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Summary Background Expanding outbreaks of circulating vaccine-derived type 2 poliovirus (cVDPV2) across Africa after the global withdrawal of trivalent oral poliovirus vaccine (OPV) in 2016 are delaying global polio eradication. We aimed to assess the effect of outbreak response campaigns with monovalent type 2 OPV (mOPV2) and the addition of inactivated poliovirus vaccine (IPV) to routine immunisation. Methods We used vaccination history data from children under 5 years old with non-polio acute flaccid paralysis from a routine surveillance database (the Polio Information System) and setting-specific OPV immunogenicity data from the literature to estimate OPV-induced and IPV-induced population immunity against type 2 poliomyelitis between Jan 1, 2015, and June 30, 2020, for 51 countries in Africa. We investigated risk factors for reported cVDPV2 poliomyelitis including population immunity, outbreak response activities, and correlates of poliovirus transmission using logistic regression. We used the model to estimate cVDPV2 risk for each 6-month period between Jan 1, 2016, and June 30, 2020, with different numbers of mOPV2 campaigns and compared the timing and location of actual mOPV2 campaigns and the number of mOPV2 campaigns required to reduce cVDPV2 risk to low levels. Findings Type 2 OPV immunity among children under 5 years declined from a median of 87% (IQR 81–93) in January–June, 2016 to 14% (9–37) in January–June, 2020. Type 2 immunity from IPV among children under 5 years increased from 3% (

Enteroviruses (EVs) are RNA viruses that can cause many clinical syndromes including acute flaccid paralysis (AFP). Within the global polio laboratory network, EVs are categorized either as polioviruses or non-polio enteroviruses (NPEVs). Specific NPEVs have been described in polio-like residual paralytic events in AFP patients. Retrospective analysis of 112 NPEV isolates from AFP patients was performed and thirty one NPEV types were identified of which 91% were Enterovirus B and 9% were Enterovirus A species. The NPEVs were distributed across the country with most patients in the eastern region (41/89; 46.1%). The highest proportion of patients were children

Background: The emergence of the Omicron variant of concern in late 2021 led to a resurgence of SARS-CoV-2 infections globally. By September 2022, Seychelles had experienced two major surges of SARS-CoV-2 infections driven by the Omicron variant. Here, we examine the genomic epidemiology of Omicron in the Seychelles between November 2021 and September 2022. Methods: We analysed 618 SARS-CoV-2 Omicron genomes identified in the Seychelles between November 2021 and September 2022 to infer virus introductions and local transmission patterns using phylogenetics and the ancestral state reconstruction approach. We then evaluated the impact of government coronavirus 2019 (COVID-19) countermeasures on the estimated number of viral introductions during the study period. Results: The genomes classified into 43 distinct Pango lineages. The first surge in Omicron cases (beginning November 2021 and peaking in January 2022) was predominated by the BA.1.1 lineage (59%) co-circulating with 11 other Omicron lineages. In the second surge (between April and June 2022), four lineages (BA.2, BA.2.10, BA.2.65 and BA.2.9) co-circulated and these were swiftly replaced by BA.5 subvariants in July 2022, which remained predominant through to September 2022. In the latter period, sporadic detections of BA.5 subvariants BQ.1, BE and BF were observed. We estimated 109 independent Omicron importations into Seychelles over the 11-month period, most of which occurred between December 2021 and March 2022 when strict government restrictions (SI>50%) were still in force. The districts Anse Royale, and Baie St. Anne Praslin appeared to be the major dispersal points fuelling local transmission. Conclusions: Our results suggest that the waves of Omicron infections in the Seychelles were driven by multiple lineages and multiple virus introductions. The introductions were followed by substantial local spread and successive lineage displacement that mirrored the global patterns.

The progression of the SARS-CoV-2 pandemic in Africa has so far been heterogeneous and the full impact is not yet well understood. Here, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations, predominantly from Europe, which diminished following the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1 and C.1.1. Although distorted by low sampling numbers and blind-spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a breeding ground for new variants.

We report the whole-genome sequences of new enterovirus D94 and D111 strains, isolated from a culture from stool specimens collected from acute flaccid paralysis (AFP) cases for poliovirus surveillance in Angola during 2010.

Background Detection of poliovirus outbreaks relies on a complex laboratory algorithm of cell-culture, polymerase chain reaction (PCR), and sequencing to distinguish wild-type and vaccine-derived polioviruses (VDPV) from Sabin-like strains. We investigated the potential for direct molecular detection and nanopore sequencing (DDNS) to accelerate poliovirus detection. Methods We analyzed laboratory data for time required to analyze and sequence serotype-2 VDPV (VDPV2) in stool collected from children with acute flaccid paralysis in Africa (May 2016–February 2020). Impact of delayed detection on VDPV2 outbreak size was assessed through negative binomial regression. Results VDPV2 confirmation in 525 stools required a median of 49 days from paralysis onset (10th–90th percentile, 29–74), comprising collection and transport (median, 16 days), cell-culture (7 days), intratypic differentiation quantitative reverse transcription PCR (3 days), and sequencing, including shipping if required (15 days). New VDPV2 outbreaks were confirmed a median of 35 days (27–60) after paralysis onset, which we estimate could be reduced to 16 days by DDNS (9–37). Because longer delays in confirmation and response were positively associated with more cases (P Conclusions DDNS could accelerate poliovirus outbreak response, reducing their size and the cost of eradication.

Background. Genomic data is key in understanding the spread and evolution of SARS-CoV-2 pandemic and informing the design and evaluation of interventions. However, SARS-CoV-2 genomic data remains scarce across Africa, with no reports yet from the Indian Ocean islands. Methods. We genome sequenced six SARS-CoV-2 positive samples from the first major infection wave in the Union of Comoros in January 2021 and undertook detailed phylogenetic analysis. Results. All the recovered six genomes classified within the 501Y.V2 variant of concern (also known as lineage B.1.351) and appeared to be from 2 sub-clusters with the most recent common ancestor dated 30th Oct-2020 (95% Credibility Interval: 06th Sep-2020 to 10th Dec-2020). Comparison of the Comoros genomes with those of 501Y.V2 variant of concern from other countries deposited into the GISAID database revealed their close association with viruses identified in France and Mayotte (part of the Comoros archipelago and a France, Overseas Department). Conclusions. The recovered genomes, albeit few, confirmed local transmission following probably multiple introductions of the SARS-CoV-2 501Y.V2 variant of concern during the Comoros’s first major COVID-19 wave. These findings demonstrate the importance of genomic surveillance and have implications for ongoing control strategies on the islands.

International audience; Since May 2019, the Central African Republic has experienced a poliomyelitis outbreak caused by type 2 vaccine-derived polioviruses (VDPV-2s). The outbreak affected Bangui, the capital city, and 10 districts across the country. The outbreak resulted from several independent emergence events of VDPV-2s featuring recombinant genomes with complex mosaic genomes. The low number of mutations (

Since the Global Polio Eradication Initiative (GPEI) was launched in 1988, the number of polio cases worldwide has declined approximately 99.99%; only two countries (Afghanistan and Pakistan) have never interrupted wild poliovirus (WPV) transmission (1). The primary means of detecting poliovirus circulation is through surveillance for acute flaccid paralysis (AFP) among children aged

Background Environmental surveillance (ES) for poliovirus is increasingly important for polio eradication, often detecting circulating virus before paralytic cases are reported. The sensitivity of ES depends on appropriate selection of sampling sites, which is difficult in low-income countries with informal sewage networks. Methods We measured ES site and sample characteristics in Nigeria during June 2018–May 2019, including sewage physicochemical properties, using a water-quality probe, flow volume, catchment population, and local facilities such as hospitals, schools, and transit hubs. We used mixed-effects logistic regression and machine learning (random forests) to investigate their association with enterovirus isolation (poliovirus and nonpolio enteroviruses) as an indicator of surveillance sensitivity. Results Four quarterly visits were made to 78 ES sites in 21 states of Nigeria, and ES site characteristic data were matched to 1345 samples with an average enterovirus prevalence among sites of 68% (range, 9%–100%). A larger estimated catchment population, high total dissolved solids, and higher pH were associated with enterovirus detection. A random forests model predicted “good” sites (enterovirus prevalence >70%) from measured site characteristics with out-of-sample sensitivity and specificity of 75%. Conclusions Simple measurement of sewage properties and catchment population estimation could improve ES site selection and increase surveillance sensitivity.

A public health catch-22 In 2016, the serotype 2 component of the oral poliovirus vaccine given to children was withdrawn. This measure was taken to prevent vaccine-associated disease outbreaks caused by mutation in the live attenuated vaccine. Children around the world now have poor immunity to serotype 2 poliovirus because the inactivated vaccine is far less effective and a new oral vaccine is not yet ready. Using a statistical model, Macklin et al. discovered that most current outbreaks of polio in several countries across Asia and sub-Saharan Africa are likely associated with the serotype 2 vaccine strain (see the Perspective by Donlan and Petri). To block transmission when poliovirus outbreaks occur requires deployment of the only tool in the box: the existing live attenuated serotype 2 oral vaccine, which increases the risk of vaccine-derived disease. Science , this issue p. 401 ; see also p. 362

Objective: This article summarises the progress made since the introduction of environmental surveillance in the African Region. Method: Country selection was based on the poor AFP performance indicators i.e. Non polio AFP rate and stool adequacy. It was recommended that any country not meeting the required indicators should consider environmental surveillance activity as an additional tool to support AFP surveillance. The sites selection considered proximity to the target population, the size of the population to be sampled and the sensitivity of the sampling site. Results: One hundred and fifty three sites have been established in Africa since 2011. In 2011, Nigeria was first country to introduce environmental surveillance and currently with of 59 validated sites, followed by Kenya in 2013 validating and sampling 9 sites and Angola 4 active sites in 2014. In 2014, Cameroon introduced ES and 31 sites followed by Niger with 9 sites and Madagascar with 23 sites. Later in the same year, Chad introduced ES activity and 4 active sites were selected. In 2015 Senegal introduced 3 sites, Guinea and Burkina Faso introduced 4 sites each. , and. In 2016, a total of 179 Sabins, 36 Sabin 2s, 196 non polio enteroviruses (NPEV) and 1 vaccine-derived polioviruses (VDPV) were reported in Nigeria. Cameroon and Chad isolated 14 and 4 Sabins and 72 and 40 NPEV respectively. In Madagascar a total of 39 Sabins, 11 Sabin 2s and 277 NPEV were isolated. In other countries a majority of NPEV were isolated (data not shown). Conclusion: This report describes the progress and expansion of environmental surveillance that contributed to the identification of polioviruses from the environment and the interruption of wild poliovirus transmission in the African Region.

The Global Polio Eradication Initiative (GPEI) has made substantial progress since its launch in 1988; only 37 wild poliovirus type 1 (WPV1) cases were detected in 2016, the lowest annual count ever. Wild poliovirus type 3 has not been detected since November 2012, and wild poliovirus type 2 was officially declared eradicated in September 2015. This success is attributable to the wide use of live oral poliovirus vaccines (OPVs). Since 2001, numerous outbreaks were caused by the emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (1). In 2015, circulating VDPV type 2 (cVDPV2) outbreaks were detected in five countries worldwide (Nigeria, Pakistan, Guinea, Burma, and South Sudan), and VDPV2 single events were reported in 22 countries. These events prompted the GPEI to withdraw the type 2 component (Sabin2) of trivalent OPV (tOPV) in a globally coordinated, synchronized manner in April 2016 (2,3), at which time all OPV-using countries switched to using bivalent OPV (bOPV), containing Sabin types 1 and 3. This report details for the first time the virologic tracking of elimination of a live vaccine that has been withdrawn from routine and mass immunization systems worldwide (3). To secure elimination, further monitoring is warranted to detect any use of tOPV or monovalent OPV type 2 (mOPV2).

The World Health Organization, African Region is heading toward eradication of the three types of wild polio virus, from the Region. Cases of wild poliovirus (WPV) types 2 and 3 (WPV2 and WPV3) were last reported in 1998 and 2012, respectively, and WPV1 reported in Nigeria since July 2014 has been the last in the entire Region. This scenario in Nigeria, the only endemic country, marks a remarkable progress. This significant progress is as a result of commitment of key partners in providing the much needed resources, better implementation of strategies, accountability, and innovative approaches. This is taking place in the face of public emergencies and challenges, which overburden health systems of countries and threaten sustainability of health programmes. Outbreak of Ebola and other diseases, insecurity, civil strife and political instability led to displacement of populations and severely affected health service delivery. The goal of eradication is now within reach more than ever before and countries of the region should not relent in their efforts on polio eradication. WHO and partners will redouble their efforts and introduce better approaches to sustain the current momentum and to complete the job. The carefully planned withdrawal of oral polio vaccine type II (OPV2) with an earlier introduction of one dose of inactivated poliovirus vaccine (IPV), in routine immunization, will boost immunity of populations and stop cVDPVs. Environmental surveillance for polio viruses will supplement surveillance for AFP and improve sensitivity of detection of polio viruses.

Primary B-cell immunodeficiencies are risk factors for the generation of vaccine-derived polioviruses. We report immunodeficiency-associated vaccine-derived poliovirus serotype 3 in an 11-week-old boy with X-linked agammaglobulinemia. Unique characteristics of this case include early age of presentation, high viral evolutionary rate, and the child’s perinatal exposure to human immunodeficiency virus.

Highlights • Efficient laboratories are key to the success of any disease programme. • PEI resources have contributed efforts in strengthening laboratory capacity in the region. • These contributions have not been systematically documented as lesson learnt. • With PEI programme on the ramp down, this paper documents it contributions for posterity., Background The laboratory has always played a very critical role in diagnosis of the diseases. The success of any disease programme is based on a functional laboratory network. Health laboratory services are an integral component of the health system. Efficiency and effectiveness of both clinical and public health functions including surveillance, diagnosis, prevention, treatment, research and health promotion are influenced by reliable laboratory services. The establishment of the African Regional polio laboratory for the Polio Eradication Initiative (PEI) has contributed in supporting countries in their efforts to strengthen laboratory capacity. On the eve of the closing of the program, we have shown through this article, examples of this contribution in two countries of the African region: Côte d’Ivoire and the Democratic Republic of Congo. Methods Descriptive studies were carried out in Côte d’Ivoire (RCI) and Democratic Republic of Congo (DRC) from October to December 2014. Questionnaires and self-administered and in-depth interviews and group discussions as well as records and observation were used to collect information during laboratory visits and assessments. Results The PEI financial support allows to maintain the majority of the 14 (DRC) and 12 (RCI) staff involved in the polio laboratory as full or in part time members. Through laboratory technical staff training supported by the PEI, skills and knowledge were gained to reinforce laboratories capacity and performance in quality laboratory functioning, processes and techniques such as cell culture. In the same way, infrastructure was improved and equipment provided. General laboratory quality standards, including the entire laboratory key elements was improved through the PEI accreditation process. Conclusion The Polio Eradication Initiative (PEI) is a good example of contribution in strengthening public health laboratories systems in the African region. It has established strong Polio Laboratory network that contributed to the strengthening of capacities and its expansion to surveillance of other viral priority diseases such as measles, yellow fever, Influenza, MERS-CoV and Ebola. This could serve as lesson and good example of laboratory based surveillance to improving diseases prevention, detection and control in our middle and low income countries as WHO and partners are heading to polio eradication in the world.

Background Efficient implementation of the global eradication strategies consisting of Acute Flaccid Paralysis (AFP) surveillance and mass immunization campaigns led to interruption of indigenous wild poliovirus transmission in Cameroon in 1999. Objectives This study describes type 1 and type 3 wild poliovirus (WPV) importation, incidence, geographic distribution and control since the original interruption of transmission in Cameroon. Study design Stool samples from AFP patients under the age of 15 years in Cameroon were collected nationwide and subjected to virus isolation on RD and L20B cell cultures. Resulting virus isolates were typed by intratypic differentiation (ITD) and analysis of the VP1 coding sequence of the viral genome. Surveillance data originating from Cameroon between 2000 and 2014 were considered for retrospective descriptive analyses. Results From 2003 to 2009, multiple WPV importation events from neighboring countries affected mainly in the northern regions of Cameroon but did not led to sustained local transmission. Throughout this period, 16 WPV1 and 5 WPV3 were detected and identified as members of multiple clusters within type-specific West Africa B genotypes (WEAF-B). In 2013–2014, a polio outbreak associated to a highly evolved (“orphan”) WPV1 affected four southern regions of Cameroon. Conclusions The appearance of highly evolved lineage of type 1 WPV suggests potential surveillance gap and underscore the need to maintain comprehensive polio immunization activities and sensitive surveillance systems in place as long as any country in the world remains endemic for WPV.

We followed the dynamics of capsid amino acid replacement among 403 Nigerian outbreak isolates of type 2 circulating vaccine-derived poliovirus (cVDPV2) from 2005 through 2011. Four different functional domains were analyzed: (i) neutralizing antigenic (NAg) sites, (ii) residues binding the poliovirus receptor (PVR), (iii) VP1 residues 1 to 32, and (iv) the capsid structural core. Amino acid replacements mapped to 37 of 43 positions across all 4 NAg sites; the most variable and polymorphic residues were in NAg sites 2 and 3b. The most divergent of the 120 NAg variants had no more than 5 replacements in all NAg sites and were still neutralized at titers similar to those of Sabin 2. PVR-binding residues were less variable (25 different variants; 0 to 2 replacements per isolate; 30/44 invariant positions), with the most variable residues also forming parts of NAg sites 2 and 3a. Residues 1 to 32 of VP1 were highly variable (133 different variants; 0 to 6 replacements per isolate; 5/32 invariant positions), with residues 1 to 18 predicted to form a well-conserved amphipathic helix. Replacement events were dated by mapping them onto the branches of time-scaled phylogenies. Rates of amino acid replacement varied widely across positions and followed no simple substitution model. Replacements in the structural core were the most conservative and were fixed at an overall rate ∼20-fold lower than the rates for the NAg sites and VP1 1 to 32 and ∼5-fold lower than the rate for the PVR-binding sites. Only VP1 143-Ile, a non-NAg site surface residue and known attenuation site, appeared to be under strong negative selection. IMPORTANCE The high rate of poliovirus evolution is offset by strong selection against amino acid replacement at most positions of the capsid. Consequently, poliovirus vaccines developed from strains isolated decades ago have been used worldwide to bring wild polioviruses almost to extinction. The apparent antigenic stability of poliovirus obscures a dynamic of continuous change within the neutralizing antigenic (NAg) sites. During 7 years of a large outbreak in Nigeria, the circulating type 2 vaccine-derived polioviruses generated 120 different NAg site variants via multiple independent pathways. Nonetheless, overall antigenic evolution was constrained, as no isolate had fixed more than 5 amino acid differences from the Sabin 2 NAg sites, and the most divergent isolates were efficiently neutralized by human immune sera. Evolution elsewhere in the capsid was also constrained. Amino acids binding the poliovirus receptor were strongly conserved, and extensive variation in the VP1 amino terminus still conserved a predicted amphipathic helix.

Recommendation for publication. Recommendation from the Ministry of Health. (PDF 42Â kb)

The Phylogeny of VDPVs from Uganda, Republic of Democratic Congo (RDC/DRC), Nigeria and Madagascar. (PDF 140Â kb)

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A retrospective study to identify VAPP cases from the entire Uganda was conducted between January 2003 and December 2011. Eleven of the 106 AFP cases were VAPPs. The VAPP rate ranged from 0 to 3.39 cases per 1,000,000 birth cohorts and the peak was in 2009 when there was scaling up of OPV immunization activities following an importation of wild poliovirus in the country. All the subsequent polio suspect cases since then have been vaccine-associated polio cases. Our data support the strategy to withdraw OPV and introduce IPV progressively in order to mitigate against the paralysis arising from Sabin polioviruses.

A paralytic poliomyelitis outbreak occurred in Namibia in 2006, almost exclusively among adults. Nineteen cases were virologically confirmed as due to wild poliovirus type 1 (WPV1), and 26 were classified as polio compatible. Eleven deaths occurred among confirmed and compatible cases (24%). Of the confirmed cases, 97% were aged 15-45 years, 89% were male, and 71% lived in settlement areas in Windhoek. The virus was genetically related to a virus detected in 2005 in Angola, which had been imported earlier from India. The outbreak is likely due to immunity gaps among adults who were inadequately vaccinated during childhood. This outbreak underscores the ongoing risks posed by poliovirus importations, the importance of maintaining strong acute flaccid paralysis surveillance even in adults, and the need to maintain high population immunity to avoid polio outbreaks in the preeradication period and outbreaks due to vaccine-derived polioviruses in the posteradication era.

TOC summary: These viruses can emerge independently where immunity to poliovirus is inadequate., Polioviruses isolated from 70 acute flaccid paralysis patients from the Democratic Republic of Congo (DRC) during 2004–2011 were characterized and found to be vaccine-derived type 2 polioviruses (VDPV2s). Partial genomic sequencing of the isolates revealed nucleotide sequence divergence of up to 3.5% in the viral protein 1 capsid region of the viral genome relative to the Sabin vaccine strain. Genetic analysis identified at least 7 circulating lineages localized to specific geographic regions. Multiple independent events of VDPV2 emergence occurred throughout DRC during this 7-year period. During 2010–2011, VDPV2 circulation in eastern DRC occurred in an area distinct from that of wild poliovirus circulation, whereas VDPV2 circulation in the southwestern part of DRC (in Kasai Occidental) occurred within the larger region of wild poliovirus circulation.

Ebola Virus Disease (EVD) outbreak was confirmed in Liberia on March 31st 2014. A response comprising of diverse expertise was mobilized and deployed to the country to contain transmission of Ebola and give relief to a people already impoverished from protracted civil war. This paper describes the epidemiological and surveillance response to the EVD outbreak in Lofa County in Liberia from March to September 2014. Five of the 6 districts of Lofa were affected. The most affected districts were Voinjama/Guardu Gbondi and Foya. By 26th September, 2014, a total of 619 cases, including 19.4% probable cases, 20.3% suspected cases and 44.2% confirmed cases were recorded by the Ebola Emergency Response Team (EERT) of Lofa County. Adults (20-50 years) were the most affected. Overall fatality rate was 53.3%. Twenty two (22) cases were reported among the Health Care Workers with a fatality rate of 81.8%. Seventy eight percent (78%) of the contacts successfully completed 21 days follow-up while 134 (6.15%) that developed signs and symptoms of EVD were referred to the ETU in Foya. The contributions of the weak health systems as well as socio-cultural factors in fueling the epidemic are highlighted. Importantly, the lessons learnt including the positive impact of multi-sectorial and multidisciplinary and coordinated response led by the government and community. Again, given that the spread of infectious disease can be considered a security threat every effort has to put in place to strengthen the health systems in developing countries including the International Health Regulation (IHR)’s core capacities. Key words: Ebola virus disease, outbreak, epidemiology and surveillance, socio-cultural factors, health system, West Africa.

Patients with primary immunodeficiency are prone to persistently excrete Sabin-like virus after administration of live-attenuated oral polio vaccine and have an increased risk for vaccine-derived paralytic polio. We report a case of type 3 immunodeficiency-associated vaccine-derived poliovirus in a child in South Africa who was born with X-linked immunodeficiency syndrome.

Since the launch of the Global Polio Eradication Initiative in 1988 [1], worldwide poliomyelitis incidence has declined by >99%. Four World Health Organization (WHO) regions have certified the eradication of indigenous WPVs: the Region of the Americas, in 1994 [2]; the Western Pacific Region, in 2000 [3]; the Europe Region, in 2002 [4]; and the South-East Asia Region (which includes India), in March 2014 [5]. WPV2 was last detected in Uttar Pradesh, India, in 1999 [6], and WPV3 was last detected in northern Nigeria, in November 2012 (updates are available at: http://www.polioeradication.org). In India, once the world's reservoir of the most intense polio endemicity, WPV was last detected in early 2011 [7]. Since 2011, only 3 countries have never interrupted indigenous WPV transmission [8]: Pakistan [9], Afghanistan [10], and Nigeria [11]. All WPV cases reported in 2013 were associated with only 2 WPV1 genotypes (isolates within a genotype share >85% VP1 sequence identity): the SOAS (South Asia) genotype, endemic to parts of northern Pakistan, with recent spread to Afghanistan and the Middle East [12]; and the WEAF-B (West Africa B) genotype, endemic to parts of northern Nigeria, with recent spread to the Horn of Africa [13]. The WHO African Region began polio eradication activities in 1995 [14]. The number of countries in AFR reporting WPV transmission declined from 25 in 1995 to only 1 (Nigeria) by 2008 [8], a milestone achieved through sustained efforts in (1) routine and supplementary immunization activities (SIAs; mass immunization campaigns) with oral poliovirus vaccine (OPV), (2) sensitive surveillance for cases of acute flaccid paralysis (AFP), and (3) laboratory-based poliovirus (PV) surveillance. The challenge of armed conflict in the DRC, Angola, and other African countries was met by Days of Tranquility, in which hostilities were suspended for the purpose of national immunization days [15]. The last cases associated with WPV indigenous to the DRC and neighboring Angola were reported in 2001 [14]. However, immunity gaps widened in many newly polio-free African countries, as OPV coverage rates declined and natural immunity from WPV infection no longer occurred. Starting in 2002, WPV1 and WPV3 spread from northern Nigeria in successive waves across West and Central Africa, and WPV1 and WPV3 were imported into Southern and Central Africa from India [13, 16–19]. The imported outbreak viruses were repeatedly rolled back in most African countries [8, 20], but sustained WPV transmission was reestablished in the DRC and Angola [20, 21]. The widespread outbreaks in the DRC prompted the launch of SIAs, reinforcement of routine immunization, retrospective assessments of age-specific population immunity [22], and intensified surveillance for AFP cases coupled with virologic characterization of PV isolates [21]. In this report, we describe reconstruction of the pathways of spread of the imported WPV1 from India to Angola, the DRC, and the Congo by phylogenetic analysis of the 906-nucleotide region encoding the major capsid protein, VP1. VP1 sequence relationships are routinely analyzed by virologists in the Global Polio Laboratory Network [23]. The rapid evolution of PV in nature (approximately 1% substitutions per site per year, equivalent to approximately 1–2 nucleotide substitutions per week over the entire genome) [24] permits precise reconstruction of genetic relationships between isolates, discrimination between PV-endemic source reservoirs and reinfected areas, and establishment of the timing of importation events. We document frequent WPV1 transmission across the borders of Angola, the DRC, and the Congo; the geographic distribution of multiple lineage groups within the DRC; and the detection of gaps in AFP surveillance by the appearance of orphan lineages.

International audience; BACKGROUND: After the 2001-2002 poliomyelitis outbreak due to recombinant vaccine-derived polioviruses (VDPVs) in the Toliara province of Madagascar, another outbreak reoccurred in the same province in 2005. METHODS: We conducted epidemiological and virological investigations for each polio case patient and for their contacts. RESULTS: From May to August 2005, a total of 5 cases of acute flaccid paralysis were reported among unvaccinated or partially vaccinated children 2-3 years old. Type-3 or type-2 VDPV was isolated from case patients and from healthy contacts. These strains were classified into 4 recombinant lineages that showed complex mosaic genomic structures originating from different vaccine strain serotypes and probably from human enterovirus C (HEV-C) species. Genetic relatedness could be observed among these 4 lineages. Vaccination coverage of the population was very low (

Virological surveillance is an important element in the Polio Eradication Initiative to provide information rapidly about circulating wild polioviruses. Molecular tools have been developed to identify the serotype of the poliovirus strains and whether they are of vaccine or wild origin (intratypic differentiation) and to perform the molecular epidemiology of wild strains. The main objective of this study was to show that restriction fragment length polymorphism (RFLP) is a tool that can be used for molecular epidemiology of wild polioviruses. This is retrospective study of poliovirus type 1 strains received at the Institut Pasteur of Bangui (IPB), a WHO Regional Reference Laboratory for Africa, since 1994. We describe our experience with isolates from Western and Central Africa and show a positive correlation between the genotypes as determined by sequencing the gene for the VP1 capsid protein and the RFLP patterns. Although genomic sequencing is the gold standard method for detailed molecular epidemiology analysis of poliovirus isolates, these results show that RFLP is a potentially valuable tool for molecular epidemiological analysis of poliovirus type 1 strains: it could be used by many laboratories as a rapid method for ITD and genotype screening where sequencing capacity is not readily available.

A type 2 vaccine-derived poliovirus (VDPV), differing from Sabin 2 at 2.5% (22/903) of VP1 nucleotide (nt) positions, was isolated from an incompletely immunized 21-month-old Nigerian child who developed acute flaccid paralysis in 2002. Sequences upstream of nt position 620 (within the 5'-untranslated region [5'-UTR]) and downstream of nt position 5840 (in the 3C(pro) region) were derived from species C enteroviruses unrelated to the oral poliovirus vaccine (OPV) strains. The two substitutions associated with the attenuated phenotype had either recombined out (A(481)-->G in the 5'-UTR) or reverted (Ile(143)-->Thr in VP1). The VDPV isolate had lost the temperature sensitive phenotype of Sabin 2 and it was antigenically distinct from the parental OPV strain, having amino acid substitutions in or near neutralizing antigenic sites 1 and 3. The date of the initiating OPV dose, calculated from the number of synonymous substitutions in the capsid region, was estimated to be approximately 16 to 18 months before onset of paralysis, a finding inconsistent with the most recent mass OPV campaign (conducted 12 days before onset of paralysis) as being the source of infection. Although no related type 2 VDPVs were detected in Nigeria or elsewhere, the VDPV was found in an area where conditions favor VDPV emergence and spread.

To the Editor: Since the Global Polio Eradication Initiative was launched in 1988, indigenous transmission of wild poliovirus (WPV) has been interrupted in all countries except Afghanistan, Pakistan, and Nigeria (1). However, during 2003–2011, outbreaks resulting from importation of WPV occurred in 29 previously polio-free countries in Africa, including Central African Republic (CAR) (1–3). In 2011, 350 WPV cases were reported from 12 countries in Africa, a 47% decrease from the 657 cases reported by 12 countries in Africa in 2010 (1). In CAR, the last case of poliomyelitis caused by indigenous transmission of wild poliovirus was reported in 2000, but importation of WPV type 1 has been reported (4). We describe the importation of WPV1 and WPV3 into CAR during successive events in 2008, 2009, and 2011. To investigate importation of WPV into CAR, we conducted a study using fecal samples collected from patients in CAR who had acute flaccid paralysis (AFP) during 2008–2011. The samples were analyzed for virus isolation, typing, and intratypic differentiation at the Regional Reference Laboratory for Polio, Institut Pasteur de Bangui, using World Health Organization (WHO) standard procedures (5). Isolated WPV strains were sent to the Centers for Disease Control and Prevention (Atlanta, Georgia, USA) or the National Institute for Communicable Diseases (Johannesburg, South Africa) for sequencing according to WHO guidelines (6–8). Cases were classified as laboratory confirmed or polio-compatible according to WHO recommendations; a polio-compatible case was defined as AFP for which stool samples were not adequate or a situation in which the patient was lost to follow up or had residual paralysis 60 days after testing. Of 141 AFP cases from 2008, three, from Bangui, Ouham, and Ouaka districts, were laboratory confirmed as WPV1; this cluster was designated B2D1B (Figure). Sequencing results showed that the virus in this cluster belonged to the South Asia A (Indian) genotype, which was circulating in Angola and Democratic Republic of Congo at that time (Figure). Figure Clusters of polio cases caused by wild poliovirus importations, Central African Republic, 2008–2011. Each circle represents 1 case of acute flaccid paralysis confirmed as polio. Black circles, cluster B2D1B, 2008 poliovirus (PV) type 1 SOAS importation ... Of 163 AFP cases from 2009, 14 in Ouham-Pende district were laboratory confirmed as WPV3; this cluster was designated D2B2B1. Sequencing results showed that the virus in this cluster belonged to West Africa B genotype, which was circulating in Nigeria and southern Chad at that time (Figure). Of 142 AFP cases from 2011, four in Ouham district were laboratory confirmed as WPV1; this cluster was designated I6C2B4C1A2. Sequencing results showed that the virus in this cluster belonged to West Africa B genotype, which was circulating in south Chad and Nigeria at the time (Figure). The importation of wild poliovirus strains into CAR appeared to follow 3 different routes. In 2008, WPV1 originated from Democratic Republic of Congo and was first detected in the capital, Bangui, which is located in the southern part of the country. Two more cases were detected in 2 other districts, in the north (Ouham) and in the middle (Ouaka) of the country. During that year, 2 AFP cases were classified as polio-compatible; these cases originated from Haute Kotto and Ouham districts. In 2008, routine coverage of oral polio vaccine (OPV) was 45%, 33%, and 57% for Bangui and Sanitary Regions 3 and 4, respectively. (Sanitary regions are equivalent to provinces and have several districts under their jurisdiction; Bangui is considered a Sanitary Region containing 8 districts.) To interrupt wild poliovirus circulation, health authorities implemented 4 rounds of national immunization days, 2 using monovalent OPV (mOPV) type 1 and 2 using trivalent OPV; 1 local immunization day using mOPV1 was also instituted. In 2009, WPV3 was imported from southern Chad to the Ouham-Pende district in CAR. This insecure district is difficult to access, but routine OPV coverage was reported as 61% for 2009, compared with the country’s official OPV coverage of 55%. The apparently higher coverage in areas of insecurity is likely the result of inaccurate target population estimates. Five additional AFP cases were classified as polio-compatible; these occurred in Ouham (1), Ouham Pende (2), Mambere Kadei (1), and Mbomou (1) districts. To interrupt wild poliovirus circulation, 8 supplementary immunization activities were organized. The 2011 polio outbreak occurred in the district of Ouham and was caused by WPV1 poliovirus imported from southern Chad (Figure). Fourteen additional cases of AFP were classified as polio-compatible; these occurred in Ouham-Pende (6), Ouham (1), Ombela M’Poko (1), Kemo (1), Ouaka (1), Haute Kotto (2), and Mbomou (2) districts. Routine OPV coverage for this insecure and difficult-to-access region was 55% for 2010 and 58% for 2011. CAR is one of the countries with the highest predicted risk for WPV circulation after importation (9). The 3 WPV importation events we report demonstrate that current immunization levels in this country are insufficient to guard against polio. High, sustained levels of routine OPV coverage in every district, supplemented by high-quality supplementary immunization activities, will help prevent future outbreaks. Surveillance standards must also be maintained to ensure the rapid detection of WPV importation, thus enabling timely response and containment.