Epidemiology of intussusception among infants in Togo, 2015-2018.

INTRODUCTION: intussusception is the leading cause of bowel obstruction in infants and young children. We describe the epidemiology and diagnostic and treatment characteristics of intussusception among Togolese infants over a 4-year period. METHODS: we implemented active surveillance among infants younger than 1 year of age admitted with intussusception from 2015 to 2018 at Sylvanus Olympio Teaching Hospital and in 2018 at Campus Teaching Hospital. Brighton Collaboration Level 1 case definition criteria were used to confirm the diagnosis of intussusception. RESULTS: during four years, 41 cases of intussusception, with an annual range of 8 to 14 cases (median: 10) were reported; and the highest number of cases (89%) was enrolled at Sylvanus Olympio teaching hospital. Intussusception was uncommon in the first 2 months of life, peaked from 5 to 7 months old (63%), with male predominance (63%), and showed no significant seasonality. One third of cases (34%) were transferred to the sentinel surveillance site from another health facility; and the median delay in seeking care was 4 days (range: 0-11) with ≥ 48-hour delay in 59% of cases. Clinical symptoms, ultrasound and surgery were combined to diagnose intussusception in all the cases (100%). The treatment was exclusively surgical, and intestinal resection was common (28/41, 68%). A high case fatality rate (23%) was observed and the average length of hospital stay was 10 days (range: 1-23). CONCLUSION: active surveillance for intussusception in Togo has highlighted exclusive use of surgical therapy; often associated to an intestinal resection with a very high case fatality rate.

Phylogeography and resistome of pneumococcal meningitis in West Africa before and after vaccine introduction.

Despite contributing to the large disease burden in West Africa, little is known about the genomic epidemiology of Streptococcus pneumoniae which cause meningitis among children under 5 years old in the region. We analysed whole-genome sequencing data from 185 S. pneumoniae isolates recovered from suspected paediatric meningitis cases as part of the World Health Organization (WHO) invasive bacterial diseases surveillance from 2010 to 2016. The phylogeny was reconstructed, accessory genome similarity was computed and antimicrobial-resistance patterns were inferred from the genome data and compared to phenotypic resistance from disc diffusion. We studied the changes in the distribution of serotypes pre- and post-pneumococcal conjugate vaccine (PCV) introduction in the Central and Western sub-regions separately. The overall distribution of non-vaccine, PCV7 (4, 6B, 9V, 14, 18C, 19F and 23F) and additional PCV13 serotypes (1, 3, 5, 6A, 19A and 7F) did not change significantly before and after PCV introduction in the Central region (Fisher's test P value 0.27) despite an increase in the proportion of non-vaccine serotypes to 40 % (n=6) in the post-PCV introduction period compared to 21.9 % (n=14). In the Western sub-region, PCV13 serotypes were more dominant among isolates from The Gambia following the introduction of PCV7, 81 % (n=17), compared to the pre-PCV period in neighbouring Senegal, 51 % (n=27). The phylogeny illustrated the diversity of strains associated with paediatric meningitis in West Africa and highlighted the existence of phylogeographical clustering, with isolates from the same sub-region clustering and sharing similar accessory genome content. Antibiotic-resistance genotypes known to confer resistance to penicillin, chloramphenicol, co-trimoxazole and tetracycline were detected across all sub-regions. However, there was no discernible trend linking the presence of resistance genotypes with the vaccine introduction period or whether the strain was a vaccine or non-vaccine serotype. Resistance genotypes appeared to be conserved within selected sub-clades of the phylogenetic tree, suggesting clonal inheritance. Our data underscore the need for continued surveillance on the emergence of non-vaccine serotypes as well as chloramphenicol and penicillin resistance, as these antibiotics are likely still being used for empirical treatment in low-resource settings. This article contains data hosted by Microreact.

Etiology of Pediatric Meningitis in West Africa Using Molecular Methods in the Era of Conjugate Vaccines against Pneumococcus, Meningococcus, and Haemophilus influenzae Type b.

Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for N. meningitidis, S. pneumoniae, and H. influenzae used in routine meningitis surveillance. A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and Plasmodium. Overall, Escherichia coli was the most prevalent (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and Plasmodium detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.

Whole Genome Analysis of African G12P[6] and G12P[8] Rotaviruses Provides Evidence of Porcine-Human Reassortment at NSP2, NSP3, and NSP4.

Group A rotaviruses (RVA) represent the most common cause of pediatric gastroenteritis in children <5 years, worldwide. There has been an increase in global detection and reported cases of acute gastroenteritis caused by RVA genotype G12 strains, particularly in Africa. This study sought to characterize the genomic relationship between African G12 strains and determine the possible origin of these strains. Whole genome sequencing of 34 RVA G12P[6] and G12P[8] strains detected from the continent including southern (South Africa, Zambia, Zimbabwe), eastern (Ethiopia, Uganda), central (Cameroon), and western (Togo) African regions, were sequenced using the Ion Torrent PGM method. The majority of the strains possessed a Wa-like backbone with consensus genotype constellation of G12-P[6]/P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, while a single strain from Ethiopia displayed a DS-1-like genetic constellation of G12-P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2. In addition, three Ethiopian and one South African strains exhibited a genotype 2 reassortment of the NSP3 gene, with genetic constellation of G12-P[8]-I1-R1-C1-M1-A1-N1-T2-E1-H1. Overall, 10 gene segments (VP1-VP4, VP6, and NSP1-NSP5) of African G12 strains were determined to be genetically related to cognate gene sequences from globally circulating human Wa-like G12, G9, and G1 strains with nucleotide (amino acid) identities in the range of 94.1-99.9% (96.5-100%), 88.5-98.5% (93-99.1%), and 89.8-99.0% (88.7-100%), respectively. Phylogenetic analysis showed that the Ethiopian G12P[6] possessing a DS-1-like backbone consistently clustered with G2P[4] strains from Senegal and G3P[6] from Ethiopia with the VP1, VP2, VP6, and NSP1-NSP4 genes. Notably, the NSP2, NSP3, and NSP4 of most of the study strains exhibited the closest relationship with porcine strains suggesting the occurrence of reassortment between human and porcine strains. Our results add to the understanding of potential roles that interspecies transmission play in generating human rotavirus diversity through reassortment events and provide insights into the evolutionary dynamics of G12 strains spreading across selected sub-Saharan Africa regions.

Etiology of Pediatric Bacterial Meningitis Pre- and Post-PCV13 Introduction Among Children Under 5 Years Old in Lomé, Togo.

BACKGROUND: Pediatric bacterial meningitis (PBM) causes severe morbidity and mortality within Togo. Thus, as a member of the World Health Organization coordinated Invasive Bacterial Vaccine Preventable Diseases network, Togo conducts surveillance targeting Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae, at a sentinel hospital within the capital city, Lomé, in the southernmost Maritime region. METHODS: Cerebrospinal fluid was collected from children <5 years with suspected PBM admitted to the Sylvanus Olympio Teaching Hospital. Phenotypic detection of pneumococcus, meningococcus, and H. influenzae was confirmed through microbiological techniques. Samples were shipped to the Regional Reference Laboratory to corroborate results by species-specific polymerase chain reaction. RESULTS: Overall, 3644 suspected PBM cases were reported, and 98 cases (2.7%: 98/3644) were confirmed bacterial meningitis. Pneumococcus was responsible for most infections (67.3%: 66/98), followed by H. influenzae (23.5%: 23/98) and meningococcus (9.2%: 9/98). The number of pneumococcal meningitis cases decreased by 88.1% (52/59) postvaccine introduction with 59 cases from July 2010 to June 2014 and 7 cases from July 2014 to June 2016. However, 5 cases caused by nonvaccine serotypes were observed. Fewer PBM cases caused by vaccine serotypes were observed in infants <1 year compared to children 2-5 years. CONCLUSIONS: Routine surveillance showed that PCV13 vaccination is effective in preventing pneumococcal meningitis among children <5 years of age in the Maritime region. This complements the MenAfriVac vaccination against meningococcal serogroup A to prevent meningitis outbreaks in the northern region of Togo. Continued surveillance is vital for estimating the prevalence of PBM, determining vaccine impact, and anticipating epidemics in Togo.

[Etiological and evolving profile of renal disability of children in hospital in Togo]. / Profil étiologique et évolutif de l'insuffisance rénale de l'enfant en milieu hospitalier au Togo.

OBJECTIVE: To determine the etiological and evolutionary profile of renal failure of chidren in Togo. METHODS: This is a cross-sectional study over the period of 12 months (2016-2017) including children aged 1 to 18 years hospitalized in the pediatric ward of Sylvanus Olympio university teaching hospital of Lome (Togo) for renal failure. RESULTS: Of 2374 patients hospitalized in our unit, 58 (2.4%) had renal failure. The mean age was 8.17±4 years with a sex ratio of 1.32. The average consultation time was 11.9 days. The mean duration of hospitalization was 12.7±7.7 days. Thirty-seven patients (63.8%) were referred from a peripheral center. Thirty-seven children out of 58 (63.1%) were oligoanuric. Renal failure was acute in 94.8% and chronic in 5.2%. Anemia was found in 84.4% of children. The main etiologies found were severe malaria (63.8%), glomerulonephritis (10.3%) and nephrotic syndrome (10.3%). Thirteen children (22.4%) benefited from dialysis sessions. The evolution was favorable in 79.3% of the cases. CONCLUSION: The renal failure of child is relatively common in our daily practice. The low socio-economic level and the lack of adapted equipment make the care difficult.

Evidence of the impact of monovalent rotavirus vaccine on childhood acute gastroenteritis hospitalization in Togo.

BACKGROUND: Monovalent rotavirus vaccine (RV1) was introduced in the immunization schedule of Togo in June 2014. We evaluated the impact of rotavirus vaccines on acute gastroenteritis (AGE) and rotavirus-associated hospitalizations in Togolese children. METHODS: Sentinel surveillance for AGE (defined as ≥3 liquid or semi-liquid stools/24 h lasting <7 days) hospitalizations among children <5 years of age was conducted in two sites in the capital city, Lome. ELISA was used for diagnosis of rotavirus infection in children with AGE. Additionally, review of hospitalization registers was performed at five hospitals to assess trends in AGE hospitalizations among children aged <5 years. For the vaccine impact assessment, pre-rotavirus vaccine introduction (July 2010-June 2014) and post-rotavirus vaccine introduction (July 2014-June 2016) periods were compared for annual changes in proportions of hospitalizations associated with AGE and rotavirus. RESULTS: During the pre-vaccine period, sentinel surveillance showed that 1017 patients were enrolled and 57% (range, 53-62%) tested positive for rotavirus, declining to 42% (23% reduction) in the first post-vaccine year and to 26% (53% reduction) in the second post-vaccine year; declines were most marked among infants. The patient register review showed that, compared with pre-vaccine rotavirus seasons, declines in hospitalizations due to all-cause AGE during post-vaccine rotavirus seasons were 48% among <1 year age-group in both first and second years following vaccine introduction. Among 1-4 year olds no reduction was noted in the first year and a 19% decline occurred in the second year. CONCLUSIONS: We report rapid and marked reduction in the number of AGE hospitalizations and the proportion of AGE hospitalizations attributable to rotavirus in the first two years post- RV1 implementation in Togo. It is necessary to monitor long-term vaccine impact on rotavirus disease burden through continued surveillance.

Etiology of Severe Acute Watery Diarrhea in Children in the Global Rotavirus Surveillance Network Using Quantitative Polymerase Chain Reaction.

Background: The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction. Methods: We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children <5 years of age during 2013-2014 from 16 countries. We used previously developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs). Results: Rotavirus remained the leading etiology (overall weighted AF, 40.3% [95% confidence interval {CI}, 37.6%-44.3%]), though the AF was substantially lower in the Americas (AF, 12.2 [95% CI, 8.9-15.6]), based on samples from a country with universal rotavirus vaccination. Norovirus GII (AF, 6.2 [95% CI, 2.8-9.2]), Cryptosporidium (AF, 5.8 [95% CI, 4.0-7.6]), Shigella (AF, 4.7 [95% CI, 2.8-6.9]), heat-stable enterotoxin-producing Escherichia coli (ST-ETEC) (AF, 4.2 [95% CI, 2.0-6.1]), and adenovirus 40/41 (AF, 4.2 [95% CI, 2.9-5.5]) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% CI, 48.3%-61.5%) in rotavirus vaccine age-ineligible children to 20.0% (95% CI, 12.4%-30.4%) in age-eligible children. Conclusions: Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of rotavirus vaccine introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea.

Early Evidence of Impact of Monovalent Rotavirus Vaccine in Togo.

Togo introduced monovalent rotavirus vaccine starting 19 June 2014. We compared all-cause acute gastroenteritis (AGE) hospitalizations and rotavirus-associated hospitalizations during the prevaccine period (July 2008-June 2014) to 1 year after vaccine introduction (July 2014-June 2015). The proportion of children with AGE who tested positive for rotavirus declined from 53% (645/1223) in prevaccine years to 36% (68/187) in the postvaccine year (P< .01). The decline only occurred in children <1 year of age who were eligible for vaccination and was greatest during the rotavirus season months, supporting that it was associated with vaccine implementation.

Whole-genome analyses of DS-1-like human G2P[4] and G8P[4] rotavirus strains from Eastern, Western and Southern Africa.

Group A rotaviruses (RVAs) with distinct G and P genotype combinations have been reported globally. We report the genome composition and possible origin of seven G8P[4] and five G2P[4] human RVA strains based on the genetic evolution of all 11 genome segments at the nucleotide level. Twelve RVA ELISA positive stool samples collected in the representative countries of Eastern, Southern and West Africa during the 2007-2012 surveillance seasons were subjected to sequencing using the Ion Torrent PGM and Illumina MiSeq platforms. A reference-based assembly was performed using CLC Bio's clc_ref_assemble_long program, and full-genome consensus sequences were obtained. With the exception of the neutralising antigen, VP7, all study strains exhibited the DS-1-like genome constellation (P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2) and clustered phylogenetically with reference strains having a DS-1-like genetic backbone. Comparison of the nucleotide and amino acid sequences with selected global cognate genome segments revealed nucleotide and amino acid sequence identities of 81.7-100 % and 90.6-100 %, respectively, with NSP4 gene segment showing the most diversity among the strains. Bayesian analyses of all gene sequences to estimate the time of divergence of the lineage indicated that divergence times ranged from 16 to 44 years, except for the NSP4 gene where the lineage seemed to arise in the more distant past at an estimated 203 years ago. However, the long-term effects of changes found within the NSP4 genome segment should be further explored, and thus we recommend continued whole-genome analyses from larger sample sets to determine the evolutionary mechanisms of the DS-1-like strains collected in Africa.

Surveillance for rotavirus gastroenteritis in children less than 5 years of age in Togo.

BACKGROUND: Rotavirus is the most common cause of severe gastroenteritis and dehydration in young children in both industrialized and developing countries. The anticipated introduction of rotavirus vaccine into Togo's national immunization program highlights the need for baseline data on the burden of this disease. METHODS: We conducted sentinel surveillance for rotavirus gastroenteritis among children <5 years of age in Sylvanus Olympio Teaching Hospital of Lome (Togo) from February 2008 through January 2012, based on the World Health Organization's generic protocol. Rotavirus was detected in stool specimens by enzyme linked immunosorbent assay. The strain characterization by genotyping was performed at Noguchi Memorial Institute for Medical Research in Accra (Ghana) and at Medunsa campus in Pretoria (South Africa). RESULTS: 803 children with acute gastroenteritis were enrolled and of which 390 (48%) were positive for rotavirus. The difference of age among children with rotavirus and nonrotavirus gastroenteritis was significant (P < 0.010) with rotavirus cases younger than nonrotavirus cases. From December to February, significantly (P < 0.002) more cases of rotavirus gastroenteritis were enrolled compared with other months of the year. Vomiting (P = 0.04) was more common in children with rotavirus than nonrotavirus gastroenteritis. The most common G-P combinations were G3P[6] (23%), G1P[8] (12%), G1P[6/8] (8%), G2P[6] (7%), G12P[6] (7%) and G3/12P[6] (6%). CONCLUSIONS: The prevalence of rotavirus is high among children with acute gastroenteritis in Togo. Continued and extended rotavirus surveillance will be important to monitor changes in the epidemiology of rotavirus disease and the impact of vaccination after introduction.