Emergence of vaccine-derived polioviruses, Democratic Republic of Congo, 2004-2011.

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.

Twenty-five years of outpatient influenza surveillance in South Africa, 1984-2008.

INTRODUCTION: Understanding the seasonality of influenza can help inform prevention and clinical treatment strategies. The aim of this manuscript is to describe the trends and epidemiology of outpatient influenza in South Africa prior to the influenza A(H1N1) pandemic. METHODS: Throughout each year, participating healthcare practitioners sent throat swabs from patients with influenza-like illness (ILI) to the National Institute for Communicable Diseases for influenza testing by immunofluorescence and viral culture through the Viral Watch influenza surveillance program. RESULTS: From 1984 to 2004, participating sites were restricted to 1 province and the annual number of specimens ranged from 91 to 534. In 2005 the program was expanded. By 2008 the program included all 9 provinces; 1276 specimens were submitted that year. The mean week of onset was the first week of June and the mean peak was the first week of July. The duration of the season ranged from 6 to 18 weeks with a mean of 10 weeks. The mean annual influenza detection rate was 28% (range, 23%-41%). Influenza A(H3N2) predominated in 14 (56%) of the 25 years, seasonal influenza A(H1N1) in 7 (28%), and influenza B in 2 (8%), and in 2 years multiple types cocirculated. CONCLUSIONS: The program has provided valuable data on the timing of the influenza season each year that can be useful to direct the timing of vaccination and assist clinicians in deciding whether to prescribe empirical antiviral therapy.

Introduction of 2009 pandemic influenza A virus subtype H1N1 into South Africa: clinical presentation, epidemiology, and transmissibility of the first 100 cases.

BACKGROUND: We documented the introduction of 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) into South Africa and describe its clinical presentation, epidemiology, and transmissibility. METHODS: We conducted a prospective descriptive study of the first 100 laboratory-confirmed cases of A(H1N1)pdm09 infections identified through active case finding and surveillance. Infected patients and the attending clinicians were interviewed, and close contacts were followed up to investigate household transmission. FINDINGS: The first case was confirmed on 14 June 2009, and by 15 July 2009, 100 cases were diagnosed. Forty-two percent of patients reported international travel within 7 days prior to onset of illness. Patients ranged in age from 4 to 70 years (median age, 21.5 years). Seventeen percent of household contacts developed influenza-like illness, and 10% of household contacts had laboratory-confirmed A(H1N1)pdm09 infection. We found a mean serial interval (± SD) of 2.3 ± 1.3 days (range, 1-5 days) between successive laboratory-confirmed cases in the transmission chain. CONCLUSIONS: A(H1N1)pdm09 established itself rapidly in South Africa. Transmissibility of the virus was comparable to observations from outside of Africa and to seasonal influenza virus strains.

Evolutionary dynamics of 2009 pandemic influenza A virus subtype H1N1 in South Africa during 2009-2010.

BACKGROUND: The 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) was first detected in June 2009 in South Africa and later resulted in extensive transmission throughout Africa. Established routine surveillance programs and collaboration between private and public sector laboratories allowed for comprehensive molecular epidemiological and antigenic investigation of the first and second waves of 2009-2010 pandemic influenza in South Africa. METHODS: We used reverse-transcription polymerase chain reaction to screen for influenza virus in 9792 specimens recovered during 2009 and 6915 specimens recovered during 2010 from inpatients and outpatients with influenza-like illness or severe acute respiratory illness symptoms identified by surveillance programs. Influenza-positive specimens were subjected to genetic and antigenic characterization. Bayesian and maximum likelihood analyses of the hemagglutinin genes of 96 A(H1N1)pdm09 strains were used for molecular epidemiological investigations. Hemagglutination inhibition assays and sequencing of the PB2 and neuraminidase genes were used to investigate pathogenicity and resistance mutations. RESULTS: The A(H1N1)pdm09 epidemic occurred as a second epidemic peak following seasonal influenza A virus subtype H3N2 cases in 2009 and in 2010. Progressive drift away from the A/California/7/2009 vaccine strain was observed at both the nucleotide and amino acid level, with 2010 strains clustering separate to 2009 strains. A few unique clusters of amino acid changes in severe cases were identified, but most strains were antigenically similar to the vaccine strain, and no resistance or known pathogenicity mutations were detected. CONCLUSION: Despite limited drift observed over the 2 seasons in South Africa, circulating A(H1N1)pdm09 strains remained antigenically similar to strains identified in other northern and southern hemisphere countries from 2010 and 2011.

Immunodeficiency-associated vaccine-derived poliovirus type 3 in infant, South Africa, 2011.

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.

Advances in childhood immunisation in South Africa: where to now? Programme managers' views and evidence from systematic reviews.

BACKGROUND: The Expanded Programme on Immunisation (EPI) is one of the most powerful and cost-effective public health programmes to improve child survival. We assessed challenges and enablers for the programme in South Africa, as we approach the 2015 deadline for the Millennium Development Goals. METHODS: Between September 2009 and September 2010 we requested national and provincial EPI managers in South Africa to identify key challenges facing EPI, and to propose appropriate solutions. We collated their responses and searched for systematic reviews on the effectiveness of the proposed solutions; in the Health Systems Evidence, Cochrane Library, and PubMed electronic databases. We screened the search outputs, selected systematic reviews, extracted data, and assessed the quality of included reviews (using AMSTAR) and the quality of the evidence (using GRADE) in duplicate; resolving disagreements by discussion and consensus. RESULTS: Challenges identified by EPI managers were linked to healthcare workers (insufficient knowledge of vaccines and immunisation), the public (anti-immunisation rumours and reluctance from parents), and health system (insufficient financial and human resources). Strategies proposed by managers to overcome the challenges include training, supervision, and audit and feedback; strengthening advocacy and social mobilisation; and sustainable EPI funding schemes, respectively. The findings from reliable systematic reviews indicate that interactive educational meetings, audit and feedback, and supportive supervision improve healthcare worker performance. Structured and interactive communication tools probably increase parents' understanding of immunisation; and reminders and recall, use of community health workers, conditional cash transfers, and mass media interventions probably increase immunisation coverage. Finally, a national social health insurance scheme is a potential EPI financing mechanism; however, given the absence of high-quality evidence of effects, its implementation should be pilot-tested and the impacts and costs rigorously monitored. CONCLUSION: In line with the Millennium Development Goals, we have to ensure that our children's right to health, development and survival is respected, protected and promoted. EPI is central to this vision. We found numerous promising strategies for improving EPI performance in South Africa. However, their implementation would need to be tailored to local circumstances and accompanied by high-quality monitoring and evaluation. The strength of our approach comes from having a strong framework for interventions before looking for systematic reviews. Without a framework, we would have been driven by what reviews have been done and what is easily researchable; rather than the values and preferences of key immunisation stakeholders.

Elevated influenza-related excess mortality in South African elderly individuals, 1998-2005.

BACKGROUND: Although essential to guide control measures, published estimates of influenza-related seasonal mortality for low- and middle-income countries are few. We aimed to compare influenza-related mortality among individuals aged ≥65 years in South Africa and the United States. METHODS: We estimated influenza-related excess mortality due to all causes, pneumonia and influenza, and other influenza-associated diagnoses from monthly age-specific mortality data for 1998-2005 using a Serfling regression model. We controlled for between-country differences in population age structure and nondemographic factors (baseline mortality and coding practices) by generating age-standardized estimates and by estimating the percentage excess mortality attributable to influenza. RESULTS: Age-standardized excess mortality rates were higher in South Africa than in the United States: 545 versus 133 deaths per 100,000 population for all causes (P<.001) and 63 vs 21 deaths per 100,000 population for pneumonia and influenza (P=.03). Standardization for nondemographic factors decreased but did not eliminate between-country differences; for example, the mean percentage of winter deaths attributable to influenza was 16% in South Africa and 6% in the United States (P<.001). For all respiratory causes, cerebrovascular disease, and diabetes, age-standardized excess death rates were 4-8-fold greater in South Africa than in the United States, and the percentage increase in winter deaths attributable to influenza was 2-4-fold higher. CONCLUSIONS: These data suggest that the impact of seasonal influenza on mortality among elderly individuals may be substantially higher in an African setting, compared with in the United States, and highlight the potential for influenza vaccination programs to decrease mortality.

Advocating for efforts to protect African children, families, and communities from the threat of infectious diseases: report of the First International African Vaccinology Conference.

One means of improving healthcare workers' knowledge of and attitudes to vaccines is through running vaccine conferences which are accessible, affordable, and relevant to their everyday work. Various vaccinology conferences are held each year worldwide. These meetings focus heavily on basic science with much discussion about new developments in vaccines, and relatively little coverage of policy, advocacy, and communication issues. A negligible proportion of delegates at these conferences come from Africa, home to almost 40% of the global burden of vaccine-preventable diseases. To the best of our knowledge, no major vaccinology conference has ever been held on the African continent apart from World Health Organization (WHO) meetings. The content of the first International African Vaccinology Conference was planned to be different; to focus on the science, with a major part of discussions being on clinical, programmatic, policy, and advocacy issues. The conference was held in Cape Town, South Africa, from 8 to 11 November 2012. The theme of the conference was "Advocating for efforts to protect African children, families, and communities from the threat of infectious diseases". There were more than 550 registered participants from 55 countries (including 37 African countries). There were nine pre-conference workshops, ten plenary sessions, and 150 oral and poster presentations. The conference discussed the challenges to universal immunisation in Africa as well as the promotion of dialogue and communication on immunisation among all stakeholders. There was general acknowledgment that giant strides have been made in Africa since the global launch of the Expanded Programme on Immunisation in 1974. For example, there has been significant progress in introducing new and under-utilised vaccines; including hepatitis B, Haemophilus influenza type b, pneumococcal conjugate, rotavirus, meningococcal A conjugate, and human papillomavirus vaccines. In May 2012, African countries endorsed the Global Vaccine Action Plan at the World Health Assembly. However, more than six million children remain incompletely vaccinated in Africa leading to more than one million vaccine-preventable deaths annually. In addition, there are persistent problems with leadership and planning, vaccine stock management, supply chain capacity and quality, provider-parent communication, and financial sustainability. The conference delegates agreed to move from talking to taking concrete actions around children's health, and to ensure that African governments commit to saving children's lives. They would advocate for lower costs of immunisation programmes in Africa, perhaps through bulk buying and improved administration of vaccine rollout through the New Partnership for Africa's Development.

The Cape Town Declaration on Vaccines 2012: Unlocking the full potential of vaccines in Africa.

Delegates at the first International African Vaccinology Conference noted, with dismay, that many African children have limited access to existing and new vaccines as a consequence of weak immunisation programmes, lack of political will, and high vaccine prices. This inequality is a denial of the African child her basic right to a healthy life, and jeopardises long term economic growth on the continent. In addition, there is insufficient emphasis in Africa on adolescent and adult immunisation. The delegates documented various concerns and made various commitments; contained in this Cape Town Declaration on Vaccines, adopted on 11 November 2012. Finally, delegates confirmed their agreement with the goals and strategic objectives of the Global Vaccine Action Plan, and committed to hold African leaders accountable for its implementation during the Decade of Vaccines. The full list of registered conference delegates is provided as supplementary data to this manuscript.

A North/South collaboration between two national public health institutes--a model for global health protection.

Rapid international spread of emerging infections has increased interest in strategic collaborations, as they may be the best way to protect populations. Strategic collaborations can build capacity in less-resourced settings. As specialised institutions that provide a stable locus of expertise, continuity of experience, scientific knowledge, and appropriate human, technical, and financial resources, national public health institutes (NPHIs) are well-prepared to tackle public health challenges. We describe how a collaboration between the NPHIs of England and South Africa built a mutually beneficial professional relationship to help implement the WHO International Health Regulations, build capacity for health protection, and promote the exchange of information, advice, and expertise. We illustrate how this can be achieved in a mutually beneficial way.

Phylogenetic studies of influenza B viruses isolated in southern Africa: 1998-2001.

Influenza B viruses isolated in southern Africa during the period from 1998 to 2001 were analysed by sequence analysis of the viral haemagglutinin HA1 subunit and the phylogenetic relationships were determined. Influenza B activity varied considerably in South Africa during the 4-year study period with no activity detected in 2000. Phylogenetic analysis revealed that viruses isolated in 1998 from a localised outbreak in Durban belonged to two distinct sub-lineages. Some of the influenza B viruses isolated throughout South Africa in 1999 as well as several viruses obtained from Mozambique in the same year were closely related to the B/Yamanashi/166/98-like viruses. In contrast, the majority of the 1999 isolates, represented by B/Johannesburg/5/99, exhibited considerable drift from the B/Yamanashi/166/98 stain. The viruses isolated during the 2001 season fell into two sub-lineages, one of which had evolved from the B/Johannesburg/5/99-like viruses and the other which had evolved from the group of viruses that included one of the 1998 Durban isolates. These molecular epidemiological studies reveal a diverse and complex pattern of influenza B virus strains circulating in southern Africa.

Influenza epidemiology and vaccine effectiveness among patients with influenza-like illness, viral watch sentinel sites, South Africa, 2005-2009.

BACKGROUND: There is limited data on the epidemiology of influenza and few published estimates of influenza vaccine effectiveness (VE) from Africa. In April 2009, a new influenza virus strain infecting humans was identified and rapidly spread globally. We compared the characteristics of patients ill with influenza A(H1N1)pdm09 virus to those ill with seasonal influenza and estimated influenza vaccine effectiveness during five influenza seasons (2005-2009) in South Africa. METHODS: Epidemiological data and throat and/or nasal swabs were collected from patients with influenza-like illness (ILI) at sentinel sites. Samples were tested for seasonal influenza viruses using culture, haemagglutination inhibition tests and/or polymerase chain reaction (PCR) and for influenza A(H1N1)pdm09 by real-time PCR. For the vaccine effectiveness (VE) analysis we considered patients testing positive for influenza A and/or B as cases and those testing negative for influenza as controls. Age-adjusted VE was calculated as 1-odds ratio for influenza in vaccinated and non-vaccinated individuals. RESULTS: From 2005 through 2009 we identified 3,717 influenza case-patients. The median age was significantly lower among patients infected with influenza A(H1N1)pdm09 virus than those with seasonal influenza, 17 and 27 years respectively (p<0.001). The vaccine coverage during the influenza season ranged from 3.4% in 2009 to 5.1% in 2006 and was higher in the ≥50 years (range 6.9% in 2008 to 13.2% in 2006) than in the <50 years age group (range 2.2% in 2007 to 3.7% in 2006). The age-adjusted VE estimates for seasonal influenza were 48.6% (4.9%, 73.2%); -14.2% (-9.7%, 34.8%); 12.0% (-70.4%, 55.4%); 67.4% (12.4%, 90.3%) and 29.6% (-21.5%, 60.1%) from 2005 to 2009 respectively. For the A(H1N1)pdm09 season, the efficacy of seasonal vaccine was -6.4% (-93.5%, 43.3%). CONCLUSION: Influenza vaccine demonstrated a significant protective effect in two of the five years evaluated. Low vaccine coverage may have reduced power to estimate vaccine effectiveness.

The survival of influenza A(H1N1)pdm09 virus on 4 household surfaces.

We investigated the survival of a pandemic strain of influenza A H1N1 on a variety of common household surfaces where multiple samples were taken from 4 types of common household fomite at 7 time points. Results showed that influenza A H1N1sw virus particles remained infectious for 48 hours on a wooden surface, for 24 hours on stainless steel and plastic surfaces, and for 8 hours on a cloth surface, although virus recovery from the cloth may have been suboptimal. Our results suggest that pandemic influenza A H1N1 can survive on common household fomites for extended periods of time, and that good hand hygiene and regular disinfection of commonly touched surfaces should be practiced during the influenza season to help reduce transmission.

Afriflu2--second international workshop on influenza vaccination in the African continent--8 November 2012, Cape Town (South Africa).

The second meeting of the Afriflu conferences took place in Cape Town, South Africa, with over 60 participants from 15 countries in Africa and also outside the continent. Significant progress in surveillance has been made in better understanding the illness burden of influenza on the continent, which limited evidence suggests is greater than that in the developed world. In southern Africa HIV and TB coinfections play a major role in increasing hospitalisation and mortality, while elsewhere in Africa other cofactors still need to be determined. There is currently no indigenous vaccine production in sub-Saharan Africa and only one facility, based in South Africa, capable of filling imported bulk. Innovative vaccine strategies will need to be explored, such as maternal immunisation, and also the possibility of other influenza vaccine options, such as live attenuated influenza vaccine for young children. Sustained indigenous vaccine production is essential for the continent to have vaccine security in the event of a pandemic even though establishing local production faces considerable challenges especially ensuring adequate markets on the continent. There is an urgent need to develop effective communication messages for decision makers as well as healthcare workers addressing the importance of influenza even in the face of the major competing health burdens of the continent.

Measles outbreak in South Africa: epidemiology of laboratory-confirmed measles cases and assessment of intervention, 2009-2011.

BACKGROUND: Since 1995, measles vaccination at nine and 18 months has been routine in South Africa; however, coverage seldom reached >95%. We describe the epidemiology of laboratory-confirmed measles case-patients and assess the impact of the nationwide mass vaccination campaign during the 2009 to 2011 measles outbreak in South Africa. METHODS: Serum specimens collected from patients with suspected-measles were tested for measles-specific IgM antibodies using an enzyme-linked immunosorbent assay and genotypes of a subset were determined. To estimate the impact of the nationwide mass vaccination campaign, we compared incidence in the seven months pre- (1 September 2009-11 April 2010) and seven months post-vaccination campaign (24 May 2010-31 December 2010) periods in seven provinces of South Africa. RESULTS: A total of 18,431 laboratory-confirmed measles case-patients were reported from all nine provinces of South Africa (cumulative incidence 37 per 100,000 population). The highest cumulative incidence per 100,000 population was in children aged <1 year (603), distributed as follows: <6 months (302/100,000), 6 to 8 months (1083/100,000) and 9 to 11 months (724/100,000). Forty eight percent of case-patients were ≥ 5 years (cumulative incidence 54/100,000). Cumulative incidence decreased with increasing age to 2/100,000 in persons ≥ 40 years. A single strain of measles virus (genotype B3) circulated throughout the outbreak. Prior to the vaccination campaign, cumulative incidence in the targeted vs. non-targeted age group was 5.9-fold higher, decreasing to 1.7 fold following the campaign (P<0.001) and an estimated 1,380 laboratory-confirmed measles case-patients were prevented. CONCLUSION: We observed a reduction in measles incidence following the nationwide mass vaccination campaign even though it was conducted approximately one year after the outbreak started. A booster dose at school entry may be of value given the high incidence in persons >5 years.

Zoonotic diseases and human health: the human influenza example.

Over the past few decades a large number of new and emerging infectious diseases have been recognised in humans, partly because of improved diagnostic technologies and increased awareness and also, partly because of dynamic ecological changes between human hosts and their exposure to animals and the environment (Coker et al. 2011). Some 177 new pathogenic organisms have been recognised to be 'emerging', that is, have newly arisen or been newly introduced into human populations; almost three quarters of these, 130 (73%), have come from zoonotic origins (Cascio et al. 2011; Cutler, Fooks & Van Der Poel 2010; Taylor, Latham & Woolhouse 2001; Woolhouse & Gowtage-Sequeria 2005). One of the most prevalent and important human infectious disease is influenza, a disease responsible globally for a quarter million deaths annually. In the USA alone the toll from influenza is estimated at 36 000 deaths and 226 000 hospitalisations, and it ranks as the most important cause of vaccine preventable mortality in that country (CDC 2010). The epidemiological behaviour of human influenza clearly defines it as an emerging infectious disease and the recent understanding of its zoonotic origins has contributed much to the understanding of its behaviour in humans (Fauci 2006).

Introduction of inactivated polio vaccine (IPV) into the routine immunization schedule of South Africa.

South Africa is currently the only country on the African continent using inactivated polio vaccine (IPV) for routine immunization in a sequential schedule in combination with oral polio vaccine (OPV). IPV is a component of an injectable pentavalent vaccine introduced nationwide in April 2009 and administered according to EPI schedule at 6, 10 and 14 weeks with a booster dose at 18 months. OPV is administered at birth and together with the first IPV dose at 6 weeks, which stimulates gut immune system producing a memory IgA response (OPV), followed by IPV to minimize the risk of vaccine associated paralytic polio (VAPP). OPV is also given to all children under 5 years of age as part of regular mass immunizations campaigns. The decision to incorporate IPV into the routine schedule was not based on cost-effectiveness, which it is not. Other factors were taken into account: Firstly, the sequence benefits from the initial mucosal contact with live(vaccine) virus which promotes the IgA response from subsequent IPV, as well as herd immunity from OPV, together with the safety of IPV. Secondly, given the widespread and increasing use of IPV in the developed world, public acceptance of vaccination in general is enhanced in South Africa which is classified as an upper middle income developing country. Thirdly, to address equity concerns because of the growing use of IPV in the private sector. Fourthly, the advent of combination vaccines facilitated the incorporation of IPV into the EPI schedule.

Epidemiologic and virologic assessment of the 2009 influenza A (H1N1) pandemic on selected temperate countries in the Southern Hemisphere: Argentina, Australia, Chile, New Zealand and South Africa.

UNLABELLED: INTRODUCTION AND SETTING: Our analysis compares the most comprehensive epidemiologic and virologic surveillance data compiled to date for laboratory-confirmed H1N1pdm patients between 1 April 2009 - 31 January 2010 from five temperate countries in the Southern Hemisphere-Argentina, Australia, Chile, New Zealand, and South Africa. OBJECTIVE: We evaluate transmission dynamics, indicators of severity, and describe the co-circulation of H1N1pdm with seasonal influenza viruses. RESULTS: In the five countries, H1N1pdm became the predominant influenza strain within weeks of initial detection. South Africa was unique, first experiencing a seasonal H3N2 wave, followed by a distinct H1N1pdm wave. Compared with the 2007 and 2008 influenza seasons, the peak of influenza-like illness (ILI) activity in four of the five countries was 3-6 times higher with peak ILI consultation rates ranging from 35/1,000 consultations/week in Australia to 275/100,000 population/week in New Zealand. Transmission was similar in all countries with the reproductive rate ranging from 1.2-1.6. The median age of patients in all countries increased with increasing severity of disease, 4-14% of all hospitalized cases required critical care, and 26-68% of fatal patients were reported to have ≥1 chronic medical condition. Compared with seasonal influenza, there was a notable downward shift in age among severe cases with the highest population-based hospitalization rates among children <5 years old. National population-based mortality rates ranged from 0.8-1.5/100,000. CONCLUSIONS: The difficulty experienced in tracking the progress of the pandemic globally, estimating its severity early on, and comparing information across countries argues for improved routine surveillance and standardization of investigative approaches and data reporting methods.