Alex Gasasira

Molecular Evidence of Sexual Transmission of Ebola Virus

A suspected case of sexual transmission from a male survivor of Ebola virus disease (EVD) to his female partner (the patient in this report) occurred in Liberia in March 2015. Ebola virus (EBOV) genomes assembled from blood samples from the patient and a semen sample from the survivor were consistent with direct transmission. The genomes shared three substitutions that were absent from all other Western African EBOV sequences and that were distinct from the last documented transmission chain in Liberia before this case. Combined with epidemiologic data, the genomic analysis provides evidence of sexual transmission of EBOV and evidence of the persistence of infective EBOV in semen for 179 days or more after the onset of EVD. (Funded by the Defense Threat Reduction Agency and others.).

Implications of a Circulating Vaccine-Derived Poliovirus in Nigeria

BACKGROUND The largest recorded outbreak of a circulating vaccine-derived poliovirus (cVDPV), detected in Nigeria, provides a unique opportunity to analyze the pathogenicity of the virus, the clinical severity of the disease, and the effectiveness of control measures for cVDPVs as compared with wild-type poliovirus (WPV). METHODS We identified cases of acute flaccid paralysis associated with fecal excretion of type 2 cVDPV, type 1 WPV, or type 3 WPV reported in Nigeria through routine surveillance from January 1, 2005, through June 30, 2009. The clinical characteristics of these cases, the clinical attack rates for each virus, and the effectiveness of oral polio vaccines in preventing paralysis from each virus were compared. RESULTS No significant differences were found in the clinical severity of paralysis among the 278 cases of type 2 cVDPV, the 2323 cases of type 1 WPV, and the 1059 cases of type 3 WPV. The estimated average annual clinical attack rates of type 1 WPV, type 2 cVDPV, and type 3 WPV per 100,000 susceptible children under 5 years of age were 6.8 (95% confidence interval [CI], 5.9 to 7.7), 2.7 (95% CI, 1.9 to 3.6), and 4.0 (95% CI, 3.4 to 4.7), respectively. The estimated effectiveness of trivalent oral polio vaccine against paralysis from type 2 cVDPV was 38% (95% CI, 15 to 54%) per dose, which was substantially higher than that against paralysis from type 1 WPV (13%; 95% CI, 8 to 18%), or type 3 WPV (20%; 95% CI, 12 to 26%). The more frequent use of serotype 1 and serotype 3 monovalent oral polio vaccines has resulted in improvements in vaccine-induced population immunity against these serotypes and in declines in immunity to type 2 cVDPV. CONCLUSIONS The attack rate and severity of disease associated with the recent cVDPV identified in Nigeria are similar to those associated with WPV. International planning for the management of the risk of WPV, both before and after eradication, must include scenarios in which equally virulent and pathogenic cVDPVs could emerge.

Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in Northern Nigeria

ABSTRACT Since 2005, a large poliomyelitis outbreak associated with type 2 circulating vaccine-derived poliovirus (cVDPV2) has occurred in northern Nigeria, where immunization coverage with trivalent oral poliovirus vaccine (tOPV) has been low. Phylogenetic analysis of P1/capsid region sequences of isolates from each of the 403 cases reported in 2005 to 2011 resolved the outbreak into 23 independent type 2 vaccine-derived poliovirus (VDPV2) emergences, at least 7 of which established circulating lineage groups. Virus from one emergence (lineage group 2005-8; 361 isolates) was estimated to have circulated for over 6 years. The population of the major cVDPV2 lineage group expanded rapidly in early 2009, fell sharply after two tOPV rounds in mid-2009, and gradually expanded again through 2011. The two major determinants of attenuation of the Sabin 2 oral poliovirus vaccine strain (A481 in the 5′-untranslated region [5′-UTR] and VP1-Ile143) had been replaced in all VDPV2 isolates; most A481 5′-UTR replacements occurred by recombination with other enteroviruses. cVDPV2 isolates representing different lineage groups had biological properties indistinguishable from those of wild polioviruses, including efficient growth in neuron-derived HEK293 cells, the capacity to cause paralytic disease in both humans and PVR-Tg21 transgenic mice, loss of the temperature-sensitive phenotype, and the capacity for sustained person-to-person transmission. We estimate from the poliomyelitis case count and the paralytic case-to-infection ratio for type 2 wild poliovirus infections that ∼700,000 cVDPV2 infections have occurred during the outbreak. The detection of multiple concurrent cVDPV2 outbreaks in northern Nigeria highlights the risks of cVDPV emergence accompanying tOPV use at low rates of coverage in developing countries.

Outbreak of Type 2 Vaccine-Derived Poliovirus in Nigeria: Emergence and Widespread Circulation in an Underimmunized Population

Wild poliovirus has remained endemic in northern Nigeria because of low coverage achieved in the routine immunization program and in supplementary immunization activities (SIAs). An outbreak of infection involving 315 cases of type 2 circulating vaccine-derived poliovirus (cVDPV2; >1% divergent from Sabin 2) occurred during July 2005–June 2010, a period when 23 of 34 SIAs used monovalent or bivalent oral poliovirus vaccine (OPV) lacking Sabin 2. In addition, 21 “pre-VDPV2” (0.5%–1.0% divergent) cases occurred during this period. Both cVDPV and pre-VDPV cases were clinically indistinguishable from cases due to wild poliovirus. The monthly incidence of cases increased sharply in early 2009, as more children aged without trivalent OPV SIAs. Cumulative state incidence of pre-VDPV2/cVDPV2 was correlated with low childhood immunization against poliovirus type 2 assessed by various means. Strengthened routine immunization programs in countries with suboptimal coverage and balanced use of OPV formulations in SIAs are necessary to minimize risks of VDPV emergence and circulation.

Using immunization delivery strategies to accelerate progress in Africa towards achieving the Millennium Development Goals

Integration of health services brings together common functions within and between organizations to solve common problems, developing a commitment to a shared vision and goals, and using common technologies and resources to achieve these goals. Integration has been the frustrated rally call of Primary Health Care for 30 years. This paper discusses the process of integrating child survival strategies and other heath services with immunization in Africa. Immunization is arguably the most successful health programme throughout the continent, making it the logical vehicle for add-on services. Strong health systems are the best way of delivering cost-effective child survival interventions in a most sustainable manner. But the reality in many African countries is that health systems have been weak for a number of reasons. Joining additional cost-effective child survival interventions on to immunization services may provide the needed boost. The unacceptably high childhood mortality in parts of Africa makes it the ideal location to undertake this exercise. The urgency to scale-up child survival interventions that have proven cost-effective is especially important if the Millennium Development Goals (MDGs) are to be met by 2015. Africa has more to loose than most in failing to scale up to meet these goals, bearing as it does the highest burden of childhood mortality in the world. But so far, prospects do not look good for achieving MDG-4 for the countries with the highest mortality rates. The timeliness of this initiative towards integration could not be better. In the last five years, countries in Africa have received massive injections of financial resources for polio eradication and measles control as well as additional funding for a range of immunization-strengthening activities and the introduction of new and under-utilized vaccines. While the data to support integration are limited, the information to hand suggests the effectiveness of the strategy. Where immunization performance is strong, immunization contacts may be excellent vehicles for additional interventions such as de-worming or Integrated Management of Childhood Illness (IMCI). But where an immunization service is struggling, adding another child survival intervention on to immunization might be the straw that breaks its back. Health managers have a wide range of options for adding on to immunization services, but the best choice will depend very much on local situations.

Effectiveness of Immunization against Paralytic Poliomyelitis in Nigeria

BACKGROUND The number of cases of paralytic poliomyelitis has declined in Nigeria since the introduction of newly licensed monovalent oral poliovirus vaccines and new techniques of vaccine delivery. Understanding the relative contribution of these vaccines and the improved coverage to the decline in incident cases is essential for future planning. METHODS We estimated the field efficacies of monovalent type 1 oral poliovirus vaccine and trivalent oral poliovirus vaccine, using the reported number of doses received by people with poliomyelitis and by matched controls as identified in Nigerias national surveillance database, in which 27,379 cases of acute flaccid paralysis were recorded between 2001 and 2007. Our estimates of vaccine coverage and vaccine-induced immunity were based on the number of doses received by children listed in the database who had paralysis that was not caused by poliovirus. RESULTS The estimated efficacies per dose of monovalent type 1 oral poliovirus vaccine and trivalent oral poliovirus vaccine against type 1 paralytic poliomyelitis were 67% (95% confidence interval [CI], 39 to 82) and 16% (95% CI, 10 to 21), respectively, and the estimated efficacy per dose of trivalent oral poliovirus vaccine against type 3 paralytic poliomyelitis was 18% (95% CI, 9 to 26). In the northwestern region of Nigeria, which reported the majority of cases during the study period, coverage with at least one dose of vaccine increased from 59 to 78%. Between 2005 and 2007, vaccine-induced immunity levels among children under the age of 5 years more than doubled, to 56%. CONCLUSIONS The higher efficacy of monovalent type 1 oral poliovirus vaccine (four times as effective as trivalent oral poliovirus vaccine) and the moderate gains in coverage dramatically increased vaccine-induced immunity against serotype 1 in northern Nigeria. Further increases in coverage in Nigerian states with infected populations are required to achieve the levels of vaccine-induced immunity associated with the sustained elimination achieved in other parts of the country.

Reduced evolutionary rate in reemerged Ebola virus transmission chains.

Surveillance of Ebola virus disease flare-ups uncovers a reduced rate of Ebola virus evolution during persistent infections. On 29 June 2015, Liberia’s respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak (“flare-up”) of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over.

Key issues in the persistence of poliomyelitis in Nigeria: a case-control study.

BACKGROUND The completion of poliomyelitis eradication is a global emergency for public health. In 2012, more than 50% of the worlds cases occurred in Nigeria following an unanticipated surge in incidence. We aimed to quantitatively analyse the key factors sustaining transmission of poliomyelitis in Nigeria and to calculate clinical efficacy estimates for the oral poliovirus vaccines (OPV) currently in use. METHODS We used acute flaccid paralysis (AFP) surveillance data from Nigeria collected between January, 2001, and December, 2012, to estimate the clinical efficacies of all four OPVs in use and combined this with vaccination coverage to estimate the effect of the introduction of monovalent and bivalent OPV on vaccine-induced serotype-specific population immunity. Vaccine efficacy was determined using a case-control study with CIs based on bootstrap resampling. Vaccine efficacy was also estimated separately for north and south Nigeria, by age of the children, and by year. Detailed 60-day follow-up data were collected from children with confirmed poliomyelitis and were used to assess correlates of vaccine status. We also quantitatively assessed the epidemiology of poliomyelitis and programme performance and considered the reasons for the high vaccine refusal rate along with risk factors for a given local government area reporting a case. FINDINGS Against serotype 1, both monovalent OPV (median 32.1%, 95% CI 26.1-38.1) and bivalent OPV (29.5%, 20.1-38.4) had higher clinical efficacy than trivalent OPV (19.4%, 16.1-22.8). Corresponding data for serotype 3 were 43.2% (23.1-61.1) and 23.8% (5.3-44.9) compared with 18.0% (14.1-22.1). Combined with increases in coverage, this factor has boosted population immunity in children younger than age 36 months to a record high (64-69% against serotypes 1 and 3). Vaccine efficacy in northern states was estimated to be significantly lower than in southern states (p≤0.05). The proportion of cases refusing vaccination decreased from 37-72% in 2008 to 21-51% in 2012 for routine and supplementary immunisation, and most caregivers cited ignorance of either vaccine importance or availability as the main reason for missing routine vaccinations (32.1% and 29.6% of cases, respectively). Multiple regression analyses highlighted associations between the age of the mother, availability of OPV at health facilities, and the primary source of health information and the probability of receiving OPV (all p<0.05). INTERPRETATION Although high refusal rates, low OPV campaign awareness, and heterogeneous population immunity continued to support poliomyelitis transmission in Nigeria at the end of 2012, overall population immunity had improved due to new OPV formulations and improvements in programme delivery. FUNDING Bill & Melinda Gates Foundation Vaccine Modeling Initiative, Royal Society.

Measles Resurgence Following a Nationwide Measles Vaccination Campaign in Nigeria, 2005–2008

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

Ebola and Its Control in Liberia, 2014–2015

Several factors explain the successful response to the outbreak in this country.