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Africa bears the brunt of diarrheal mortality globally. Rotavirus vaccination rates are high across the continent and demonstrate impact on diarrheal disease reduction. Nevertheless, there is room for significant improvement in managing rotavirus vaccine coverage, in access to recognized public services such as appropriate medical care, including oral rehydration therapy and improved water and sanitation.

G3 rotaviruses rank among the most common rotavirus strains worldwide in humans and animals. However, despite a robust long-term rotavirus surveillance system from 1997 at Queen Elizabeth Central Hospital in Blantyre, Malawi, these strains were only detected from 1997 to 1999 and then disappeared and re-emerged in 2017, five years after the introduction of the Rotarix rotavirus vaccine. Here we analysed representative 27 whole genome sequences (G3P[4], n=20; G3P[6], n=1; and G3P[8], n=6) randomly selected each month between November 2017 and August 2019 to understand how G3 strains re-emerged in Malawi. We found four genotype constellations that were associated with the emergent G3 strains and co-circulated in Malawi post-Rotarix vaccine introduction: G3P[4] and G3P[6] strains with the DS-1-like genetic backbone genes (G3-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2) and G3-P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2), G3P[8] strains with the Wa-like genetic backbone genes (G3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1), and reassortant G3P[4] strains consisting of the DS-1-like genetic backbone genes and a Wa-like NSP2 (N1) gene (G3-P[4]-I2-R2-C2-M2-A2-N1-T2-E2-H2). Time-resolved phylogenetic trees demonstrated that the most recent common ancestor for each RNA segment of the emergent G3 strains was between 1996 and 2012, possibly through introductions from outside the country due to the limited genetic similarity with G3 strains which circulated before their disappearance in the late 1990s. Further genomic analysis revealed that the reassortant DS-1-like G3P[4] strains acquired a Wa-like NSP2 genome segment (N1 genotype) through intergenogroup reassortment; an artiodactyl-like VP3 through intergenogroup interspecies reassortment; and VP6, NSP1 and NSP4 segments through intragenogroup reassortment likely before importation into Malawi. Additionally, the emergent G3 strains contain amino acid substitutions within the antigenic regions of the VP4 proteins which could potentially impact the binding of rotavirus vaccine-induced antibodies. Altogether, our findings show that multiple strains with either Wa-like or DS-1-like genotype constellations have driven the re-emergence of G3 strains. The findings also highlight the role of human mobility and genome reassortment events in the cross-border dissemination and evolution of rotavirus strains in Malawi necessitating the need for long-term genomic surveillance of rotavirus in high disease burden settings to inform disease prevention and control.

Hepatitis E virus (HEV) infection is a globally neglected health problem with a high burden in resource-poor communities. Pregnant women are at increased risk of complications. This pilot study sought to assess the seroprevalence of HEV infection in pregnant women at Dr George Mukhari Academic Hospital, South Africa.Stored serum samples from 384 HIV-uninfected pregnant women attending the antenatal clinic were initially screened for HEV total antibody. Positive samples were further evaluated for the presence of IgG and IgM antibody isotypes, using commercial ELISA assays. HEV RNA was assessed in antibody-positive samples utilizing qRT-PCR assay.The sample consisted of women with a median age of 31 years (interquartile range: 28-35 years). Total HEV antibody was detected in 12/384 (3.13%, 95% CI: 1.80-5.38) of these pregnant women. All 12 samples were IgG HEV antibody positive, but none tested positive for IgM antibody or for HEV RNA, demonstrating a lack of current or recent exposure.Our study revealed a low seroprevalence of HEV among pregnant women from an urban area north of Pretoria. This observation warrants further attention to the circulation of HEV in this population, and a greater understanding of the epidemiology of the infection in South Africa.

Enteric fever continues to impact millions of people who lack adequate access to clean water and sanitation. The typhoid and paratyphoid fever burden in South Asia is broadly acknowledged, but current estimates of incidence, severity, and cost of illness from India are lacking. This supplement addresses this gap in our knowledge, presenting findings from two years of surveillance, conducted at multiple sites between October 2017 and February 2020, in the Surveillance for Enteric Fever in India (SEFI) network. Results provide contemporaneous evidence of high disease burden and cost of illness—the latter borne largely by patients in the absence of universal healthcare coverage in India. Against a backdrop of immediate priorities in the COVID-19 pandemic, these data are a reminder that typhoid, though often forgotten, remains a public health problem in India. Typhoid conjugate vaccines, produced by multiple Indian manufacturers, and recommended for use in high burden settings, ensure that the tools to tackle typhoid are an immediately available solution to this public health problem.

Genotype G3 rotaviruses rank among the most common rotavirus strains worldwide in humans and animals. However, despite a robust long-term rotavirus surveillance system from 1997 in Blantyre, Malawi, these strains were only detected from 1997 to 1999 and then disappeared and re-emerged in 2017, five years after the introduction of the Rotarix rotavirus vaccine. Here we analysed 27 whole genome sequences to understand how G3 strains re-emerged in Malawi. We randomly selected samples each month between November 2017 and August 2019 from stool samples of children hospitalised with acute diarrhoea at the Queen Elizabeth Hospital in Blantyre, Malawi. We found three genotypes namely G3P[4] (n=20), G3P[6] (n=1) and G3P[8] (n=6) associated with the re-emergence of G3 strains in Malawi post-Rotarix vaccine introduction. The identified genotypes co-circulated at different time points and were associated with three typical human G3 strains consisting of either a Wa-like or DS-1-like genetic constellation and reassortant strains possessing Wa-like and DS-1-like genetic backbones. Time-resolved phylogenetic trees demonstrated that the most recent common ancestor for each segment of the re-emerged G3 strains emerged between 1996 and 2012, possibly through introductions from outside the country due to the limited genetic similarity with G3 strains which circulated before their disappearance in the late 1990s. Further genomic analysis revealed that the reassortant DS-1-like G3P[4] strains acquired a Wa-like NSP2 genome segment (N1 genotype) through intergenogroup reassortment; an artiodactyl-like VP3 through intragenogroup interspecies reassortment; and VP6, NSP1 and NSP4 segments through intragenogroup reassortment likely before importation into Malawi. Additionally, the re-emerged G3 strains contain amino acid substitutions within the antigenic regions of the VP4 proteins which could potentially impact the binding of rotavirus vaccine-induced antibodies. Altogether, our findings shows that multiple rather than a single genotype have driven the re-emergence of G3 strains likely from other countries highlighting the role of human mobility and genome reassortment events in the dissemination and evolution of rotavirus strains in Malawi necessitating the need for long-term genomic surveillance of rotavirus in high disease burden settings to inform disease prevention and control.

Objectives: Recently, histo-blood group antigens (HBGAs) have been identified as receptors or attachment factors of several viral pathogens. Among rotaviruses, HBGAs interact with the outer viral protein, VP4, which has been identified as a potential susceptibility factor, although the findings are inconsistent throughout populations due to HBGA polymorphisms. We investigated the association between HBGA phenotypes and rotavirus infection in children with acute gastroenteritis in northern Pretoria, South Africa. Methods: Paired diarrheal stool and saliva samples were collected from children aged ≤ 59 months (n = 342) with acute moderate to severe diarrhea, attending two health care facilities. Rotaviruses in the stool samples were detected by commercial EIA and the rotavirus strains were characterized by RT-PCR targeting the outer capsid VP7 (G-type) and VP4 (P-type) antigens for genotyping. Saliva-based ELISAs were performed to determine A, B, H, and Lewis antigens for blood group typing. Results: Blood type O was the most common blood group (62.5%) in this population, followed by groups A (26.0%), B (9.3%), and AB (2.2%). The H1-based secretors were common (82.7%) compared to the non-secretors (17.3%), and the Lewis antigen positive phenotypes (Le(a+b+)) were predominant (54.5%). Blood type A children were more likely to be infected by rotavirus (38.8%) than any other blood types. P[4] rotaviruses (21/49; 42.9%) infected only secretor individuals, whereas P[6] rotaviruses (3/49; 6.1%) only infected Le(a−b−), although the numbers were very low. On the contrary, P[8] rotaviruses infected children with a wide range of blood group phenotypes, including Le(a−b−) and non-secretors. Conclusions: Our findings demonstrated that Lewis antigens, or the lack thereof, may serve as susceptibility factors to rotaviral infection by specific VP4 genotypes as observed elsewhere. Potentially, the P[8] strains remain the predominant human VP4 genotype due to their ability to bind to a variety of HBGA phenotypes.

Introduction Hepatitis E virus (HEV) is an important cause of enterically transmitted viral hepatitis and a significant contributor to maternal mortality in endemic regions around the world, yet the global response has been limited. HEV is a disease of poverty, and the populations experiencing the greatest burden of HEV-associated illness are not benefitting from existing interventions, including WASH strategies and immunization. Areas covered Though a vaccine exists (HEV 239, Hecolin®, Xiamen Innovax Biotech, China), it is only licensed and available in the private market in China and has yet to be prequalified by the WHO for use in endemic settings and outbreaks. This review of the current state of HEV disease and subsequent recommendations for a coordinated public health response are intended to guide the global health community towards breaking the current 'vicious cycle,' in which a lack of data prevents actions that would improve health outcomes. Expert opinion Vaccine implementation in future outbreaks, targeted studies assessing vaccine effectiveness and immunogenicity in endemic regions and populations, improved understanding of the global burden, and improvements in diagnostic and epidemiologic tools are urgently needed. Strategies for implementing routine vaccination programs, improving water, sanitation, and hygiene in endemic regions.

Introduction The lungs have three main fissures: the right oblique fissure (ROF), right horizontal fissure (RHF), and left oblique fissure (LOF). These can be complete, incomplete or absent; quantifying the degree of completeness of these fissures is novel. Standard textbooks often refer to the fissures as complete, but awareness of variation is essential in thoracic surgery. Materials and methods Fissures in 81 pairs of cadaveric lungs were classified. Oblique fissures were measured from lung hila posteriorly to the lung hila anteriorly; and the RHF measured from the ROF to the anteromedial lung edge. The degree of completeness of fissures was expressed as a percentage of the total projected length were they to be complete. The frequency and location of accessory fissures was noted. Results LOF were complete in 66/81 (81.5%), incomplete in 13/81 (16.0%) and absent in 2/81 (2.47%); ROF were complete in 52/81 (64.2%), incomplete in 29/81 (35.8%) and never absent; RHF were more variable, complete in 18/81 (22.2%), incomplete in 54/81 (66.7%) and absent in 9/81 (11.1%). LOF and ROF were on average 97.1% and 91.6% complete, respectively, being deficient posteriorly at the lung hila. The RHF on average 69.4% complete, being deficient anteromedially. There were accessory fissures in 10 left and 19 right lungs. Conclusions This study provides a projection of the anatomy thoracic surgeons may encounter at operation, in particular the variable RHF. This knowledge is essential for optimal outcomes in both benign and oncological procedures influenced by the fissures.

Typhoid and other invasive salmonelloses continue to cause an estimated 14.8 million cases and > 200 000 deaths annually, largely affecting children in low- and middle-income countries. However, recent strides in global policy have paved the way for accelerated progress with prevention and control efforts. To translate these recent advancements at the global level into real impact in communities at the local level, the Coalition against Typhoid, based at the Sabin Vaccine Institute, convened the 11th International Conference on Typhoid and Other Invasive Salmonelloses in Hanoi, Vietnam, in March 2019. Here, we review the significant topics and research discussed at the conference, including diagnostics, environmental surveillance, drug resistance, burden of disease, and vaccines, as well as additional prevention and control interventions.

After the unprecedented success and acceleration of the global agenda towards typhoid fever control with a strong World Health Organization recommendation and the approval of funding from Gavi, the Vaccine Alliance (Gavi), for the use of a new typhoid conjugate vaccine (TCV), we should turn our minds to the challenges that remain ahead. Despite the evidence showing the safety and clinical efficacy of TCV in endemic populations in developing countries, we should remain vigilant and explore hurdles for the full public health impact of TCV, including vaccine supply for the potential global demand, immunization strategies to optimize the effectiveness and long-term protection provided by the vaccines, potential use of TCV in outbreak settings, and scenarios for addressing chronic carriers. Finally, challenges face endemic countries with poor surveillance systems concerning awareness of the need for TCV and the extent of the issue across their populations, and how to target immunization strategies appropriately.

Rotavirus claims thousands of lives of children globally every year with a disproportionately high burden in low- and lower-middle income countries where access to health care is limited. Oral, live-attenuated rotavirus vaccines have been evaluated in multiple settings in both low- and high-income populations and have been shown to be safe and efficacious. However, the vaccine efficacy observed in low-income settings with high rotavirus and diarrheal mortality was significantly lower than that seen in high-income populations where rotavirus mortality is less common. Rotavirus vaccines have been introduced and rolled out in more than 112 countries, providing the opportunity to assess effectiveness of the vaccines in these different settings. We provide an overview of the efficacy, effectiveness, and impact of rotavirus vaccines, focusing on high-mortality settings and identify the knowledge gaps for future research. Despite lower efficacy, rotavirus vaccines substantially reduce diarrheal disease and mortality and are cost-effective in countries with high burden. Continued evaluation of the effectiveness, impact, and cost–benefit of rotavirus vaccines, especially the new candidates that have been recently approved for global use, is a key factor for new vaccine introductions in countries, or for a switch of vaccine product in countries with limited resources.

The G2P[4] genotype is among the rotavirus strains that circulate commonly in humans. Several countries have reported its immediate upsurge after the introduction of rotavirus vaccination, raising concern about sub-optimal vaccine effectiveness against this genotype in the long term. This study aimed to gain insight into the evolution of post-vaccine Zambian G2P[4] group A rotavirus (RVA) strains and their overall genetic make-up by analysis of sequence alignments at the amino acid (AA) level. Twenty-nine Zambian G2P[4] rotavirus strains were subjected to whole-genome sequencing using the Illumina MiSeq® platform. All the strains exhibited the typical DS-1-like genotype constellation, and the nucleotide sequences of the 11 genome segments showed high nucleotide similarities (>97%). Phylogenetic analyses together with representative global G2P[4] RVA showed that Zambian strains clustered into human lineages IV (for VP2, VP4, VP7, NSP1, and NSP5), V (for VP1, VP3, VP6, NSP2, and NSP3), and XXIII (for NSP4). The AA differences between the lineages where the study strains clustered and lineages of global reference strains were identified and analyzed. Selection pressure analysis revealed that AA site seven in the Viral Protein 3 (VP3) genome segment was under positive selection. This site occurs in the region of intrinsic disorder in the VP3 protein, and Zambian G2P[4] strains could potentially be utilizing this intrinsically disordered region to survive immune pressure. The Zambian G2P[4] strains from 2012 to 2016 comprised the G2P[4] strains that have been circulating globally since the early 2000s, highlighting the epidemiological fitness of these contemporary G2P[4] strains. Continuous whole-genome surveillance of G2P[4] strains remains imperative to understand their evolution during the post-vaccination period.

Vaccine candidates for

Resource allocation under non-emergency conditions is often challenging. Within the context of a Public Health Emergency (PHE), allocation decisions become significantly more difficult as decisions are often necessary on very short timelines, where relevant information (either evidence or information “on the ground”) is changing or incomplete, there is significant potential for harm, and resources are scarce, in unpredictable supply, and likely in high demand. An intentional value-based decision-making approach in such circumstances can clarify the values that ought to guide decisions, offering transparency and consistency, among other benefits. We use the example of vaccine allocation during the COVID-19 pandemic to explore value-based decision-making within a PHE context. We describe several core values that are relevant to PHE decision-making and outline their implications for approaches to vaccine allocation. While we focus on vaccine allocation, the values discussed are relevant to other system-level decisions in both emergency and non-emergency situations. Tips for leaders wishing to adopt a value-based approach to decision-making are offered.

Remote monitoring is a type of telehealth whereby health care is delivered to patients outside traditional settings by allowing health data to be exchanged between patients and health care providers using telecommunication techniques (e.g., video conferencing) or stand-alone devices (e.g., portable heart rate monitors). The goals of remote monitoring centre around promoting home-based self-management to improve patient outcomes and/or reduce health system usage. CADTH’s Health Technology Assessment included the following analyses: A Realist Review: This sought to identify key perceived or actual mechanisms of remote monitoring programs. Substantial evidence was available regarding the use of remote monitoring programs for heart failure (n = 64) and cardiac rehabilitation (n = 23), limited evidence was available for atrial fibrillation (n = 4), and none was available for hypertension. A Perspectives and Experiences Review: This thematic synthesis of primary qualitative research sought to understand and describe peoples’ experiences with and perspectives on remote monitoring programs for cardiac conditions. CADTH also engaged patients and caregivers directly in a patient engagement section. An Ethics Review: This sought to identify and reflect upon key ethical issues that should be considered when contemplating the implementation of remote monitoring programs. Overall, the vast majority of sampled patients, caregivers, and health professionals consistently found or perceived remote monitoring programs across different cardiac conditions to be easy to use and beneficial to health. Remote monitoring programs may be an attractive adjunct as opposed to an alternative to existing health professionals and services. Although remote monitoring programs may ultimately reduce avoidable hospitalizations, they may increase net costs and workload during set-up and operational phases without careful pathway design and expectations management. More research is needed to identify the costs and cost-effectiveness of remote monitoring programs across chronic cardiac conditions.

The 11th African Rotavirus Symposium was held in Lilongwe, Malawi from May 28th to 30th 2017. Over 270 delegates (73% from Africa) from 40 countries of which 30 (75%) were from African countries attended the symposium. Participants in this symposium included research scientists, clinicians, immunization managers, public health officials, policymakers and vaccine manufacturers. At the time of the symposium, 38 of the 54 (70%) countries in Africa had introduced rotavirus vaccines into their national immunization schedules. Delegates shared progress from rotavirus surveillance and vaccine impact monitoring, demonstrating the impact of the vaccine against rotavirus diarrheal hospitalizations. Data supported the beneficial effect and safety of WHO pre-qualified available vaccines up to 2017 (RotaTeq, Rotarix). This symposium highlighted the dramatic impact of the rotavirus vaccination, called for urgent adoption of these vaccines in remaining countries, particularly those with high disease burden and large birth cohorts (e.g. Nigeria, Democratic Republic of Congo) to attain the full public health benefits of rotavirus vaccination in Africa.

In recent years, there has been a resurgence of interest in the development of vaccines against Shigella driven by the growing awareness of the impact of this pathogen on global health [...]

The 13th African Rotavirus Symposium was held as a virtual event hosted by the University of Nairobi, Kenya and The Kenya Paediatric Association on 3rd and 4th November 2021. This biennial event organized under the auspices of the African Rotavirus Network shapes the agenda for rotavirus research and prevention on the continent, attracting key international and regional opinion leaders, researchers, and public health scientists. The African Rotavirus Network is a regional network of institutions initially established in 1999, and now encompassing much of the diarrheal disease and rotavirus related research in Africa, in collaboration with the World Health Organization African Regional Office (WHO-AFRO), Ministries of Health, and other partners. Surges in SARS-CoV2 variants and concomitant travel restrictions limited the meeting to a webinar platform with invited scientific presentations and scientific presentations from selected abstracts. The scientific program covered updates on burden of diarrheal diseases including rotavirus, the genomic characterization of rotavirus strains pre- and post-rotavirus vaccine introduction, and data from clinical evaluation of new rotavirus vaccines in Africa. Finally, 42 of the 54 African countries have fully introduced rotavirus vaccination at the time of the meeting, including the two recently WHO pre-qualified vaccines from India. Nonetheless, the full benefit of rotavirus vaccination is yet to be realized in Africa where approximately 80% of the global burden of rotavirus mortality exists.

Shigella is the leading cause of global diarrheal deaths that currently lacks a licensed vaccine. Shigellosis drives antimicrobial resistance and leads to economic impact through linear growth faltering. Today, there is a robust pipeline of vaccines in clinical development which are broadly divided into parenteral glycoconjugate vaccines, consisting of O-antigen conjugated to carrier proteins, and oral live attenuated vaccines, which incorporate targeted genetic mutations seeking to optimize the balance between reactogenicity, immunogenicity and ultimately protection. Proof of efficacy has previously been shown with both approaches but for various reasons no vaccine has been licensed to date. In this report, we outline the requirements for a Shigella vaccine and describe the current pipeline in the context of the many candidates that have previously failed or been abandoned. The report refers to papers from individual vaccine developers in this special supplement of Vaccines which is focused on Shigella vaccines. Once readouts of safety and immunogenicity from current trials of lead candidate vaccines among the target population of young children in low- and middle-income countries are available, the likely time to licensure of a first Shigella vaccine will become clearer.

ObjectivesThere is no consensus on who might be qualified to conduct ethical analysis in the field of health technology assessment (HTA). Is there a specific expertise or skill set for doing this work? The aim of this article is to (i) clarify the concept of ethics expertise and, based on this, (ii) describe and specify the characteristics of ethics expertise in HTA.MethodsBased on the current literature and experiences in conducting ethical analysis in HTA, a group of members of the Health Technology Assessment International (HTAi) Interest Group on Ethical Issues in HTA critically analyzed the collected information during two face-to-face workshops. On the basis of the analysis, working definitions of “ethics expertise” and “core competencies” of ethics experts in HTA were developed. This paper reports the output of the workshop and subsequent revisions and discussions online among the authors.ResultsExpertise in a domain consists of both explicit and tacit knowledge and is acquired by formal training and social learning. There is a ubiquitous ethical expertise shared by most people in society; nevertheless, some people acquire specialist ethical expertise. To become an ethics expert in the field of HTA, one needs to acquire general knowledge about ethical issues as well as specific knowledge of the ethical domain in HTA. The core competencies of ethics experts in HTA consist of three fundamental elements: knowledge, skills, and attitudes.ConclusionsThe competencies described here can be used by HTA agencies and others involved in HTA to call attention to and strengthen ethical analysis in HTA.

Background The COVID-19 pandemic has resulted in significant changes to healthcare systems which impact the delivery of surgical training. This study aimed to investigate the qualitative impact of COVID-19 on surgical training in the United Kingdom (UK) & Republic of Ireland (ROI) Methods This national, collaborative, cross-sectional study involving 13 surgical trainee associations distributed a pan-surgical specialty questionnaire on the impact of COVID-19 on surgical training over 4 weeks in May 2020. Various aspects of training were assessed. Results 810 completed responses were analysed (males = 401, females = 390) from all deaneries and training grades. The perceived negative overall impact of the pandemic on surgical training experience was significant. (Weighted average = 8.66). 41% of respondents (n = 301) were redeployed with 74% redeployed for >4 weeks. Complete loss of training was reported in elective operating (69.5%), outpatient activity (67.3%) and endoscopy (69.5%). A reduction of >50% was reported in emergency operating (48%) and completion of work-based assessments (WBAs) (46%). 3.3% (n = 17) of respondents reported plans to leave medicine altogether. Cancellations in study leave and regional teaching programmes without rescheduling were reported in 72% and 60% of the cohort respectively. Elective operative exposure and WBAs completion were the primary reported factors affecting potential trainee progression. Only 9% of trainees reported that they would definitely meet all required competencies. Conclusion COVID-19 has had a negative impact on surgical training across all grades and specialties, with implications for trainee progression, recruitment and retention of the surgical workforce. Further investigation of the long-term impact at a national level is required.

Background: G12 rotaviruses were first observed in sub-Saharan Africa in 2004 and since then have continued to emerge and spread across the continent and are reported as a significant human rotavirus genotype in several African countries, both prior to and after rotavirus vaccine introduction. This study investigated the genetic variability of 15 G12 rotavirus strains associated with either P[6] or P[8] identified between 2010 and 2014 from Ethiopia, Kenya, Rwanda, Tanzania, Togo and Zambia. Methods: The investigation was carried out by comparing partial VP7 and partial VP4 sequences of the African G12P[6] and G12P[8] strains with the available GenBank sequences and exploring the recognized neutralization epitopes of these strains. Results: The findings suggested that the VP7 and VP4 genes of the G12 strains circulating in African countries are closely related at the nucleotide and amino acid level, irrespective of country of origin and year of detection, although there was a unique clustering of the Ethiopian strains. Neutralization epitope screening revealed that rotavirus VP4 P[8] genes associated with G12 had amino acids similar to those reported globally including the vaccines RotaTeq and Rotarix. Conclusions: At present it appears to be unlikely that widespread vaccine use has driven the molecular evolution and sustainability of G12 strains in Africa. Continuous monitoring of rotavirus genotypes is recommended to assess the long-term impact of rotavirus vaccination on the dynamic nature of rotavirus evolution on the continent.

Rotavirus G1P[8] strains account for more than half of the group A rotavirus (RVA) infections in children under five years of age, globally. A total of 103 stool samples previously characterized as G1P[8] and collected seven years before and seven years after introducing the Rotarix® vaccine in South Africa were processed for whole-genome sequencing. All the strains analyzed had a Wa-like constellation (G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1). South African pre- and post-vaccine G1 strains were clustered in G1 lineage-I and II while the majority (84.2%) of the P[8] strains were grouped in P[8] lineage-III. Several amino acid sites across ten gene segments with the exception of VP7 were under positive selective pressure. Except for the N147D substitution in the antigenic site of eight post-vaccine G1 strains when compared to both Rotarix® and pre-vaccine strains, most of the amino acid substitutions in the antigenic regions of post-vaccine G1P[8] strains were already present during the pre-vaccine period. Therefore, Rotarix® did not appear to have an impact on the amino acid differences in the antigenic regions of South African post-vaccine G1P[8] strains. However, continued whole-genome surveillance of RVA strains to decipher genetic changes in the post-vaccine period remains imperative.

Despite the contribution of currently licensed live, oral rotavirus vaccines (LORVs) to alleviating the burden of severe disease and death from rotavirus gastroenteritis, those vaccines have proven less efficacious in resource-limited settings than in high- and middle-income countries. It has been proposed that the residual burden of rotavirus disease might be overcome with parenterally administered vaccines, or next-generation rotavirus vaccines (NGRV). To better define the progress of development of these vaccines, a meeting of vaccine developers and manufacturers engaged in NGRV research and development was convened in Geneva in June 2019. Several NRGVs are in various stages of preclinical development, and two have already entered clinical testing. The vaccine platforms include subunit protein, inactivated whole virus, virus-like particle and RNA-based vaccines. Meeting participants included groups involved in NGRV development, scientists investigating correlates of protection of rotavirus vaccines, and representatives of international organizations with insight into considerations for vaccine introduction. This report summarizes the presentations shared at the meeting.

Background: G12 rotaviruses were first observed in sub-Saharan Africa in 2004 and since then have continued to emerge and spread across the continent and are reported as a significant human rotavirus genotype in several African countries, both prior to and after rotavirus vaccine introduction. This study investigated the genetic variability of 15 G12 rotavirus strains with either P[6] or P[8] identified between 2010 and 2014 from Ethiopia, Kenya, Rwanda, Tanzania, Togo and Zambia.Methods: The investigation was carried out by comparing VP7 and partial VP4 sequences of the African G12P[6] and G12P[8] strains with the available GenBank sequences and mapping the recognized neutralization epitopes of these strains.Results: The findings suggested that the VP7 and VP4 genes of the G12 strains circulating in African countries are homologous at the nucleotide and amino acid level, irrespective of country of origin and year of detection, although there was a unique clustering of the Ethiopian strains. The study strains shared a common ancestry with G12 strains circulating globally. Neutralization epitope mapping revealed that rotavirus VP4 P[8] genes associated with G12 had amino acids similar to those reported globally including the vaccines RotaTeq® P[8] and Rotarix®.Conclusions: It is unlikely that widespread vaccine use has driven the molecular evolution and sustainability of G12 strains in Africa. Furthermore, it is too early post vaccine introduction to indicate any effect of vaccine-induced pressure on maintaining the stability of these strains in circulation. Continuous monitoring of rotavirus genotypes is recommended to assess the long-term impact of rotavirus vaccination on the dynamic nature of rotavirus evolution on the continent.

The African Rotavirus Network organised the 12

Highlights • This article reports post-vaccine rotavirus G and P genotypes in Nairobi County. • G1P[8] dominance has decreased following the introduction of Rotarix. • There has been an increased prevalence of G2 genotypes following Rotarix introduction. • There has been a change in genetic diversity of rotavirus strains in Nairobi, Kenya., Background Rotaviruses are primary etiological agents of gastroenteritis in young children. In Kenya, G1P8 monovalent vaccine (Rotarix) was introduced in July 2014 for mandatory vaccination of all newborns at 6 and 10 weeks of age. Since then, no studies have been done to identify the rotavirus genotypes circulating in Nairobi County, Kenya, following the vaccine introduction, hence the post-vaccine genotype distribution is not known. Objectives The aim of this study was to determine the post-vaccine occurrence of rotavirus genotypes in children

Background Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function. Methods Infants 5 weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5 mg), probiotic (1010 Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10 weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14 weeks of age based on detection of VP6-specific IgA at ≥20 U/ml in previously seronegative infants or a fourfold rise in concentration. Results The study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): −1.4%, 16.2%), p = 0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: −4.4%, 13.2%), p = 0.272). 16 serious adverse events were recorded, none related to study interventions. Conclusions Zinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation. Trial registration The trial was registered in India (CTRI/2012/05/002677).

Background Monovalent rotavirus vaccine, Rotarix (GlaxoSmithKline), was introduced in Kenya in July 2014 and is recommended to infants as oral doses at ages 6 and 10 weeks. A multisite study was established in 2 population-based surveillance sites to evaluate vaccine impact on the incidence of rotavirus-associated hospitalizations (RVHs). Methods Hospital-based surveillance was conducted from January 2010 to June 2017 for acute diarrhea hospitalizations among children aged, Following the national introduction of the rotavirus vaccine in Kenya, our impact evaluation across 2 surveillance sites indicates a substantial reduction in childhood hospitalization due to rotavirus-associated and all-cause severe diarrhea.

Introduction: Rotavirus is the leading cause of hospitalizations and deaths from diarrhea. 33 African countries had introduced rotavirus vaccines by 2016. We estimate reductions in rotavirus hospitalizations and deaths for countries using rotavirus vaccination in national immunization programs and the potential of vaccine introduction across the continent. Areas covered: Regional rotavirus burden data were reviewed to calculate hospitalization rates, and applied to under-5 population to estimate baseline hospitalizations. Rotavirus mortality was based on 2013 WHO estimates. Regional pre-licensure vaccine efficacy and post-introduction vaccine effectiveness studies were used to estimate summary effectiveness, and vaccine coverage was applied to calculate prevented hospitalizations and deaths. Uncertainties around input parameters were propagated using boot-strapping simulations. In 29 African countries that introduced rotavirus vaccination prior to end 2014, 134,714 (IQR 112,321–154,654) hospitalizations and 20,986 (IQR 18,924–22,822) deaths were prevented in 2016. If all African countries had introduced rotavirus vaccines at benchmark immunization coverage, 273,619 (47%) (IQR 227,260–318,102) hospitalizations and 47,741 (39%) (IQR 42,822–52,462) deaths would have been prevented. Expert commentary: Rotavirus vaccination has substantially reduced hospitalizations and deaths in Africa; further reductions are anticipated as additional countries implement vaccination. These estimates bolster wider introduction and continued support of rotavirus vaccination programs.

Health care providers' interpretation of law can have intended and unintended effects on health care delivery in Canada. At times, health care providers encounter situations where they perceive the law to conflict with their sense of what is most ethically justified. In many cases, these health care providers feel especially torn because they assume that the legal requirements must dictate the decision, and cannot be explored or questioned. We challenge this assumption: the law is not as cut-and-dried as some assume; therefore, its significance to health care decisions should be carefully considered. Within a systematic ethics process, legal considerations can be a source of values and information and can create opportunities for further dialogue. This approach is justified because it appropriately reflects the relationship of the law to ethics. This way of thinking about the law and ethics also avoids potentially harmful consequences of legalistic approaches to decision-making, such as breakdowns in communication, adversarial relationships, and a reduction of ethically complex decisions to simple rule following.

Histo-blood group antigens (HBGAs) expressed on enterocytes are proposed receptors for rotaviruses and can be measured in saliva. Among 181 Pakistani infants in a G1P[8] rotavirus vaccine trial who were seronegative at baseline, anti-rotavirus immunoglobulin A seroconversion rates after 3 vaccine doses differed significantly by salivary HBGA phenotype, with the lowest rate (19%) among infants who were nonsecretors (ie, who did not express the carbohydrate synthesized by FUT2), an intermediate rate (30%) among secretors with non-blood group O, and the highest rate (51%) among secretors with O blood group. Differences in HBGA expression may be responsible for some of the discrepancy in the level of protection detected for the current rotavirus vaccines in low-income versus high-income settings.

As of January 2016, 80 countries have introduced rotavirus vaccines into their national immunization programs. Many have documented significant declines in rotavirus-specific and all-cause diarrheal illnesses following vaccine introduction. Two globally licensed rotavirus vaccines have been associated with a low risk of intussusception in several studies. In July 2014, the Rotavirus Organization of Technical Allies Council convened a meeting of research and advocacy organizations, public health experts, funders, and vaccine manufacturers to discuss post-marketing intussusception surveillance and rotavirus vaccine impact data. Meeting objectives were to evaluate updated data, identify and prioritize research gaps, discuss best practices for intussusception monitoring in lower-income settings and risk communication, and provide insight to country-level stakeholders on best practices for intussusception monitoring and communication. Meeting participants agreed with statements from expert bodies that the benefits of vaccination with currently available rotavirus vaccines outweigh the low risk of vaccination-associated intussusception. However, further research is needed to better understand the relationship of intussusception to wild-type rotavirus and rotavirus vaccines and delineate potential etiologies and mechanisms of intussusception. Additionally, evidence from research and post-licensure evaluations should be presented with evidence of the benefits of vaccination to best inform policymakers deciding on vaccine introduction or vaccination program sustainability.

Two rotavirus vaccines have been licensed in >100 countries worldwide since 2006. As of October 2105 these vaccines have been implemented in the national immunization programs of 79 countries including 36 low-income countries that are eligible for support for vaccine purchase from Gavi the Vaccine Alliance. Rotavirus vaccines were initially introduced in Australia and countries of the Americas and Europe after completion of successful clinical trials in these regions and the impact of routine vaccination in reducing the health burden of severe childhood gastroenteritis in these regions has been well documented. Because of concerns around the performance of orally administered rotavirus vaccines in developing countries vaccine implementation in these settings only began after additional clinical trials were completed and the World Health Organization issued a global recommendation for use of rotavirus vaccines in 2009. This supplementary issue of Clinical Infectious Diseases includes a collection of articles describing the impact and effectiveness of routine rotavirus vaccination in developing countries that were among the early adopters of rotavirus vaccine. The data highlight the benefits of vaccination and should provide valuable evidence to sustain vaccine use in these countries and encourage other countries to adopt routine rotavirus vaccination to reduce the health burden of severe childhood gastroenteritis. (c) The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions e-mail journals.permissions@oup.com.

The burden of enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi is substantial and has high impact in toddlers and young children. This burden is relatively well documented in Asia, and this supplement provides new data on the substantial burden in several sub-Saharan African countries. Challenges in standardized surveillance and imperfect diagnostic tools have resulted in patchy local disease data, which are not well acknowledged or integrated into local country evidence and health awareness for decision making. There is a need to strengthen diagnostics for the generation of burden data in country. Furthermore, the guidelines and training for treatment of enteric fever cases in Africa are sorely needed to help mitigate the inappropriate use of antimicrobial treatment. Classic water safety and access to sanitation development remain powerful tools for the control of typhoid fever, yet the huge economic costs and long timelines are unlikely to provide a short- to middle-term solution. Emerging threats, including multidrug resistance and increasing urbanization in regions such as sub-Saharan Africa, warrant focused attention to shorter-term interventions including immunization, and must include vaccine strategies with the new typhoid conjugate vaccines.

Rotavirus gastroenteritis is the leading cause of diarrhea-associated hospitalization and death in children younger than 5 years of age,1 with more than 85% of the approximately 200,000 annual rotavirus deaths occurring in Africa and Asia.2 Since improvements in water, sanitation, and hygiene do not prevent rotavirus transmission, as they do with the spread of bacterial enteropathogens, the implementation of a rotavirus vaccine is essential to prevent death and complications from childhood diarrhea. Two rotavirus vaccines — Rotarix (an attenuated G1P8 rotavirus manufactured by GlaxoSmithKline) and RotaTeq (containing five human–bovine reassortant rotaviruses, manufactured by Merck), attained prequalification by the World Health . . .

The 11

Rotavirus infection is the global leading cause of diarrhea-associated morbidity and mortality among children younger than 5 years.To examine the extent of rotavirus infection among children younger than 5 years by country and the number of deaths averted because of the rotavirus vaccine.This report builds on findings from the Global Burden of Disease Study 2016, a cross-sectional study that measured diarrheal diseases and their etiologic agents. Models were used to estimate burden in data-sparse locations.Diarrhea due to rotavirus infection.Rotavirus-associated mortality and morbidity by country and year and averted deaths attributable to the rotavirus vaccine by country.Rotavirus infection was responsible for an estimated 128 500 deaths (95% uncertainty interval [UI], 104 500-155 600) among children younger than 5 years throughout the world in 2016, with 104 733 deaths occurring in sub-Saharan Africa (95% UI, 83 406-128 842). Rotavirus infection was responsible for more than 258 million episodes of diarrhea among children younger than 5 years in 2016 (95% UI, 193 million to 341 million), an incidence of 0.42 cases per child-year (95% UI, 0.30-0.53). Vaccine use is estimated to have averted more than 28 000 deaths (95% UI, 14 600-46 700) among children younger than 5 years, and expanded use of the rotavirus vaccine, particularly in sub-Saharan Africa, could have prevented approximately 20% of all deaths attributable to diarrhea among children younger than 5 years.Rotavirus-associated mortality has decreased markedly over time in part because of the introduction of the rotavirus vaccine. This study suggests that prioritizing vaccine introduction and interventions to reduce diarrhea-associated morbidity and mortality is necessary in the continued global reduction of rotavirus infection.

Rotavirus A (RVA) exhibits a wide genotype diversity globally. Little is known about the genetic composition of genotype P[6] from Africa. This study investigated possible evolutionary mechanisms leading to genetic diversity of genotype P[6] VP4 sequences. Phylogenetic analyses on 167 P[6] VP4 full-length sequences were conducted, which included six porcine-origin sequences. Of the 167 sequences, 57 were newly acquired through whole genome sequencing as part of this study. The other 110 sequences were all publicly-available global P[6] VP4 full-length sequences downloaded from GenBank. The strength of association between the phenotypic features and the phylogeny was also determined. A number of reassortment and mixed infections of RVA genotype P[6] strains were observed in this study. Phylogenetic analyses demostrated the extensive genetic diversity that exists among human P[6] strains, porcine-like strains, their concomitant clades/subclades and estimated that P[6] VP4 gene has a higher substitution rate with the mean of 1.05E-3 substitutions/site/year. Further, the phylogenetic analyses indicated that genotype P[6] strains were endemic in Africa, characterised by an extensive genetic diversity and long-time local evolution of the viruses. This was also supported by phylogeographic clustering and G-genotype clustering of the P[6] strains when Bayesian Tip-association Significance testing (BaTS) was applied, clearly supporting that the viruses evolved locally in Africa instead of spatial mixing among different regions. Overall, the results demonstrated that multiple mechanisms such as reassortment events, various mutations and possibly interspecies transmission account for the enormous diversity of genotype P[6] strains in Africa. These findings highlight the need for continued global surveillance of rotavirus diversity.

A 47 year old presented to the emergency department with a severely painful left knee after she was hit while skiing by a fellow skier who approached at high speed from behind. The pain occurred immediately after impact with the skier, with marked general swelling of the joint and she was unable to bear weight. On examination, the limb was neurovascularly intact and the skin was not broken. She had no relevant medical, family, or social history. Anteroposterior (AP) and lateral x rays of her left knee were taken (fig 1⇓). Fig 1 Anteroposterior radiograph of patient’s left knee 1. What does the radiograph show and what is the diagnosis? 2. How would you classify this injury? 3. How would you manage this patient? ### 1. What does the radiograph show and what is the diagnosis? #### Short answer The AP radiograph shows a fracture line extending from the medial proximal tibia border and a vertical fracture line extending into the joint. The lateral image shows some posterior displacement of the segment. The diagnosis is tibial plateau fracture. #### Discussion Tibial plateau fractures are intra-articular fractures that show extension of the fracture line into the joint surface of the proximal tibia. They can exist in isolation or be accompanied by other injuries either to local structures of the knee or elsewhere on the patient. Identifying extension into the joint is vital as it affects the urgency and decision making process for treatment, as well as the prognosis. Neurovascular status is a key component in evaluation of the injury, as the common peroneal nerve …

The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction.We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children5 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).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.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.

Highlights • 10th African Rotavirus Symposium, Bamako, Mali, 1–2 June 2016. • Reaching every child in Africa with rotavirus vaccines. • Global gathering of rotavirus researchers, scientists, and policy-makers., The Center for Vaccine Development – Mali (CVD – Mali), the World Health Organization’s regional office in Africa (WHO/AFRO), and the CVD at the University of Maryland School of Medicine hosted the 10th African Rotavirus Symposium in Bamako, Mali on 1–2 June 2016. The symposium is coordinated by WHO/AFRO, the Regional Rotavirus Reference Laboratories, and the African Rotavirus Network (ARN), with support from the Bill & Melinda Gates Foundation. The event brings together leading rotavirus researchers, scientists, and policy-makers from across Africa and the world. Over 150 participants, from 31 countries, including 27 in Africa, joined forces to address the theme “Reaching Every Child in Africa with Rotavirus Vaccines.” This symposium, the first in francophone Africa, occurred at an unprecedented time when 33 African countries had introduced rotavirus vaccines into their national immunization programs. The symposium concluded with a Call to Action to introduce rotavirus vaccines in the 21 remaining African countries, to increase access in countries with existing vaccination programs, and to continue surveillance and research on rotavirus and other diarrheal diseases.

Summary Background The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting with a high prevalence of HIV infection needs to be established. We assessed the vaccine effectiveness of monovalent human rotavirus vaccine in preventing admission to hospital for acute rotavirus diarrhoea, after its introduction at age 6 and 14 weeks into South Africa's national immunisation programme. Methods This case-control study was done at seven hospitals in South Africa between April 19, 2010, and Oct 31, 2012. The hospitals were located in a range of urban, peri-urban, and rural settings, with varying rates of population HIV infection. Cases were children aged from 18 weeks to 23 months who were age-eligible to have received at least one dose of the human rotavirus vaccine (ie, those born after June 14, 2009) admitted to hospital with laboratory-confirmed acute rotavirus diarrhoea, and the primary control group was children admitted to hospital with diarrhoea testing negative for rotavirus. A second control group comprised children admitted to a subset of three of the seven hospitals with respiratory illness. The primary endpoint was adjusted vaccine effectiveness (1 – adjusted odds ratio × 100%) in children aged from 18 weeks to 23 months and was calculated by unconditional logistic regression. This study is registered on the South African National Clinical Trial Register, number DOH-27-0512-3247. Findings Of 540 rotavirus-positive cases, 278 children (52%) received two doses, 126 (23%) one dose, and 136 (25%) no doses of human rotavirus vaccine, compared with 1434 rotavirus-negative controls of whom 856 (60%) received two doses, 334 (23%) one dose, and 244 (17%) no doses. Adjusted vaccine effectiveness using rotavirus-negative controls was 57% (95% CI 40–68) for two doses and 40% (16–57) for one dose; estimates were similar when respiratory controls were used as the control group. Adjusted vaccine effectiveness for two doses was similar between age groups 18 weeks–11 months (54%, 95% CI 32–68) and 12–23 months (61%, 35–77), and was similar in HIV-exposed-uninfected (64%, 95% CI 34–80) and HIV-unexposed-uninfected children (54%, 31–69). Interpretation Human rotavirus vaccine provided sustained protection against admission to hospital for acute rotavirus diarrhoea during the first and second years of life. This finding is encouraging and establishes the public health value of rotavirus vaccine in an African setting, especially as rotavirus vaccines are introduced into an increasing number of African countries. Funding GAVI Alliance (with support from PATH).

Background Current oral rotavirus vaccines perform suboptimally in resource-poor settings. We investigated the effect of an additional dose and later schedule on the immunogenicity of monovalent rotavirus vaccine (RV1) in a developing country. Methods Infants received RV1 at 6 and 10, 10 and 14, or 6, 10, and 14 weeks of age. The primary objective was to compare antirotavirus immunoglobulin A (IgA) seroconversion at 18 weeks in the 6/10/14 arm to the cumulative seroconversion (highest result at 14 or 18 weeks) in the 6/10 arm. Results Overall, 480 (76.2%) of 630 randomized infants completed the trial per protocol. Seroconversion in the 6/10/14 arm was 36.7% (95% CI, 29.8, 44.2) compared to 36.1% (CI, 29.0, 43.9) in the 6/10 arm, (P=1.0); the result from the 10/14 arm was 38.5% (CI, 31.2, 46.3). Seroconversion in the 6/10 arm at 14 weeks (post hoc) was lower at 29.7% (CI, 23.1, 37.3). Conclusions In Pakistani infants, the immunogenicity of RV1 did not increase significantly with 3 doses at 6, 10, and 14 weeks compared to 2 doses at 6 and 10 weeks. Additional strategies should be evaluated for improving rotavirus vaccine immunogenicity in high burden countries.

Group A rotaviruses (RVAs) are the leading cause of severe gastroenteritis and eventually death among infants and young children worldwide, and disease prevention and management through vaccination is a public health priority. In August 2009, Rotarix™ was introduced in the South African Expanded Programme on Immunisation. As a result, substantial reductions in RVA disease burden have been reported among children younger than 5 years old. Rotavirus strain surveillance post-vaccination is crucial to, inter alia, monitor and study the evolution of vaccine escape strains. Here, full-genome sequence data for the 11 gene segments from 11 South African G1P[8] rotavirus strains were generated, including 5 strains collected from non-vaccinated children during the 2004-2009 rotavirus seasons and 6 strains collected from vaccinated children during the 2010 rotavirus season. These data were analyzed to gain insights into the overall genetic makeup and evolution of South African G1P[8] rotavirus strains and to compare their genetic backbones with those of common human Wa-like RVAs from other countries, as well as with the Rotarix™ and RotaTeq™ G1P[8] vaccine components. All 11 South African G1P[8] strains revealed a complete Wa-like genotype constellation of G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. On the basis of sequence similarities, the South African G1P[8] strains (with the exception of strain RVA/Human-wt/ZAF/1262/2004/G1P[8]) were closely related to each other (96-100% identity in all gene segments). Comparison to the Rotarix™ and RotaTeq™ G1P[8] vaccine components revealed a moderate nucleotide identity of 89-96% and 93-95%, respectively. The results indicated that none of the gene segments of these 11 South African G1P[8] strains were vaccine-derived. This study illustrates that large-scale next generation sequencing will provide crucial information on the influence of the vaccination program on evolution of rotavirus strains. This is the first report to describe full genomic analyses of G1P[8] RVA strains collected from both non-vaccinated and vaccinated children in South Africa.

Before the introduction of rotavirus vaccine in Egypt, information on the burden of disease and the circulating rotavirus genotypes is critical to monitor vaccine effectiveness.A cohort of 348 Egyptian children was followed from birth to 2 years of age with twice-weekly home visits to detect diarrheal illness. VP7 and VP4 genes were genotyped by reverse-transcription polymerase chain reaction and DNA sequencing.Forty percentage of children had rotavirus-associated diarrhea at least once by their second birthday. One hundred and twelve children experienced a single rotavirus diarrheal episodes (RDE) at a median age of 9 months; while 27 infants had their second RDE at a median age of 15 months and 1 infant had 3 RDE at the age of 2, 16 and 22 months. Of the 169 RDE, 82% could be assigned a G-type, while 58% had been identified a P-type. The most prevalent genotype was G2 (32%), followed by G1 (24%) and G9 (19%). G2P[4] rotavirus episodes were significantly associated with fever (P = 0.03) and vomiting (P = 0.06) when compared with other genotypes. G2 strains were the predominant genotype causing 50% of the second RDE while G9 represented 25% of the second RDE.Genotypes identified are similar to those detected globally except for absence of G4. Our finding that 75% of the second RDE were due to G2 and G9 indicates a possible reduction in natural protection afforded by these types compared with G1, where 90% of G1 cases did not experience a second xposure, indicating greater protection against recurrent symptomatic infection.

Animal–human interspecies transmission is thought to play a significant role in influencing rotavirus strain diversity in humans. Proving this concept requires a better understanding of the complete genetic constellation of rotaviruses circulating in various animal species. However, very few whole genomes of animal rotaviruses, especially in developing countries, are available. In this study, complete genetic configuration of the first African camel rotavirus strain (RVA/Camel-wt/SDN/MRC-DPRU447/2002/G8P[11]) was assigned a unique G8-P[11]-I2-R2-C2-M2-A18-N2-T6-E2-H3 genotype constellation that has not been reported in other ruminants. It contained a novel NSP1 genotype (genotype A18). The evolutionary dynamics of the genome segments of strain MRC-DPRU447 were rather complex compared to those found in other camelids. Its genome segments 1, 3, 7–10 were closely related (>93% nucleotide identity) to those of human–animal reassortant strains like RVA/Human-tc/ITA/PA169/1988/G6P[14] and RVA/Human-wt/HUN/Hun5/1997/G6P[14], segments 4, 6 and 11 shared common ancestry (>95% nucleotide identity) with bovine rotaviruses like strains RVA/Cow-wt/CHN/DQ-75/2008/G10P[11] and RVA/Cow-wt/KOR/KJ19-2/XXXX/G6P[7], whereas segment 2 was closely related (94% nucleotide identity) to guanaco rotavirus strain RVA/Guanaco-wt/ARG/Rio_Negro/1998/G8P[1]. Its genetic backbone consisted of DS-1-like, AU-1-like, artiodactyl-like and a novel A18 genotype. This suggests that strain MRC-DPRU447 potentially emerged through multiple reassortment events between several mammalian rotaviruses of at least two genogroups or simply strain MRC-DPRU447 display a unique progenitor genotypes. Close relationship between some of the genome segments of strain MRC-DPRU447 to human rotaviruses suggests previous occurrence of reassortment processes combined with interspecies transmission between humans and camels. The whole genome data for strain MRC-DPRU447 adds to the much needed animal rotavirus data from Africa which is limited at the moment.

Countries in Africa have begun introducing rotavirus vaccines in their national immunization programs, and wide-scale rollout across the continent is expected during the next few years. In preparation for vaccine introduction, many countries initiated surveillance for rotavirus and other studies to document disease burden, to describe the epidemiology and to monitor circulating rotavirus strains in Africa. In addition, 2 countries sought to systematically investigate cases of intussusception, a rare adverse event that has been associated with rotavirus vaccines in some settings. The ongoing surveillance provided data that will serve as a baseline against which the impact of rotavirus vaccines in Africa can be assessed.