EDUCATION: Poliomyelitis/ Dengue

(SEE BELOW FOR ARTICLE ON DENGUE)

POLIOMYELITIS

Introduction: Poliomyelitis, often called polio or infantile paralysis, is a virally induced infectious disease which spreads via the fecal-oral route. The virus enters the body through the mouth when people eat food or drink water that is contaminated with faeces. Polio viruses spread very easily in areas with poor hygiene.

History(1): The effects of a polio infection have been known since prehistory. Egyptian paintings and carvings depict otherwise healthy people with withered limbs, walking with canes at a young age, etc It was first recognized as a medical entity by Jakob Heine in 1840.

Disease Burden: Once a major global killer, polio is now endemic only in four countries(2). The total number of cases reported in 2006, so far, is 1646 (till 14th Nov 2006)(3). Polio cases have decreased by over 99% since 1988 when the estimated number of cases was more than 350 000 in more than 125 endemic countries(4). The currently endemic four countries are India, Nigeria, Pakistan and Afghanistan. Nepal has reported two cases this year (till 14th Nov 2006)(3). The last case was reported on 1st of August.

Clinical Picture: The poliovirus is a small RNA virus that has three different strains and is extremely infectious. The virus invades the nervous system, and the onset of paralysis can occur in a matter of hours. While polio can strike a person at any age, over fifty percent of the cases occur in children between the ages of three and five.
The incubation period of polio, from the time of first exposure to first symptoms, ranges from three to thirty five days(5). After initial infection with poliovirus, virus particles are excreted in the feces for several weeks and are highly transmissible to others in a community.
Initial infection is of cells in the lining of the small intestine. Immunization interrupts the process here. After multiplication there, viraemia occurs, with distribution of virus to other parts of the body. Flu-like symptoms are typical of viraemia from any cause. The virus has an affinity for the cell bodies of motor neurons, which carry commands to the muscles.
The clinical spectrum of distribution of various types of polio are(5): A) 95% have no or almost no symptoms or their disease is indistinguishable from influenza. B)1% have non-paralytic polio. C)Less than 1% have paralytic (spinal or bulbar) polio.
In spinal polio, the virus affects the anterior horn cells in the spinal column and the affected limb becomes floppy and poorly controlled — the condition of acute flaccid paralysis (AFP).
In spinal with bulbar symptoms, the upper part of the cervical spinal cord is affected (C3-4-5) and then diaphragm paralysis requires ventilator support. In bulbar polio, the motor neurons arising from the brainstem and passing in the various cranial nerves are affected. In 2006 there are still polio survivors who must use ventilator, spend their entire day or most of their day in an iron lung or attached to an assistive respiratory machine to stay alive(1)

Prevention: Immunization is the sole effective means of preventing poliomyelitis. Both killed and live attenuated vaccines are available. Two types of vaccines used throughout the world are: 1. Inactivated(Salk) Polio vaccine (IPV) 2. Oral (Sabin) polio vaccine (OPV). According to Expanded Programme on Immunization (EPI) schedule of Nepal, OPV are given at 6, 10 and 14 weeks of life. The coverage of three doses of oral polio vaccine in children less than one year in Nepal is 84 %6.

Vaccine history(1): During the late 1940's and early 1950's, a research group headed by Dr. John Enders at Boston's Children's Hospital successfully cultivated the polio virus in human tissue. This highly significant breakthrough ultimately allowed for the development of vaccines against polio. Enders and his colleagues were recognized for their labors with a Nobel Prize in 1954. Hilary Koprowski, claimed to have created the first successful polio vaccine (in 1950) but his vaccine, a live attenuated virus taken orally, was still in the research stage and would not be ready for use until five years after Jonas Salk's polio vaccine reached the market. From 58,000 cases in 1952 and 35,000 in U.S. in 1953, Salk's vaccine reduced the number of cases of polio to only 5,600 in 1957. With the addition of Sabin's vaccine after 1961, only 161 cases were recorded in the U.S. in 1964. The last wild virus case of polio in the U.S. occurred in 1979. Albert Sabin used samples of difficult-to-manufacture attenuated virus given to him by Hilary Koprowski to make his own vaccine. Koprowski would later complain that the polio vaccine he had discovered became known as the Sabin vaccine.

Global Polio Eradication Initiative(4): In 1988, the forty-first World Health Assembly passed a resolution to eradicate polio by 2000, a measure which was inspired by Rotary International's 1985 pledge to raise $120 million toward immunising all of the world's children against the disease. It marked the launch of the Global Polio Eradication Initiative, the world’s largest public health campaign, spearheaded by the World Health Organization (WHO), Rotary International, the US Centers for Disease Control and Prevention (CDC) and UNICEF.
Overall, in the 17 years since the Global Polio Eradication Initiative was launched, the number of cases has fallen by over 99%, from an estimated more than 350 000 cases in 1988 to 1951 reported cases in 2005. In 1994, the World Health Organization (WHO) Region of the Americas (36 countries) was certified polio-free, followed by the WHO Western Pacific Region (37 countries and areas including China) in 2000 and the WHO European Region (51 countries) in June 2002.
Despite these achievements, the Global Polio Eradication Initiative faces an increase in global cases in 2006, due to an ongoing outbreak in northern Nigeria, and a new outbreak in western Uttar Pradesh, India.
Before a WHO region can be certified polio-free, three conditions must be satisfied: (a) at least three years of zero polio cases due to wild poliovirus; (b) excellent certification standard surveillance; (c) each country must illustrate the capacity to detect, report and respond to “imported” polio cases.
Since 1988, more than five million people who would otherwise have been paralysed are today walking because they have been immunized against polio due to Global Polio Eradication Initiative.

The Road Ahead: The independent technical oversight body for global polio eradication met on 11-12 October 2006 to review global progress in the past year and recommend steps to end poliovirus transmission rapidly in the remaining four endemic areas, limit international spread of the virus and prepare for eventual eradication of polio and cessation of oral polio vaccination.
To limit international spread, an issue of interest to Nepal, the committee has advised on continuing supplementary immunization activities in countries bordering endemic areas of Nigeria and India and establishing a standing recommendation on polio immunization for travellers from polio-infected areas under the International Health Regulations 2005(7).
Once polio is eradicated, the world can celebrate not only the eradication of a disease but the delivery of a global public good – something from which every person, regardless of race, sex, ethnicity, economic status or religious belief, can benefit for all time, no matter where they live.

Narayan K.C, MBBS 4th Year student, Maharajgunj Cmapus, Institute of Medicine.

References:
1.Poliomyelitis: History. www.wikipedia.com/poliomyelits (Accessed 21 Nov 2006)
2. Global Polio Eradication Initiative. Global Situation: Monthly situation reports: September 2006. www.polioeradication.org/content/general/current_monthly_sitrep.asp (Accessed 20 Nov 2006)
3. Global Polio Eradication Initiative. Global Situtation: Wild Polio Virus Weekly Update. www.polioeradication.org/casecount.asp (Accessed 20 Nov 2006)
4. World Health Organization. WHO Sites: Media centre: Fact sheets: Fact Sheet no 114 (revised September 2006). www.who.int/mediacentre/factsheets/fs114/en/ (Accessed 21 Nov 2006)
5. Park K. Textbook of Preventive and Social Medicine 15th Ed. Jabalpur: Banarsidas Bhanot Publishers, 1997
6. Department of Health Services. Annual report 2059/60 (2002/2003). Kathmandu: Department of Health Services, His Majesty's Government of Nepal, 2003.
7. Global Polio Eradication Initiative. Advisory Committee for Polio Eradication 2006. www.polioeradication.org/content/general/2006ACPE.asp (Accessed 20 Nov 2006)


DENGUE FEVER

In the recent days, dengue has been in the news headlines and has become an important matter of public health concern. Dengue is now endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, South-east Asia and the Western Pacific(1); South-east Asia and the Western Pacific being most seriously affected. Currently an estimated 50 million cases of dengue infection worldwide every year(2,3) and, 2500 million people being at risk of dengue infection. The health burden of dengue in SE Asia only is estimated to be 0.42 DALYs per 1000 population (52% due to premature mortality, 48% due to morbidity)(4). The global prevalence of dengue has grown dramatically in recent decades. Not only is the number of cases increasing as the disease is spreading to new areas, but explosive outbreaks are occurring as its epidemiological pattern is changing(5).

Regarding history of Dengue Fever, the first reported epidemics of Dengue Fever occurred in 1779-1780 in Asia, Africa, and North America. A pandemic of dengue began in Southeast Asia after World War II and has spread around the globe since then. In the 1980s, Dengue Haemorrhagic Fever began a second expansion into Asia when Sri Lanka, India, and the Maldives Islands had their first major Dengue Haemorrhagic Fever epidemics; Pakistan first reported an epidemic of dengue fever in 1994. The epidemics in Sri Lanka and India were associated with multiple dengue virus serotypes.

Dengue fever is a severe, flu-like illness that affects infants, young children and adults, but seldom causes death. Infections produce a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal hemorrhagic disease(6). The clinical features of dengue fever vary according to the age of the patient. Infants and young children may have a non-specific febrile illness with rash. Older children and adults may have either a mild febrile syndrome or the classical incapacitating disease with abrupt onset and high fever, severe headache, pain behind the eyes, muscle and joint pains, and rash.

Dengue haemorrhagic fever is a potentially deadly complication that is characterized by high fever, haemorrhagic phenomena--often with enlargement of the liver--and in severe cases, circulatory failure. Vascular damage plays a key role in the pathophysiology of dengue hemorrhagic fever as evidenced by soluble intercellular adhesion molecule and vascular cell adhesion molecule and the presence of circulating endothelial cells (CECs)(7). The illness commonly begins with a sudden rise in temperature accompanied by facial flush and other non-specific constitutional symptoms of dengue fever. The fever usually continues for two to seven days and can be as high as 40-41°C, possibly with febrile convulsions and haemorrhagic phenomena.

In moderate DHF cases, all signs and symptoms abate after the fever subsides. In severe cases, the patient's condition may suddenly deteriorate after a few days of fever; the temperature drops, followed by signs of circulatory failure, and the patient may rapidly go into a critical state of shock and die within 12-24 hours, or quickly recover following appropriate volume replacement therapy.

Dengue Fever is caused by one of four closely related but antigenically distinct, virus serotypes (DEN-1, DEN-2, DEN-3, DEN-4) of the genus Flavivirus. Recovery from infection by one provides lifelong immunity against that serotype but confers only partial and transient protection against subsequent infection by the other three. So persons living in a dengue-endemic area can have more than one dengue infection during their lifetime. There is good evidence that sequential infection increases the risk of more serious disease resulting in Dengue Hemorrhagic Fever.

Dengue is primarily a disease of tropical and sub tropical regions around the world, predominantly found in urban and semi-urban areas. Dengue viruses are transmitted to humans through the bites of infective female Aedes mosquitoes. Aedes aegypti, a domestic, day-biting mosquito that prefers to feed on humans, is the most common Aedes species. Mosquitoes generally acquire the virus while feeding on the blood of an infected person. After virus incubation for 8-10 days, an infected mosquito is capable, during probing and blood feeding, of transmitting the virus, to susceptible individuals for the rest of its life. Infected female mosquitoes may also transmit the virus to their offspring by transovarial (via the eggs) transmission, but the role of this in sustaining transmission of virus to humans has not yet been delineated.

Humans are the main amplifying host of the virus, although studies have shown that in some parts of the world monkeys may become infected and perhaps serve as a source of virus for uninfected mosquitoes. The virus circulates in the blood of infected humans for two to seven days, at approximately the same time as they have fever; Aedes mosquitoes may acquire the virus when they feed on an individual during this period.

There is no specific treatment for dengue fever. However, careful clinical management frequently saves the lives of DHF patients. With appropriate intensive supportive therapy, mortality may be reduced to less than 1%. Maintenance of the circulating fluid volume is the central feature of DHF case management.

No dengue vaccine is available. The health burden due to dengue in SE asia could be reduced by 82% by an effective vaccine(4).Recently, however, attenuated candidate vaccine viruses have been developed. Initial evidences with a live attenuated chimeric Dengue serotype 2 vaccine have shown it to be highly effective and safe(8). Research is also being conducted to develop second-generation recombinant vaccine viruses. Therefore, an effective dengue vaccine for public use may not be available for 5 to 10 years.

At present, the only method of controlling or preventing dengue and DHF is to combat the vector mosquitoes. In Asia and the Americas, Aedes aegypti breeds primarily in man-made containers like earthenware jars, metal drums and concrete cisterns used for domestic water storage, as well as discarded plastic food containers, used automobile tyres and other items that collect rainwater. In Africa it also breeds extensively in natural habitats such as tree holes and leaf axils. Vector control is implemented using environmental management and chemical methods. Proper solid waste disposal and improved water storage practices, including covering containers to prevent access by egg laying female mosquitoes are among methods that are encouraged through community-based programmes.

Roshan Shrestha, MBBS 4th year student, Maharajgunj Campus, Institute of Medicine.
Saroj P. Kandel, MBBS 4th year student, Maharajgunj Campus, Institute of Medicine.

References:
1.Halstead SB. Dengue. Curr Opin Infect Dis 2002; 15:471-6.
2.WHO. Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control. 2nd ed. Geneva: WHO, 1997.
3.Mackenzie JS, Gubler DJ, Petersen LR. Emerging flaviviruses: The spread and resurgence of japanese encephalitis, west nile and dengue viruses. Nat Med 2004; 10:S98-S109.
4.Shepard DS, Suaya JA, Halstead SB, Nathan MB, Gubler DJ, Mahoney RT, Wang DN, Meltzer MI. Cost-effectiveness of a pediatric dengue vaccine. Vaccine 2004; 22:1275-80.
5.Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev. 11:480–96.
6.Burke DS, Monath TP. Flaviviruses. In: Knipe DM, Howley PM, eds. Fields Virology. 4th ed. Vol. 1. Baltimore: Lippincott Williams and Wilkins, 2001:1043-125.
7.Cardier JE, Rivas B, Romano E, Rothman AL, Perez-Perez C, Ochoa M, et al. Evidence of vascular damage in dengue disease: demonstration of high levels of soluble cell adhesion molecules and circulating endothelial cells. Endothelium. 2006 Sep-Oct;13(5):335-40.
8.Durbin AP, McArthur JH, Marron JA, Blaney JE, Thumar B, Wanionek K, et al. rDEN2/4.30(ME), A Live Attenuated Chimeric Dengue Serotype 2 Vaccine Is Safe and Highly Immunogenic in Healthy Dengue-Naïve Adults. Human Vaccines November/December 2006; 2:6, 255-260