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.

Clinical and genomic features of a Listeria monocytogenes fatal case of meningitis in Madagascar.

Listeriosis constitutes a significant public health threat due to its high mortality rate. This study investigates the microbiological and genomic characteristics of Listeria monocytogenes isolates in Madagascar, where listeriosis is a notifiable disease. The analysis focuses on a fatal case of meningeal listeriosis in a 12-year-old child. Genomic analysis revealed a novel cgMLST type (L2-SL8-ST8-CT11697; CC8, serogroup Iia) with typical virulence and antibiotic resistance profiles. These isolates, unique to Madagascar, formed an independent clade in the phylogenetic tree. This study presents the first genomic characterization of Listeria isolates in Madagascar, highlighting the necessity of ongoing genomic surveillance to strengthen listeriosis prevention and control strategies in the region.

Implementation of the WHO Tricycle protocol for surveillance of extended-spectrum ß-lactamase producing Escherichia coli in humans, chickens, and the environment in Madagascar: a prospective genomic epidemiology study.

BACKGROUND: Antimicrobial resistance (AMR) is a major public health threat, affecting not only people but also animals and the environment. The One Health dimension of AMR is well known; however, data are lacking on the circulation of resistance-conferring genes, particularly in low-income countries. In 2017, WHO proposed a protocol called Tricycle, focusing on extended-spectrum ß-lactamase (ESBL)-Escherichia coli surveillance in the three sectors (humans, animals, and the environment). We implemented Tricycle in Madagascar to assess ESBL-E coli prevalence and describe intrasector and intersector circulation of ESBL-E coli and plasmids. METHODS: In this prospective study, we collected blood culture data from hospitalised patients with a suspected bloodstream infection processed from May 1, 2018, to April 30, 2019, and rectal swabs from healthy pregnant women from July 30, 2018, to April 27, 2019, both from three hospitals in Antananarivo, Madagascar; and caeca from farm chickens and surface waters from the Ikopa river, wastewater, and slaughterhouse effluents in the Antananarivo area, Madagascar, from April 9, 2018, to April 30, 2019. All samples were tested for ESBL-E coli. The genomes of all isolates were sequenced using a short-read method on NextSeq 500 and NovaSeq 6000 platforms (Illumina, San Diego, CA, USA) and those carrying plasmid replicons using an additional long-read method on a MinION platform (Oxford Nanopore Technologies, Oxford, UK). We characterised genomes of isolated strains (sequence type, resistance and virulence gene content, and plasmid replicons). We then compared isolates using the variant calling method (single-nucleotide polymorphism). FINDINGS: Data from 1056 blood cultures were collected and 289 pregnant women, 246 chickens, and 28 surface waters were sampled. Of the blood cultures, 18 contained E coli, of which seven (39%) were ESBL. ESBL-E coli was present in samples from 86 (30%) of 289 pregnant women, 140 (57%) of 246 chickens, and 28 (100%) of 28 surface water samples. The wet season (November to April) was associated with higher rates of carriage in humans (odds ratio 3·08 [1·81-5·27]) and chickens (2·79 [1·65-4·81]). Sequencing of 277 non-duplicated isolates (82 from pregnant women, 118 from chickens, and 77 from environmental samples) showed high genetic diversity (90 sequence types identified) with sector-specific genomic features. Single nucleotide polymorphism (SNP) analysis revealed that 169 (61%) of 277 isolates grouped into 44 clusters (two or more isolates) of closely related isolates (<40 SNPs), of which 24 clusters contained isolates from two sectors and five contained isolates from all three sectors. ESBL genes were all blaCTX-M variants (215 [78%] of 277 being blaCTX-M-15) and were located on a plasmid in 113 (41%) of 277 isolates. These ESBL-carrying plasmids were mainly IncF (63 [55%] of 114; one strain carried two plasmids) and IncY (42 [37%] of 114). The F31/36:A4:B1 (n=13) and F-:A-:B53 (n=8) pMLST subtypes, and the IncY plasmids, which were all highly conserved, were observed in isolates of differing genetic backgrounds from all sectors and were transferable in vitro by conjugation. INTERPRETATION: Despite sector-specific population structures, both ESBL-E coli strains and plasmids are circulating among humans, chickens, and the environment in Antananarivo, Madagascar. The Tricycle protocol can be implemented in a low-income country and represents a powerful tool for investigating dissemination of AMR from a One Health perspective. FUNDING: Fondation Mérieux and INSERM, Université Paris Cité.

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.

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.

Novel Streptococcus suis Sequence Type 834 among Humans, Madagascar.

Two cases of meningitis caused by Streptococcus suis occurred in Madagascar, 1 in 2015 and 1 in 2016. We report the characterization of the novel sequence type, 834, which carried the mrp+/sly+/epf+ virulence marker and a mutation G→T at position 174, leading to a substitution mutS1 to mutS284.