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Background: Streptococcus pneumoniae is an important cause of pneumonia, sepsis, and meningitis, which are leading causes of child mortality. Pneumococcal conjugate vaccines (PCVs) protect against disease and nasopharyngeal colonization with vaccine serotypes, reducing transmission to and among unvaccinated individuals. Mozambique introduced 10-valent PCV (PCV10) in 2013. In 2017-2019, 13-valent PCV (PCV13) replaced PCV10, and in September 2019 the schedule changed from three primary doses to two primary doses and a booster; the booster-containing schedule may increase indirect effects. We examined pneumococcal carriage in Mozambique to establish a baseline for estimating the impact of policy changes and to estimate the long-term impact of PCV10 in children aged <5 years., Methods: We calculated prevalence of carriage of PCV10 serotypes and the 3 additional PCV13 serotypes ('PCV13-unique') among children aged <5 years and their household members in southern Mozambique, between October 2018 and July 2019. Nasopharyngeal swabs were cultured, and isolates underwent Quellung serotyping. For children, we compared these "long-term post-PCV10" data with prior surveys ("pre-PCV" (2012-2013) and "post-PCV10" (2015-2016)) that used the same methods., Results: In 2018-2019, among 1319 children aged under five years, 1064 (80.7 %) were colonized with pneumococcus, among 614 children aged 5- < 18 years, 355 (57.8 %) were colonized, and among 804 adults (aged ≥18 years), 285 (35.4 %) were colonized. The most frequently observed serotypes were 19 A (n = 154, 8.5 % of isolates) and 6 A (n = 107, 5.9 %), both PCV13-unique serotypes. Overall carriage prevalence among children under five years remained stable at approximately 80 % across the carriage studies conducted between 2012 and 2019; between 2015 and 2016 and 2018-2019, the prevalence of PCV10-type carriage declined from 17.7 % to 10.1 %., Conclusions: Despite substantial declines in PCV10-type carriage initially following vaccine introduction, the continued circulation of PCV10 serotypes and relative high prevalence of PCV13-unique serotypes underscore the need to understand the impact of policy changes on pneumococcus transmission., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Support for project reports financial support was provided by the Bill & Melinda Gates Foundation (INV-006502). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Background: Mozambique introduced 10-valent-pneumococcal conjugate vaccine (PCV10) in 2013. We aimed to evaluate the indirect effect of PCV10 on invasive pneumococcal disease (IPD) and clinical severe pneumonia (CSP) in infants aged less than 10 weeks., Methods: Routine surveillance data for IPD and CSP among admitted infants less than 10 weeks of age were analyzed to compare IPD and CSP incidence using demographic surveillance data from pre- and post-PCV10 periods. IPD was defined as isolation of pneumococcus from blood or cerebrospinal fluid, and CSP according to World Health Organization criteria., Results: The incidence of IPD and CSP among infants less than 10 weeks decreased by 87% [incidence rate ratio (IRR): 0.13; 95% confidence interval (CI): 0.02-0.95] from 283/100,000 in the pre-PCV to 36/100,000 children year at risk (CYAR) post-PCV, and by 62% (IRR: 0.38; 95% CI: 0.27-0.52) from 4100/100,000 pre-PCV to 1550/100,000 CYAR post-PCV periods, respectively. Vaccine-type IPD incidence declined by 92% (IRR: 0.18; 95% CI: 0.02-1.34) from 205/100,000 pre-PCV to 36/100,000 CYAR post-PCV, though the reduction was not statistically significant. The mortality rate due to IPD among infants less than 10 weeks declined from 47/100,000 CYAR in the pre-PCV to 0 in the post-PCV period. Mortality due to CSP declined by 29% (IRR: 0.71; 95% CI: 0.34-1.50), from 457/100,000 CYAR in the pre-PCV to 324/100,000 in the post-PCV periods., Conclusions: PCV10 introduction led to substantial declines in the incidence of IPD, CSP and associated mortality in infants too young to be vaccinated (less than 10 weeks) in Mozambique, suggesting indirect protection., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Rectovaginal group B Streptococcus (GBS) colonisation in pregnant individuals at the time of labour is a major risk factor for invasive GBS disease by age 7 days (early-onset disease). We aimed to investigate the prevalence of rectovaginal GBS colonisation at the time of labour among pregnant women and vertical transmission to their newborns across selected low-income and middle-income African and south Asian countries., Methods: This prospective, observational study was undertaken at 11 maternity and obstetric care facilities based in Ethiopia, Kenya, Mozambique, Nigeria, Mali, South Africa, Bangladesh, India, and Bhutan. HIV-negative pregnant women aged 18-45 years who were in the early stages of labour and at least 37 weeks' gestation were eligible for inclusion. Lower vaginal and rectal swabs and urine were collected from the women, and swabs of the umbilicus, outer ear, axillary fold, rectum, and throat were obtained from their newborns, for GBS culture. Standardised sampling and culture using direct plating and selective media broth for detection of GBS colonisation was undertaken at the sites. Serotyping of GBS isolates was done in South Africa. The primary outcome was the prevalence of rectovaginal GBS among pregnant women, analysed in participants with available data. This study is registered with the South African National Clinical Trials Register, number DOH-27-0418-4989., Findings: 6922 pregnant women were enrolled from Jan 10, 2016, to Dec 11, 2018, of whom 6514 (94·1%; 759-892 per country) were included in the analysis; data from Bhutan were not included in the study due to issues with specimen collection and processing. Overall, the prevalence of maternal GBS colonisation was 24·1% (95% CI 23·1-25·2; 1572 of 6514); it was highest in Mali (41·1% [37·7-44·6]; 314 of 764) and lowest in Ethiopia (11·6% [9·5-14·1]; 88 of 759). The overall rate of vertical transmission of GBS from women with rectovaginal GBS colonisation was 72·3% (70·0-74·4; 1132 of 1566); it was highest in Mozambique (79·2% [73·3-84·2]; 168 of 212) and lowest in Bangladesh (55·8%, 47·5-63·8; 77 of 138). The five most common GBS colonising serotypes were Ia (37·3% [34·9-39·7]; 586 of 1572), V (28·5% [26·3-30·8]; 448 of 1572), III (25·1% [23·0-27·3]; 394 of 1572), II (9·2% [7·8-10·7]; 144 of 1572), and Ib (6·5% [5·4-7·8]; 102 of 1572). There was geographical variability in serotype proportion distribution; serotype VII was the third most common serotype in India (8·6% [5·3-13·7]; 15 of 174) and serotype VI was mainly identified in Bangladesh (5·8% [3·0-11·0]; eight of 138) and India (5·7% [3·2-10·3]; ten of 174)., Interpretation: Our study reported a high prevalence of GBS colonisation in most settings, with some geographical variability even within African countries. Our findings suggest that serotypes not included in current multivalent capsular-polysaccharide GBS vaccines prevail in some regions, so vaccine efficacy and post-licensure effectiveness studies should assess the effect of vaccination on maternal GBS colonisation given the potential for replacement by non-vaccine serotypes., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests SAM declares grant funding to his institution for research on GBS, separate from this study, from Pfizer, GlaxoSmithKline, and Minervax. GK declares grant funding to his institution for research on GBS from the Bill & Melinda Gates Foundation and PATH. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Most malaria burden estimates rely on modelling infection prevalence to case incidence data, with insufficient attention having been paid to the changing clinical presentation of severe disease and its relationship with changing transmission intensity. We present 20 years of longitudinal surveillance data to contribute to the understanding of the relationship between malaria transmission and the burden and clinical presentation of severe malaria and to inform policy., Methods: This retrospective analysis of clinical surveillance hospital data included all children younger than 15 years admitted with malaria to Manhiça District Hospital (MDH), Mozambique, from July 1, 1997, to June 30, 2017. Case fatality ratios (CFRs) were calculated as the number of patients who died having a specific diagnosis or syndrome divided by the total number of patients with known outcome admitted with that diagnosis or syndrome., Findings: Over the study period, 32 138 children were admitted to MDH with a malaria diagnosis. Malaria accounted for a large proportion of admissions, ranging from 4083 (76·9%) of 5307 admissions in 2000-01 to 706 (27·5%) of 2568 admissions in 2010-11. Since 2000-02, the absolute and relative number of malaria admissions and deaths presented a decreasing trend. The age pattern of patients with malaria shifted to older ages with a median age of 1·7 years (IQR 0·9-3·0) in 1997-2006 and 2·6 years (IQR 1·3-4·4) in 2006-17, although most malaria deaths (60-88% in 2009-17) still occurred in children younger than 5 years. The clinical presentation of severe malaria changed, with an increase in cerebral malaria and a decrease in severe anaemia and respiratory distress, leading to similar yearly cases for the three syndromes. CFRs for severe malaria fluctuated between 1·1% (2 of 186 in 2014-15) and 7·2% (11 of 152 in 2010-11), varying by severe malaria syndrome (3·3% [70 of 2105] for severe anaemia, 5·1% [191 of 3777] for respiratory distress, and 14·8% [72 of 487] for cerebral malaria). Overall malaria CFRs (1·8% [543 of 30 163]) did not vary by age group., Interpretation: Despite the unprecedented scale up of malaria control tools, malaria still represented around 30-40% of paediatric hospital admissions in 2006-17. The age shift towards older children was not accompanied by an increase in severe malaria or deaths; however, control programmes should consider adapting their high-risk target groups to include older children. Malaria remains a leading cause of disease and health-care system use and the massive unfinished malaria control agenda warrants intensified efforts., Funding: Spanish Agency for International Cooperation and Development., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Klebsiella spp. are important pathogens associated with bacteremia among admitted children and is among the leading cause of death in children < 5 years in postmortem studies, supporting a larger role than previously considered in childhood mortality. Herein, we compared the antimicrobial susceptibility, mechanisms of resistance, and the virulence profile of Klebsiella spp. from admitted and postmortem children., Methods: Antimicrobial susceptibility and virulence factors of Klebsiella spp. recovered from blood samples collected upon admission to the hospital (n = 88) and postmortem blood (n = 23) from children < 5 years were assessed by disk diffusion and multiplex PCR., Results: Klebsiella isolates from postmortem blood were likely to be ceftriaxone resistant (69.6%, 16/23 vs. 48.9%, 43/88, p = 0.045) or extended-spectrum β-lactamase (ESBL) producers (60.9%, 14/23 vs. 25%, 22/88, p = 0.001) compared to those from admitted children. bla CTX-M-15 was the most frequent ESBL gene: 65.3%, 9/14 in postmortem isolates and 22.7% (5/22) from admitted children. We found higher frequency of genes associated with hypermucoviscosity phenotype and invasin in postmortem isolates than those from admitted children: rmpA (30.4%; 7/23 vs. 9.1%, 8/88, p = 0.011), wzi-K1 (34.7%; 8/23 vs. 8%; 7/88, p = 0.002) and traT (60.8%; 14/23 vs. 10.2%; 9/88, p < 0.0001), respectively. Additionally, serine protease auto-transporters of Enterobacteriaceae were detected from 1.8% (pic) to 12.6% (pet) among all isolates. Klebsiella case fatality rate was 30.7% (23/75)., Conclusion: Multidrug resistant Klebsiella spp. harboring genes associated with hypermucoviscosity phenotype has emerged in Mozambique causing invasive fatal disease in children; highlighting the urgent need for prompt diagnosis, appropriate treatment and effective preventive measures for infection control.

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., (Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society 2020.)

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.

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.

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., Competing Interests: Dr. Beutel Sigauque currently works for John Snow, Inc with the Maternal and Child Survival Program in Mozambique. However, at the time this work was done, Dr. Sigauque was an employee of Fundação Manhiça / Centro de Investigação em Saúde da Manhiça (CISM), Maputo, Moçambique. This change in affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no other conflicts of interest to declare.

Background: Despite the widespread use and availability of rapidly acting anti-malarials, the fatality rate of severe malaria in sub-Saharan Africa remains high. Adjunctive therapies that target the host response to malaria infection may further decrease mortality over that of anti-malarial agents alone. Peroxisome proliferator-activated receptor-gamma agonists (e.g. rosiglitazone) have been shown to act on several pathways implicated in the pathogenesis of severe malaria and may improve clinical outcome as an adjunctive intervention., Methods: In this study, the safety and tolerability of adjunctive rosiglitazone in paediatric uncomplicated malaria infection was evaluated in Mozambique, as a prelude to its evaluation in a randomized controlled trial in paediatric severe malaria. The study was a prospective, randomized, double-blind, placebo-controlled, phase IIa trial of rosiglitazone (0.045 mg/kg/dose) twice daily for 4 days versus placebo as adjunctive treatment in addition to Mozambican standard of care (artemisinin combination therapy Coartem ® ) in children with uncomplicated malaria. The primary outcomes were tolerability and safety, including clinical, haematological, biochemical, and electrocardiographic evaluations., Results: Thirty children were enrolled: 20 were assigned to rosiglitazone and 10 to placebo. Rosiglitazone treatment did not induce hypoglycaemia nor significantly alter clinical, biochemical, haematological, or electrocardiographic parameters., Conclusions: Adjunctive rosiglitazone was safe and well-tolerated in children with uncomplicated malaria, permitting the extension of its evaluation as adjunctive therapy for severe malaria. The trial is registered with Clinicaltrials.gov, NCT02694874.

Hypoglycemia is a life-threatening complication of several diseases in childhood. We describe the prevalence and incidence of hypoglycemia among admitted Mozambican children, establishing its associated risk factors. We retrospectively reviewed clinical data of 13 years collected through an ongoing systematic morbidity surveillance in Manhiça District Hospital in rural Mozambique. Logistic regression was used to identify risk factors for hypoglycemia and death. Minimum community-based incidence rates (MCBIRs) for hypoglycemia were calculated using data from the demographic surveillance system. Of 49,089 children < 15 years hospitalized in Manhiça District Hospital, 45,573 (92.8%) had a glycemia assessment on admission. A total of 1,478 children (3.2%) presented hypoglycemia (< 3 mmol/L), of which about two-thirds (972) were with levels < 2.5 mmol/L. Independent risk factors for hypoglycemia on admission and death among hypoglycemic children included prostration, unconsciousness, edema, malnutrition, and bacteremia. Hypoglycemic children were significantly more likely to die (odds ratio [OR] = 7.11; P < 0.001), with an associated case fatality rate (CFR) of 19.3% (245/1,267). Overall MCBIR of hypoglycemia was 1.57 episodes/1,000 child years at risk (CYAR), significantly decreasing throughout the study period. Newborns showed the highest incidences (9.47 episodes/1,000 CYAR, P < 0.001). Hypoglycemia remains a hazardous condition for African children. Symptoms and signs associated to hypoglycemia should trigger the verification of glycemia and the implementation of life-saving corrective measures., (© The American Society of Tropical Medicine and Hygiene.)

Background: Community-acquired methicillin-sensitive Staphylococcus aureus (CA-MSSA) is responsible for the majority of skin and soft-tissue infections. CA-MSSA can also cause life-threatening infections, possibly in relation to particular virulence factors, including Panton-Valentine leukocidin (PVL)., Methods: We describe a severe CA-MSSA necrotizing pneumonia complicated with multifocal osteomyelitis, pericardial effusion and endocarditis in a 6-year-old boy admitted to a Mozambican hospital. Staphylococcus aureus isolation and antibiotic susceptibility testing were performed by conventional microbiology. Additionally, microarray assay was used for molecular characterization., Results: Blood culture confirmed the presence of S. aureus susceptible to most antimicrobial agents, including methicillin. Molecular characterization confirmed the presence of PVL, together with alpha and beta haemolysin genes., Conclusions: To our knowledge, this is the first reported case of disseminated CA-MSSA disease with confirmed PVL exotoxin in sub-Saharan Africa. PVL-positive CA-MSSA should be considered in the differential diagnosis of community-acquired pneumonia, making laboratory testing a higher priority., (© The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)