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1.  A Statistical Model of the International Spread of Wild Poliovirus in Africa Used to Predict and Prevent Outbreaks 
PLoS Medicine  2011;8(10):e1001109.
Using outbreak data from 2003–2010, Kathleen O'Reilly and colleagues develop a statistical model of the spread of wild polioviruses in Africa that can predict polio outbreaks six months in advance.
Outbreaks of poliomyelitis in African countries that were previously free of wild-type poliovirus cost the Global Polio Eradication Initiative US$850 million during 2003–2009, and have limited the ability of the program to focus on endemic countries. A quantitative understanding of the factors that predict the distribution and timing of outbreaks will enable their prevention and facilitate the completion of global eradication.
Methods and Findings
Children with poliomyelitis in Africa from 1 January 2003 to 31 December 2010 were identified through routine surveillance of cases of acute flaccid paralysis, and separate outbreaks associated with importation of wild-type poliovirus were defined using the genetic relatedness of these viruses in the VP1/2A region. Potential explanatory variables were examined for their association with the number, size, and duration of poliomyelitis outbreaks in 6-mo periods using multivariable regression analysis. The predictive ability of 6-mo-ahead forecasts of poliomyelitis outbreaks in each country based on the regression model was assessed. A total of 142 genetically distinct outbreaks of poliomyelitis were recorded in 25 African countries, resulting in 1–228 cases (median of two cases). The estimated number of people arriving from infected countries and <5-y childhood mortality were independently associated with the number of outbreaks. Immunisation coverage based on the reported vaccination history of children with non-polio acute flaccid paralysis was associated with the duration and size of each outbreak, as well as the number of outbreaks. Six-month-ahead forecasts of the number of outbreaks in a country or region changed over time and had a predictive ability of 82%.
Outbreaks of poliomyelitis resulted primarily from continued transmission in Nigeria and the poor immunisation status of populations in neighbouring countries. From 1 January 2010 to 30 June 2011, reduced transmission in Nigeria and increased incidence in reinfected countries in west and central Africa have changed the geographical risk of polio outbreaks, and will require careful immunisation planning to limit onward spread.
Please see later in the article for the Editors' Summary
Editors' Summary
During the first half of the 20th century, polio (poliomyelitis) was one of the most feared infectious diseases in industrialized countries, paralyzing thousands of young children every year. The virus that causes polio enters the human body through ingestion of contaminated water or food, multiplies in the gut, and is shed through the feces (stool) into the environment, where it spreads rapidly if sanitation or personal hygiene is poor. Most people infected with poliovirus have no symptoms, but about one in 200 infected people develop paralytic polio, in which poliovirus invades and destroys the nerve cells that control the arm and leg muscles, leading to acute flaccid paralysis (AFP; limb paralysis). In the worst cases, poliovirus paralyzes the muscles involved in breathing, which can be fatal unless patients are helped to breathe with an “iron lung” or ventilator. There is no cure for paralytic polio, and although AFP usually lasts less than two weeks, some patients never regain full use of their limbs.
Why Was This Study Done?
From 1955 onwards, routine polio vaccination rapidly reduced or eliminated wild polio (polio occurring through natural infection) in developed countries, but the disease remained common in developing countries. Consequently, in 1988, the Global Polio Eradication Initiative was launched. Between 1988 and 2009, routine vaccination and supplementary immunization activities (additional doses of polio vaccine given to all young children on national immunization days) reduced the annual number of children paralyzed by polio from 350,000 to about 1,600 and the number of countries where polio is endemic (always present) from 125 to four. Unfortunately, continued circulation of wild polioviruses in Nigeria and India resulted in reinfection of 19 African countries in 2009 and re-establishment of polio transmission in four countries. A better understanding of the factors that affect the distribution and timing of wild polio outbreaks might help experts prevent such outbreaks and could facilitate global polio eradication. Here, the researchers develop a statistical model of the spread of wild polioviruses in Africa and assess its ability to predict polio outbreaks in individual African countries.
What Did the Researchers Do and Find?
The researchers used routine AFP surveillance to identify children who developed polio in Africa between 2003 and 2010. They determined whether each case was associated with the importation of wild poliovirus based on genetic analysis the polioviruses and then used “multivariable regression analysis” to identify factors associated with the number, size, and duration of polio outbreaks. During the study period, 142 genetically distinct polio outbreaks (involving one to 228 cases) were recorded in 25 African countries, with the average number of outbreaks in each country declining with reduced population movements from each infected country. The estimated number of people migrating into a country from an infected country was associated with the number of outbreaks in that country. Thus, countries with a high rate of immigration from Nigeria and other countries where polio is still endemic had more polio outbreaks than countries with less immigration from these countries. A country's mortality rate for children under 5 years of age (an indicator of sanitary conditions and access to health care) was also associated with the number of outbreaks, and immunization coverage was associated with the size, duration, and number of outbreaks. Finally, in 82% of instances, for a randomly selected country where an outbreak was observed, the statistical model predicted six months ahead of time more outbreaks for that country than for any randomly selected country where there were no outbreaks. That is, the model's predictive ability was 82%.
What Do These Findings Mean?
These findings indicate that outbreaks of polio in Africa over the study period resulted mainly from continued transmission in Nigeria and other countries that reported polio cases and from poor immunization status. They also highlight how the geographical risk of polio is changing over time in Africa. Importantly, the risk factors included by the researchers in their statistical model are sufficient to describe the scale and geographical distribution of polio outbreaks in Africa six months in advance with a high predictive ability. Although the accuracy of the predictions made by the model is limited by the structure of the model and by the data fed into it, the information provided by this and other predictive models should help the Global Polio Eradication Initiative plan its future immunization and surveillance campaigns and should facilitate the elimination of polio from Africa.
Additional Information
Please access these websites via the online version of this summary at
The Global Polio Eradication Initiative provides information about polio and about global efforts to eradicate the disease; its website includes links to videos about global polio elimination efforts
The World Health Organization provides information about polio and attempts to eradicate the disease (in several languages)
The US Centers for Disease Control and Prevention provides information about polio vaccination
The UK National Health Service Choices website has information on polio
MedlinePlus provides links to more resources on polio (in English and Spanish)
Personal stories about polio are available through the British Polio Fellowship Heritage Project; the National Museum of American History Whatever happened to polio? website includes an archive of polio-related pictures
PMCID: PMC3196484  PMID: 22028632
2.  Support for children identified with acute flaccid paralysis under the global polio eradication programme in Uttar Pradesh, India: a qualitative study 
BMC Public Health  2012;12:229.
Cases of polio in India declined after the implementation of the polio eradication programme especially in these recent years. The programme includes surveillance of acute flaccid paralysis (AFP) to detect and diagnose cases of polio at early stage. Under this surveillance, over 40,000 cases of AFP are reported annually since 2007 regardless of the number of actual polio cases. Yet, not much is known about these children. We conducted a qualitative research to explore care and support for children with AFP after their diagnosis.
The research was conducted in a district of western Uttar Pradesh classified as high-risk area for polio. In-depth interviews with parents of children with polio (17), with non-polio AFP (9), healthcare providers (40), and key informants from community including international and government officers, religious leaders, community leaders, journalists, and academics (21) were performed.
Minimal medicine and attention were provided at government hospitals. Therefore, most parents preferred private-practice doctors for their children with AFP. Many were visited at homes to have stool samples collected by authorities. Some were visited repetitively following the sample collection, but had difficulty in understanding the reasons for these visits that pertained no treatment. Financial burden was a common concern among all families. Many parents expressed resentment for their children's disease, notably have been affected despite receiving multiple doses of polio vaccine. Both parents and healthcare providers lacked information and knowledge, furthermore poverty minimised the access to available healthcare services. Medicines, education, and transportation means were identified as foremost needs for children with AFP and residual paralysis.
Despite the high number of children diagnosed with AFP as part of the global polio eradication programme, we found they were not provided with sufficient medical support following their diagnosis. Improvement in the quality and sufficiency of the healthcare system together with integration of AFP surveillance with other services in these underprivileged areas may serve as a key solution.
PMCID: PMC3331818  PMID: 22439606
Acute flaccid paralysis; AFP Surveillance; Healthcare; India; Poliomyelitis; Pulse Polio Programme; Residual paralysis
3.  Surveillance of acute flaccid paralysis in Akwa Ibom State, Nigeria 2004–2009 
The last case of wild polio virus transmission occurred in Akwa Ibom state in October 2001; however, combination high routine immunization coverage with OPV, high quality AFP surveillance, mass immunization campaign in which two doses of potent oral polio vaccine is administered to eligible children and mop-up campaigns in areas with identified immunization or surveillance gaps has help the state in maintaining a free polio status for over ten years. This study was carried out to describe the characteristics of reported acute flaccid paralysis cases between 2004 and 2009, and to evaluate the performance of the acute flaccid paralysis surveillance system using indicators recommended by the World Health Organization.
A retrospective study was conducted among children, 0-15 years, by the World Health Organization (WHO) and Epidemiology unit of State Ministry of Health (SMOH), Uyo. The demographic characteristics and the results of isolation and identification of polio and other enteroviruses in stool samples sent to the WHO Polio Laboratory Ibadan for cases was analyzed.
A total of 521 cases of AFP (270 males and 251 females) aged 0 month to=15 years were reported by the surveillance system between 2004 and 2009. Those below 5 years of age accounted for 82.5% of cases reported and investigated. Of the 521 cases investigated 512 (98.3%) received at least three doses of oral polio vaccine, while 9(1.7) never received any oral polio vaccine (zero-dose). In all 5.1% of the isolates were Sabin, 7.9% non polio enterovirus (NPEV) and 2.3% were classified by national expert committee as compatible with poliomyelitis. There was consistent and steady increase in three critical indicators; Non polio AFP rate in children <15 years from 4.5 to 6.4 per 100 000 population, proportion of AFP cases with 2 stool specimens collected within 14 days of onset of paralysis from 57% in 2005 to 91% in 2009 and proportion of Local Government Areas (Districts) meeting both core indicators from 23% in 2005 to 87% in 2009. The highest numbers of cases were seen in the months of March, May and September.
This study showed high levels of surveillance performance with some challenges in reverse the cold chain system, the continuation and sustained AFP case detection, prompt investigation and response, improvement in the reserve cold chain system would achieve optimal standards recommended by WHO and might provide a good model for the eradication of poliomyelitis.
PMCID: PMC3215554  PMID: 22145065
Acute flaccid paralysis; Surveillance; Poliomyelitis; Nigeria
4.  Acute Flaccid Paralysis and Its Differential Diagnosis in in Kurdistan Province, Western Iran; an 11-Year Surveillance 
Iranian Journal of Pediatrics  2014;24(2):131-139.
The surveillance of acute flaccid paralysis (AFP) is a key strategy for monitoring the progress of poliomyelitis eradication and is a sensitive measure for detecting potential cases of poliomyelitis and poliovirus infection. This study was conducted to describe the characteristics of patients reported with AFP, and to evaluate the performance of the surveillance system in Kurdistan province, western Iran, using indicators recommended by the World Health Organization (WHO).
This observational study was conducted from January 2000 to December 2010 at the Kurdistan Center for Disease Control and the Department of Pediatrics. All children who fulfilled the WHO definition for AFP were included in our study. The stool samples of all the children were sent for poliovirus isolation. All the patients were evaluated for 60 days after the onset of symptoms to identify the signs of residual weakness.
One-hundred thirty nine children aged <15 years were reported to the Center for Diseases Control with AFP. In 138 (99%) stool samples no poliovirus was isolated. None of the patients was diagnosed as having acute poliomyelitis or polio-compatible paralysis. Guillain-Barré syndrome was the most frequent final diagnosis (79 cases) followed by Transverse Myelitis (7 cases) and Encephalitis (6 cases). By detecting 1.3 to 3.6 (mean 3.2) AFP cases per 100 000 population in Kurdistan during the study period, we achieved the WHO target for AFP surveillance. All performance indicators but one consistently met the WHO requirements and therefore demonstrated the effectiveness of the AFP surveillance program in Kurdistan.
The effective surveillance system in Kurdistan and its evaluation may serve as a model for the surveillance of other infectious diseases.
PMCID: PMC4268831  PMID: 25535530
Poliomyelitis; Paralysis; Surveillance; Epidemiology; Acute Flaccid Paralysis
5.  Evaluation of AFP surveillance indicators in polio-free Ghana, 2009–2013 
BMC Public Health  2014;14:687.
Ghana recorded the last case of indigenous wild poliovirus in 1999 but suffered two more outbreaks in 2003 and 2008. Following the World Health Organization (WHO) guidelines, transmission was interrupted through high routine immunisation coverage with live-attenuated oral polio vaccine (OPV), effective acute flaccid paralysis (AFP) surveillance and supplementary immunisation activities (SIA). This article describes the results of a five-year surveillance of AFP in polio-free Ghana, evaluate the surveillance indicators and identify areas that need improvement.
We investigated 1345 cases of AFP from children aged less than 15 years reported to the Disease Surveillance Department from January 2009 to December 2013. Data on demographic characteristics, vaccination history, clinical presentation and virological investigation on stool specimens collected during investigation were analysed.
Of the specimens analysed, 56% were from males and 76.3% were from children less than 5 years of age. Twenty-four percent of the children received up to 3 doses of OPV, 57% received at least 4 doses while the status of 19% was unknown. Core AFP surveillance indicators were partly met for non-polio AFP rate while the WHO target for stool adequacy and timeliness was exceeded over the period of study. All the cases were classified virologically, however no wild polio was found. Sixty-day follow-up was conducted for 56.3% of cases and 8.6% cases classified as compactible with polio.
Both laboratory and epidemiological surveillance for AFP were efficient and many WHO targets were met. However, due to the risk of poliovirus importation prior to global eradication, longterm surveillance is required to provide a high degree of confidence in prevention of poliovirus infection in Ghana. Thus, efforts should be made to strengthen regional performance and to follow–up on all AFP cases in order to establish proper diagnoses for the causes of the AFP leading to proper care.
PMCID: PMC4094438  PMID: 24996415
Surveillance; Indicators; AFP; Regional Reference Polio Laboratory; Ghana
6.  An epidemiological analysis of acute flaccid paralysis and its surveillance system in Iraq, 1997-2011 
BMC Infectious Diseases  2014;14:448.
Acute flaccid paralysis surveillance (AFP) is an essential strategy of the WHO’s Polio Eradication Initiative. This is the first study conducted to estimate the incidence, etiology, distribution, and surveillance performance of AFP in Iraq.
Surveillance data about the AFP cases under the age of 15 years reported from Iraq during January 1997 to December 2011 were depended in the current study.
A total of 4974 cases of AFP were reported from Iraq during the study period, with an annual incidence of 2.5/100,000 population. Guillain-Barré syndrome represented more than half of the reported cases (N = 2611, 52.5%), followed by traumatic neuritis (N = 715, 14.4%), and other CNS infections (N = 292, 5.9%). Poliomyelitis accounted for 166 (3.3%) of cases, the last reported case being in January 2000. Surveillance performance showed that all, but two, indicators were below the required WHO recommended levels.
AFP surveillance remains the gold standard method for poliomyelitis detection. It witnessed dramatic changes over the last two decades. This has raised people’s and clinicians’ awareness to the importance of promptness in notifying suspected cases and timely transportation of stool specimens to the National Poliovirus Laboratory in Baghdad, or alternatively having more than one laboratory for poliovirus detection in the country, all of which are very useful measures to increase the surveillance performance in the country.
PMCID: PMC4159501  PMID: 25141887
7.  Reasons and circumstances for the late notification of Acute Flaccid Paralysis (AFP) cases in health facilities in Luanda 
As the polio eradication effort enters the end game stage, surveillance for Acute Flaccid Paralysis in children becomes a pivotal tool. Thus given the gaps in AFP surveillance as identified in the cases of late notification, this study was designed to explore the reasons and circumstances responsible for late notification of AFP and collection of inadequate stools (more than 14 days of onset of paralysis until collection of the 2nd stool specimen) of AFP cases in health facilities equipped to manage AFP cases.
Eleven AFP cases with inadequate stools were reported from January 2 to July 8, 2012 - Epidemiological Weeks 1-27. The families of these cases were interviewed with an in-depth interview guide. The staff of the seven health units, where they later reported, was also enlisted for the study which used in-depth interview guide in eliciting information from them.
Ignorance and wrong perception of the etiology of the cases as well as dissatisfaction with the health units as the major reasons for late reporting of AFP cases. The first port of call is usually alternative health care system such as traditional healers and spiritualists because the people hold the belief that the problem is spiritually induced. The few, who make it to health units, are faced with ill equipped rural health workers who wait for the arrival of more qualified staff, who may take days to do so.
An understanding of the health seeking behavior of the population is germane to effective AFP surveillance. There is thus a need to tailor AFP surveillance to the health seeking behavior of the populations and expand it to community structures.
PMCID: PMC4242050  PMID: 25426197
Polio; acute flaccid paralysis; late notification; surveillance; Luanda; Angola
8.  Human Enteroviruses isolated during acute flaccid paralysis surveillance in Ghana: implications for the post eradication era 
Surveillance of acute flaccid surveillance (AFP) has been used world-wide to monitor the control and eradication of circulating wild polioviruses. The Polio Laboratory since its accreditation in 1996 has supported the Disease Surveillance Department for AFP surveillance. This study aims to isolate and characterize human enteroviruses from patients with AFP in Ghana.
Stool suspension was prepared from 308 samples received in 2009 from the surveillance activities throughout the country and inoculated on both RD and L20B cell lines. Isolates that showed growth on L20B were selected for real-time RT-PCR using degenerate and non-degenerate primers and probes. RD isolates were however characterized by microneutralisation technique with antisera pools from RIVM, The Netherlands and viruses that were untypable subjected to neutralization assay using antibodies specific for E71.
Of the 308 samples processed, 17 (5.5%) grew on both L20B and RD cells while 32 (10.4%) grew on RD only. All 28 isolates from L20B were characterized by rRT-PCR as Sabin-like polioviruses. No wild poliovirus or VDPV was found. However from the microneutralisation assay, six different enteroviruses were characterized. Among these, Coxsackie B viruses were most predominant followed by Echovirus. Three children from whom non-polio enteroviruses were isolated had residual paralysis while one child with VAPP found. The non-polio enteroviruses circulated throughout the country with the majority (20.7%) from Ashanti region.
This study showed the absence of wild or vaccine-derived poliovirus circulation in the country. However, the detection of three non-polio enteroviruses and one Sabin-like poliovirus with residual paralysis call for continuous surveillance even in the post polio eradication era.
PMCID: PMC3473960  PMID: 23077695
Poliovirus; non-polio enterovirus; surveillance; acute flaccid paralysis; Ghana
9.  Enhanced surveillance of acute flaccid paralysis following importation of wild poliovirus in Xinjiang Uygur Autonomous Region, China 
BMC Infectious Diseases  2014;14:113.
After being polio free for more than 10 years, an outbreak occurred in China in 2011 in Xinjiang Uygur Autonomous Region (Xinjiang) following the importation of wild poliovirus (WPV) originating from neighboring Pakistan.
To strengthen acute flaccid paralysis (AFP) surveillance in Xinjiang, “zero case daily reporting” and retrospective searching of AFP cases were initiated after the confirmation of the WPV outbreak. To pinpoint all the polio cases in time, AFP surveillance system was expanded to include persons of all ages in the entire population in Xinjiang.
Totally, 578 AFP cases were reported in 2011 in Xinjiang, including 21 WPV cases, 23 clinical compatible polio cases and 534 non-polio AFP cases. Of the 44 polio cases, 27 (61.4%) cases were reported among adults aged 15–53 years. Strengthening AFP surveillance resulted in an increase in the number of non-polio AFP cases in 2011 (148 children < 15 years) compared with 76 cases < 15 years in 2010. The AFP surveillance system in Xinjiang was sensitive enough to detect polio cases, with the AFP incidence of 3.28/100,000 among children < 15 years of age.
Incorporating adult cases into the AFP surveillance system is of potential value to understand the overall characteristics of the epidemic and to guide emergency responses, especially in countries facing WPV outbreak following long-term polio free status. The AFP surveillance system in Xinjiang was satisfactory despite limitations in biological sample collection.
PMCID: PMC3941572  PMID: 24576083
Acute flaccid paralysis; Wild poliovirus; Clinical compatible polio cases; China
10.  Evaluation of Acute Flaccid Paralysis in Hamadan, Iran from 2002 to 2009 
Epidemiology and Health  2011;33:e2011011.
To achieve a polio-free certification in Iran, a nationwide active surveillance program for acute flaccid paralysis (AFP) was set up following World Health Organization guidelines. This article describes the results of an eight-year surveillance of AFP in Hamadan, in the west of Iran.
A standard set of minimum core variables were collected. All cases of non-polio AFP in children aged <15 years old were reported. Two stool specimens were collected within 14 days of the onset of paralysis.
During the eight-year survey, 88 AFP cases aged <15 years old were reported. About 40% (35/88) of cases were aged ≤5 years, 56% (49/88) were boys, 19 (21.6%) had fever at the onset of paralysis, 74 (84.0%) had complete paralysis within four days of onset, and 22 (24.7%) had asymmetric paralysis. More than one AFP case was detected per 100,000 children aged <15 years old in all years. The risk of AFP in patients aged <5 years old was almost double that of older patients. Guillain-Barré Syndrome was the major leading cause of AFP (66/88). Adequate stool specimens were collected from 85% of AFP patients. All stool specimens were tested virologically, but no wild polioviruses were detected.
The active surveillance of non-polio AFP was efficient over the last eight years and exceeded 1.0 case per 100,000 children aged <15 years old. Nonetheless, there was a decreasing trend in the detection of AFP cases during the last two years and should be the focus of the policymakers' special attention, although AFP cases were still above the target level.
PMCID: PMC3221035  PMID: 22111031
Paralysis; Poliomyelitis; Population surveillance; Guillain-Barré syndrome; Iran
11.  An evaluation of the sensitivity of acute flaccid paralysis surveillance for poliovirus infection in Australia 
World Health Organization (WHO) targets for acute flaccid paralysis (AFP) surveillance, including the notification of a minimum rate of AFP among children, are used to assess the adequacy of AFP surveillance for the detection of poliovirus infection. Sensitive surveillance for poliovirus infection in both developed and developing countries is essential to support global disease eradication efforts. We applied recently developed methods for the quantitative evaluation of disease surveillance systems to evaluate the sensitivity of AFP surveillance for poliovirus infection in Australia.
A scenario tree model which accounted for administrative region, age, population immunity, the likelihood of AFP, and the probability of notification and stool sampling was used to assess the sensitivity of AFP surveillance for wild poliovirus infection among children aged less than 15 years in Australia. The analysis was based on historical surveillance data collected between 2000 and 2005. We used a surveillance time period of one month, and evaluated the ability of the surveillance system to detect poliovirus infection at a prevalence of 1 case per 100 000 persons and 1 case per million persons.
There was considerable variation in the sensitivity of AFP surveillance for poliovirus infection among Australian States and Territories. The estimated median sensitivity of AFP surveillance in Australia among children aged less than 15 years was 8.2% per month at a prevalence of 1 case per 100,000 population, and 0.9% per month at a prevalence of 1 case per million population. The probability that Australia is free from poliovirus infection given negative surveillance findings following 5 years of continuous surveillance was 96.9% at a prevalence of 1 case per 100,000 persons and 56.5% at a prevalence of 1 case per million persons.
Given the ongoing risk of poliovirus importation prior to global eradication, long term surveillance is required to provide a high degree of confidence in freedom from poliovirus infection in Australia, particularly if a low prevalence of infection is assumed. Adherence to the WHO surveillance targets would considerably improve the sensitivity of surveillance for poliovirus infection in Australia.
PMCID: PMC2761398  PMID: 19788763
12.  Surveillance of acute flaccid paralysis in the Marches region (Italy): 1997–2007 
The last case of poliomyelitis due to transmission of indigenous wild poliovirus occurred in Italy in 1982, however, it is important to guarantee a high quality surveillance as there is a risk of importation of cases from areas where polio is endemic. Stopping poliovirus transmission is pursued through a combination of high infant immunization coverage and surveillance for wild poliovirus through reporting and laboratory testing of all cases of acute flaccid paralysis (AFP) among children under fifteen years of age. The aim of this study was to describe and to evaluate 11 years of active surveillance in the Marches (Italy) in terms of: incidence, aetiology and clinical manifestation of AFP cases.
The active Acute Flaccid Paralysis surveillance has been carried out in the Marches region since February 1997 by the Chair of Hygiene which established a regional hospital network. Active surveillance involves 15 hospital centres.
In the considered period, 0–15 years population varied between 187,051 in 1997 to 201,625 in 2007, so the number of AFP expected cases is 2 per year. From February 1997 to October 2007, 27 cases were found with rates of 1.0/100,000 in 1997; 2.0/100,000 in 1998; 1.0/100,000 in 1999; 0.5/100,000 in 2000; 2.5/100,000 in 2001; 1.0/100,000 in 2002; 0 in 2003; 0.5/100,000 in 2004; 1.5/100,000 in 2005; 2.0/100,000 in 2006; 1.5/100,000 in 2007. In 29.6% of cases two stool samples were collected in 14 days from the symptoms onset. The 60-days follow-up is available for 23 out of 27 cases reported. In 44.5% of cases the definite diagnosis was Guillain Barrè syndrome.
In general, the surveillance activity is satisfactory even if in presence of some criticalities in biological samples collection. The continuation of surveillance, in addition to the maintenance of current levels of performance, will tend to a further and more detailed sensitization of all workers involved, in order to obtain spontaneous and prompt reporting, and to achieve the optimal standards recommended by the WHO both in the collection of biological samples and the availability of 60 days follow-up, with the goal of eradicating polio from all countries.
PMCID: PMC2576306  PMID: 18844987
13.  Non-Polio Enteroviruses from Acute Flaccid Paralysis Surveillance in Shandong Province, China, 1988–2013 
Scientific Reports  2014;4:6167.
Enteroviruses (EVs) are important human pathogens associated with various clinical syndromes. This study represents an overview of non-polio enteroviruses (NPEVs) isolated from acute flaccid paralysis (AFP) surveillance in Shandong Province, China from 1988 to 2013. Altogether 792 and 170 NPEV isolates were isolated from stool specimens of 9263 AFP cases and 1059 contacts, respectively. Complete VP1 sequencing and typing on all 962 isolates revealed 53 NPEV types in which echovirus (E) 6 (7.6%), E14 (7.6%), E11 (7.4%), coxsackievirus (CV) B3 (7.4%), E25 (5.6%), CVB5 (4.9%), E7 (4.5%) and EV-A71 (4.4%) were the eight most commonly reported serotypes. Distinct summer–fall seasonality was observed, with June–October accounting for 79.3% of isolation from AFP cases with known month of specimen collection. Increase of isolation of EV-A71 and CVA—the predominant pathogens for the hand, foot, and mouth disease—was observed in recent years. Sequence analysis on VP1 coding region of EV-A71 and E6 suggested Shandong strains had great genetic divergence with isolates from other countries. The results described in this study provide valuable information on the circulation and emergence of different EV types in the context of limited EV surveillance in China.
PMCID: PMC4141246  PMID: 25145609
14.  Worldwide Incidence of Malaria in 2009: Estimates, Time Trends, and a Critique of Methods 
PLoS Medicine  2011;8(12):e1001142.
Richard Cibulskis and colleagues present estimates of the worldwide incidence of malaria in 2009, together with a critique of different estimation methods, including those based on risk maps constructed from surveys of parasite prevalence, and those based on routine case reports compiled by health ministries.
Measuring progress towards Millennium Development Goal 6, including estimates of, and time trends in, the number of malaria cases, has relied on risk maps constructed from surveys of parasite prevalence, and on routine case reports compiled by health ministries. Here we present a critique of both methods, illustrated with national incidence estimates for 2009.
Methods and Findings
We compiled information on the number of cases reported by National Malaria Control Programs in 99 countries with ongoing malaria transmission. For 71 countries we estimated the total incidence of Plasmodium falciparum and P. vivax by adjusting the number of reported cases using data on reporting completeness, the proportion of suspects that are parasite-positive, the proportion of confirmed cases due to each Plasmodium species, and the extent to which patients use public sector health facilities. All four factors varied markedly among countries and regions. For 28 African countries with less reliable routine surveillance data, we estimated the number of cases from model-based methods that link measures of malaria transmission with case incidence. In 2009, 98% of cases were due to P. falciparum in Africa and 65% in other regions. There were an estimated 225 million malaria cases (5th–95th centiles, 146–316 million) worldwide, 176 (110–248) million in the African region, and 49 (36–68) million elsewhere. Our estimates are lower than other published figures, especially survey-based estimates for non-African countries.
Estimates of malaria incidence derived from routine surveillance data were typically lower than those derived from surveys of parasite prevalence. Carefully interpreted surveillance data can be used to monitor malaria trends in response to control efforts, and to highlight areas where malaria programs and health information systems need to be strengthened. As malaria incidence declines around the world, evaluation of control efforts will increasingly rely on robust systems of routine surveillance.
Please see later in the article for the Editors' Summary
Editors' Summary
Malaria is a life-threatening disease caused by the Plasmodium parasite, which is transmitted to people through the bites of infected mosquitoes. According to latest estimates from the World Health Organization (WHO), in 2009, there were 225 million cases of malaria and an estimated 781,000 deaths worldwide—most deaths occurring among children living in the WHO African Region (mainly sub-Saharan Africa). Knowing the burden of malaria in any country is an essential component of public health planning and accurately estimating the global burden is essential to monitor progress towards the United Nations' Millennium Development Goals.
Currently, there are generally two approaches used to estimate malaria incidence:
One method uses routine surveillance reports of malaria cases compiled by national health ministries, which are analyzed to take into account some deficincies in data collection, such as incomplete reporting by health facilities, the potential for overdiagnosis of malaria among patients with fever, and the use of private health facilities or none at all. The second method uses population-based surveys of Plasmodium prevalence and case incidence from selected locations in malaria endemic areas and then uses this information to generate risk maps and to estimate the case incidence of malaria per 1,000 population, for all of the world's malaria endemic regions. The Malaria Atlas Project—a database of malaria epidemiology based on medical intelligence and satellite-derived climate data—uses this second method.
Why Was This Study Done?
In order for malaria epidemiology to be as accurate as possible, an evaluation of the strengths and weaknesses of both methods is necessary. In this study, the researchers analyzed the merits of the estimates calculated by using the different approaches, to highlight areas in which both methods need to be improved to provide better assessments of malaria control.
What Did the Researchers Do and Find?
The researchers estimated the number of malaria cases in 2009, for each of the 99 countries with ongoing malaria transmission using a combination of the two methods. The researchers used the first method for 56 malaria endemic countries outside the WHO African Region, and for nine African countries which had the quality of data necessary to calculate estimates using the researchers statistical model—which the researchers devised to take the upper and lower limits of case detection into account. The researchers used the second method for 34 countries in the African Region to classify malaria risk into low-transmission and high-transmission categories, and then to derive incidence rates for populations from observational studies conducted in populations in which there were no malaria control activities. For both methods, the researchers conducted a statistical analysis to determine the range of uncertainty.
The researchers found that using a combination of methods there was a combined total of 225 million malaria cases, in the 99 countries malaria endemic countries—the majority of cases (78%) were in the WHO African region, followed by the Southeast Asian (15%) and Eastern Mediterranean regions. In Africa, there were 214 cases per 1,000 population, compared with 23 per 1,000 in the Eastern Mediterranean region, and 19 per 1,000 in the Southeast Asia region. Sixteen countries accounted for 80% of all estimated cases globally—all but two countries were in the African region. The researchers found that despite the differences between methods 1 and 2, the ratio of the upper and lower limit for country estimates was approximately the same.
What Do These Findings Mean?
Using the combined methods, the incidence of malaria was estimated to be lower than previous estimates, particularly outside of Africa. Nevertheless the methods suggest that malaria surveillance systems currently miss the majority of cases, detecting less than 10% of those estimated to occur globally. Although the best assessment of malaria burden and trends should rely on a combination of surveillance and survey data, accurate surveillance is the ultimate goal for malaria control programs, especially as routine surveillance has advantages for estimating case incidence, spatially and through time. However, as the researchers have identified in this study, strengthening surveillance requires a critical evaluation of inherent errors and these errors must be adequately addressed in order to have confidence in estimates of malaria burden and trends, and therefore, the return on investments for malaria control programs.
Additional Information
Please access these Web sites via the online version of this summary at
This study is further discussed in a PLoS Medicine Perspective by Ivo Mueller and colleagues
The WHO provides information on malaria and produces the World Malaria Report each year, summarizing global progress in malaria control
More information is available on The Malaria Atlas Project
PMCID: PMC3243721  PMID: 22205883
15.  Characterization of a Novel Enterovirus Serotype and an Enterovirus EV-B93 Isolated from Acute Flaccid Paralysis Patients 
PLoS ONE  2013;8(11):e80040.
Non-polio enteroviruses (NPEVs) are among the most common viruses infecting humans worldwide. Most of these infections are asymptomatic but few can lead to systemic and neurological disorders like Acute Flaccid Paralysis (AFP). Acute Flaccid Paralysis is a clinical syndrome and NPEVs have been isolated frequently from the patients suffering from AFP but little is known about their causal relationship. The objective of this study was to identify and characterize the NPEV serotypes recovered from 184 stool samples collected from AFP patients in Federally Administered Tribal Areas (FATA) in north-west of Pakistan. Overall, 44 (95.6 %) isolates were successfully typed through microneutralization assay as a member of enterovirus B species including echovirus (E)-2, E-3, E-4, E-6, E-7, E-11, E-13, E-14, E-21 and E-29 while two isolates (PAK NIH SP6545B and PAK NIH SP1202B) remained untypeable. The VP1 and capsid regions analysis characterized these viruses as EV-B93 and EV-B106. Phylogenetic analysis confirmed that PAK NIH isolates had high genetic diversity and represent distinct genotypes circulating in the country. Our findings highlight the role of NPEVs in AFP cases to be thoroughly investigated especially in high disease risk areas, with limited surveillance activities and health resources.
PMCID: PMC3820551  PMID: 24244603
16.  Clinical Assessment of Self-Reported Acute Flaccid Paralysis in a Population-Based Setting in Guatemala 
Historically, poliovirus infection has been an important cause of acute flaccid paralysis (AFP) worldwide; however, successful elimination of wild-type poliovirus in much of the world has highlighted the importance of other causes of AFP. Despite the evolving etiology, AFP surveillance in most developing countries still focuses on poliovirus detection and fails to detect many AFP cases, particularly among adults. We assessed 41 subjects self-reporting symptoms suggestive of AFP during a population-based health survey in the Department of Santa Rosa, Guatemala. Thirty-five (85%) of the suspected cases were not hospitalized. Most subjects (37) did not have features consistent with AFP or had other diagnoses explaining weakness. We identified two adults who had not received medical attention for a clinical illness consistent with Guillain-Barré syndrome, the most important cause of non-poliovirus AFP. Usual surveillance methods for AFP, particularly in developing countries, may underestimate the true burden of non-poliovirus AFP.
PMCID: PMC2844551  PMID: 20348524
17.  Acute flaccid paralysis surveillance: A 6 years study, Isfahan, Iran 
Poliomyelitis is still an endemic disease in many areas of the world including Africa and South Asia. Iran is polio free since 2001. However, due to endemicity of polio in neighboring countries of Iran, the risk of polio importation and re-emergence of wild polio virus is high. Case definition through surveillance system is a well-defined method for maintenance of polio eradication in polio free countries.
In a cross-sectional survey from 2007 to 2013, we reviewed all the records of under 15 years old patients reported to Acute Flaccid Paralysis Committee (AFPC) in Isfahan province, Iran. All cases were visited by members of the AFPC. Three stool samples were collected from each reported case within 2 weeks of onset of paralysis and sent to National Polio Laboratory in Tehran, Iran, for poliovirus isolation. Data were analyzed by SSPS software (version 22). Student's t-test and Chi-square was used to compare variables. Statistical significance level was set at P < 0.05.
In this 6-year period 85 cases were analyzed, 54 patients were male (63.5%) and 31 were female (36.5%). The mean age of patients was 5.7 ± 3.9 years. The most common cause of paralysis among these patients was Guillian–Barré syndrome (83.5%). We did not found any poliomyelitis caused by wild polio virus. Only one case of vaccine associated poliomyelitis was reported.
Since 1992, Iran has a routine and high percent coverage of polio vaccination program for infants (>94%), with six doses of oral polio vaccine (OPV). Accurate surveillance for poliomyelitis is essential for continuing eradication.
PMCID: PMC4434443  PMID: 26015925
Acute flaccid paralysis; poliomyelitis; surveillance
18.  Characterization of the Non-Polio Enterovirus Infections Associated with Acute Flaccid Paralysis in South-Western India 
PLoS ONE  2013;8(4):e61650.
Non-polio enteroviruses (NPEVs) have been reported frequently in association with acute flaccid paralysis (AFP) cases during Polio Surveillance Programs (PSPs) worldwide. However, there is limited understanding on the attributes of their infections. This study reports characteristics of NPEVs isolated from AFP cases, investigated during PSPs held in 2009–2010, in Karnataka and Kerala states of south-western India having varied climatic conditions. NPEV cell culture isolates derived from stool specimens that were collected from 422 of 2186 AFP cases (<1–14 years age) and 17 of 41 asymptomatic contacts; and details of all AFP cases/contacts were obtained from National Polio Laboratory, Bangalore. The distribution of NPEV infections among AFP cases and circulation pattern of NPEV strains were determined by statistical analysis of the data. Genotyping of all NPEV isolates was carried out by partial VP1 gene sequencing and phylogenetic analysis. NPEV positive AFP cases were significantly higher in children aged <2 years; with residual paralysis; in summer months; and in regions with relatively hot climate. Genotyping of NPEVs identified predominance of human enteroviruses (HEV)-B species [81.9%—Echoviruses (E): 57.3%; coxsackieviruses (CV) B: 15%; numbered EVs: 8.9%; CVA9: 0.7%] and low levels of HEV-A [14.5%—CVA: 6%; numbered EVs: 8.5%] and HEV-C [3.6%—CVA: 2.6%; numbered EVs: 1%] species, encompassing 63 genotypes. EV76 (6.3%) and each of E3, CVB3 and E9 (4.97%) were found frequently during 2009 while E11 (6.7%), CVB1 (6.1%), E7 (5.1%) and E20 (5.1%) were detected commonly in 2010. A marked proportion of AFP cases from children aged <2 years; presenting with fever; and from north and south interior parts of Karnataka state was detected with E/numbered EVs than that found with CVA/CVB. This study highlights the extensive genetic diversity and diverse circulation patterns of NPEV strains in AFP cases from different populations and climatic conditions.
PMCID: PMC3632520  PMID: 23630606
19.  An outbreak following importation of wild poliovirus in Xinjiang Uyghur Autonomous Region, China, 2011 
After more than 10 years without a case of wild poliovirus (WPV) in China, an outbreak occurred in 2011 in Xinjiang Uyghur Autonomous Region.
Acute flaccid paralysis (AFP) case surveillance was strengthened with epidemiological investigations and specimen collection and serological surveys were conducted among hospitalized patients.
There were 21 WPV cases and 23 clinical compatible polio cases reported. WPV was isolated from 14 contacts of AFP cases and 13 in the healthy population. Incidence of WPV and clinical compatible polio cases were both highest among children <1 years, however, 24/44 (54.5%) polio cases were reported among adults aged 15–39 years.
High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Expansion of AFP case surveillance and use of serologic surveys to estimate population immunity should be conducted rapidly to guide preparedness and response planning for future WPV outbreaks.
PMCID: PMC4336520  PMID: 25636581
Wild poliovirus; Importation; Acute flaccid paralysis; Supplementary immunization activities; Serological survey
20.  Viral Aetiology of Acute Flaccid Paralysis Surveillance Cases, before and after Vaccine Policy Change from Oral Polio Vaccine to Inactivated Polio Vaccine 
Journal of Tropical Medicine  2014;2014:814908.
Since 1992, surveillance for acute flaccid paralysis (AFP) cases was introduced in Malaysia along with the establishment of the National Poliovirus Laboratory at the Institute for Medical Research. In 2008, the Ministry of Health, Malaysia, approved a vaccine policy change from oral polio vaccine to inactivated polio vaccine (IPV). Eight states started using IPV in the Expanded Immunization Programme, followed by the remaining states in January 2010. The objective of this study was to determine the viral aetiology of AFP cases below 15 years of age, before and after vaccine policy change from oral polio vaccine to inactivated polio vaccine. One hundred and seventy-nine enteroviruses were isolated from the 3394 stool specimens investigated between 1992 and December 2012. Fifty-six out of 107 virus isolates were polioviruses and the remaining were non-polio enteroviruses. Since 2009 after the sequential introduction of IPV in the childhood immunization programme, no Sabin polioviruses were isolated from AFP cases. In 2012, the laboratory AFP surveillance was supplemented with environmental surveillance with sewage sampling. Thirteen Sabin polioviruses were also isolated from sewage in the same year, but no vaccine-derived poliovirus was detected during this period.
PMCID: PMC3977537  PMID: 24772175
21.  Epidemiology and Surveillance of Hepatocellular Carcinoma 
Liver Cancer  2012;1(1):2-14.
Hepatocellular carcinoma (HCC) is one of the most frequently occurring malignancies and has a high mortality rate. The incidence of HCC differs greatly according to the geographic area. East and Southeast Asia, as well as middle and West Africas have the highest prevalence of HCC. The risk factors for developing HCC are well known and include cirrhosis, hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, alcohol consumption, smoking, diabetes, and nonalcoholic steatohepatitis. Cirrhosis is the most significant risk factor, and there is a correlation between the degree of noninvasively measured liver fibrosis and the risk of HCC occurrence. HBV exerts carcinogenic effects by several mechanisms, including host genome integration, and studies have revealed that HBV replication predicts HCC development. HCV induces multistep carcinogenesis from inflammation, to fibrosis and liver cancer. HCC is an appropriate target for surveillance programs for early cancer detection. Currently, liver ultrasonography (US) combined with serum alpha-fetoprotein (AFP, a biomarker of HCC) measurement every 6 months is the standard method of HCC surveillance. Although US is the most widely used tool, its sensitivity in detecting early HCC (i.e., within the Milan criteria) during surveillance is only 63%. AFP is the representative biomarker for both HCC surveillance and diagnosis; however, the unsatisfactory performance of AFP as a surveillance tool means that a novel biomarker or combination with other serum markers is required. Des-gamma-carboxy prothrombin and AFP-L3 are candidate biomarkers that are complementary to AFP. The strategies of HCC surveillance vary in different countries according to the healthcare system, the resources available, and health insurance coverage. Many studies have shown that the rate of early cancer detection and rate of application of curative therapies were increased, as was the survival time, by HCC surveillance, which should now become a part of standard care, rather than just a recommendation. Improved US technology and the discovery of new biomarkers are necessary to make further progress in HCC surveillance.
PMCID: PMC3747543  PMID: 24159567
Biomarker; Epidemiology; Hepatocellular carcinoma; Surveillance; Ultrasound
22.  Development of a Poliovirus Neutralization Test with Poliovirus Pseudovirus for Measurement of Neutralizing Antibody Titer in Human Serum ▿ 
Clinical and Vaccine Immunology : CVI  2011;18(11):1889-1894.
In the Global Polio Eradication Initiative, laboratory diagnosis plays a critical role by isolating and identifying poliovirus (PV) from the stool samples from acute flaccid paralysis (AFP) cases. In recent years, reestablishment of PV circulation in countries where PV was previously eliminated has occurred because of decreased herd immunity, possibly due to poor vaccination coverage. To monitor the vulnerability of countries to PV circulation, surveillance of neutralizing-antibody titers against PV in susceptible populations is essential in the end game of the polio eradication program. In this study, we have developed a PV neutralization test with type 1, 2, and 3 PV pseudoviruses to determine the neutralizing-antibody titer against PV in human serum samples. With this test, the neutralizing-antibody titer against PV could be determined within 2 days by automated interpretation of luciferase signals without using infectious PV strains. We validated the pseudovirus PV neutralization test with 131 human serum samples collected from a wide range of age groups (ages 1 to >60 years) by comparison with a conventional neutralization test. We found good correlation in the neutralizing-antibody titers determined by these tests. These results suggest that a pseudovirus PV neutralization test would serve as a safe and simple procedure for the measurement of the neutralizing-antibody titer against PV.
PMCID: PMC3209023  PMID: 21880850
23.  Evaluation of the Acute Flacid Paralysis (AFP) Surveillance System in Bikita District Masvingo Province 2010 
BMC Research Notes  2014;7:252.
AFP is a rare syndrome and serves as a proxy for poliomyelitis. The main objective of AFP surveillance is to detect circulating wild polio virus and provide data for developing effective prevention and control strategies as well planning and decision making. Bikita district failed to detect a case for the past two years.
A total of 31 health workers from 14 health centres were interviewed. Health worker knowledge on AFP was low in Bikita. The system was acceptable, flexible, and representative but not stable and not sensitive since it missed1 AFP case. The system was not useful to the district since data collected was not locally used in anyway. The cost of running the system was high. The district had no adequate resources to run the system. Reasons for not reporting cases was that the mothers were not bringing children with AFP and ignorance of health workers on syndromes captured under AFP.
Health worker’s knowledge on AFP was low and all interviewed workers needed training surveillance. The system was found to be flexible but unacceptable. Reasons for failure to detect AFP cases could be, no cases reporting to the centres, lack of knowledge on health workers hence failure to recognise symptoms, high staff turnover.
PMCID: PMC4016670  PMID: 24742014
Acute flacid paralysis; Surveillance; Bikita
24.  Potential for the Australian and New Zealand paediatric intensive care registry to enhance acute flaccid paralysis surveillance in Australia: a data-linkage study 
BMC Infectious Diseases  2013;13:384.
Australia uses acute flaccid paralysis (AFP) surveillance to monitor its polio-free status. The World Health Organization criterion for a sensitive AFP surveillance system is the annual detection of at least one non-polio AFP case per 100,000 children aged less than 15 years, a target Australia has not consistently achieved. Children exhibiting AFP are likely to be hospitalised and may be admitted to an intensive care unit. This provides a potential opportunity for active AFP surveillance.
A data-linkage study for the period from 1 January 2005 to 31 December 2008 compared 165 non-polio AFP cases classified by the Polio Expert Panel with 880 acute neurological presentations potentially compatible with AFP documented in the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry.
Forty-two (25%) AFP cases classified by the Polio Expert Panel were matched to case records in the ANZPIC Registry. Of these, nineteen (45%) cases were classified as Guillain-Barré syndrome on both registries. Ten additional Guillain-Barré syndrome cases recorded in the ANZPIC Registry were not notified to the national AFP surveillance system.
The identification of a further ten AFP cases supports inclusion of intensive care units in national AFP surveillance, particularly specialist paediatric intensive care units, to identify AFP cases that may not otherwise be reported to the national surveillance system.
PMCID: PMC3765192  PMID: 23964831
Acute flaccid paralysis; Clinical surveillance; Poliovirus; Paediatric intensive care
25.  Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP 
AIM: To evaluate diagnostic value of α-fetoprotein (AFP)-L3 and prothrombin induced by vitamin K absence-II (PIVKA-II) in hepatocellular carcinoma (HCC).
METHODS: One hundred and sixty-eight patients during routine HCC surveillance were included in this study. Of the 168 patients, 90 (53.6%) had HCC including newly developed HCC (n = 82) or recurrent HCC after treatment (n = 8). Sera were obtained during their first evaluation for HCC development and at the time of HCC diagnosis before commencing HCC treatment. HCC was diagnosed by histological examination, appropriate imaging characteristics-computed tomography or magnetic resonance imaging. Control sera were collected from 78 patients with benign liver disease (BLD), which were obtained during routine surveillance with a suspicion of HCC. AFP, AFP-L3 and PIVKA-II were measured in the same serum by microchip capillary electrophoresis and liquid-phase binding assay on a micro-total analysis system Wako i30 auto analyzer. The performance characteristics of three tests and combined tests for the diagnosis of HCC were obtained using receiver operating characteristic curves in all populations and subgroups with AFP < 20 ng/mL.
RESULTS: Of 90 HCC patients, 38 (42.2%) patients had AFP < 20 ng/mL, 20 (22.2%) patients had AFP 20-200 ng/mL and 32 (35.6%) patients had AFP > 200 ng/mL. Of the 78 BLD patients, 74 (94.9%) patients had AFP < 20 ng/mL. After adjustment for age and HBV infection status, AFP-L3 levels were higher in HCC than in BLD among patients with low AFP levels (< 20 ng/mL) (P < 0.001). In a total of 168 patients, areas under the curve (AUC) for HCC were 0.879, 0.887, 0.801 and 0.939 for AFP, AFP-L3, PIVKA-II and the combined markers, respectively. The combined AUC for three markers showed higher value than the AUCs of individual marker (P < 0.05). AFP-L3 had higher AUC value than PIVKA-II for HCC detection in entire patients (P = 0.043). With combination of AFP-L3 (cut-off > 5%) and PIVKA-II (cut-off > 40 AU/L), the sensitivity were 94.4% and specificity were 75.6% in all patients. In 112 patients with low AFP levels (< 20 ng/mL), AUCs of AFP-L3, PIVKA-II and combine AFP-L3 and PIVKA-II tests were 0.824, 0.774 and 0.939, respectively. AFP-L3 with a cut-off value of 5% showed sensitivity of 71.1% and specificity of 83.8%, and PIVKA-II with a cut-off value of 40 AU/L had sensitivity of 57.9% and specificity of 95.9% in patients with low AFP levels. The combination of AFP-L3 and PIVKA-II increased the sensitivity and specificity up to 92.1% and 79.7%, respectively, in low AFP group. Combined markers detected 81.8% of early stage HCC (Union for International Cancer Control stage I), 86.7% of small sized tumor (< 2 cm) and 91.7% of single tumor of HCC in the low AFP group. In multivariate analysis, AFP-L3 was correlated with AFP and tumor size, and PIVKA-II was correlated with laboratory tests including serum aspartate aminotransferase, total bilirubin, platelets and albumin levels. PIVKA-II had no correlation with AFP, AFP-L3 or tumor characteristics.
CONCLUSION: Combined determination of AFP-L3 and PIVKA-II could improve the diagnostic value for HCC detection in patients with or without increased AFP levels.
PMCID: PMC3554817  PMID: 23372355
α-fetoprotein; Prothrombin induced by vitamin K absence-II; Hepatocellular carcinoma; Diagnosis; Tumor marker

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