Browsing by Author "Armah, G."
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Item Aetiology of acute lower respiratory infections among children under five years in Accra, Ghana(Pathogens, 2015-01) Adiku, T.K.; Asmah, R.H.; Rodrigues, O.; Goka, B.; Obodai, E.; Adjei, A.A.; Donkor, E.S.; Armah, G.The study aimed to investigate the aetiological agents and clinical presentations associated with acute lower respiratory infections (ALRI) among children under five years old at the Korle-Bu Teaching Hospital in Ghana. This was a cross-sectional study carried from February to December 2001. Nasopharyngeal aspirates and venous blood specimens obtained from 108 children with features suggestive of ALRI, were cultured and the isolated bacterial organisms were identified biochemically. Nasopharyngeal aspirates were also tested for Respiratory Syncitial Virus (RSV) antigen using a commercial kit (Becton Dickinson Directigen RSV test kit). A multiplex reverse transcription-PCR (RT-PCR) was also used to detect and characterize RSV using extracted RNA. Socio-demographic and clinical data were also obtained from the study subjects. Bronchopneumonia (55.5%), bronchiolitis (25%), lobar pneumonia (10.2), non-specific ALRI (4.6%), TB, bronchitis and respiratory distress (0.67%) were diagnosed. The prevalence of septicaemia was 10% and bacteria isolated were Staphylococcus aureus, Streptococcus pneumoniae and enteric bacteria, including Salmonella spp., Enterobacter spp and Klebsiella spp, were isolated. Out of the 108 cases, 18% tested positive for RSV, with two cases having RSV as the only aetiological pathogen detected. The subtyping analysis of RSV strains by a multiplex RT-PCR showed that subgroups A and B circulated in the season of analysis. © 2015 by the authorsItem Analyses of health outcomes from the 5 sites participating in the Africa and Asia clinical efficacy trials of the oral pentavalent rotavirus vaccine(Vaccine, 2012-04) Breiman, R.F.; Zaman, K.; Armah, G.; Sow, S.O.; Anh, D.D.; Victor, J.C.; Hille, D.; Ciarlet, M.; Neuzil, K.M.Background: Efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq®, against severe rotavirus gastroenteritis (RVGE) was evaluated in two double-blind, placebo-controlled, multicenter Phase III clinical trials conducted in GAVI-eligible countries in Africa (Ghana, Kenya, and Mali) and in Asia (Bangladesh and Vietnam) from March 2007 through March 2009. The findings from each continent have been analyzed and presented separately, according to a single identical protocol. Ad hoc analyses combining data from the five sites were performed to further assess the impact of PRV. Methods: 6674 infants (4705 infants from Africa and 1969 infants from Asia), randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age according to each country's EPI schedule, were included in the per protocol efficacy analysis. Breastfeeding and concomitant administration of EPI vaccines, including OPV, were allowed. Episodes of gastroenteritis (GE) in infants who presented to study facilities were captured and scored using the 20-point Vesikari scale. Stool samples were analyzed by rotavirus-specific EIA to detect presence of rotavirus antigen and RT-PCR to determine the G/P genotypes. We assessed efficacy to prevent all-cause GE and RVGE at a variety of cut-off points (score ≥ 11, severe; score ≥ 15, very severe). Results: Vaccine efficacy (VE) against RVGE, regardless of serotype, through the entire follow-up period for any severity, severe (score ≥ 11), and very severe (score ≥ 15) was 33.9%, 95% CI (22.7, 43.5), 42.5%, 95% CI (27.4, 54.6), and 51.2%, 95% CI (26.3, 68.2), respectively. Through the first year of life, VE against severe RVGE was 58.9%, 95% CI (40.0, 72.3) and against all-cause severe GE was 23.0%, 95% CI (5.4, 37.3). VE against severe RVGE caused by non-vaccine G serotypes, G8 and G9, through the entire follow-up period was 87.5%, 95% CI (6.8, 99.7) and 48.0%, 95% CI (-5.5, 75.6), respectively. All G8 strains were associated with P2A[6] (a P-type not contained in PRV), while the majority of the G9 strains were associated with P1A[8] (a P-type contained in PRV). Conclusions: Combining data from the 5 sites strengthens the precision of VE estimates and reveals rising VE with increased RVGE severity. Extrapolating data from VE against severe GE and RVGE suggest that 39% of severe GE episodes during the first year of life were due to rotavirus, highlighting substantial, potentially preventable, public health burden of RVGE. PRV provides protection against non-vaccine serotypes (G8P2A[6]). © 2011.Item Comparison of two clinical severity scoring systems in two multi-center, developing country rotavirus vaccine trials in Africa and Asia(Vaccine, 2012-04) Lewis, K.D.C.; Dallas, M.J.; Victor, J.C.; Ciarlet, M.; Mast, T.C.; Ji, M.; Armah, G.; Zaman, K.; Ferraro, A.; Neuzil, K.M.Background: Clinical severity scoring systems are used in rotavirus vaccine efficacy and effectiveness studies to define the primary endpoint, severe rotavirus gastroenteritis (RVGE). Understanding how scoring systems perform in diverse settings is critical for proper design and interpretation. This investigation aims to understand how the Vesikari scoring system (VSS) and Clark scoring system (CSS) categorize severe disease among children under 2 years of age using data from two Phase III efficacy trials conducted in five developing countries in Africa and Asia. Methods: Signs and symptoms were collected on trial participants who presented to a medical facility with study-defined gastroenteritis. Severity scores were calculated using pre-established VSS and CSS criteria and compared to identify differences in the proportions of severe RVGE within regions and sites, and by gender and age. Results: In Africa and Asia, 40.6% and 56.0% of rotavirus-positive episodes were severe according to the VSS, while 9.5% and 6.3% of episodes were severe according to the CSS (Fisher's Exact, p≤ 0.001). Using the mean scores in these trials (VSS: ≥10 Africa, ≥11 Asia; CSS: Africa and Asia ≥10) as the severity thresholds, agreement between scoring system severity classifications improved substantially within each region (Africa: kappa = 0.67; Asia: kappa = 0.78) as compared to the original severity classification (Africa: kappa = 0.27; Asia: kappa = 0.10). Using the mean score, 17.1% and 9.5% of severe VSS cases in Africa and Asia, respectively, were classified as not severe according to the CSS and 14.7% and 9.5% of severe CSS cases in Africa and Asia were classified as not severe according to the VSS. Conclusion: The two scoring systems performed differently among developing country populations in Africa and Asia, with the VSS classifying more cases as severe in both regions. One accurate and reliable scoring system should be developed and implemented for all trials so that results may be more comparable. © 2011 Elsevier Ltd.Item Cost-effectiveness of rotavirus vaccination in Ghana: Examining impacts from 2012 to 2031(Vaccine, 2018-11) Nonvignon, J.; Atherly, D.; Pecenka, C.; Aikins, M.; Gazley, L.; Groman, D.; Narh, C.T.; Armah, G.Background: Diarrhea causes about 10% of all deaths in children under five years globally, with rotavirus causing about 40% of all diarrhea deaths. Ghana introduced rotavirus vaccination as part of routine immunization in 2012 and it has been shown to be effective in reducing disease burden in children under five years. Ghana's transition from low to lower-middle income status in 2010 implies fewer resources from Gavi as well as other major global financing mechanisms. Ghana will soon bear the full cost of vaccines. The aim of this study was to estimate the health impact, costs and cost-effectiveness of rotavirus vaccination in Ghana from introduction and beyond the Gavi transition. Methods: The TRIVAC model is used to estimate costs and effects of rotavirus vaccination from 2012 through 2031. Model inputs include demographics, disease burden, health system structure, health care utilization and costs as well as vaccine cost, coverage, and efficacy. Model inputs came from local data, the international literature and expert consultation. Costs were examined from the health system and societal perspectives. Results: The results show that continued rotavirus vaccination could avert more than 2.2 million cases and 8900 deaths while saving US$6 to US$9 million in costs over a 20-year period. The net cost of vaccination program is approximately US$60 million over the same period. The societal cost per DALY averted is US$238 to US$332 with cost per case averted ranging from US$27 to US$38. The cost per death averted is approximately US$7000. Conclusion: The analysis shows that continued rotavirus vaccination will be highly cost-effective, even for the period during which Ghana will assume responsibility for purchasing vaccines after transition from Gavi support. © 2017 The AuthorsItem Decline in severe diarrhea hospitalizations after the introduction of rotavirus vaccination in Ghana: A prevalence study(BMC Infectious Diseases, 2014-08) Enweronu-Laryea, C.C.; Boamah, I.; Sifah, E.; Diamenu, S.K.; Armah, G.Background: Almost all diarrhea deaths in young children occur in developing countries. Immunization against rotavirus, the leading cause of childhood severe dehydrating acute diarrhea may reduce the burden of severe diarrhea in developing countries. Ghana introduced rotavirus and pneumococcal vaccination in the national expanded program on immunization in May 2012.Methods: Review of all-cause diarrheal hospitalization data for children aged 59 months and younger at 2 pediatric referral hospitals in southern Ghana from 2008 to 2014. The proportion of acute diarrhea (defined as 3 or more watery, non-bloody stools within 24 hours that has lasted for less than 7 days) cases caused by rotavirus was determined. Temporal trend and age group distribution of all-cause diarrhea and rotavirus gastroenteritis before and after introduction of the new vaccines were compared.Results: Of the 5847 children hospitalized with all-cause diarrhea during the 74 months (January 2008 - February 2014), 3963 (67.8%) children were recruited for rotavirus surveillance and stool specimens were tested for rotavirus in 3160/3963 (79.7%). Median monthly hospitalization for all-cause diarrhea reduced from 84 [interquartile range (IQR) 62 - 105] during the 52 months pre-vaccination introduction to 46 (IQR 42 - 57) in the 22 months after implementation of vaccination. Significant decline in all-cause diarrhea hospitalization occurred in children aged 0 - 11 months: 56.3% (2711/4817) vs. 47.2% 486/1030 [p = 0.0001, 95% confidence interval (CI) 0.77 - 0.88] and there was significant reduction of rotavirus gastroenteritis hospitalization: 49.7% (1246/2505) vs. 27.8% (182/655) [p = 0.0001, 95% CI 0.32 - 0.47] before and after vaccine introduction respectively.Conclusions: Implementation of rotavirus vaccination program may have resulted in significant reduction of severe diarrhea hospitalization even though this observational study could not exclude the effect of other confounding factors. Continued surveillance is recommended to monitor the progress of this program. © 2014 Enweronu-Laryea et al.; licensee BioMed Central Ltd.Item Decline in severe diarrhea hospitalizations after the introduction of rotavirus vaccination in Ghana: a prevalence study(2014-08-06) Enweronu-Laryea, C.C.; Boamah, I.; Sifah, E.; Diamenu, S.K.; Armah, G.Abstract Background Almost all diarrhea deaths in young children occur in developing countries. Immunization against rotavirus, the leading cause of childhood severe dehydrating acute diarrhea may reduce the burden of severe diarrhea in developing countries. Ghana introduced rotavirus and pneumococcal vaccination in the national expanded program on immunization in May 2012. Methods Review of all-cause diarrheal hospitalization data for children aged 59 months and younger at 2 pediatric referral hospitals in southern Ghana from 2008 to 2014. The proportion of acute diarrhea (defined as 3 or more watery, non-bloody stools within 24 hours that has lasted for less than 7 days) cases caused by rotavirus was determined. Temporal trend and age group distribution of all-cause diarrhea and rotavirus gastroenteritis before and after introduction of the new vaccines were compared. Results Of the 5847 children hospitalized with all-cause diarrhea during the 74 months (January 2008 – February 2014), 3963 (67.8%) children were recruited for rotavirus surveillance and stool specimens were tested for rotavirus in 3160/3963 (79.7%). Median monthly hospitalization for all-cause diarrhea reduced from 84 [interquartile range (IQR) 62 – 105] during the 52 months pre-vaccination introduction to 46 (IQR 42 - 57) in the 22 months after implementation of vaccination. Significant decline in all-cause diarrhea hospitalization occurred in children aged 0 - 11 months: 56.3% (2711/4817) vs. 47.2% 486/1030 [p = 0.0001, 95% confidence interval (CI) 0.77 – 0.88] and there was significant reduction of rotavirus gastroenteritis hospitalization: 49.7% (1246/2505) vs. 27.8% (182/655) [p = 0.0001, 95% CI 0.32 - 0.47] before and after vaccine introduction respectively. Conclusions Implementation of rotavirus vaccination program may have resulted in significant reduction of severe diarrhea hospitalization even though this observational study could not exclude the effect of other confounding factors. Continued surveillance is recommended to monitor the progress of this program.Item Emergence and Characterization of Serotype G9 Rotavirus Strains from Africa(Journal of Infectious Diseases, 2010) Page, N.; Esona, M.; Armah, G.; Nyangao, J.; Mwenda, J.; Sebunya, T.; Basu, G.; Pyndiah, N.; Potgieter, N.; Geyer, A.; Steele, A.D.Serotype G9 strains have been detected sporadically and in localized outbreaks in various African countries, including South Africa, Botswana, Malawi, Kenya, Cameroon, Nigeria, Ghana, Guinea-Bissau, Libya, and Mauritius. Serotype G9 strains were analyzed to investigate genogroup characteristics, including subgroup specificity, electropherotype, and P and G genotypes. In addition, the antigenic composition of the South African G9 strains was assessed. African G9 strains were associated with both DS-1–like characteristics and Wa-like characteristics, indicating the predisposition of G9 strains to frequently reassort. Despite these reassortment events, serotype G9 strains appear to maintain antigenic character in the outer capsid protein, as evident with the reaction of the South African G9 strains with the G9-specific monoclonal antibody F45:1. Phylogenetic analysis clustered African G9 strains geographically, regardless of genogroup characteristics, into 1 lineage (IIId). Two groups of G9 strains, originating in India and Japan, were identified in this lineage. Continuous surveillance of circulating rotavirus strains in Africa is vital to prepare for future vaccine implementation on a continent that clearly needs such preventative medicines.Item Emerging OP354-Like P[8] Rotaviruses Have Rapidly Dispersed from Asia to Other Continents(Molecular Biology and Evolution, 2015-08) Zeller, M.; Heylen, E.; Damanka, S.; Pietsch, C.; Donato, C.; Tamura, T.; Kulkarni, R.; Arora, R.; Cunliffe, N.; Maunula, L.; Potgieter, C.; Tamim, S.; De Coster, S.; Zhirakovskaya, E.; Bdour, S.; O'Shea, H.; Kirkwood, C.D.; Seheri, M.; Nyaga, M.M.; Mphahlele, J.; Chitambar, S.D.; Dagan, R.; Armah, G.; Tikunova, N.; Van Ranst, M.; Matthijnssens, J.The majority of human group A rotaviruses possess the P[8] VP4 genotype. Recently, a genetically distinct subtype of the P[8] genotype, also known as OP354-like P[8] or lineage P[8]-4, emerged in several countries. However, it is unclear for how long the OP354-like P[8] gene has been circulating in humans and how it has spread. In a global collaborative effort 98 (near-)complete OP354-like P[8] VP4 sequences were obtained and used for phylogeographic analysis to determine the viral migration patterns. During the sampling period, 1988–2012, we found that South and East Asia acted as a source from which strains with the OP354-like P[8] gene were seeded to Africa, Europe, and North America. The time to the most recent common ancestor (TMRCA) of all OP354-like P[8] genes was estimated at 1987. However, most OP354-like P[8] strains were found in three main clusters with TMRCAs estimated between 1996 and 2001. The VP7 gene segment of OP354-like P[8] strains showed evidence of frequent reassortment, even in localized epidemics, suggesting that OP354like P[8] genes behave in a similar manner on the evolutionary level as other P[8] subtypes. The results of this study suggest that OP354-like P[8] strains have been able to disperse globally in a relatively short time period. This, in combination with a relatively large genetic distance to other P[8] subtypes, might result in a lower vaccine effectiveness, underscoring the need for a continued surveillance of OP354-like P[8] strains, especially in countries where rotavirus vaccination programs are in place.Item Enterotoxigenic Escherichia coli (ETEC) vaccines: Priority activities to enable product development, licensure, and global access(Elsevier, 2021) Khalil, I.; Walker, R.; Porter, C.K.; Muhib, F.; Chilengi, R.; Cravioto, A.; Guerrant, R.; Svennerholm, A.; Qadri, F.; Baqar, S.; Kosek, M.; Kang, G.; Lanata, C.; Armah, G.; Wierzba, T.; Hasso-Agopsowicz, M.; Giersing, B.; Bourgeois, L.A.Diarrhoeal disease attributable to enterotoxigenic Escherichia coli (ETEC) causes substantial morbidity and mortality predominantly in paediatric populations in low- and middle-income countries. In addition to acute illness, there is an increasing appreciation of the long-term consequences of enteric infections, including ETEC, on childhood growth and development. Provision of potable water and sanitation and appropriate clinical care for acute illness are critical to reduce the ETEC burden. However, these interven tions are not always practical and may not achieve equitable and sustainable coverage. Vaccination may be the most cost-effective and equitable means of primary prevention; however, additional data are needed to accelerate the investment and guide the decision-making process for ETEC vaccines. First, to understand and quantify the ETEC disease burden, additional data are needed on the associa tion between ETEC infection and physical and cognitive stunting as well as delayed educational attain ment. Furthermore, the role of inappropriate or inadequate antibiotic treatment of ETEC-attributable diarrhoea may contribute to the development of antimicrobial resistance (AMR) and needs further eluci dation. An ETEC vaccine that mitigates acute diarrhoeal illness and minimizes the longer-term disease manifestations could have significant public health impact and be a cost-effective countermeasure. Herein we review the ETEC vaccine pipeline, led by candidates compatible with the general parameters of the Preferred Product Characteristics (PPC) recently developed by the World Health Organization. Additionally, we have developed an ETEC Vaccine Development Strategy to provide a framework to underpin priority activities for researchers, funders and vaccine manufacturers, with the goal of address ing globally unmet data needs in the areas of research, product development, and policy, as well as com mercialization and delivery. The strategy also aims to guide prioritization and co-ordination of the priority activities needed to minimize the timeline to licensure and use of ETEC vaccines, especially in in low- and middle-income countries, where they are most urgently neededItem Epidemiology of rotavirus diarrhea among children younger than 5 years in Enugu, south east, Nigeria(Pediatric Infectious Disease Journal, 2014) Tagbo, B.N.; Mwenda, J.M.; Armah, G.; Obidike ., E.O.; Okafor, U.H.; Oguonu, T.; Ozumba, U.C.; Eke, C.B.; Chukwubuike, C.; Edelu, B.O.; Ezeonwu, B.U.; Amadi, O.; Okeke, I.B.; Nnani, O.R.; Ani, O.S.; Ugwuezeonu, I.; Benjamin-Pujah, C.; Umezinne, N.; Ude, N.; Nwodo, C.; Ezeonyebuchi, M.C.; Umesie, E.; Okafor, V.; Ogude, N.; Osarogborum, V.O.; Ezebilo, S.K.; Goitom, W.G.; Abanida, E.A.; Elemuwa, C.; Nwagbo, D.FSevere rotavirus diarrhea in children is a major cause of morbidity globally and mortality in developing countries. It is estimated to be responsible for >453,000 deaths in children <5 years of age globally and 232,000 in the African region. The aim of the current study was to determine the prevalence of rotavirus gastroenteritis among hospitalized children <5 years of age in Enugu and to support awareness and advocacy efforts for the introduction of rotavirus vaccines in Nigeria. METHODS:: World Health Organization-standardized case forms were used to collect data from eligible children with non-bloody diarrhea from October 2010 to September 2012. Data collected included socio-demographic and clinical information. Stool samples were obtained from recruited children and tested for rotavirus antigen using the Oxoid Prospect ELISA Kit (Basingstoke, United Kingdom). RESULTS:: Of the 615 diarrhea stool samples collected, 344 (56%) were positive for human rotavirus. Of the 344 positive samples, 329 (96%) were children <2 years of age, while 247 (77%) were <1 year of age. Peak rotavirus season occurred during the cold dry months of December to April during which 95% of all cases occurred. CONCLUSIONS:: This study found a relatively high incidence of severe rotavirus-associated diarrhea disease in Nigeria and infants were the most affected. It highlights the urgent need for introduction of rotavirus vaccine into the national immunization program and the need to adequately equip health facilities to enable them administer intravenous fluids to severe diarrhea patients to reduce morbidity and mortality. © 2013 Lippincott Williams and Wilkins.Item Etiology of severe acute watery diarrhea in children in the global rotavirus surveillance network using quantitative polymerase chain reaction(Journal of Infectious Diseases, 2017) Operario, D.J.; Platts-Mills, J.A.; Nadan, S.; Page, N.; Seheri, M.; Mphahlele, J.; Praharaj, I.; Kang, G.; Araujo, I.T.; Leite, J.P.G.; Cowley, D.; Thomas, S.; Kirkwood, C.D.; Dennis, F.; Armah, G.; Mwenda, J.M.; Wijesinghe, P.R.; Rey, G.; Grabovac, V.; Berejena, C.; Simwaka, C.J.; Uwimana, J.; Sherchand, J.B.; Thu, H.M.; Galagoda, G.; Bonkoungou, I.J.O.; Jagne, S.; Tsolenyanu, E.; Enweronu-Laryea, C.; Borbor, S.A.; Liu, J.; McMurry, T.; Lopman, B.; Parashar, U.; Gentsch, J.; Steele, A.D.; Cohen, A.; Serhan, F.; Houpt, E.R.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 14 643 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. © The Author 2017.Item Evaluation of cost-effectiveness of live oral pentavalent reassortant rotavirus vaccine introduction in Ghana(Vaccine, 2012-03) Abbott, C.; Tiede, B.; Armah, G.; Mahmoud, A.Background: Globally, rotavirus gastroenteritis is the most common identifiable cause of severe diarrhea in children under 5. Recently introduced rotavirus vaccines from Merck & Co. and GlaxoSmithKline have the potential to save hundreds of thousands of lives. Efficacy results in Ghana suggest Merck & Co.'s live oral pentavalent rotavirus vaccine (RotaTeq ®) prevents 65.0% of severe gastroenteritis due to rotavirus infection in children under 5. The announcement by Merck and GSK to make their rotavirus vaccines available for developing nations at reduced prices provides Ghana with the opportunity to introduce rotavirus vaccines into the national immunization program after investigation of the medical, economic and political implications. Methods: We estimated the average costs of treating children with diarrhea in the Ashanti region of Ghana as inpatients and outpatients. Using these results, data from rotavirus surveillance studies, and recent rotavirus vaccine efficacy evaluation, we estimated the cost-effectiveness of introducing RotaTeq in Ghana. Results: Based on our prospective calculations, we estimated an average inpatient and outpatient costs of $233.97 and $17.09, respectively, for treating childhood diarrhea. Using the 2003 birth cohort, RotaTeq introduction could save 1554 lives and avert 93,109 disability-adjusted life-years (DALYs) annually. At a market price of $5 per dose, introducing RotaTeq would have a base-case cost of $62.26 per DALY averted, at a market price of $3.50 per dose, a base-case cost of $39.59 per DALY averted and at market cost of $1 per dose, a base-case cost of $1.81 per DALY averted. All three values are below the 2009 Ghana per capita GDP. Thus, RotaTeq introduction into Ghana will be very cost-effective. Sensitivity analyses suggest these results are robust. Conclusions: RotaTeq vaccination for children under five in Ghana would be a highly cost-effective public health intervention. Ghanaian health officials should seek GAVI funding and evaluate how to maximize RotaTeq access. © 2012 Elsevier Ltd.Item Evaluation of Intussusception after Monovalent Rotavirus Vaccination in Africa(New England Journal of Medicine, 2018-05) Tate, J.E.; Mwenda, J.M.; Armah, G.; Jani, B.; Omore, R.; Ademe, A.; Mujuru, H.; Mpabalwani, E.; Ngwira, B.; Cortese, M.M.; Mihigo, R.Background Postlicensure evaluations have identified an association between rotavirus vaccination and intussusception in several high- and middle-income countries. We assessed the association between monovalent human rotavirus vaccine and intussusception in lower-income sub-Saharan African countries. Methods Using active surveillance, we enrolled patients from seven countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe) who had intussusception that met international (Brighton Collaboration level 1) criteria. Rotavirus vaccination status was confirmed by review of the vaccine card or clinic records. The risk of intussusception within 1 to 7 days and 8 to 21 days after vaccination among infants 28 to 245 days of age was assessed by means of the self-controlled case-series method. Results Data on 717 infants who had intussusception and confirmed vaccination status were analyzed. One case occurred in the 1 to 7 days after dose 1, and 6 cases occurred in the 8 to 21 days after dose 1. Five cases and 16 cases occurred in the 1 to 7 days and 8 to 21 days, respectively, after dose 2. The risk of intussusception in the 1 to 7 days after dose 1 was not higher than the background risk of intussusception (relative incidence [i.e., the incidence during the risk window vs. all other times], 0.25; 95% confidence interval [CI], <0.001 to 1.16); findings were similar for the 1 to 7 days after dose 2 (relative incidence, 0.76; 95% CI, 0.16 to 1.87). In addition, the risk of intussusception in the 8 to 21 days or 1 to 21 days after either dose was not found to be higher than the background risk. Conclusions The risk of intussusception after administration of monovalent human rotavirus vaccine was not higher than the background risk of intussusception in seven lower-income sub-Saharan African countries. (Funded by the GAVI Alliance through the CDC Foundation.)Item Evolution of a G6P[6] rotavirus strain isolated from a child with acute gastroenteritis in Ghana, 2012(Journal of General Virology, 2015-08) Agbemabiese, C.A.; Nakagomi, T.; Suzuki, Y.; Armah, G.; Nakagomi, O.Unusual human G6P[6] rotavirus A (RVA) strains have been reported sporadically in Europe and Africa, but how they evolved was not fully understood. The whole genome of a Ghanaian G6P[6] strain designated PML1965 (2012) was analysed to understand how it evolved in Africa and to learn how its G6 VP7 gene was related to that of rotaviruses of human and artiodactyl origin. The genotype constellation of RVA/Human-wt/GHA/PML1965/2012/G6P[6] was G6-P-[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2. It shared sublineages with G6P[6] strains previously detected in Italy and Africa in all genome segments except the VP6 gene of a few Burkinabe and Cameroonian strains and both the VP6 and NSP4 genes of Guinea Bissau strains. The VP7 gene of the G6P[6] strains appeared to derive from those of human G6P[9] strains, and they were distantly related to the VP7 genes of artiodactyl G6 or human G6P[14] strains. The time of the most recent common ancestor of the VP7 sequences of G6P[6] strains was estimated to be the year 1998. The evolutionary rates of the VP7 genes in bovine and human G6 rotaviruses were 6.93 × 10(-4) and 3.42 × 10(-3) nucleotide substitutions site(-1) year(-1), respectively, suggesting an accelerated adaptive process in the new host. The sequences of the remaining 10 genome segments of PML1965 clustered with those of G2 and G8 human rotaviruses detected in Africa possessing the DS-1-like genetic background. In conclusion, PML1965 evolved from G2 or G8 RVA strains with DS-1-like background, acquiring the G6 VP7 gene from a human G6P[9] RVA and not from an artiodactyl G6 RVA strain.Item A Farm To Fork Risk Assessment For The Use Of Wastewater In Agriculture In Accra, Ghana(Plos One, 2015-11-10) Antwi-Agyei, P.; Cairncross, S.; Peasey, A.; Price, V.; Bruce, J.; Baker, K.; Moe, C.; Ampofo, J.; Armah, G.; Ensink, J.The need to minimise consumer risk, especially for food that can be consumed uncooked, is a continuing public health concern, particularly in places where safe sanitation and hygienic practices are absent. The use of wastewater in agriculture has been associated with disease risks, though its relative significance in disease transmission remains unclear. This study aimed at identifying key risk factors for produce contamination at different entry points of the food chain. Over 500 produce and ready-to-eat salad samples were collected from fields, markets, and kitchens during the dry and wet seasons in Accra, Ghana, and over 300 soil and irrigation water samples were collected. All samples were analysed for E. coli, human adenovirus and norovirus using standard microbiological procedures, and real time RT-PCR. Finally, critical exposures associated with microbial quality of produce were assessed through observations and interviews. The study found that over 80% of produce samples were contaminated with E. coli, with median concentrations ranging from 0.64 to 3.84 Log E. coli/g produce. Prepared salad from street food vendors was found to be the most contaminated (4.23 Log E. coli/g), and that consumption of salad exceeded acceptable health limits. Key risk factors identified for produce contamination were irrigation water and soil at the farm level. Storage duration and temperature of produce had a significant influence on the quality of produce sold at markets, while observations revealed that the washed water used to rinse produce before sale was dirty. The source of produce and operating with a hygiene permit were found to influence salad microbial quality at kitchens. This study argues for a need to manage produce risk factors at all domains along the food chain, though it would be more effective to prioritise at markets and kitchens due to cost, ease of implementation and public health significance.Item Hospital health care cost of diarrheal disease in northern Ghana(2010-09-01) Aikins, M.; Armah, G.; Akazili, J.; Hodgson, A.Diarrhea caused by rotaviruses is one of the most frequent causes of hospitalization among pediatric patients in rural communities of developing countries in sub-Saharan Africa and Southeast Asia, and it is a major cause of death in these communities. The complexity of diarrhea and the increasing cost of treatment puts additional burden on the health sector. To demonstrate the economic burden of diarrhea to policy makers, this study was conducted to estimate the treatment cost of diarrhea in children <5 years old in Ghana using the World Health Organization protocol for cost data collection and estimation. The study was undertaken in Navrongo War Memorial Hospital in northern Ghana. Cost estimates were made for 3 treatment scenarios observed: (1) treatment by rehydration, (2) treatment by rehydration and antibiotics, and (3) treatment of diarrhea and other diseases. The average outpatient treatment costs for the 3 treatment scenarios were US$3.86, $4.10, and $4.35 respectively, and the average treatment costs for hospitalization (inpatient care) were $65.14, $97.40, and $133.86 respectively. The annual national treatment costs, based on the 3 treatment scenarios, ranged from $907,116 to $1,851,280 for outpatients clinic visits and from $701,833 to $4,581,213 for hospitalizations. The average length of stay for the inpatients ranged from 2.3 to 4.9 days. The study did not cover patient costs (ie, household costs).Item Molecular Detection and Epidemiology of Shiegella Spp. and Enterotoxigenic Escherichia Coli (ETEC) Infections Among Children with Acute Gastroenteritis in Accra, Ghana(University of Ghana, 2013-07) Amenyedor, A.; Dzudzor, B.; Armah, G.Background: Diarrhoea remains an important public health problem and is the second leading cause of mortality and morbidity in children throughout the world, especially in developing countries. In Ghana, diarrhoea is the third common cause of hospital attendance of young children. It is responsible for 13.1% of hospitalizations among these children and an annual average of 5, 193 deaths in children under 5 years of age. Bacterial enteropathogenic agents of diarrhoea and mechanisms responsible for disease pathogenesis are generally known. However, knowledge on the true prevalence and contribution of these bacteria to the disease burden is very limited. This study strives to optimize available PCR methods to facilitate accurate diagnosis of Enterotoxigenic E. coli and Shigella spp. infections and contribute baseline information on diarrhoeal bacterial enteropathogens. Main Objective: To provide a new method for the routine screening and detection of Enterotoxigenic E. coli and Shigella spp. in diarrhoeal stool samples via PCR. Design: Two hundred archived stool samples from previous diarrhoeal surveillance study were retrieved from the Department of Electron Microscopy/Histopathology of Noguchi Memorial Institute for Medical Research for analysis. Total DNA was extracted and conventional PCR used to identify Enterotoxigenic E. coli (ETEC) and Shigella spp.. The incidence and prevalence was then computed. Results: 4 (2%) samples screened were positive for heat-labile toxin producing ETEC with all detections occurring in the 0-12 month year group. Heat-stable toxin producing ETEC and Shigella were not detected. Conclusion: The overall prevalence of ETEC-LT in this study was 2%. Conventional PCR may be used for the routine screening of diarrhoeal stool samples for ETEC-LT, ETEC- ST, and Shigella. This method of screening diarrhoeal stool samples is fast and specific. Taking into account the promptness with which results are made available for health care delivery and management, this method can be said to be relatively cheaper in comparison to the gold standard, culturing.Item A Multiplex PCR/LDR Assay for Viral Agents of Diarrhea with the Capacity to Genotype Rotavirus(Scientific Reports, 2018-09) Mirza, A.H.; Das, S.; Pingle, M.R.; Rundell, M.S.; Armah, G.; Gyan, B.; Hodinka, R.L.; Larone, D.H.; Spitzer, E.D.; Barany, F.; Golightly, L.M.Rotavirus and noroviruses are major causes of diarrhea. Variable rotavirus vaccination efficacy in Africa and Asia is multifactorial, including the diversity of circulating strains and viral co-infection. We describe a multiplexed assay that detects and genotypes viruses from stool specimens. It includes a one-step reverse transcriptase PCR reaction, a ligase detection reaction (LDR), then hybridization of fluorescent products to micro-beads. In clinical samples it detects rotavirus, caliciviruses (sapovirus and norovirus), mixed infections, and genotypes or genogroups of rotaviruses and noroviruses, respectively. The assay also has the capacity to detect hepatitis A. The assay was validated on reference isolates and 296 stool specimens from the US and Ghana. The assay was 97% sensitive and 100% specific. The genogroup was concordant in 100% of norovirus, and the genotype in 91% and 89% of rotavirus G- and P-types, respectively. Two rare rotavirus strains, G6P[6] and G6P[8], were detected in stool specimens from Ghana. The high-throughput assay is sensitive, specific, and may be of utility in the epidemiological surveillance for rare and emerging viral strains post-rotavirus vaccine implementation. © 2018, The Author(s).Item New oligonucleotide primers for P-typing of rotavirus strains: Strategies for typing previously untypeable strains(Journal of Clinical Virology 42(4):368-73, 2008) Simmonds, M.K.; Armah, G.; Asmah, R.; Banerjee, I.; Damanka, S.; Esona, M.; Gentsch, J.R.; Gray, J.J.; Kirkwood, C.; Page, N.; Iturriza-Gómara, M.Background: The use of molecular methods for rotavirus characterisation provides increased sensitivity for typing, and allows the identification of putative reassortant strains. However, due to the constant accumulation of point mutations through genetic drift; and to the emergence of novel genotypes; and possibly zoonotic transmission and subsequent reassortment, the reagents and methods used for genotyping require close monitoring and updating. Objectives: To design and evaluate a new VP4 consensus oligonucleotide primer pair that provides increased sensitivity and allows typing of strains that were untypeable using available methods. Study Design: A total of 489 rotavirus-positive faecal specimens from studies conducted between 1996 and 2006 were used for the evaluation of the new VP4 primers which was performed in the WHO Rotavirus Collaborating and Reference centres in the US, Australia, South Africa and the UK. Result: The new primer pair allowed P-typing of rotavirus strains and provided increased sensitivity, allowing typing of a significant number of strains that previously could not be P-typed.Item Prevalence of enteric infections among hospitalized patients in two referral hospitals in Ghana(BioMed Central Ltd., 2016) Akuffo, R.; Armah, G.; Clemens, M.; Kronmann, K.C.; Jones, A.H.; Agbenohevi, P.; Sagoe, K.; Puplampu, N.; Talla Nzussouo, N.; Ampofo, W.; Koram, K.; Duplessis, C.; Dueger, E.Background: In pea seeds (Pisum sativum L.), the presence of the Def locus determines abscission event between its funicle and the seed coat. Cell wall remodeling is a necessary condition for abscission of pea seed. The changes in cell wall components in wild type (WT) pea seed with Def loci showing seed abscission and in abscission less def mutant peas were studied to identify the factors determining abscission and non-abscission event. Methods: Changes in pectic polysaccharides components were investigated in WT and def mutant pea seeds using immunolabeling techniques. Pectic monoclonal antibodies (1 → 4)-β-d-galactan (LM5), (1 → 5)-α-l-arabinan(LM6), partially de-methyl esterified homogalacturonan (HG) (JIM5) and methyl esterified HG (JIM7) were used for this study. Results: Prior to abscission zone (AZ) development, galactan and arabinan reduced in the predestined AZ of the pea seed and disappeared during the abscission process. The AZ cells had partially de-methyl esterified HG while other areas had highly methyl esterified HG. A strong JIM5 labeling in the def mutant may be related to cell wall rigidity in the mature def mutants. In addition, the appearance of pectic epitopes in two F3 populations resulting from cross between WT and def mutant parents was studied. As a result, we identified that homozygous dominant lines (Def/Def) showing abscission and homozygous recessive lines (def/def) showing non-abscission had similar immunolabeling pattern to their parents. However, the heterogeneous lines (Def/def) showed various immunolabeling pattern and the segregation pattern of the Def locus. Conclusions: Through the study of the complexity and variability of pectins in plant cell walls as well as understanding the segregation patterns of the Def locus using immunolabeling techniques, we conclude that cell wall remodeling occurs in the abscission process and de-methyl esterification may play a role in the non-abscission event in def mutant. Overall, this study contributes new insights into understanding the structural and architectural organization of the cell walls during abscission.