Short- and Long-term Outcomes of Group B Streptococcus Invasive Disease in Mozambican Children: Results of a Matched Cohort and Retrospective Observational Study and Implications for Future Vaccine Introduction.

BACKGROUND: Invasive group B Streptococcus disease (iGBS) in infancy, including meningitis or sepsis, carries a high risk of mortality and neurodevelopmental impairment (NDI). We present data on iGBS from 2 decades of surveillance in Manhiça, Mozambique, with a focus on NDI. METHODS: Morbidity surveillance databases in a rural Mozambican district hospital were screened for iGBS cases. From February 2020 to March 2021, surviving iGBS patients (n = 39) plus age- and sex-matched children without iGBS (n = 119) were assessed for neurocognitive development, vision, and hearing. The role of GBS in stillbirths and infant deaths was investigated using minimally invasive tissue sampling (MITS). RESULTS: Ninety iGBS cases were included, with most children being <3 months of age (85/90). The in-hospital case fatality rate was 14.4% (13/90), increasing to 17.8% (3 additional deaths) when considering mortality during the 6 months postdiagnosis. Fifty percent of the iGBS exposed infants and 10% of those unexposed showed any NDI. Surviving GBS conferred a 11-fold increased adjusted odds of moderate/severe NDI (odds ratio, 2.8 [95% confidence interval, .92-129.74]; P = .06) in children aged 0-5 years. For older children (6-18 years), no differences in NDI were found between exposed and unexposed. Motor domain was the most affected among young GBS survivors. Three stillbirths and 4 early neonatal deaths (of the 179 MITS performed) were attributed to iGBS. CONCLUSIONS: In absence of preventive strategies, such as intrapartum antibiotics, iGBS remains a significant cause of perinatal and infant disease and death. GBS also causes major longer-term neurodevelopmental sequelae, altogether justifying the need for maternal GBS vaccination strategies to increase perinatal and infant survival

Postdischarge Mortality Prediction in Sub-Saharan Africa.

BACKGROUND: Although the burden of postdischarge mortality (PDM) in low-income settings appears to be significant, no clear recommendations have been proposed in relation to follow-up care after hospitalization. We aimed to determine the burden of pediatric PDM and develop predictive models to identify children who are at risk for dying after discharge. METHODS: Deaths after hospital discharge among children aged <15 years in the last 17 years were reviewed in an area under demographic and morbidity surveillance in Southern Mozambique. We determined PDM over time (up to 90 days) and derived predictive models of PDM using easily collected variables on admission. RESULTS: Overall PDM was high (3.6%), with half of the deaths occurring in the first 30 days. One primary predictive model for all ages included young age, moderate or severe malnutrition, a history of diarrhea, clinical pneumonia symptoms, prostration, bacteremia, having a positive HIV status, the rainy season, and transfer or absconding, with an area under the curve of 0.79 (0.75-0.82) at day 90 after discharge. Alternative models for all ages including simplified clinical predictors had a similar performance. A model specific to infants <3 months old was used to identify as predictors being a neonate, having a low weight-for-age z score, having breathing difficulties, having hypothermia or fever, having oral candidiasis, and having a history of absconding or transfer to another hospital, with an area under the curve of 0.76 (0.72-0.91) at day 90 of follow-up. CONCLUSIONS: Death after discharge is an important although poorly recognized contributor to child mortality. A simple predictive algorithm based on easily recognizable variables could readily be used to identify most infants and children who are at a high risk of dying after discharge

Maternal Carriage of Group B Streptococcus and Escherichia coli in a District Hospital in Mozambique.

BACKGROUND: In low-income countries, data on prevalence and effects of group B Streptococcus (GBS) and Escherichia coli (E. coli) colonization among pregnant women are scarce, but necessary to formulate prevention strategies. We assessed prevalence of GBS and E. coli colonization and factors associated among pregnant women, its effect in newborns and acceptability regarding the utilized sampling methods in a semirural Mozambican hospital. METHODS: Pregnant women were recruited from June 2014 to January 2015, during routine antenatal clinics at gestational age ≥ 34 weeks (n = 200); or upon delivery (n = 120). Maternal risk factors were collected. Vaginal and vagino-rectal samples for GBS and E. coli determination were obtained and characterized in terms of antimicrobial resistance and serotype. Anti-GBS antibodies were also determined. Neonatal follow-up was performed in the first 3 months after birth. Semistructured interviews were performed to investigate acceptability of sample collection methods. RESULTS: In total, 21.3% of women recruited were GBS carriers, while 16.3% were positive for E. coli. Prevalence of HIV was 36.6%. No association was found between being colonized by GBS and E. coli and maternal risk factors. GBS isolates were fully susceptible to penicillin and ampicillin. Serotypes V (32.4%), Ia (14.7%) and III (10.3%) were the most commonly found and 69.2% of the women tested had immunoglobuline G antibodies against GBS. E. coli isolates showed resistance to ampicillin in 28.9% and trimethoprim/sulfamethoxazole in 61.3% of the cases. CONCLUSION: Prevalence of GBS and/or E. coli colonization among pregnant women is high in this semirural community and comparable with those reported in similar settings. Four serotypes accounted for nearly 70% of all isolates of GBS. Population-based data on infant GBS infections would enable the design of prevention strategies for GBS disease in Mozambique

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

Different pattern of stool and plasma gastrointestinal damage biomarkers during primary and chronic HIV infection

Introduction: Primary HIV infection (PHI) is the initial phase after HIV acquisition characterized by high viral replication, massive inflammatory response and irreversible immune-damage, particularly at the gastrointestinal level. In this study we aimed to characterize the dynamics of gastrointestinal damage biomarkers during the different phases of HIV infection and assess their association with HIV-disease markers and their accuracy to differentiate PHI from chronic HIV infection (CHI). Methods: PHI-individuals (n = 57) were identified as HIV-seronegative/HIV-RNA positive and were followed up for one year at the Manhiça District Hospital in Mozambique. Ten plasma and 12 stool biomarkers were quantified by Luminex or ELISA and levels were compared to CHI-naive (n = 26), CHI on antiretroviral-treatment (ART; n = 30) and HIV-uninfected individuals (n = 58). Regression models adjusted by time point were used to estimate the association of the biomarkers with HIV-disease markers. Receiver operating curves were compared for the best accuracy to distinguish PHI from CHI. Results: Soluble (s)CD14 was significantly associated with the CD4/CD8 ratio (P < 0.05) and viremia levels (P < 0.0001) during PHI. Plasma zonulin and stool lactoferrin were significantly higher in PHI as compared to CHI-individuals (P < 0.05). Plasma zonulin demonstrated the best accuracy to identify PHI among HIV-infected individuals (AUC = 0.85 [95% CI 0.75–0.94]). Using a cutoff value of plasma zonulin ≥ 8.75 ng/mL the model identified PHI with 87.7% sensitivity (95% CI 76.3–94.9) and 69.2% specificity (95% CI 48.2–85.7). An adjusted multivariate model including age, plasma zonulin and sCD14 further increased the classification performance (AUC = 0.92 [95% CI 0.86–0.99]). Conclusions: While the stool biomarkers did not provide any predictive ability to distinguish PHI from CHI-individuals, plasma sCD14 and zonulin were significantly associated with HIV-disease markers and PHI identification, respectively. These inflammatory biomarkers may be useful to monitor changes in gastrointestinal integrity during HIV infection

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

<div><p>Background</p><p>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.</p><p>Methods</p><p>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).</p><p>Results</p><p>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 (<i>P</i><0.001); VT pneumococcal colonization was 18.6% for children with and 23.4% for children without pneumonia (<i>P</i> = 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).</p><p>Conclusion</p><p>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.</p></div

Characteristics of children aged <5 years with and without pneumonia in Manhiça and Maputo, Mozambique, 2014–2016.

<p>Characteristics of children aged <5 years with and without pneumonia in Manhiça and Maputo, Mozambique, 2014–2016.</p

Distribution of serotypes among children aged < 5 years with pneumococcal colonization in Manhiça and Maputo, Mozambique, 2014–2016.

<p>Distribution of serotypes among children aged < 5 years with pneumococcal colonization in Manhiça and Maputo, Mozambique, 2014–2016.</p

Factors associated with vaccine-type^a pneumococcal colonization in children aged < 5 years in Manhiça and Maputo, Mozambique, 2014–2016.

<p>Factors associated with vaccine-type<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0199363#t003fn001" target="_blank">^a</a> pneumococcal colonization in children aged < 5 years in Manhiça and Maputo, Mozambique, 2014–2016.</p