Hypoglycemia and Risk Factors for Death in 13 Years of Pediatric Admissions in Mozambique

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 Manhica 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 Manhica 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

Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria.

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

Geographical migration and fitness dynamics of Streptococcus pneumoniae

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59–1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient

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

Hypoglycemia and Risk Factors for Death in 13 Years of Pediatric Admissions in Mozambique

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 Manhica 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 Manhica 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

Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria

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(R)) 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

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