Background

We assessed the distribution of pneumococcal serotypes in children with microbiologically-confirmed invasive pneumococcal disease (IPD) before (2014-2015) and after (2016-2019) PCV10 introduction in Nepal in 2015.

Methods

Children (aged 2 months to <14 years) admitted to Patan Hospital, Nepal with pneumococcus detected in blood, CSF or pleural fluid were included. Serotyping was by Quellung method.

Results

Pre-vaccine, 6/22 (27.3%) IPD cases were age <2 years; post-vaccine, 5/36 (13.9%) were <2 years. Ratio of vaccine-type to non-vaccine-type IPD among <2y olds was 5:1 pre-vaccine and 2:3 post-vaccine; among >=2y olds, the ratio was 13:1 pre-vaccine and 7:1 post-vaccine. Most (32/41, 78%) vaccine-type IPD was serotype 1: 3/7 among <2 year olds (n=1 post-vaccine); 29/34 among >=2 year olds (n=17/19 post-vaccine were >4 years old). Among 44 IPD cases detected from blood, 36 (82%) were vaccine-type (n=29 were ST1), and 7 were non-vaccine-type (6C, 10A (n=2), 19A, 24F, 38, 41). Of 13 detected from CSF (1 culture, 3 PCR and 9 Binax-only), 5 were serotyped (1, 14, 6B, 6A/B, 7F) .The 3 pleural fluid cases were serotypes 1 (n=2) and 19A.

Conclusions

Post-PCV10 introduction, IPD among <2 year olds fell; although a high proportion of ST1 IPD remains, most were >4 years old.

Background

Community carriage of pneumococcal serotypes in children was assessed pre- and post-PCV10 introduction in Nepal to monitor pneumococcal vaccine impact. Molecular serotyping by microarray enabled detection of multiple-serotype carriage plus non-encapsulated pneumococcal lineages, related Streptococcus species and selected antimicrobial resistance genes.

Methods

Nasopharyngeal swabs were collected from healthy Nepalese children in 2014-15 (pre-PCV10) and 2017-18 (post-PCV10). DNA was extracted from plate sweeps of 1,241 and 1,445 swab cultures for pre- and post-vaccine periods respectively and analysed by Senti-SP molecular serotyping microarray.

Results

Comparing carriage among children pre- and post-PCV10, there was a decrease in PCV10 serotype carriage (37% vs 17%) and an increase in non-vaccine serotype carriage (67% vs 73%). There was no change for non-encapsulated pneumococcal lineages (16% vs 16%), an increase in related Streptococcal species (22% vs 25%) and an increase in detection of antimicrobial resistance genes (65% vs 74%). Multiple pneumococcal serotype carriage decreased (24% vs 16%) and multiple carriage including non-encapsulated pneumococci and related Streptococcal species also decreased (45% vs 41%).

Conclusions

Introduction of PCV10 in Nepal has resulted in a decrease in vaccine type carriage within two years. However, increases in carriage of non-vaccine types as well as antimicrobial resistance genes and related Streptococcal species were observed.

Background

S. pneumoniae is one of the most common causes of paediatric bacterial pneumonia. In low-income countries such as Nepal, CRP level and blood culture can be useful in diagnosis assessment. We assessed the association between CRP/blood culture, and pneumonia with end-point consolidation.

Methods

We included children less than 5 years of age admitted with suspected pneumonia to Patan Hospital in 2018 and 2019, whose chest xray, CRP level and blood culture were done. CRP levels >40 mg/dl were considered elevated.

Results

There was a significant difference (p<0.001) in CRP levels between EPC-pneumonia and non-EPC pneumonia cases with a median (IQR) CRP of 46.2 (16, 215) in 141 EPC-pneumonia cases and a median (IQR) CRP of 13 (4, 35) in non-EPC pneumonia cases. The sensitivity and specificity of CRP >40mg/dl to detect EPC pneumonia were 50% and 84% respectively. The area under the ROC curve was 0.727 indicating good discrimination between EPC-pneumonia and non-EPC pneumonia. Among the EPC-pneumonia cases, 62% had elevated CRP and 3.5% had S. pneumoniae positive blood cultures.

Conclusions

There was a significant association between CRP and EPC pneumonia. Blood culture had low sensitivity to detect bacterial pneumonia, nevertheless, CRP may be a useful tool in diagnosis of bacterial pneumonia.

Background

The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced in Nepal in 2015. We compared the nasopharyngeal carriage of PCV10 and non-PCV10 serotypes of pneumococcus between pre-vaccine (2015) and post-vaccine (2017-2018) years in two different regions of Nepal.

Methods

Nasopharyngeal samples obtained in healthy Nepalese children aged 6-59 months in urban (Patan, Kathmandu) and 6-23 months in rural (Okhaldhunga) settings were transported in STGG (Skim Milk-Tryptone-Glucose-Glycerol) media, cultured for pneumococcus and serotyped by the Quellung method.

Results

The carriage prevalence decreased for all PCV10-type serotypes except 7F in both the settings. PCV10-type prevalence decreased from 29.7% in rural and 17.2% in urban children pre-vaccine to 9.0% and 8.6% post-vaccine, respectively. Pre-vaccine, the most frequently found serotypes in both settings were 19F, 6B, 14. Post-vaccine, the non-PCV10 serotypes were more common; serotypes 34, 6C, 19A and 15B were most common in rural and 6A, 34, 11A, 6C and 15B in urban settings.

Conclusions

Since the introduction of PCV10, carriage prevalence of PCV10 serotypes have reduced and non-PCV10 serotypes have increased in both settings raising the possibility of replacement disease. Continued monitoring of changes in PCV10-serotypes and non-PCV10 serotypes, especially those covered by PCV13, is important to assess vaccine impact.

Background

S. pneumoniae is a major cause of bacterial pneumonia and an important cause of invasive bacterial disease (IBD) in children under-five years of age in Nepal. Pneumococcal conjugate vaccine, PCV10, was introduced in 2015 with a 2+1 schedule.

Methods

We assessed the programmatic impact of PCV10 introduction using surveillance for nasopharyngeal (NP) colonisation, pneumonia and IBD. NP swabs from pneumonia inpatients and from healthy children, blood cultures from inpatients with suspected IBD, and chest x-rays from inpatient pneumonia cases were obtained over a 6-year period (2014-2019).

Results

The proportion of pneumonia cases with radiographic endpoint-consolidation (likely bacterial) was 34% lower (95%CI 19-46%) in 2018 compared with the pre-vaccine period (2014-2015). Vaccine serotype (VT) carriage in children under 2-years of age with pneumonia in 2019 was 78% lower (95%CI 30-93%) than in the pre-vaccine period.

Among healthy 6-23 month old children (urban and rural cohorts), VT-carriage declined 74% (95%CI 43-82%) by 2019. An increase in PCV13-additional-serotype carriage was seen in 2018 among rural-children (prevalence-ratio 1.65, 95%CI 1.17-2.32), but not urban-children.

Serotype 1 remains the dominant serotype detected in cases of invasive pneumococcal disease.

Conclusions

A decrease in prevalence of endpoint-consolidation-pneumonia and a decrease in vaccine-serotype circulation have been observed post PCV introduction in Nepal.

Background

Streptococcus pneumoniae causes substantial morbidity and mortality globally, with serotype-specific disease burden varying geographically. Currently there are two widely used pneumococcal conjugate vaccines (PCV). Evidence is limited regarding their comparative serotype-specific immunogenicity and efficacy.

Methods

We conducted a systematic-review and network meta-analysis of studies in which the immunogenicity of PCVs was directly compared in head-to-head randomised trials. Network meta-analysis incorporates both direct pair-wise comparisons and indirect comparisons (e.g. PCV10 vs PCV7, and PCV13 vs PCV7) thereby increasing overall statistical precision for the main comparison of interest (PCV10 vs PCV13). The difference in immunogenicity, as measured by geometric mean ratio (GMR), was examined by serotype.

Results

27 trials were included in the network meta-analysis, 4 directly comparing PCV10 and PCV13, 7 comparing PCV7 and PCV10, and 16 comparing PCV7 and PCV13. For the 10 common serotypes, immunogenicity at 1 month after the primary vaccination series was higher for PCV13 for 7 serotypes, with GMRs ranging from 1.18 to 2.50. In contrast, serotype 5, 18C and 19F favoured PCV10. Similar results were observed post-booster dose except for serotype 5 and 7F.

Conclusions

Variation in serotype-specific immunogenicity exists between PCV10 and PCV13, indicating that further investigation into whether this translates to heterogeneity in protection is needed.

Background

PCV status, necessary for assessing vaccine impact, is often incomplete or unknown. For children admitted with pneumonia in Kathmandu, Nepal, we compared vaccine histories from caregivers vs medical records to determine if these provided similar estimates of coverage.

Methods

Between 2016-2019, patients aged 6 months to 14 years admitted with pneumonia at Patan Hospital, enrolled into a pneumococcal carriage study had their number of PCV doses collected by caregiver recall and/or from hospital medical records. Records, created at birth, are updated when they receive routine vaccinations there; for vaccinations administered elsewhere, vaccine history is obtained from caregivers during any hospital admission. Cases were excluded from analyses if both caregiver recall and medical records were cited as the source.

Results

Of the 1,603 inpatients enrolled, 1,201 (80%) had data from either caregiver recall or medical records. PCV coverage (3 doses) was higher for caregiver recall than medical records (43% vs 35%; p=0.03), while Hib vaccine coverage was similar (91% vs 87%; p=0.16).

Conclusions

Although caregiver recall provided statistically higher estimates of vaccine coverage than medical records, the estimates were generally similar. Medical records may be incomplete (underestimate) and caregiver recall may have recall bias (overestimate); the truth may be in between.

Background

Routine immunization with 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in Kathmandu in 2015 with doses administered at 6 weeks, 10 weeks and 9 months of age. We assessed the impact of PCV10 on the prevalence of radiographic changes in children aged 2 months to 14 years with a clinical diagnosis of pneumonia admitted to Patan Hospital, Kathmandu.

Methods

Digitalized chest radiographs were interpreted using standardized WHO criteria as primary endpoint pneumonia (PEP), other infiltrate or normal, by two specific readers. A third reader arbitrated upon all discordant results.

Results

From March 2014 to December 2018, 1755 children were enrolled, of whom 1692 (96%) had interpretable radiographs. The proportion of children with PEP decreased annually from 84/189 (44%) in 2014 to 105/414 (25%) in 2018 (p<0.001). PEP was associated with age, occurring in 247/1090 (22%) children <2 years of age, in comparison with 120/175 (69%) children ≥5 years of age (p<0.001), and carriage of PCV10 serotypes, occurring in 95/188 (51%) children with PCV10 carriage in comparison with 459/1504 (31%) children with non-PCV10 serotypes or no carriage (p<0.001).

Conclusions

The prevalence of PEP in children hospitalized with pneumonia decreased from 2014 to 2018 in association with the implementation of PCV10 immunization in Kathmandu.