Effect of 10-Valent Pneumococcal Conjugate Vaccine on Streptococcus pneumoniae Nasopharyngeal Carriage Among Children Less Than 5 Years Old: 3 Years Post-10-Valent Pneumococcal Conjugate Vaccine Introduction in Mozambique.

BACKGROUND: Mozambique introduced 10-valent pneumococcal conjugate vaccine (PCV10) in 2013 with doses at ages 2, 3, and 4 months and no catch-up or booster dose. We evaluated PCV10 impact on the carriage of vaccine-type (VT), non-VT, and antimicrobial non-susceptible pneumococci 3 years after introduction. METHODS: We conducted cross-sectional carriage surveys among HIV-infected and HIV-uninfected children aged 6 weeks to 59 months: 1 pre-PCV10 (2012-2013 [Baseline]) and 2 post-PCV10 introductions (2014-2015 [Post1] and 2015-2016 [Post2]). Pneumococci isolated from nasopharyngeal swabs underwent Quellung serotyping and antimicrobial susceptibility testing. Non-susceptible isolates (intermediate or resistant) were defined using Clinical and Laboratory Standards Institute 2018 breakpoints. We used log-binomial regression to estimate changes in the pneumococcal carriage between survey periods. We compared proportions of non-susceptible pneumococci between Baseline and Post2. RESULTS: We enrolled 720 children at Baseline, 911 at Post1, and 1208 at Post2. Baseline VT carriage was similar for HIV-uninfected (36.0%, 110/306) and HIV-infected children (34.8%, 144/414). VT carriage was 36% (95% confidence interval [CI]: 19%-49%) and 27% (95% CI: 11%-41%) lower in Post1 vs baseline among HIV-uninfected and HIV-infected children, respectively. VT carriage prevalence declined in Post2 vs Post1 for HIV-uninfected but remained stable for HIV-infected children. VT carriage prevalence 3 years after PCV10 introduction was 14.5% in HIV-uninfected and 21.0% in HIV-infected children. Pneumococcal isolates non-susceptible to penicillin declined from 66.0% to 56.2% (P= .0281) among HIV-infected children. CONCLUSIONS: VT and antimicrobial non-susceptible pneumococci carriage dropped after PCV10 introduction, especially in HIV-uninfected children. However, VT carriage remained common, indicating ongoing VT pneumococci transmission.

Dried blood spots for Streptococcus pneumoniae and Haemophilus influenzae detection and serotyping among children < 5 years old in rural Mozambique.

BACKGROUND: Dried blood spots (DBS) have been proposed as potentially tool for detecting invasive bacterial diseases. METHODS: We evaluated the use of DBS for S. pneumoniae and H. influenzae detection among children in Mozambique. Blood for DBS and nasopharyngeal (NP) swabs were collected from children with pneumonia and healthy aged < 5 years. Bacterial detection and serotyping were performed by quantitative PCR (qPCR) (NP and DBS; lytA gene for pneumococcus and hpd for H. influenzae) and culture (NP). Combined detection rates were compared between children with pneumonia and healthy. RESULTS: Of 325 children enrolled, 205 had pneumonia and 120 were healthy. Pneumococci were detected in DBS from 20.5 and 64.2% of children with pneumonia and healthy, respectively; NP specimens were positive for pneumococcus in 80.0 and 80.8%, respectively. H. influenzae was detected in DBS from 22.9% of children with pneumonia and 59.2% of healthy; 81.4 and 81.5% of NP specimens were positive for H. influenzae, respectively. CONCLUSION: DBS detected pneumococcal and H. influenzae DNA in children with pneumonia and healthy. Healthy children were often DBS positive for both bacteria, suggesting that qPCR of DBS specimens does not differentiate disease from colonization and is therefore not a useful diagnostic tool for children.

Invasive disease potential of Streptococcus pneumoniae serotypes before and after 10-valent pneumococcal conjugate vaccine introduction in a rural area, southern Mozambique.

BACKGROUND: Invasive pneumococcal disease (IPD) is a significant cause of morbidity and mortality among children worldwide. In April 2013, Mozambique introduced 10-valent PCV (PCV10) into the National Expanded Program on immunization using a three-dose schedule at 2, 3, and 4 months of age. We aimed to evaluate the invasive disease potential of pneumococcal serotypes among children in our region before and after PCV10 introduction. METHODS: We used data from ongoing population-based surveillance for IPD and cross-sectional pneumococcal carriage surveys among children aged <5 years in Manhiҫa, Mozambique. To determine the invasive disease potential for each serotype pre- and post-PCV10 introduction, odds ratios (OR) and 95% confidence intervals (95% CI) were calculated comparing serotype-specific prevalence in IPD and in carriage. For each serotype, OR and 95% CI > 1 indicated high invasive disease potential and OR and 95% CI < 1 indicated low invasive disease potential. RESULTS: In the pre-PCV10 period, 524 pneumococcal isolates were obtained from 411 colonized children and IPD cases were detected in 40 children. In the post-PCV10 period, 540 pneumococcal isolates were obtained from 507 colonized children and IPD cases were detected in 30 children. The most prevalent serotypes causing IPD pre-PCV10 were 6A (17.5%), 6B (15.0%), 14 (12.5%), 23F (10.0%) and 19F (7.5%), and post-PCV10 were 6A (36.7%), 13 (10%), 1 (10.0%), 6B (6.7%) and 19A (6.7%). Serotypes associated with high invasive disease potential pre-PCV10 included 1 (OR:22.3 [95% CI 2.0; 251.2]), 6B (OR:3.1 [95% CI 1.2; 8.1]), 14 (OR: 3.4 [95% CI 1.2; 9.8]) and post-PCV10 included serotype 6A (OR:6.1[95% CI 2.7; 13.5]). CONCLUSION: The number of serotypes with high invasive disease potential decreased after PCV10 introduction. Serotype 6A, which is not included in PCV10, was the most common cause of IPD throughout the study and showed a high invasive potential in the post-PCV10 period.

A comparison of all-cause and cause-specific mortality by household socioeconomic status across seven INDEPTH network health and demographic surveillance systems in sub-Saharan Africa.

BACKGROUND: Understanding socioeconomic disparities in all-cause and cause-specific mortality can help inform prevention and treatment strategies. OBJECTIVES: To quantify cause-specific mortality rates by socioeconomic status across seven health and demographic surveillance systems (HDSS) in five countries (Ethiopia, Kenya, Malawi, Mozambique, and Nigeria) in the INDEPTH Network in sub-Saharan Africa. METHODS: We linked demographic residence data with household survey data containing living standards and education information we used to create a poverty index. Person-years lived and deaths between 2003 and 2016 (periods varied by HDSS) were stratified in each HDSS by age, sex, year, and number of deprivations on the poverty index (0-8). Causes of death were assigned to each death using the InterVA-4 model based on responses to verbal autopsy questionnaires. We estimated rate ratios between socioeconomic groups (2-4 and 5-8 deprivations on our poverty index compared to 0-2 deprivations) for specific causes of death and calculated life expectancy for the deprivation groups. RESULTS: Our pooled data contained almost 3.5 million person-years of observation and 25,038 deaths. All-cause mortality rates were higher among people in households with 5-8 deprivations on our poverty index compared to 0-2 deprivations, controlling for age, sex, and year (rate ratios ranged 1.42 to 2.06 across HDSS sites). The poorest group had consistently higher death rates in communicable, maternal, neonatal, and nutritional conditions (rate ratios ranged 1.34-4.05) and for non-communicable diseases in several sites (1.14-1.93). The disparities in mortality between 5-8 deprivation groups and 0-2 deprivation groups led to lower life expectancy in the higher-deprivation groups by six years in all sites and more than 10 years in five sites. CONCLUSIONS: We show large disparities in mortality on the basis of socioeconomic status across seven HDSS in sub-Saharan Africa due to disparities in communicable disease mortality and from non-communicable diseases in some sites. Life expectancy gaps between socioeconomic groups within sites were similar to the gaps between high-income and lower-middle-income countries. Prevention and treatment efforts can benefit from understanding subpopulations facing higher mortality from specific conditions.

Early Declines in Vaccine Type Pneumococcal Carriage in Children Less Than 5 Years Old After Introduction of 10-valent Pneumococcal Conjugate Vaccine in Mozambique

Pneumococcal carriage is a precursor of invasive pneumococcal disease. Mozambique introduced 10-valent pneumococcal conjugate vaccine (PCV10) in April 2013, using a 3-dose schedule without a booster. We evaluated PCV10 impact on pneumococcal carriage and colonization density by HIV status. Methods: We conducted 2 cross-sectional surveys (pre and post PCV10 introduction) among children 6 weeks to 59 months old. Participants included HIV-infected children presenting for routine care at outpatient clinics and a random sample of HIV-uninfected children from the community. We collected demographic data, vaccination history and nasopharyngeal swabs. Swabs were cultured and isolates serotyped by Quellung. We selected serotypes 11A, 19A and 19F for bacterial density analyses. We compared vaccine-type (VT) carriage prevalence from the pre-PCV10 with the post-PCV10 period by HIV status. Findings: Prevalence of VT carriage declined from 35.9% (110/306) pre already defined in the background. It should be pre-PCV (PCV) to 20.7% (36/174 fully vaccinated) post PCV (P < 0.001) in HIV-uninfected and from 34.8% (144/414) to 19.7% (27/137 fully vaccinated) (P = 0.002) in HIV-infected children. Colonization prevalence for the 3 serotypes (3, 6A, 19A) included in the 13-valent PCV but not in PCV10 increased from 12.4% (38/306) to 20.7% (36/174 fully vaccinated) (P = 0.009) among HIV- uninfected children, mainly driven by 19A; no significant increase was observed in HIV-infected children. VT carriage among unvaccinated children decreased by 30% (P = 0.005) in HIV-infected children, with no significant declines observed in HIV-uninfected children. Conclusion: Declines in VT carriage were observed in both HIV-uninfected and HIV-infected children after PCV10 introduction with an early signal of herd effect especially in HIV-infected children. Ongoing monitoring of increases in 19A carriage and disease is necessary.

Early Declines in Vaccine Type Pneumococcal Carriage in Children Less Than 5 Years Old After Introduction of 10-valent Pneumococcal Conjugate Vaccine in Mozambique.

BACKGROUND: Pneumococcal carriage is a precursor of invasive pneumococcal disease. Mozambique introduced 10-valent pneumococcal conjugate vaccine (PCV10) in April 2013, using a 3-dose schedule without a booster. We evaluated PCV10 impact on pneumococcal carriage and colonization density by HIV status. METHODS: We conducted 2 cross-sectional surveys (pre and post PCV10 introduction) among children 6 weeks to 59 months old. Participants included HIV-infected children presenting for routine care at outpatient clinics and a random sample of HIV-uninfected children from the community. We collected demographic data, vaccination history and nasopharyngeal swabs. Swabs were cultured and isolates serotyped by Quellung. We selected serotypes 11A, 19A and 19F for bacterial density analyses. We compared vaccine-type (VT) carriage prevalence from the pre-PCV10 with the post-PCV10 period by HIV status. FINDINGS: Prevalence of VT carriage declined from 35.9% (110/306) pre already defined in the background. It should be pre-PCV (PCV) to 20.7% (36/174 fully vaccinated) post PCV (P < 0.001) in HIV-uninfected and from 34.8% (144/414) to 19.7% (27/137 fully vaccinated) (P = 0.002) in HIV-infected children. Colonization prevalence for the 3 serotypes (3, 6A, 19A) included in the 13-valent PCV but not in PCV10 increased from 12.4% (38/306) to 20.7% (36/174 fully vaccinated) (P = 0.009) among HIV- uninfected children, mainly driven by 19A; no significant increase was observed in HIV-infected children. VT carriage among unvaccinated children decreased by 30% (P = 0.005) in HIV-infected children, with no significant declines observed in HIV-uninfected children. CONCLUSION: Declines in VT carriage were observed in both HIV-uninfected and HIV-infected children after PCV10 introduction with an early signal of herd effect especially in HIV-infected children. Ongoing monitoring of increases in 19A carriage and disease is necessary.

Pneumococcal carriage and serotype distribution among children with and without pneumonia in Mozambique, 2014-2016.

BACKGROUND: Pneumococcal colonization is a precursor to pneumonia, and pneumococcal conjugate vaccines (PCV) can decrease vaccine-type (VT) colonization. Pneumococcal colonization studies are traditionally done among healthy children in the community; however, VT colonization prevalence may differ between these children and those with pneumonia. We assessed overall and VT pneumococcal colonization and factors associated with colonization among children with and without pneumonia after Mozambique introduced 10-valent PCV (PCV10) in 2013. METHODS: We used data from ongoing pneumonia surveillance in children aged <5 years and from cross-sectional nasopharyngeal colonization surveys conducted in October 2014 -April 2015 and October 2015 -May 2016. Pneumonia was defined using WHO standard criteria for radiologically confirmed pneumonia. Children with pneumonia enrolled from January 2014 -April 2016 were compared to children without pneumonia enrolled from the cross-sectional surveys. Clinical data and nasopharyngeal (NP) swabs were collected from each child. NP specimens were cultured for pneumococci, and culture-negative specimens from children with pneumonia underwent polymerase chain reaction (PCR). RESULTS: Of 778 and 927 children with and without pneumonia, 97.4% and 27.0% were exposed to antibiotics before swab collection, respectively. Based on culture, pneumococcal colonization was 45.1% for children with and 84.5% for children without pneumonia (P<0.001); VT pneumococcal colonization was 18.6% for children with and 23.4% for children without pneumonia (P = 0.02). The addition of PCR in children with pneumonia increased overall and VT-pneumococcal colonization to 79.2% and 31.1%, respectively. In multivariable analysis including PCR results, pneumonia was associated with VT pneumococcal colonization (adjusted OR: 1.4, 95%CI: 1.10-1.78). CONCLUSION: Vaccine-type pneumococcal colonization remains common among children with and without pneumonia post-PCV10 introduction in Mozambique. In a population of children with high antibiotic exposure, the use of PCR for culture-negative NP swabs can improve assessment of pneumococcal colonization and circulating serotypes.

Invasive bacterial disease trends and characterization of group B streptococcal isolates among young infants in southern Mozambique, 2001-2015.

BACKGROUND: Maternal group B streptococcal (GBS) vaccines under development hold promise to prevent GBS disease in young infants. Sub-Saharan Africa has the highest estimated disease burden, although data on incidence and circulating strains are limited. We described invasive bacterial disease (IBD) trends among infants <90 days in rural Mozambique during 2001-2015, with a focus on GBS epidemiology and strain characteristics. METHODS: Community-level birth and mortality data were obtained from Manhiça's demographic surveillance system. IBD cases were captured through ongoing surveillance at Manhiça district hospital. Stored GBS isolates from cases underwent serotyping by multiplex PCR, antimicrobial susceptibility testing, and whole genome sequencing. RESULTS: There were 437 IBD cases, including 57 GBS cases. Significant declines in overall IBD, neonatal mortality, and stillbirth rates were observed (P<0.0001), but not for GBS (P = 0.17). In 2015, GBS was the leading cause of young infant IBD (2.7 per 1,000 live births). Among 35 GBS isolates available for testing, 31 (88.6%) were highly related serotype III isolates within multilocus sequence types (STs) 17 (68.6%) or 109 (20.0%). All seven ST109 isolates (21.9%) had elevated minimum inhibitory concentration (MIC) to penicillin (≥0.12 µg/mL) associated with penicillin-binding protein (PBP) 2x substitution G398A. Epidemiologic and molecular data suggest this is a well-established clone. CONCLUSION: A notable young infant GBS disease burden persisted despite improvements in overall maternal and neonatal health. We report an established strain with pbp2x point mutation, a first-step mutation associated with reduced penicillin susceptibility within a well-known virulent lineage in rural Mozambique. Our findings further underscores the need for non-antibiotic GBS prevention strategies.

Invasive bacterial disease trends and characterization of group B streptococcal isolates among young infants in southern Mozambique, 2001-2015

Maternal group B streptococcal (GBS) vaccines under development hold promise to prevent GBS disease in young infants. Sub-Saharan Africa has the highest estimated disease burden, although data on incidence and circulating strains are limited. We described invasive bacterial disease (IBD) trends among infants <90 days in rural Mozambique during 2001-2015, with a focus on GBS epidemiology and strain characteristics. Methods: Community-level birth and mortality data were obtained from Manhiça's demographic surveillance system. IBD cases were captured through ongoing surveillance at Manhiça district hospital. Stored GBS isolates from cases underwent serotyping by multiplex PCR, antimicrobial susceptibility testing, and whole genome sequencing. Results: There were 437 IBD cases, including 57 GBS cases. Significant declines in overall IBD, neonatal mortality, and stillbirth rates were observed (P<0.0001), but not for GBS (P = 0.17). In 2015, GBS was the leading cause of young infant IBD (2.7 per 1,000 live births). Among 35 GBS isolates available for testing, 31 (88.6%) were highly related serotype III isolates within multilocus sequence types (STs) 17 (68.6%) or 109 (20.0%). All seven ST109 isolates (21.9%) had elevated minimum inhibitory concentration (MIC) to penicillin (≥0.12 µg/mL) associated with penicillin-binding protein (PBP) 2x substitution G398A. Epidemiologic and molecular data suggest this is a well-established clone. Conclusion: A notable young infant GBS disease burden persisted despite improvements in overall maternal and neonatal health. We report an established strain with pbp2x point mutation, a first-step mutation associated with reduced penicillin susceptibility within a well-known virulent lineage in rural Mozambique. Our findings further underscores the need for non-antibiotic GBS prevention strategies.