Impact of 10-Valent Pneumococcal Conjugate Vaccine on Bacterial Meningitis in Madagascar.

BACKGROUND: The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in Madagascar in 2012. The objective of this study was to determine the impact of PCV10 on bacterial meningitis in hospitalized children <5 years of age. METHODS: During 2010-2017, data from the hospital admission logbook were recorded for bacterial meningitis and pneumonia hospitalizations in children <5 years of age. Between April 2011 and December 2017, 3312 cerebrospinal fluid (CSF) samples collected from children who fulfilled the World Health Organization case definition of suspected bacterial meningitis were analyzed at the sentinel site laboratory (SSL) by microscopy, culture, and antigen detection tests. A total of 2065 CSF samples were referred to the regional reference laboratory for real-time polymerase chain reaction (RT-PCR) analysis. 2010-2011 was defined as the prevaccine period, 2012 as vaccine introduction year, and 2013-2017 the postvaccine period. The number of cases, causative agent, and pneumonia hospitalizations were compared before and after PCV10 introduction. RESULTS: In the prevaccine period, bacterial meningitis and pneumonia hospitalizations accounted for 4.5% and 24.5% of all hospitalizations while there were 2.6% and 19%, respectively, in the postvaccine period (P < .001). In samples tested at the SSL, 154 were positive with 80% Streptococcus pneumoniae and 20% other bacteria. Pneumococcal meningitis diagnosed by RT-PCR declined from 14% in 2012 to 3% in 2017. Also, 14% of children with pneumococcal meningitis died. CONCLUSIONS: Following PCV10 introduction, pneumococcal meningitis, bacterial meningitis, and pneumonia hospitalizations declined. Surveillance should continue to monitor the impact of PCV10.

Monovalent rotavirus vaccine effectiveness and long-term impact among children <5 years old in Antananarivo, Madagascar, 2010-2022.

BACKGROUND: Monovalent rotavirus vaccine substantially reduced rotavirus disease burden after introduction (May 2014) in Madagascar. We examined the effectiveness and long-term impact on acute watery diarrhea and rotavirus-related hospitalizations among children <5 years old at two hospitals in Antananarivo, Madagascar (2010-2022). METHODS: We used a test-negative case-control design to estimate monovalent rotavirus vaccine effectiveness (VE) against laboratory-confirmed rotavirus hospitalizations among children age 6-23 months with documented vaccination status adjusted for year of symptom onset, rotavirus season, age group, nutritional status, and clinical severity. To evaluate the impact, we expanded to children age 0-59 months with acute watery diarrhea. First, we used admission logbook data to compare the proportion of all hospitalizations attributed to diarrhea in the pre-vaccine (January 2010-December 2013), transition period (January 2014-December 2014), and post-vaccine (January 2015-December 2022) periods. Second, we used active surveillance data (June 2013-May 2022) to describe rotavirus positivity and detected genotypes by vaccine introduction period and surveillance year (1 June-31 May). RESULT: Adjusted VE of at least one dose against hospitalization due to rotavirus diarrhea among children age 6-23 months was 61 % (95 % CI: -39 %-89 %). The annual median proportion of hospitalizations attributed to diarrhea declined from 28 % in the pre-vaccine to 10 % in the post-vaccine period. Rotavirus positivity among hospitalized children age 0-59 months with acute watery diarrhea was substantially higher during the pre-vaccine (59 %) than the post-vaccine (23 %) period. In the pre-vaccine period, G3P[8] (76 %) and G2P[4] (12 %) were the dominant genotypes detected. Although genotypes varied by surveillance year, G1P[8] and G2P[4] represented >50 % of the genotypes detected post-introduction. CONCLUSIONS: Rotavirus vaccine has been successfully implemented in Madagascar's routine childhood immunization program and had a large impact on rotavirus disease burden, supporting continued use of rotavirus vaccines in Madagascar.

Diarrhea hospitalization costs among children <5 years old in Madagascar.

BACKGROUND: Following a recommendation by the World Health Organization, Madagascar introduced rotavirus vaccine in 2014. Though national rotavirus vaccine coverage has remained <80%, rotavirus hospitalizations declined by 78%. Gavi, the Vaccine Alliance, has provided financial support for rotavirus vaccine, however the Malagasy government has increasing responsibility for the financial cost. METHODS: In this evaluation, we describe the direct medical, direct non-medical, and indirect cost of illness due to diarrhea among children <5 years old at a public pediatric referral hospital. A 3-part structured questionnaire was administered during and following the hospitalization and the child's hospital record was reviewed. RESULTS: In total, 96 children were included in this analysis. The median total cost of the illness was $156.00 (IQR: 104.00, 210.86) and the median direct medical cost was $107.22. Service delivery costs represented a median of 44% of the inpatient costs; medications and diagnostic tests represented a median of 28% and 20% of the total costs of the hospitalization, respectively. The median percentage of the total illness costs paid by the household was 67%. Among households with income of <$61/month, the median costs of the illness paid by the household were $78.55, representing a median of 168% of the household's monthly expenses. Among households earning >$303/month, the median costs paid by the household were $147.30, representing a median of 53% of the household's monthly expenses. Among all household income levels, caregivers commonly paid these bills from savings, borrowed money, and donations. CONCLUSIONS: Our findings will be useful in assessing the cost-effectiveness of rotavirus vaccine by decisionmakers. These results may also help hospital administrators and healthcare providers better understand the financial constraints of families.

Draft Genome Sequence of a Chryseobacterium indologenes Strain Isolated from a Blood Culture of a Hospitalized Child in Antananarivo, Madagascar.

We report here the draft genome sequence of a Chryseobacterium indologenes strain, isolated from a blood culture of a 2.2-year-old child admitted to the hospital for vomiting and coughing. The genome was composed of 5,063,674 bp and had 37.04% GC content. We detected 4,796 genes with predicted protein-coding functions, including those associated with antibiotic resistance.

Epidemiology of Early-onset Bacterial Neonatal Infections in Madagascar.

BACKGROUND: Little is known about early-onset neonatal bacterial infections (EONBI) in Madagascar. Our aim was to determine their epidemiology to improve their management. METHODS: Inborn neonates at risk for EONBI and admitted in the neonatal unit of 2 tertiary hospitals in Antananarivo, Madagascar, were included in a prospective study from April 2012 to March 2013. Using a clinical algorithm, blood culture, gastric fluid culture and C-reactive protein dosage were performed in newborns at high risk of infection, that is, peri partum fever, prematurity <35 weeks' gestation or birth weight <2000 g, or presenting with clinical signs of infection. EONBI was defined as a bacteremia occurring within the first week of life. RESULTS: Among 307 neonates, 75 (24.4%) had an EONBI caused by 1 (n = 59) or 2 (n = 16) bacteria (91 isolates). Gram-negative bacteria were predominant (n = 62, 82.7%), including Enterobacter cloacae (n = 26), Klebsiella pneumoniae (n = 14), Escherichia coli (n = 7) and Proteus mirabilis (n = 2). Group B Streptococcus, Acinetobacter baumanii and Enterococcus sp. represented 3.6%, 8.2% and 12.1% of the isolates, respectively. All E. cloacae and 12/14 (85.7%) K. pneumoniae were extended-spectrum ß-lactamase producers. At all, 41/91 (45.1%) bacteria were multidrug-resistant (MDR) and 34/75 (45.3%) newborns had an EONBI caused by an MDR bacteria. Neonatal asphyxia was the only factor associated with multidrug resistance (odds ratio: 4.52; CI: 1.20-16.94; P = 0.025). The EONBI-related mortality (n = 20/75, 26.7%) rose up to 38.2% (n = 13/34) in case of MDR bacteria. CONCLUSIONS: The epidemiology of EONBIs in Madagascar is comparable to that found in many low-income countries. Prevention, including improvement of hygiene during resuscitation for neonatal asphyxia, is likely to be more effective in reducing EONBI-related morbidity and mortality than using new antibiotics to counter resistance.

Analysis of Death and Survival Factors Associated with Childhood Bacterial Meningitis at a Reference Pediatric Hospital in Antananarivo, Madagascar.

BACKGROUND: Bacterial meningitis (BM) remains a global public health problem and most cases and deaths occur in Sub-Saharan Africa and especially in children less than five years old, due to a variety of factors. This study was conducted to determine the principal factors associated with death and survival of children due to BM in a typical African tertiary health facility. METHODS: A retrospective case-control study of children hospitalized for BM was conducted in the University Hospital of Tsaralalàna (CHUMET). All children aged 3 to 59 months hospitalized for bacterial meningitis and confirmed by bacteriology were included. The cases were children who died from BM, and the controls were the survivors. Data was analyzed using Stata 13. RESULTS: The factors associated with death were the number of siblings over 3 (14,48 [2,53 - 82,95]), overcrowding (9,31 [1,39 - 62,29]), time before hospitalization of more than five days (9,26 [1,36 - 62,92]), impaired consciousness (47,74 [6,24 - 364,96]), and meningococcal meningitis (36,68 [1,90 - 704,97]). CONCLUSION: These factors are mainly indicators of low socioeconomic status, clinical severity of signs and particularly virulent organisms. The early detection of patients at risk allows clinicians to give them appropriate care right from admission. Further studies are necessary especially, the evaluation of the emergency care provided.

Prevalence of Mycoplasma pneumoniae Infection in Malagasy Children.

BACKGROUND: Childhood community-acquired pneumonia is a leading cause of childhood morbidity in low-income countries. The etiologic agents are usually Staphylococcus aureus, Streptococcus pneumoniae and Mycoplasma pneumoniae. M. pneumoniae was recognized as a cofactor in asthmatic disease. High asthma prevalence was reported in Madagascar. Our aim was to clarify the prevalence of M. pneumoniae infection in this country and its relationship with asthma. METHODS: A prospective study was conducted in 351 children (from 2 to 16 years of age) from January 2012 to December 2014. According to the clinical symptoms, children were enrolled in 3 groups: "control group" (CG, n = 106), "asthma group" (n = 129) and "pneumonia group" (n = 116). The IgG and IgM M. pneumoniae status was evaluated by an enzyme-linked immunosorbent assay. Clinical signs of infection, socioeconomic data and antimicrobial treatment were recorded. RESULTS: The overall prevalence of M. pneumoniae infection was 18.2%. The multivariate analysis demonstrated that M. pneumoniae infection was significantly more frequent in the CG [pneumonia group vs. CG: odds ratio = 0.45 (0.21-0.91), P = 0.037 and asthma group vs. CG: odds ratio = 0.39 (0.18-0.87), P = 0.021]. The C-reactive protein value was significantly higher in children with M. pneumonia-positive serology (85 vs. 61 mg/L, P = 0.03). Of note, 99 (41%) children received antibiotics before attending. CONCLUSIONS: We report a prevalence of 18.2% for M. pneumoniae infection in children in Madagascar. The prevalence of M. pneumoniae infection was higher in the control patients than in asthmatic ones.