Decline in Vaccine-Type Streptococcus pneumoniae Serotypes Following Pneumococcal Conjugate Vaccine Introduction in Madagascar.

BACKGROUND: The 10-valent conjugate vaccine (PCV10) was introduced into the Extended Program on Immunization in Madagascar. We assessed the impact of PCV10 on the targeted pneumococcal serotypes among children < 5 years of age at Centre Hospitalier Universitaire Mère Enfant Tsaralalàna. METHOD: Between 2012 and December 2018, cerebrospinal fluid (CSF) samples were collected and tested for S. pneumoniae by culture, and antigen tests. The Sentinel Site Laboratory (SSL) referred available CSF samples to the Regional Reference Laboratory (RRL) for real-time polymerase chain reaction confirmatory testing and serotyping. RESULTS: In total, 3616 CSF specimens were collected. The SSL referred 2716 to the RRL; 125 were positive for S. pneumoniae. At the RRL, 115 samples that tested positive for S. pneumoniae were serotyped; PCV10 serotypes accounted for 20%. Compared to the pre-PCV period, the proportion of S. pneumoniae detected declined from 22% to 6.6%, (P < .05), the proportion of PCV10 serotypes as the cause of pneumococcal meningitis cases declined by 26% following vaccine introduction. CONCLUSIONS: In our findings, PCV10 introduction resulted in a decline of meningitis caused by S. pneumoniae and PCV10 vaccine serotypes.

The Role of Molecular Testing in Pediatric Meningitis Surveillance in Southern and East African Countries, 2008-2017.

BACKGROUND: As part of the global Invasive Bacterial Vaccine-Preventable Diseases Surveillance Network, 12 African countries referred cerebrospinal fluid (CSF) samples to South Africa's regional reference laboratory. We evaluated the utility of real-time polymerase chain reaction (PCR) in detecting and serotyping/grouping Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae (HNS). METHODS: From 2008 to 2017, CSF samples collected from children <5 years old with suspected meningitis underwent routine microbiology testing in-country, and 11 680 samples were submitted for HNS PCR at the regional reference laboratory. Unconditional logistic regression, with adjustment for geographic location, was performed to identify factors associated with PCR positivity. RESULTS: The overall HNS PCR positivity rate for all countries was 10% (1195 of 11 626 samples). In samples with both PCR and culture results, HNS PCR positivity was 11% (744 of 6747 samples), and HNS culture positivity was 3% (207 of 6747). Molecular serotype/serogroup was assigned in 75% of PCR-positive specimens (762 of 1016). Compared with PCR-negative CSF samples, PCR-positive samples were more often turbid (adjusted odds ratio, 6.80; 95% confidence interval, 5.67-8.17) and xanthochromic (1.72; 1.29-2.28), had elevated white blood cell counts (6.13; 4.71-7.99) and high protein concentrations (5.80; 4.34-7.75), and were more often HNS culture positive (32.70; 23.18-46.12). CONCLUSION: PCR increased detection of vaccine-preventable bacterial meningitis in countries where confirmation of suspected meningitis cases is impeded by limited culture capacity.

Monovalent Rotavirus Vaccine Effectiveness Against Rotavirus Hospitalizations Among Children in Zimbabwe.

BACKGROUND: Rotavirus is a leading cause of mortality among children <5 years old. We evaluated monovalent rotavirus vaccine effectiveness (VE) under conditions of routine use at 2 surveillance sites in Harare, Zimbabwe, after vaccine introduction in May 2014. METHODS: Children aged <5 years hospitalized or treated in the accident and emergency department (A&E) for acute watery diarrhea were enrolled for routine surveillance. Copies of vaccination cards were collected to document vaccination status. Among children age-eligible to receive rotavirus vaccine, we estimated VE, calculated as 1 - odds ratio, using a test-negative case-control design. RESULTS: We included 903 rotavirus-positive cases and 2685 rotavirus-negative controls in the analysis; 99% had verified vaccination status. Rotavirus-positive children had more severe diarrhea than rotavirus-negative children; 61% of cases and 46% of controls had a Vesikari score ≥11 (P < .01). Among cases and controls, 31% and 37%, respectively, were stunted for their age (P < .01). Among children 6-11 months old, adjusted 2-dose VE against hospitalization or treatment in A&E due to rotavirus of any severity was 61% (95% confidence interval [CI], 21%-81%) and 68% (95% CI, 13%-88%) against severe rotavirus disease. Stratified by nutritional status, adjusted VE was 45% (95% CI, -148% to 88%) among stunted infants and 71% (95% CI, 29%-88%) among infants with a normal height for age. CONCLUSIONS: Monovalent rotavirus vaccine is effective in preventing hospitalizations due to severe rotavirus diarrhea among infants in Zimbabwe, providing additional evidence for countries considering rotavirus vaccine introduction that live, oral rotavirus vaccines are effective in high-child-mortality settings.

Resurgent rotavirus diarrhoea outbreak five years after introduction of rotavirus vaccine in Botswana, 2018.

INTRODUCTION: Botswana had a resurgent diarrhea outbreak in 2018, mainly affecting children under five years old. Botswana introduced rotavirus vaccine (RotarixTM) into the national immunization programme in July 2012. Official rotavirus vaccine coverage estimates averaged 77.2% over the five years following introduction. MATERIALS AND METHODS: The outbreak was investigated using multiple data sources, including stool laboratory testing, immunization data review, water assessment, and vaccine storage assessment. We reviewed official reports of the routine immunization data from 2013 to 2017 and compared district-level rotavirus vaccine coverage with district-level attack rates during the outbreak. RESULTS: During the outbreak, a total of 228 stool samples were tested at the national health laboratory and 152 (67%) of the specimens were positive for rotavirus. A portion of adequate samples (80) were selected for referral to the Regional Reference Lab. The laboratory testing of 80 samples at the Regional Reference Laboratory in South Africa showed that 91% of the stool samples were positive for rotavirus, and the dominant strain 47/80 (58.7%) was G3P[8]. The immunization data showed that rotavirus vaccine coverage varied widely among districts, and there was no correlation between districts with high attack rates and those with low immunization coverage. Water assessment showed that some water sources were contaminated with E Coli. There was no problem with vaccine storage. CONCLUSION: The outbreak was caused by rotavirus G3P[8], a strain that was not common in the country prior to the outbreak. Despite the significant pressure and anxiety that outbreaks cause, the number of diarrhea cases and deaths were less compared to pre-vaccine era due to the impact of vaccination. This highlights the need for continuous implementation of high impact child survival interventions.

Measles resurgence following a nationwide measles vaccination campaign in Nigeria, 2005-2008.

INTRODUCTION: From 1990 through 2008, routine immunization coverage of measles vaccine in Nigeria ranged from 35% to 70%. Nigeria conducted a nationwide measles vaccination campaign in 2 phases during 2005-2006 that targeted children aged 9 months to 14 years; in 2008, a nationwide follow-up campaign that targeted children aged 9 months to 4 years was conducted in 2 phases. Despite these efforts, measles cases continued to occur. METHODS: This is a descriptive study that reviewed the measles immunization coverage data from administrative, World Health Organization, United Nations Children's Fund, survey, and supplemental immunization activities data. Measles surveillance data were analyzed from case-based surveillance reports. RESULTS: Confirmed measles cases increased from 383 in 2006 to 2542 in 2007 and to 9510 in 2008. Of the confirmed cases in 2008, 717 (30%) occurred in children <2 years of age, 1145 (48%) in children 2-4 years of age, and 354 (14%) were in children 5-14 years of age. In 2008, the measles case fatality rate was 1.2%. CONCLUSIONS: Suboptimal routine coverage and the wide interval between the catch-up and follow-up campaigns likely led to an accumulation of children susceptible to measles.

Cost estimates of diarrhea hospitalizations among children <5 years old in Zimbabwe.

INTRODUCTION: Diarrhoea is a leading killer of children <5 years old, accounting for 480,000 deaths in 2017. Zimbabwe introduced Rotarix into its vaccination program in 2014. In this evaluation, we estimate direct medical, direct non-medical, and indirect costs attributable to a diarrhea hospitalization in Zimbabwe after rotavirus vaccine introduction. METHODS: Children <5 years old admitted to Harare Central Hospital from June 2018 to April 2019 with acute watery diarrhea were eligible for this evaluation. A 3-part structured questionnaire was used to collect data by interview from the child's family and by review of the medical record. A stool specimen was also collected and tested for rotavirus. Direct medical costs were the sum of medications, consumables, diagnostic tests, and service delivery costs. Direct non-medical costs were the sum of transportation, meals and lodging for caregivers. Indirect costs are the lost income for household members. RESULTS: A total of 202 children were enrolled with a median age of 12 months (IQR: 7-21) and 48 (24%) had malnutrition. Children were sick for a median of 2 days and most had received outpatient medical care prior to admission. The median monthly household income was higher for well-nourished children compared to malnourished children (p < 0.001). The median total cost of a diarrhea illness resulting in hospitalization was $293.74 (IQR: 188.42, 427.89). Direct medical costs, with a median of $251.74 (IQR: 155.42, 390.96), comprised the majority of the total cost. Among children who tested positive for rotavirus, the median total illness cost was $243.78 (IQR: 160.92, 323.84). The median direct medical costs were higher for malnourished than well-nourished children (p < 0.001). CONCLUSION: Direct medical costs are the primary determinant of diarrhea illness costs in Zimbabwe. The descriptive findings from this evaluation are an important first step in calculating the cost effectiveness of rotavirus vaccine.

Impact of rotavirus vaccine introduction and genotypic characteristics of rotavirus strains in children less than 5 years of age with gastroenteritis in Ethiopia: 2011-2016.

INTRODUCTION: A monovalent rotavirus vaccine was introduced in the Ethiopian Expanded Program on Immunization from November 2013. We compared impact of rotavirus vaccine introduction on rotavirus associated acute diarrhea hospitalizations and genotypic characteristics of rotavirus strains pre-and post-vaccine introduction. METHODS: Sentinel surveillance for diarrhea among children <5 years of age was conducted at 3 hospitals in Addis Ababa, Ethiopia from 2011 to 2017. Stool specimens were collected from enrolled children and tested using an antigen capture enzyme immunoassay. Rotavirus positive samples (156 from pre- and 141 from post-vaccination periods) were further characterized by rotavirus genotyping methods to identify the predominant G and P types circulating during the surveillance era. RESULTS: A total of 788 children were enrolled during the pre- (July 2011-June 2013) and 815 children during the post-vaccination (July 2014-June 2017) periods. The proportion of diarrhea hospitalizations due to rotavirus among children <5 years of age declined by 17% from 24% (188/788) in the pre-vaccine period and to 20% (161/185) in post-vaccine introduction era. Similarly, a reduction of 18% in proportion of diarrhea hospitalizations due to rotavirus in children <12 months of age in the post (27%) vs pre-vaccine (33%) periods was observed. Seasonal peaks of rotavirus declined following rotavirus vaccine introduction. The most prevalent circulating strains were G12P[8] in 2011 (36%) and in 2012 (27%), G2P[4] (35%) in 2013, G9P[8] (19%) in 2014, G3P[6] and G2P[4] (19% each) in 2015, and G3P[8] (29%) in 2016. DISCUSSION: Following rotavirus vaccine introduction in Ethiopia, a reduction in rotavirus associated hospitalizations was seen in all age groups with the greatest burden in children <12 months of age. A wide variety of rotavirus strains circulated in the pre- and post-vaccine introduction periods.

Early impact of rotavirus vaccination in children less than five years of age in Mozambique.

BACKGROUND: Mozambique introduced rotavirus vaccine (Rotarix, GSK Biologicals) in the National Immunization Program in September 2015 with the objective of reducing the burden of total diarrheal disease and specifically severe rotavirus disease. This study aimed to evaluate the early impact of rotavirus vaccine in reducing all-cause diarrhea and rotavirus-specific hospitalizations. METHODS: We analysed stool specimens collected from children under five years old, between January 2014 and June 2017 within the National Surveillance for Acute Diarrhea. We compared annual changes in rotavirus positivity, median age of children hospitalized for rotavirus and the number of all-cause for diarrheal hospitalizations. Rotavirus detection was performed using enzyme immunoassay. RESULTS: During this period, 1296 samples were collected and analyzed. Rotavirus positivity before vaccine introduction was 40.2% (39/97) in 2014 and 38.3% (225/588) in 2015, then after vaccine introduction reduced to 12.2% and 13.5% in 2016 and 2017, respectively. The median age of children hospitalized for rotavirus was 9 and 11 months in 2014 and 2015 and 10 months in 2016 and 2017. Rotavirus hospitalizations exhibited a seasonal peak prior to vaccine introduction, between June and September in 2014 and 2015, coinciding with winter period in Mozambique. After vaccine introduction, the peak was delayed until August to December in 2016 and was substantially diminished. There was a reduction in all-cause acute diarrhea hospitalizations in children aged 0-11 months after vaccine introduction. CONCLUSION: We observed a reduction in rotavirus positivity and in the number of all-cause diarrhea hospitalizations after vaccine introduction. The data suggest rotavirus vaccine is having a positive impact on the control of rotavirus diarrheal disease in Mozambique.