalence among children aged 5–14 years was 16.6 %, 15.1 %, and 15.8 % in the three surveys (2017 vs 2009, adjPR 0.70 [0.58, 0.83]). VT prevalence among 15–44 year-olds was 6.4 %, 5.7 %, and 7.1 % in the three surveys (2017 vs 2009, adjPR 0.59 [0.46, 0.75]), while in those aged ≥ 45 years it was 4.5 %, 6.5 %, and 4.5 % respectively. Non-VT carriage increased in all age-groups. Prevalent residual serotypes were 34 and 15B (age 0–4 years), 3 and 34 (age 5–14 years), and 3 and 16F (age ≥ 15 years). Introduction of PCV was associated with reduced VT pneumococcal carriage in young, and older children, although with substantial residual prevalence. Persisting VT, and non-VT, carriage indicate significant, persistent transmission of pneumococci in the population.