Factors associated with missed and delayed DTP3 vaccination in children aged 12 - 59 months in two communities in South Africa, 2012 - 2013

Background. Although immunisation services are available to all children in South Africa (SA), many children miss or have delays in receiving vaccines. There are limited data on factors associated with missed or delayed vaccination in children in this setting. Objectives. To assess vaccination coverage and factors associated with missed and delayed diphtheria-tetanus-pertussis vaccine third dose (DTP3) vaccination in children aged 12 - 59 months in two SA communities. Methods. We used data from household-level healthcare utilisation surveys conducted in Soweto in 2012 and in Pietermaritzburg in 2013. Information on vaccination status was recorded from the Road to Health cards or vaccination history from clinics for children aged <5 years. Factors associated with missed or delayed DTP3 vaccination were assessed using unconditional logistic regression. Results. Of a total of 847 eligible children aged 12 - 59 months, 716 had available vaccination information. Overall DTP3 vaccination coverage was high for both sites: 90.6% in Pietermaritzburg and 93.9% in Soweto. However, 32.6% and 25.2% of DTP3 vaccinations were delayed (received after 18 weeks of age) in Pietermaritzburg and Soweto, respectively. The median delay for DTP3 vaccinations was 4.7 weeks (interquartile range 1.7 - 23.0). Factors associated with delayed DTP3 vaccination included being born in 2010 (adjusted odds ratio (aOR) 3.0, 95% confidence interval (CI) 1.4 - 6.3) or 2011 (aOR 2.7, 95% CI 1.3 - 5.7) compared with being born in 2008, probably due to vaccine shortages; a low level of education of the primary caregiver, with children whose caregivers had completed secondary education having lower odds of delayed vaccination (aOR 0.5, 95% CI 0.3 - 0.9) than children whose caregivers only had primary education; and maternal HIV status, with unknown status (aOR 3.5, 95% CI 1.6 - 7.6) associated with higher odds of delay than positive status. Factors associated with missed DTP3 vaccination (not vaccinated by 12 months of age) included two or more children aged <5 years in a household (aOR 2.4, 95% CI 1.2 - 4.9) compared with one child, and household monthly income <ZAR500 (aOR 3.4, 95% CI 1.1 - 11.4) compared with ≥ZAR2 000. Conclusions. Despite high overall DTP3 coverage observed in two communities, many vaccinations were delayed. Vulnerable groups identified in this study should be targeted with improved vaccination services to enhance uptake and timeliness of vaccination

Factors associated with missed and delayed DTP3 vaccination in children aged 12 - 59 months in two communities in South Africa, 2012 - 2013

Background. Although immunisation services are available to all children in South Africa (SA), many children miss or have delays in receiving vaccines. There are limited data on factors associated with missed or delayed vaccination in children in this setting.Objectives. To assess vaccination coverage and factors associated with missed and delayed diphtheria-tetanus-pertussis vaccine third dose (DTP3) vaccination in children aged 12 - 59 months in two SA communities.Methods. We used data from household-level healthcare utilisation surveys conducted in Soweto in 2012 and in Pietermaritzburg in 2013. Information on vaccination status was recorded from the Road to Health cards or vaccination history from clinics for children aged &lt;5 years. Factors associated with missed or delayed DTP3 vaccination were assessed using unconditional logistic regression.Results. Of a total of 847 eligible children aged 12 - 59 months, 716 had available vaccination information. Overall DTP3 vaccination coverage was high for both sites: 90.6% in Pietermaritzburg and 93.9% in Soweto. However, 32.6% and 25.2% of DTP3 vaccinations were delayed (received after 18 weeks of age) in Pietermaritzburg and Soweto, respectively. The median delay for DTP3 vaccinations was 4.7 weeks (interquartile range 1.7 - 23.0). Factors associated with delayed DTP3 vaccination included being born in 2010 (adjusted odds ratio (aOR) 3.0, 95% confidence interval (CI) 1.4 - 6.3) or 2011 (aOR 2.7, 95% CI 1.3 - 5.7) compared with being born in 2008, probably due to vaccine shortages; a low level of education of the primary caregiver, with children whose caregivers had completed secondary education having lower odds of delayed vaccination (aOR 0.5, 95% CI 0.3 - 0.9) than children whose caregivers only had primary education; and maternal HIV status, with unknown status (aOR 3.5, 95% CI 1.6 - 7.6) associated with higher odds of delay than positive status. Factors associated with missed DTP3 vaccination (not vaccinated by 12 months of age) included two or more children aged &lt;5 years in a household (aOR 2.4, 95% CI 1.2 - 4.9) compared with one child, and household monthly income &lt;ZAR500 (aOR 3.4, 95% CI 1.1 - 11.4) compared with ≥ZAR2 000.Conclusions. Despite high overall DTP3 coverage observed in two communities, many vaccinations were delayed. Vulnerable groups identified in this study should be targeted with improved vaccination services to enhance uptake and timeliness of vaccination.

Pneumococcal carriage in children in Ulaanbaatar, Mongolia before and one year after the introduction of the 13-valent pneumococcal conjugate vaccine.

BACKGROUND: Nasopharyngeal carriage of Streptococcus pneumoniae precedes disease, is the source of pneumococcal community spread, and the mechanism for herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few PCV impact studies in low- and middle-income countries, particularly in Asia. In 2016, Mongolia introduced the 13-valent PCV (PCV13) in a phased manner using a 2 + 1 schedule, with catch-up. We aimed to assess the impact of PCV13 introduction on nasopharyngeal pneumococcal carriage and density in children in Mongolia. METHODS: We conducted two cross-sectional carriage surveys (pre- and one year post-PCV) at community health clinics in two districts of the capital city, Ulaanbaatar in both May-July 2015 and 2017. The study analysis included 961 children too young to be vaccinated (5-8 weeks old) and 989 children eligible for vaccination (12-23 months old). Pneumococci were detected by quantitative real-time PCR and molecular serotyping performed using DNA microarray. FINDINGS: One year post-PCV introduction, PCV13 serotype carriage reduced by 52% in 12-23 month olds (adjusted prevalence ratio [aPR] 0.48 [95% confidence interval [CI] 0.39-0.59]), with evidence of non-PCV13 serotype replacement (aPR 1.55 [95% CI 1.30-1.85]), compared with the pre-PCV period. In 5-8 week olds, PCV13 serotype carriage reduced by 51% (aPR 0.49 [95% CI 0.33-0.73]) with no significant change in non-PCV13 serotype carriage (aPR 1.10 [95% CI 0.83-1.46]). An increase was observed in both PCV13 and non-PCV13 pneumococcal density post-PCV introduction. Antimicrobial resistance (AMR) genes were common, with 82.3% of samples containing at least one of the 10 AMR genes assessed. CONCLUSION: This study demonstrates substantive PCV13 impact on pneumococcal carriage one year post-vaccine introduction in Mongolia. The reductions in PCV13 serotype carriage are likely to result in reductions in pneumococcal disease including indirect effects. Increases in non-PCV13 serotypes require further monitoring

Eff ectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study

Background The 13-valent pneumococcal conjugate vaccine (PCV13) was designed to include disease-causing serotypes that are important in low-income and middle-income countries. Vaccine eff ectiveness estimates are scarce in these settings. South Africa replaced PCV7 with PCV13 in 2011 using a 2 + 1 schedule. We aimed to assess the eff ectiveness of two or more doses of PCV13 against invasive pneumococcal disease in children with HIV infection and in those not infected with HIV. Methods Cases of invasive pneumococcal disease in children aged 5 years or younger were identifi ed through national laboratory-based surveillance. Isolates were serotyped with the Quellung reaction or PCR. We sought in-hospital controls for every case, matched for age, HIV status, and study site. We aimed to enrol four controls for every case not infected with HIV and six controls for every case with HIV infection (case-control sets). With conditional logistic regression, we calculated vaccine eff ectiveness as a percentage, with the equation 1 – [adjusted odds ratio for vaccination] × 100. We included data from an earlier investigation of PCV7 to assess vaccine eff ectiveness in children exposed to but not infected with HIV and in malnourished children not infected with HIV. Findings Between January, 2012, and December, 2014, we enrolled children aged 16 weeks or older to our study: 240 were cases not infected with HIV, 75 were cases with HIV infection, 1118 were controls not infected with HIV, and 283 were controls with HIV infection. The eff ectiveness of two or more doses of PCV13 against PCV13-serotype invasive pneumococcal disease was 85% (95% CI 37 to 96) among 11 case-control sets of children not infected with HIV and 91% (–35 to 100) among three case-control sets of children with HIV infection. PCV13 eff ectiveness among 26 case-control sets of children not infected with HIV was 52% (95% CI –12 to 79) against all-serotype invasive pneumococcal disease and 94% (44 to 100) for serotype 19A. Vaccine eff ectiveness against PCV7-serotype invasive pneumococcal disease was 87% (95% CI 38 to 97) in children exposed to HIV but uninfected and 90% (53 to 98) in malnourished children not infected with HIV. Interpretation Our results indicate that PCV13 in a 2 + 1 schedule is eff ective for preventing vaccine-type pneumococcal infections in young children not infected with HIV, including those who are malnourished or who have been exposed to HIV. Although the point estimate for PCV13 vaccine eff ectiveness in children infected with HIV was high, it did not reach signifi cance, possibly because of the small sample size. These fi ndings support recommendations for widespread use of pneumococcal conjugate vaccine in low-income and middle-income countries

Determining the pneumococcal conjugate vaccine coverage required for indirect protection against vaccine-type pneumococcal carriage in low and middle-income countries: a protocol for a prospective observational study.

INTRODUCTION: Pneumococcal conjugate vaccines (PCVs) prevent disease through both direct protection of vaccinated individuals and indirect protection of unvaccinated individuals by reducing nasopharyngeal (NP) carriage and transmission of vaccine-type (VT) pneumococci. While the indirect effects of PCV vaccination are well described, the PCV coverage required to achieve the indirect effects is unknown. We will investigate the relationship between PCV coverage and VT carriage among undervaccinated children using hospital-based NP pneumococcal carriage surveillance at three sites in Asia and the Pacific. METHODS AND ANALYSIS: We are recruiting cases, defined as children aged 2-59 months admitted to participating hospitals with acute respiratory infection in Lao People's Democratic Republic, Mongolia and Papua New Guinea. Thirteen-valent PCV status is obtained from written records. NP swabs are collected according to standard methods, screened using lytA qPCR and serotyped by microarray. Village-level vaccination coverage, for the resident communities of the recruited cases, is determined using administrative data or community survey. Our analysis will investigate the relationship between VT carriage among undervaccinated cases (indirect effects) and vaccine coverage using generalised estimating equations. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the relevant ethics committees at participating sites. The results are intended for publication in open-access peer-reviewed journals and will demonstrate methods suitable for low- and middle-income countries to monitor vaccine impact and inform vaccine policy makers about the PCV coverage required to achieve indirect protection

Healthcare utilisation patterns for respiratory and gastrointestinal syndromes and meningitis in Msunduzi municipality Pietermaritzburg KwaZuluNatal Province South Africa 2013

Background. Public health facilities are used by the majority of South Africans, and healthcare utilisation surveys have been a useful tool to estimate the burden of disease in a given area.Objectives. To describe care-seeking behaviour in a periurban site with a high prevalence of HIV infection, as well as barriers to seeking appropriate healthcare.Methods. We conducted a cross-sectional household survey in 22 wards of the Msunduzi municipality in KwaZulu-Natal Province, South Africa, from October to December 2013 using a simple random sample of households selected from a 2011 census enumeration. A primary caregiver/adult decision-maker was interviewed regarding demographic data as well as health status and recent self-reported episodes of selected illnesses and healthcare utilisation.Results. Of the 2 238 eligible premises visited, 1 936 households (87%) with a total of 9 733 members were enrolled in the study. Of these, 635 (7%) reported one or more episodes of infectious illness during the study period. Public health clinics were most frequently consulted for all illnesses (361/635, 57%). Private healthcare (general practitioner, private clinic, private hospital) was sought by 90/635 of individuals (14%), only 13/635 (2%) reported seeking care from traditional healers, religious leaders or volunteers, and 71/635 (11%) did not seek any medical care for acute illnesses. Individuals in the lowest income group were more likely to seek care at public health facilities than those in the highest income group (70% v. 32%).Conclusions. Public health facility-based surveillance may be representative of disease patterns in this community, although surveillance at household level shows that high-income individuals may be excluded because they were more likely to use private healthcare, and the proportion of individuals who died at home would have been missed by facility-based surveillance. Data obtained in such surveys may be useful for public health planning.Â

Estimated severe pneumococcal disease cases and deaths before and after pneumococcal conjugate vaccine introduction in children younger than 5 years of age in South Africa

INTRODUCTION : Streptococcus pneumoniae is a leading cause of severe bacterial infections globally. A full understanding of the impact of pneumococcal conjugate vaccine (PCV) on pneumococcal disease burden, following its introduction in 2009 in South Africa, can support national policy on PCV use and assist with policy decisions elsewhere. METHODS : We developed a model to estimate the national burden of severe pneumococcal disease, i.e. disease requiring hospitalisation, pre- (2005±2008) and post-PCV introduction (2012± 2013) in children aged 0±59 months in South Africa. We estimated case numbers for invasive pneumococcal disease using data from the national laboratory-based surveillance, adjusted for specimen-taking practices. We estimated non-bacteraemic pneumococcal pneumonia case numbers using vaccine probe study data. To estimate pneumococcal deaths, we applied observed case fatality ratios to estimated case numbers. Estimates were stratified by HIV status to account for the impact of PCV and HIV-related interventions. We assessed how different assumptions affected estimates using a sensitivity analysis. Bootstrapping created confidence intervals. RESULTS : In the pre-vaccine era, a total of approximately 107,600 (95% confidence interval [CI] 83,000±140,000) cases of severe hospitalised pneumococcal disease were estimated to have occurred annually. Following PCV introduction and the improvement in HIV interventions, 41,800 (95% CI 28,000±50,000) severe pneumococcal disease cases were estimated in 2012±2013, a rate reduction of 1,277 cases per 100,000 child-years. Approximately 5000 (95% CI 3000±6000) pneumococcal-related annual deaths were estimated in the prevaccine period and 1,900 (95% CI 1000±2500) in 2012±2013, a mortality rate difference of 61 per 100,000 child-years. CONCLUSIONS : While a large number of hospitalisations and deaths due to pneumococcal disease still occur among children 0±59 months in South Africa, we found a large reduction in this estimate that is temporally associated with PCV introduction. In HIV-infected individuals the scale-up of other interventions, such as improvements in HIV care, may have also contributed to the declines in pneumococcal burden.S1 Text. Supplementary material: Estimated severe pneumococcal disease cases and deaths before and after pneumococcal conjugate vaccine introduction in children younger than 5 years of age in South Africa.S1 Table. Population denominators from the Thembisa model for children <5 years of age in South Africa, 2005-2008 and 2012-2013.S2 Table. Sensitivity analysis for case numbers showing key variables altered in analysis, 2005-2008 and 2012-2013.S3 Table. Sensitivity analysis for numbers of deaths showing key variables altered in analysis, 2005-2008 and 2012-2013.S1 Fig. Initial step in estimating the burden of invasive and non-invasive pneumococcal cases in children aged <5 years in South Africa, 2005-2008 and 2012-2013.S2 Fig. Second step in estimating the burden of invasive and non-invasive pneumococcal cases in children <5 years in South Africa, 2005-2008 and 2012-2013.S3 Fig. Tornado sensitivity diagram representing change in pneumococcal case estimates in children <5 years of age in the pre-vaccine era, when values of key variables are modified.S4 Fig. Tornado sensitivity diagram representing change in pneumococcal death estimates in children <5 years of age in the pre-vaccine era, when values of key variables are modified.The National Institute for Communicable Diseases/National Health Laboratory Service (NICD/NHLS), South Africa and the Centers for Disease Control and Prevention (CDC) Global AIDS Program (GAP) Cooperative Agreement (U62/PSO022901).http://www.plosone.orgam2017Paediatrics and Child Healt

Streptococcus pneumoniae Serotypes and Mortality in Adults and Adolescents in South Africa: Analysis of National Surveillance Data, 2003 - 2008

BACKGROUND: An association between pneumococcal serotypes and mortality has been suggested. We aimed to investigate this among individuals aged ≥15 years with invasive pneumococcal disease (IPD) in South Africa. METHODS: IPD cases were identified through national laboratory-based surveillance at 25 sites, pre-pneumococcal conjugate vaccine (PCV) introduction, from 2003-2008. We assessed the association between the 20 commonest serotypes and in-hospital mortality using logistic regression with serotype 4 (the third commonest serotype with intermediate case-fatality ratio (CFR)) as referent. RESULTS: Among 3953 IPD cases, CFR was 55% (641/1166) for meningitis and 23% (576/2484) for bacteremia (p<0.001). Serotype 19F had the highest CFR (48%, 100/207), followed by serotype 23F (39%, 99/252) and serotype 1 (38%, 246/651). On multivariable analysis, factors independently associated with mortality included serotype 1 (OR 1.9, 95%CI 1.1-3.5) and 19F (OR 2.9, 95%CI 1.4-6.1) vs. serotype 4; increasing age (25-44 years, OR 1.8, 95%CI 1.0-3.0; 45-64 years, OR 3.6, 95%CI 2.0-6.4; ≥65 years, OR 5.2, 95%CI 1.9-14.1; vs. 15-24 years); meningitis (OR 4.1, 95%CI 3.0-5.6) vs. bacteremic pneumonia; and HIV infection (OR1.7, 95%CI 1.0-2.8). On stratified multivariate analysis, serotype 19F was associated with increased mortality amongst bacteremic pneumococcal pneumonia cases, while no serotype was associated with increased mortality in meningitis cases. CONCLUSION: Mortality was increased in HIV-infected individuals, which may be reduced by increased antiretroviral therapy availability. Serotypes associated with increased mortality are included in the 10-and-13-valent PCV and may become less common in adults due to indirect effects following routine infant immunization

Assessing the impact of pneumococcal conjugate vaccines on invasive pneumococcal disease using polymerase chain reaction-based surveillance : an experience from South Africa

BACKGROUND : The use of molecular diagnostic techniques for the evaluation of the impact of pneumococcal conjugate vaccines (PCVs) has not been documented. We aimed to evaluate the impact of PCVs on invasive pneumococcal disease (IPD) using polymerase chain reaction (PCR)-based techniques and compare with results obtained from culture-based methods. METHODS : We implemented two independent surveillance programs for IPD among individuals hospitalized at one large surveillance site in Soweto, South Africa during 2009–2012: (i) PCR-based (targeting the lytA gene) syndromic pneumonia surveillance; and (ii) culture-based laboratory surveillance. Positive samples were serotyped. The molecular serotyping assay included targets for 42 serotypes including all serotypes/serogroups included in the 7-valent (PCV-7) and 13-valent (PCV-13) PCV. The Quellung reaction was used for serotyping of culture-positive cases. We calculated the change in rates of IPD (lytA- or culture-positive) among HIV-uninfected children aged <2 years from the year of PCV-7 introduction (2009) to the post-vaccine years (2011 or 2012). RESULTS : During the study period there were 607 lytA-positive and 1,197 culture-positive cases that were serotyped. Samples with lytA cycle threshold (Ct)-values ≥35 (30.2 %; 123/407) were significantly less likely to have a serotype/ serogroup detected for serotypes included in the molecular serotyping assay than those with Ct-values <35 (78.0 %; 156/200) (p < 0.001). From 2009 to 2012 rates of PCV-7 serotypes/serogroups decreased −63.8 % (95 % CI: −79.3 % to −39.1 %) among lytA-positive cases and −91.7 % (95 % CI: −98.8 % to −73.6 %) among culture-positive cases. Rates of lytA-positive non-vaccine serotypes/serogroups also significantly decreased (−71.7 %; 95 % CI: −81.1 % to −58.5 %) over the same period. Such decline was not observed among the culture-positive non-vaccine serotypes (1.2 %; 95 % CI: −96.7 % to 58.4 %). CONCLUSIONS : Significant downward trends in IPD PCV-7 serotype-associated rates were observed among patients tested by PCR or culture methods; however trends of non-vaccine serotypes/serogroups differed between the two groups. Misclassifications of serotypes/serogroups, affecting the use of non-vaccine serotypes as a control group, may have occurred due to the low performance of the serotyping assay among lytA-positive cases with high Ctvalues. Until PCR methods improve further, culture methods should continue to be used to monitor the effects of PCV vaccination programs on IPD incidence.Additional file 1: Assessing the Impact of Pneumococcal Conjugate Vaccines on Invasive Pneumococcal Disease Using Polymerase Chain Reaction-Based Surveillance: An Experience from South AfricaThis work was supported by Pfizer South Africa (investigator-initiated research agreement number: WS1167521) and the US Centers for Disease Control and Prevention (co-operative agreement number: 5U51IP000155).http://www.biomedcentral.com/bmcinfectdis/am2016Medical Virolog