Virology Club [Viral Facts & Information]

VACCINE RECOMMENDATIONS
Hepatitis B vaccine available since 1982
Routine vaccination of 0-18 year olds
Vaccination of risk groups of all ages (see section on risk groups)

TREATMENT & MEDICAL MANAGEMENT
HBV infected persons should be evaluated by their doctor for liver disease.
Alpha interferon and lamivudine are two drugs licensed for the treatment of persons with chronic hepatitis B. These drugs are effective in up to 40% of patients.
These drugs should not be used by pregnant women.
Drinking alcohol can make your liver disease worse.

TRENDS & STATISTICS
Number of new infections per year has declined from an average of 260,000 in the 1980s to about 78,000 in 2001.
Highest rate of disease occurs in 20-49-year-olds.
Greatest decline has happened among children and adolescents due to routine hepatitis B vaccination.
Estimated 1.25 million chronically infected Americans, of whom 20-30% acquired their infection in childhood.

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Hepatitis C (1)

SIGNS & SYMPTOMS
80% of persons have no signs or symptoms.
jaundice
fatigue
dark urine
abdominal pain
loss of appetite
nausea

CAUSE
Hepatitis C virus (HCV)

LONG-TERM EFFECTS
Chronic infection: 75-85% of infected persons
Chronic liver disease: 70% of chronically infected persons
Deaths from chronic liver disease: <3%
Leading indication for liver transplant

TRANSMISSION

Occurs when blood or body fluids from an infected person enters the body of a person who is not infected.
HCV is spread through sharing needles or "works" when "shooting" drugs, through needlesticks or sharps exposures on the job, or from an infected mother to her baby during birth.

Persons at risk for HCV infection might also be at risk for infection with hepatitis B virus (HBV) or HIV.

Recommendations for Testing Based on Risk for HCV Infection

PERSONS	RISK OF INFECTION	TESTING RECOMMENDED?
Injecting drug users	High	Yes
Recipients of clotting factors made before 1987	High	Yes
Hemodialysis patients	Intermediate	Yes
Recipients of blood and/or solid organs before 1992	Intermediate	Yes
People with undiagnosed liver problems	Intermediate	Yes
Infants born to infected mothers	Intermediate	After 12-18 mos. old
Healthcare/public safety workers	Low	Only after known exposure**
People having sex with multiple partners	Low	No*
People having sex with an infected steady partner	Low	No*

*Anyone who wants to get tested should ask their doctor.
** View current post-exposure prophylaxis recommendations.

PREVENTION
There is no vaccine to prevent hepatitis C.
Do not shoot drugs; if you shoot drugs, stop and get into a treatment program; if you can't stop, never share needles, syringes, water, or "works", and get vaccinated against hepatitis A & B.
Do not share personal care items that might have blood on them (razors, toothbrushes).
If you are a health care or public safety worker, always follow routine barrier precautions and safely handle needles and other sharps; get vaccinated against hepatitis B.
Consider the risks if you are thinking about getting a tattoo or body piercing. You might get infected if the tools have someone else's blood on them or if the artist or piercer does not follow good health practices.
HCV can be spread by sex, but this is rare. If you are having sex with more than one steady sex partner, use latex condoms* correctly and every time to prevent the spread of sexually transmitted diseases. You should also get vaccinated against hepatitis B.
If you are HCV positive, do not donate blood, organs, or tissue.

TREATMENT & MEDICAL MANAGEMENT
HCV positive persons should be evaluated by their doctor for liver disease.
Interferon and ribavirin are two drugs licensed for the treatment of persons with chronic hepatitis C.
Interferon can be taken alone or in combination with ribavirin. Combination therapy is currently the treatment of choice.
Combination therapy, using pegylated interferon and ribavirin, can get rid of the virus in up to40% of those with genotype 1 and up to 80% for those with genotype 2 or 3.
Drinking alcohol can make your liver disease worse.

STATISTICS & TRENDS
Number of new infections per year has declined from an average of 240,000 in the 1980s to about 25,000 in 2001.
Most infections are due to illegal injection drug use.
Transfusion-associated cases occurred prior to blood donor screening; now occurs in less than one per million transfused unit of blood.
Estimated 3.9 million (1.8%) Americans have been infected with HCV, of whom 2.7 million are chronically infected.

What is hepatitis C?
Hepatitis C is a liver disease caused by the hepatitis C virus (HCV), which is found in the blood of persons who have this disease. HCV is spread by contact with the blood of an infected person.

Q: What blood tests are available to check for hepatitis C?
A: There are several blood tests that can be done to determine if you have been infected with HCV. Your doctor may order just one or a combination of these tests. The following are the types of tests your doctor may order and the purpose for each:

Anti-HCV (antibody to HCV)
EIA (enzyme immunoassay)
This test is usually done first. If positive, it should be confirmed

RIBA (recombinant immunoblot assay)
A supplemental test used to confirm a positive EIA test

Anti-HCV does not tell whether the infection is new (acute), chronic (long-term) or is no longer present.

Qualitative tests to detect presence or absence of virus (HCV RNA)
Generic polymerase chain reaction (PCR)
Amplicor HCV™

Quantitative tests to detect amount (titer) of virus (HCV RNA)
Amplicor HCV Monitor™
Quantiplex HCV RNA (bDNA)

PCR and other tests to directly detect virus are not licensed tests and are only available on a research-basis. A single positive PCR test indicates infection with HCV. A single negative test does not prove that a person is not infected. Virus may be present in the blood and just not found by PCR. Also, a person infected in the past who has recovered may have a negative test. When hepatitis C is suspected and PCR is negative, PCR should be repeated.

Q: Can you have a "false positive" anti-HCV test result?
A: Yes. A false positive test means the test looks as if it is positive, but it is really negative. This happens more often in persons who have a low risk for the disease for which they are being tested. For example, false positive anti-HCV tests happen more often in persons such as blood donors who are at low risk for hepatitis C. Therefore, it is important to confirm a positive anti-HCV test with a supplemental test as most false positive anti-HCV tests are reported as negative on supplemental testing.

Q: Can you have a "false negative" anti-HCV test result?
A: Yes. Persons with early infection may not as yet have developed antibody levels high enough that the test can measure. In addition, some persons may lack the (immune) response necessary for the test to work well. In these persons, research-based tests such as PCR may be considered.

Q: How long after exposure to HCV does it take to test positive for anti-HCV?
A: Anti-HCV can be found in 7 out of 10 persons when symptoms begin and in about 9 out of 10 persons within 3 months after symptoms begin. However, it is important to note that many persons who have hepatitis C have no symptoms.

Q: How long after exposure to HCV does it take to test positive with PCR?
A: It is possible to find HCV within 1 to 2 weeks after being infected with the virus.

Q: Who should get tested for hepatitis C?
A: The following:

Hepatitis C is a leading indication for liver transplants.

Q: Do medical conditions outside the liver occur in persons with chronic hepatitis C?
A: A small percentage of persons with chronic hepatitis C develop medical conditions outside the liver (this is called extrahepatic). These conditions are thought to occur due to the body's natural immune system fighting against itself. Such conditions include: glomerulonephritis, essential mixed cryoglobulinemia, and porphyria cutanea tarda.

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Herpes (1)

What is genital herpes?

Herpes is a sexually transmitted disease (STD) caused by the herpes simplex viruses type 1 (HSV -1) and type 2 (HSV-2). Most individuals have no or only minimal signs or symptoms from HSV-1 or HSV-2 infection. When signs do occur, they typically appear as one or more blisters on or around the genitals or rectum. The blisters break, leaving tender ulcers (sores) that may take two to four weeks to heal the first time they occur. Typically, another outbreak can appear weeks or months after the first, but it almost always is less severe and shorter than the first episode. Although the infection can stay in the body indefinitely, the number of outbreaks tends to go down over a period of years.

How is genital herpes spread?

HSV-1 and HSV-2 can be found and released from the sores that the viruses cause, but they also are released between episodes from skin that does not appear to be broken or to have a sore. A person almost always gets HSV-2 infection during sexual contact with someone who has a genital HSV-2 infection. HSV-1 causes infections of the mouth and lips, so-called "fever blisters." A person can get HSV-1 by coming into contact with the saliva of an infected person. HSV-1 infection of the genitals almost always is caused by oral-genital sexual contact with a person who has the oral HSV-1 infection.

How common is genital herpes?

Results of a recent, nationally representative study show that genital herpes infection is common in the United States. Nationwide, 45 million people ages 12 and older, or one out of five of the total adolescent and adult population, are infected with HSV-2.

HSV-2 infection is more common in women (approximately one out of four women) than in men (almost one out of five). This may be due to male-to-female transmission being more efficient than female-to-male transmission. HSV-2 infection also is more common in blacks (45.9%) than in whites (17.6%). Race and ethnicity in the United States correlate with other, more fundamental determinants of health such as poverty, access to good quality health care, behavior for seeking health care, illicit drug use, and living in communities with a high prevalence of STDs.

Since the late 1970s, the number of Americans with genital herpes infection has increased 30%. The largest increase is currently occurring in young white teens. HSV-2 infection is now five times more common in 12- to 19-year-old whites, and it is twice as common in young adults ages 20 to 29 than it was 20 years ago.

Is genital herpes serious?

HSV-2 usually produces only mild symptoms or signs or no symptoms at all. However, HSV-2 can cause recurrent painful genital sores in many adults, and HSV-2 infection can be severe in people with suppressed immune systems. Regardless of severity of symptoms, genital herpes frequently causes psychological distress in people who know they are infected.

In addition, HSV-2 can cause potentially fatal infections in infants if the mother is shedding virus at the time of delivery. It is important that women avoid contracting herpes during pregnancy because a first episode during pregnancy causes a greater risk of transmission to the newborn. If a woman has active genital herpes at delivery, a cesarean delivery is usually performed. Fortunately, infection of an infant from women with HSV-2 infection is rare.

In the United States, HSV-2 may play a major role in the heterosexual spread of HIV, the virus that causes AIDS. Herpes can make people more susceptible to HIV infection, and it can make HIV-infected individuals more infectious.

What happens when someone is infected with genital herpes?

Most people infected with HSV-2 are not aware of their infection. However, if signs and symptoms occur during the first episode, they can be quite pronounced. The first episode usually occurs within two weeks after the virus is transmitted, and the sores typically heal within two to four weeks. Other signs and symptoms during the primary episode may include a second crop of sores, or flu-like symptoms, including fever and swollen glands. However, most individuals with HSV-2 infection may never have sores, or they may have very mild signs that they don't even notice or that they mistake for insect bites or a rash.

Most people diagnosed with a first episode of genital herpes can expect to have several symptomatic recurrences a year (typically four or five). These recurrences usually are most noticeable within the first year following the first episode.

How is genital herpes diagnosed?

The signs and symptoms associated with HSV-2 can vary greatly. Health care providers can diagnose genital herpes by visual inspection if the outbreak is typical, and by taking a sample from the sore(s). HSV infections can be difficult to diagnose between outbreaks. Blood tests which detect HSV-1 or HSV-2 infection may be helpful, although the results are not always clear cut.

Is there a cure for herpes?

There is no treatment that can cure herpes, but antiviral medications can shorten and prevent outbreaks during the period of time the person takes the medication.

How can people protect themselves against infection?

The consistent and correct use of latex condoms can help protect against infection. However, condoms do not provide complete protection because the condom may not cover the herpes sore(s), and viral shedding may nevertheless occur. If either you or your partner have genital herpes, it is best to abstain from sex when symptoms or signs are present, and to use latex condoms between outbreaks.

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Human Immunodeficiency Virus (HIV) (1)

Human Immunodeficiency Virus Type 2

In 1984, 3 years after the first reports of a disease that was to become known as AIDS, researchers discovered the primary causative viral agent, the human immunodeficiency virus type 1 (HIV-1). In 1986, a second type of HIV, called HIV-2, was isolated from AIDS patients in West Africa, where it may have been present decades earlier. Studies of the natural history of HIV-2 are limited, but to date comparisons with HIV-1 show some similarities while suggesting differences. Both HIV-1 and HIV-2 have the same modes of transmission and are associated with similar opportunistic infections and AIDS. In persons infected with HIV-2, immunodeficiency seems to develop more slowly and to be milder. Compared with persons infected with HIV-1, those with HIV-2 are less infectious early in the course of infection. As the disease advances, HIV-2 infectiousness seems to increase; however, compared with HIV-1, the duration of this increased infectiousness is shorter. HIV-1 and HIV-2 also differ in geographic patterns of infection; the United States has few reported cases.

Which countries have a high prevalence* of HIV-2 infection?

HIV-2 infections are predominantly found in Africa. West African nations with a prevalence of HIV-2 of more than 1% in the general population are Cape Verde, Côte d'Ivoire (Ivory Coast), Gambia, Guinea-Bissau, Mali, Mauritania, Nigeria, and Sierra Leone. Other West African countries reporting HIV-2 are Benin, Burkina Faso, Ghana, Guinea, Liberia, Niger, São Tomé, Senegal, and Togo. Angola and Mozambique are other African nations where the prevalence of HIV-2 is more than 1%.

*Prevalence is the proportion of cases present in a population at a given point in time.

What is known about HIV-2 in the United States?

The first case of HIV-2 infection in the United States was diagnosed in 1987. Since then, the Centers for Disease Control and Prevention (CDC) has worked with state and local health departments to collect demographic, clinical, and laboratory data on persons with HIV-2 infection.

Of the 79 infected persons, 66 are black and 51 are male. Fifty-two were born in West Africa, 1 in Kenya, 7 in the United States, 2 in India, and 2 in Europe. The region of origin was not known for 15 of the persons, although 4 of them had a malaria-antibody profile consistent with residence in West Africa. AIDS-defining conditions have developed in 17, and 8 have died.

These case counts represent minimal estimates because completeness of reporting has not been assessed. Although AIDS is reported uniformly nationwide, the reporting of HIV infection, including HIV-2 infection, differs from state to state according to state policy.

Who should be tested for HIV-2?

Because epidemiologic data indicate that the prevalence of HIV-2 in the United States is very low, CDC does not recommend routine HIV-2 testing at U.S. HIV counseling and test sites or in settings other than blood centers. However, when HIV testing is to be performed, tests for antibodies to both HIV-1 and HIV-2 should be obtained if demographic or behavioral information suggests that HIV-2 infection might be present.

Persons at risk for HIV-2 infection include

Among all HIV-infected people, the prevalence of HIV-2 is very low compared with HIV-1. However, the potential risk for HIV-2 infection in some populations (such as those listed) may justify routine HIV-2 testing for all people for whom HIV-1 testing is warranted. The decision to implement routine HIV-2 testing requires consideration of the number of HIV-2-infected persons whose infection would remain undiagnosed without routine HIV-2 testing compared with the problems and costs associated with the implementation of HIV-2 testing.

The development of antibodies is similar in HIV-1 and HIV-2. Antibodies generally become detectable within 3 months of infection. Testing for HIV-2 antibodies is available through private physicians or state and local health departments.

Are blood donors tested for HIV-2?

Since 1992, all U.S. blood donations have been tested with a combination HIV-1/HIV-2 enzyme immunoassay test kit that is sensitive to antibodies to both viruses. This testing has demonstrated that HIV-2 infection in blood donors is extremely rare. All donations detected with either HIV-1 or HIV-2 are excluded from any clinical use, and donors are deferred from further donations.

Is the clinical treatment of HIV-2 different from that of HIV-1?

Little is known about the best approach to the clinical treatment and care of patients infected with HIV-2. Given the slower development of immunodeficiency and the limited clinical experience with HIV-2, it is unclear whether antiretroviral therapy significantly slows progression. Not all of the drugs used to treat HIV-1 infection are as effective against HIV-2. In vitro (laboratory) studies suggest that nucleoside analogs are active against HIV-2, though not as active as against HIV-1. Protease inhibitors should be active against HIV-2. However, non-nucleoside reverse transcriptase inhibitors (NNRTIs) are not active against HIV-2. Whether any potential benefits would outweigh the possible adverse effects of treatment is unknown.

Monitoring the treatment response of patients infected with HIV-2 is more difficult than monitoring people infected with HIV-1. No FDA-licensed HIV-2 viral load assay is available yet. Viral load assays used for HIV-1 are not reliable for monitoring HIV-2. Response to treatment for HIV-2 infection may be monitored by following CD4+ T-cell counts and other indicators of immune system deterioration, such as weight loss, oral candidiasis, unexplained fever, and the appearance of a new AIDS-defining illness. More research and clinical experience is needed to determine the most effective treatment for HIV-2.

The optimal timing for antiretroviral therapy (i.e., soon after infection, when symptoms appear, or when CD4+ T cell counts fall below a certain level) remains under review by clinical experts. Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, by the Department of Health and Human Services Panel on Clinical Practices for Treatment of HIV Infection, may be helpful to the clinician who is caring for a patient infected with HIV-2; however, the recommendations on viral load monitoring and the use of NNRTIs would not apply to patients with HIV-2 infection. Copies of the guidelines are available from the CDC National Prevention Information Network (1 800 458-5231) and from its Web site (www.cdcnpin.org). The guidelines also are available from the HIV/AIDS Treatment Information Service (1 800 448-0440; Fax 301 519-6616; TTY 1 800 243-7012) and on the ATIS Web site (www.hivatis.org).

What is known about HIV-2 infection in children?

HIV-2 infection in children is rare. Compared with HIV-1, HIV-2 seems to be less transmissible from an infected mother to her child. However, cases of transmission from an infected woman to her fetus or newborn have been reported among women who had primary HIV-2 infection during their pregnancy. Zidovudine therapy has been demonstrated to reduce the risk for perinatal HIV-1 transmission and also might prove effective for reducing perinatal HIV-2 transmission. Zidovudine therapy should be considered for HIV-2-infected expectant mothers and their newborns, especially for women who become infected during pregnancy.

How should physicians and patients decide whether to start treatment for HIV-2?

Physicians caring for patients with HIV-2 infection should decide whether to initiate antiretroviral therapy after discussing with their patients what is known, what is not known, and the possible adverse effects of treatment.

What can be done to control the spread of HIV-2?

Continued surveillance is needed to monitor HIV-2 in the U.S. population because the possibility for further spread of HIV-2 exists, especially among injecting drug users and people with multiple sex partners. Programs aimed at preventing the transmission of HIV-1 also can help to prevent and control the spread of HIV-2.

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Human Papillomavirus (HPV) (1)

Genital HPV Infection

What is genital HPV infection?

Genital HPV infection is a sexually transmitted disease (STD) that is caused by human papillomavirus (HPV). Human papillomavirus, or HPV, is the name of a group of viruses that includes more than 100 different strains or types. Over 30 of these are sexually transmitted, and they can infect the genital area, like the skin of the penis, vulva, labia, or anus, or the tissues covering the vagina and cervix.

Some of these viruses are considered "high-risk" types and may cause abnormal Pap smears and cancer of the cervix, anus, and penis. Others are "low-risk," and they may cause mild Pap smear abnormalities and genital warts. Genital warts are single or multiple growths or bumps that appear in the genital area, and sometimes form a cauliflower-like shape.

How common is HPV?

Approximately twenty million people are currently infected with HPV. Fifty to 75% of sexually active men and women acquire genital HPV infection at some point in their lives. About 5.5 million Americans get a new genital HPV infection each year.

How do people get genital HPV infections?

The types of HPV that infect the genital area are spread primarily through sexual contact. Most HPV infections have no signs or symptoms; therefore, most infected persons are completely unaware they are infected, yet they can transmit the virus to a sex partner. Rarely, pregnant women can pass HPV to their baby during vaginal delivery. A newborn that is exposed to HPV during delivery can develop warts in the larynx (voice box).

What are the signs and symptoms of genital HPV infection?

Most people who have a genital HPV infection do not know they are infected. The virus lives in the skin or mucus membranes and usually causes no symptoms. Other people get visible genital warts.

What are genital warts?

These usually appear as soft, moist, pink or red swellings. They can be raised or flat, single or multiple, small or large. Some cluster together forming a cauliflower-like shape. They can appear on the vulva, in or around the vagina or anus, on the cervix, and on the penis, scrotum, groin, or thigh. Warts can appear within several weeks after sexual contact with an infected person, or they can take months to appear.

Genital warts are diagnosed by inspection. Visible genital warts can be removed, but no treatment is better than another, and no single treatment is ideal for all cases.

Who is at risk for genital HPV infection?

Anyone who has sex is at risk for genital HPV infection.

How is genital HPV infection diagnosed?

Most women are diagnosed with HPV on the basis of abnormal Pap smears. Pap smears are the primary screening tool for cervical cancer or pre-cancerous conditions, many of which are cell changes related to HPV. Current HPV tests are fairly sophisticated and expensive and are commercially available for women with an abnormal Pap smear. They cannot identify which HPV infections will lead to cervical cancer or pre-cancerous conditions. Research is underway to determine the role of HPV tests for cervical cancer screening.

Is there a cure for HPV?

There is no "cure" for HPV, although the infection usually goes away on its own. Cancer-related types are more likely to persist.

What is the connection between HPV infection and cervical cancer?

All types of HPV can cause mild Pap smear abnormalities that do not have serious consequences. Approximately 10 of the 30 identified genital HPV types can lead, in rare cases, to development of cervical cancer. Research has shown that for most (90%) women, cervical HPV infection becomes undetectable within two years; only a small proportion have persistent infection. Persistent infection with certain types of HPV is the key risk factor for cervical cancer.

A Pap smear can detect pre-cancerous and cancerous cells on the cervix. Frequent Pap smears and careful medical followup, with treatment if necessary, can help ensure that pre-cancerous cells in the cervix caused by HPV infection do not develop into life-threatening cervical cancer. The Pap test used in U.S. cervical cancer screening programs is responsible for greatly reducing deaths from cervical cancer. The American Cancer Society estimated that about 12,800 women in the United States were diagnosed with invasive cervical cancer in 2000. In 2001, approximately 4,600 women will die from cervical cancer.

How can genital HPV infection be prevented?

Abstinence is the most effective strategy to prevent HPV infection.

Two uninfected individuals who have no other sex partners besides each other cannot get genital HPV infection. The following practices for sexually active people will help prevent infection:

Exotic Viruses and Viruses Associated with Hemorrhagic Fevers

Dengue (2)

Reference
Family: Flaviviridae
Virus: Dengue (four types)
Geographical distribution: Entire tropical zone
Vector: Mosquito

Like yellow fever, this 'classic' arbovirus infection is also caused by a glavivirus and transmitted by Aedes aegypti mosquitoes. In adults, the clinical features are usually similar to those of the fever/rash syndrome described above, with severe joint and muscle pains; lymphadenopathy and altered perception of taste are common. Children may suffer from dengue haemorrhagic shock syndrome (DHSS). This is a dangerous complication with a mortality of 4-12 per cent and it is worrying that it appears to be on the increase, notably in South-East Asia. A brief febrile illness is followed by collapse with shock, low blood pressure, and haemorrhagic signs. There are four serotypes of dengue virus, and it is thought that DHSS may be the result of immune enhancement due to a second infection with a heterologous serotype: the virus forms complexes with pre-existing non-neutralizing antibody to the first virus and then, via Fx receptors, gains access to monocytes, in which it multiplies very easily and becomes widely disseminated.
Treatment is quite effective; it involves replacement of fluid loss, correction of electrolyte balance, and transfusion of whole blood if haemorrhage is severe.

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Ebola and Marburg Virus (2)

Reference
Family: Filoviridae
Genus: Filovirus
Important Viruses: Marburg, Ebola

The filoviruses
Propertries of the viruses

Classification
The family Filoviridae is composed of extremely pleomorphic viruses: its name derives from the Latin filum, a thread, which refers to their morphology. Recently the family has been placed in the order Mononegavirales. Marburg and Ebola viruses can be distinguished from each other by the size of their genomes and their different protein composition; they also differ serologically.

Morphology
These viruses have an extraordinary filamentous morphology and are sometimes longer than common bacteria, often with branched, circular, and bizarre-shaped forms. They have lipid envelopes, beneath which a nucleocapsid structure containing RNA can be visualized by electron microscopy. The nucleocapsids have helical symmetry.

Clinical and Pathological aspects

Clinical features
The illness caused by the Marburg and Ebola viruses is very similar, with abrupt onset after an incubation period of 3-16 days. Severe frontal headache, high fever, and back pains characterize the early phase. The patient is rapidly prostrated with diarrhoea and vomiting lasting about a week; conjunctivitis and pharyngitis are usually present. A transient non-itching maculopapular rash may appear after 5-7 days. At this time severe bleeding starts in the lungs, nose, gums, gastrointestinal tract, and conjunctiva in a large proportion of patients, preceded and accompanied by thrombocytopenia. Deaths in cases with severe shock and blood loss usually occur between days 7 and 16. The mortality may be high, ranging from 25 to 90 per cent.

Pathology
Both Marburg and Ebola are so-called pantropic viruses: they infect and cause lesions in many organs, but especially the liver and spleen, which become enlarged and dark in colour. In both these organs severe degeneration and necrosis occur. The actual mechanism of pathogenesis remains obscure but, clearly, damage to endothelial cells resulting in inreased vascular permeability followed by haemorrhage and shock is a central feature.

Epidemiology
Apart from the first recorded episode, known outbreaks of clinically apparent Marburg disease have been limited to a few individuals in Africa. By contrast, there have been large outbreaks of Ebola infection in the Suden and Zaire, where, on the basis of serological surveys, it seems to be endemic (the viruses are slightly different and are called Ebola S and Ebola Z). The outbreak in a primate facility in Reston, USA, has led to identification of a third virus, Ebola-Reston. In this outbreak in a monkey colony in the USA many macaques died, but in the four employees who were diagnosed as infected there were no clinical signs. This is an encouraging observation and may indicate that certain strains are non-pathogenic.
The disease in the Reston outbreak was a zoonosis and although monkeys were also involved in the Marburg outbreak, the precise animal reservoir is still unknown. Virus is spread mainly by close contact with infected blood, although it can also be detected in body fluids: in one case in the Marburg outbreak there was laboratory evidence of spread from semen during sexual intercourse. The virus may persist in infected individuals for at least 2 months, which presents an additional transmission hazard. Apart from direct contact with animals, very close contact with an infected patient is a prerequisite for infection, and normal isolation and barrier-nursing methods prevent transmission.

Laboratory diagnosis
Only certain laboratories, designated category IV, have the experience and high-level containment facilities to propagate these viruses in quantity. There are only a few of these facilities in the world. Virus may be isolated from blood autopsy tissue in Vero cells and identified by its characteristic morphology under the electron microscope or by immunofluorescence of impression smears of infected tissues. Specific antigen can also be detected by ELISA, and PCR can be used to detect viral RNA. A significant rise in antibody, as measured by ELISA, is also diagnostic.
You guinea-pigs can be infected by intraperitoneal injection and these diagnostic procedures can then be applied to their tissues.

Prevention and treatment
No vaccines or specific chemotherapeutic agents are available at present, although ribavirin is often administered. Since the Reston outbreak, further controls have been imposed on export and import of primates and stricter regulation introduced to protect workers in monkey units. However, outbreaks of Ebola continue to occur in Africa with regularlity. Transmission is by direct contact, droplet infection, or contact with body fluids. Healthcare staff are particularly at risk, since most or all infections involve close contact with sick patients. In hospitals with adequate facilities the attack rate in hospital staff is low; but where facilities are not adequate, transmission rates to staff of 80 per cent have been recorded.

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Hantaan (2)

Hantaviruses
The great majority of bunyaviruses are arthropod-borne and cause fever and infections of the CNS, mostly in tropical of subtropical areas. In 1978 however, a bunyavirus isolated from field mice found near the Hantaan River in Korea was later identified as the cause of haemorrhagic fever with renal syndrome, a disease of hitherto unknown aetiology prevalent in Scandinavia, Russia, and Asia, and also referred to as Korean haemorrhagic fever, nephropathia epidemica, and many other names. This agent – Hantaan virus – and subsequent isolates differed sufficiently from other bunyaviruses to be classified as a new genus, Hantavirus. More recently, hantaviruses were found to cause another severe illness, Hantavirus pulmonary syndrome. Unlike other bunyaviruses, hantaviruses are spread not by arthropod vectors but by contact with rodent excreta. Serological evidence suggests that many infections are subclinical.

Properties of the viruses
Classification
The genus, Hantavirus, belongs to the family Bunyaviridae. There are at least six species, but it seems likely that others remain to be discovered.

Morphology, genome, and replication
In so far as they have been studied in detail, these properties are generally similar to those of other members of the Bunyaviridae.

Clinical and pathological aspects
Clinical features
Haemorrhagic fever with renal syndrome (HFRS)
Haemorrhagic fever with renal syndrome (HFRS) ranges in severity from mild to a secre life-threatening infection with a mortality of c. 5 per cent. The incubation period varies widely, but is usually about 3 weeks. The onset is marked by malaise, fever, and abdominal pain and is typically followed by a hypotensive phase 5 days later. There may be thrombocytopenia, with petechiae on the face and trunk, and severe bleeding in the gastrointestinal tract and CNS. Renal function becomes impaired by the ninth day, with oliguria, proteinuria, and elevated blood urea and creatinine. About half the deaths occur at this time and are due to renal failure, pulmonary oedema, or shock. With good management, the mortality rate is about 5 per cent but may be higher. Recovery of renal function is signaled by copious diuresis about 2 weeks after onset. Convalescence is often prolonged.
Nephropathia epidemica is caused by the Puumala strain of Hantavirus; it is prevalent in Scandinavia and western Europe and resembles HFRS but is less severe, with a mortality of less than 1 per cent.

Hantavirus pulmonary syndrome (HPS)
In 1993, there was an outbreak of severe acute respiratory illness in south-western states of the USA, with a mortality rate of 50 per cent. Serological and epidemiological evidence implicated other hantaviruses, which differ genetically from those causing HFRS and appear to be found predominantly in the Americas. There is, however, considerable overlapping in the geographical distribution of the viruses, which varies with the prevalence of different species of wild rodents.
This syndrome is much more severe than HFRS, with mortality rates of c. 80 per cent. The onset is sudden, starting with cough and muscle pains, followed by dyspnoea, tachycardia, pulmonary oedema, pleural effusion, and hypotension. Blood clotting is impaired but severe haemorrhagic is not an important feature. Death is due to respiratory failure.

Epidemiology
Like filovirus infections, the prevalence of both Hantavirus syndromes depends on the distribution of the rodent hosts, which include a number of species of wild rats and mice. Individual hantaviruses are associated with particular species of rodent. HFRS first appeared in 1950, when it affected thousands of United Nations troops in Korea. In 1993 a new Hantavirus appeared in south-west USA, where it has caused well over a hundred cases of HPS. This agent was originally named after the township where it was first identified, but local protests prompted its renaming as ‘Sin Nombre’ (‘No Name’) virus. So far, this highly lethal infection has been confined to the USA, but the renal syndrome has been reported in the Far East, Asia, CIS, Scandinavia, the Balkans and Western Europe, notably Germany and Holland; several strains of Hantavirus are involved.
Although contact with rodent excreta is the prime method of transmission, a report of a small outbreak in Argentina during 1997 suggests that HPS may occasionally spread from person to person.

Laboratory diagnosis
Serological methods include ELISA for detecting specific IgM or rising titres of IgG and immunofluorescence tests on infected Vero cells. PCR tests are now being developed.

Treatment
The therapy of Hantavirus infections is largely supportive, with particular attention to maintaining the fluid and electrolyte balances. Intravenous ribavirin may be of benefit in cases of HFRS. There is as yet no vaccine.

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Junin (2)

Family: Arenaviridae
Genus: Arenavirus
Virus: Junin
Geographical distribution: Argentina
Disease: Argentinian haemorrhagic fever

Clinical features
In endemic areas, subclinical infections are frequent. Clinically apparent disease may be severe... ...The incubation period is commonly 1-2 weeks and the first signs are non-specific, including fever, headache, and sore throat. A rase on the face and neck and a worsening of the patient's general condition usually signals the next stage. In the second week of the illness there may be gastrointestinal and urogenital tract bleeding and a shock syndrome. Even if the patient survives, the convalescence is prolonged; neurological sequelae are a prominent feature.

Argentinian haemorrhagic fever

Argentinian haemorrhagic fever is caused by the Junin arenavirus. Those predominanly infected are male field workers who come into contact with the excreta of chronically infected wild rodents. Thousands of cases may occur when the maize is harvested in late spring and early summer; the case fatality rate is 10-20 per cent.

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Lassa (2)

Family: Arenaviridae
Genus: Arenavirus
Virus: Lassa
Geographical distribution: West Africa
Disease: Lassa fever

Pathology
Extrapolation of data from experimental infections of primates suggests that viral replication in humans occurs in the hilar lymph nodes and lungs following an aerosol infection. The subsequent viraemia causes wide dissemination to other organs, including liver, spleen, heart, and meninges. Bronchopneumonia, either primary viral or secondary bacterial, is a common finding. Large amounts of viral antigen are detected in autopsy samples of spleen, bone marrow, and viscera.

Exactly how these arenaviruses cause haemorrhagic fevers is an open question. Extensive macrophage infection causes release of TNF and other cytokines, and platelet activating factor. Immune complexes, complement activation, or disseminated intravascular coagulation are not thought to play any role in the pathogenesis.

Epidemiology
The distribution of arenaviruses is determined by that of the host rodents. Persistent infection of the rodent reservoir, often without overt signs of disease, maintains the virus in nature, and humans are only incidental hosts.

In rodents, infection may be transmitted vertically in utero or via milk; transmission via saliva and urine also occurs. Humans catch the disease by contact with rodent excreta, particularly urine, whichi contaminates surfaces and may enter via skin abrasions of aerosols.

Lassa fever

Lassa fever has a certain notoriety because of its first dramatic appearance in the USA in 1969, when, following the death of hospital staff in Nigeria, clinical samples were sent to the world-famous abrovirus laboratory in Yale where they infected and killed a technician and laid low the well-known virologist who was head of the unit.

The infection is endemic in rural West Africa, particularly Nigeria and Sierra Leone, where subclinical infections are frequent, but where there have also been a number of outbreaks with high mortality rates. There are more than 100,000 new infections yearly in this area, with thousands of deaths. It is the only viral haemorrhagic fever to have reached the UK, where 10 imported cases have been diagnosed in the past 20 years. Although this number is small, the serious nature of the diseases dictates continued vigilance when dealing with febrile illnesses in patients arriving from endemic areas within the previous 3 or 4 weeks. Rarely, it may spread from person to person.

Prevention and treatment
The specific treatment of choice of Lassa fever is ribavirin administered intravenously, either alone or with convalescent plasma. The drug should be adminstered as soon as possible after onset of the disease. Bacterial superinfections are common and need to be monitored carefully.

For all the haemorrhagic fevers, supportive care is often life-saving, and comprises careful maintenance of fluid and electrolyte balance, protein replacement therapy, and appropriate support for cardiac complications. Isolation and barrier-nursing experience is vital to prevent spread to other patients and to nursing staff and doctors. Control of rodents is an important method of controlling arenavirus infections, but may be impracticable in rural areas.

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Lymphocytic choriomeningitis (LCM) (2)

Family: Arenaviridae
Genus: Arenavirus
Virus: Lymphocytic choriomeningitis
Geographical distribution: Worldwide
Disease: Lymphocytic choriomeningitis

Clinical features
By contrast with these haemorrhagic fevers, LCM is a comparatively mild infection, beginning with headache, fever, and malaise. The illness usually resolves after this stage, but a small proportion of patients develop meningitis or choriomeningitis, which again usually resolves without sequelae; deaths are rare.

Lymphotcytic choriomeningitis is widespread throughout the world in house mice, which are chronically infected without clinical signs. Contact with mice or their excreta brings the virus to humans as a 'dead-end' infection, with no further spread to others.

Laboratory diagnosis
The diagnosis can be established by ELISA and immunofluorescence tests for IgM and IgG antibodies. Consensus oligonucleotide primers for New World arenaviruses are now available and diagnosis by PCR will probably become the method of choice.

Virus can be recovered from the blood and urine of acutely ill patients for several weeks. Virus may also be isolated from throat swabs and urine, and from atopsy specimens of lymphoid tissue, bone marrow, and liver.

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Machupo (2)

Family: Arenaviridae
Genus: Arenavirus
Virus: Machupo
Geographical distribution: Bolivia
Disease: Bolivian haemorrhagic fever

Bolivian haemorrhagic fever is due to another arenavirus, Machupo, which again is transmitted from rodent excreta, although person-to-person spread is not unknown. Outbreaks have occured both in town and country dwellers, but the incidence has greatly diminished in recent years.

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Virus of Central Interest to the Virology Club

West Nile Virus (1)

Reference
Symptoms of West Nile Virus Updated

Q. What are the symptoms of West Nile virus infection?

A. Most people who are infected with the West Nile virus will not have any type of illness. It is estimated that 20% of the people who become infected will develop West Nile fever: mild symptoms, including fever, headache, and body aches, occasionally with a skin rash on the trunk of the body and swollen lymph glands. The symptoms of severe infection (West Nile encephalitis or meningitis) include headache, high fever, neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle weakness, and paralysis. It is estimated that 1 in 150 persons infected with the West Nile virus will develop a more severe form of disease.

Q. What is the incubation period in humans (i.e., time from infection to onset of disease symptoms) for West Nile encephalitis?

A. Usually 3 to 14 days.

Q. How long do symptoms last?

A. Symptoms of mild disease will generally last a few days. Symptoms of severe disease may last several weeks, although neurological effects may be permanent.

Testing and Treating West Nile Encephalitis in Humans Updated

Q. I think I have symptoms of West Nile virus. What should I do?

A. Contact your health care provider if you have concerns about your health. If you or your family members develop symptoms such as high fever, confusion, muscle weakness, and severe headaches, you should see your doctor immediately.

Q. How do health care providers test for West Nile virus?

A. Your physician will first take a medical history to assess your risk for West Nile virus. People who live in or traveled to areas where West Nile virus activity has been identified are at risk of getting West Nile encephalitis; persons older than 50 years of age have the highest risk of severe disease. If you are determined to be at high risk and have symptoms of West Nile encephalitis, your provider will draw a blood sample and send it to a commercial or public health laboratory for confirmation.

Q. How is West Nile encephalitis treated?

A. There is no specific treatment for West Nile virus infection. In more severe cases, intensive supportive therapy is indicated, often involving hospitalization, intravenous fluids, airway management, respiratory support (ventilator), prevention of secondary infections (pneumonia, urinary tract, etc.), and good nursing care.

Questions and Answers about Laboratory Practice (FAQ)

Q. How are human cases of WNV diagnosed?

A. While West Nile virus (WNV) infection can be suspected in a person based on clinical symptoms and patient history, laboratory testing is required for diagnosis. The most commonly used WNV laboratory test measures antibodies that are produced very early in the infected person. These antibodies, called IgM antibodies, can be measured in blood or cerebrospinal fluid (CSF), which is the fluid surrounding the brain and spinal cord. This blood test may not be positive when symptoms first occur; however, the test is positive in 90% of infected people within 8 days of onset of symptoms.
The WNV IgM-antibody test used by CDC and state and local public health labs is not yet available at all private laboratories. Most commonly, physicians send samples to their state or local health department for testing. For tests conducted at private laboratories, frequently, the health department or CDC will confirm results in their own laboratories before officially reporting WNV cases. In some instances, health departments request additional testing from CDC before officially reporting a case to CDC's ArboNET Surveillance System. The CDC reference laboratory may repeat the initial IgM-antibody testing, supplementing the state health department laboratory results. A state may also ask CDC to perform an additional, different test on a specimen. This latter test (plaque reduction neutralization test [PRNT]) is usually performed when the state finds its initial case(s) of human WNV illness, the state results are not definitive due to equivocal laboratory testing results or insufficient specimens, the patient might have been exposed to other closely related viruses (like St. Louis encephalitis virus) which may result in a "false" positive laboratory test for WNV. These additional tests require growth of the virus and may take a week or longer (plus shipping time) to conduct. The results from the PRNT are often needed before CDC considers a human WNV infection confirmed.

Q. How does CDC decide when to report a case of WNV?

A. CDC reports a case of WNV once a state officially reports and verifies that case to CDC. The timing of the official report to CDC, relative to onset of symptoms in a person, is variable and depends on when an individual first seeks medical care and the extent of the laboratory testing, as described above, that the state determines is necessary before reporting.
At any given time, in addition to the official case count reported by CDC, there may be additional suspect cases under investigation or in various stages of testing, including supplemental or confirmatory testing.

Q. How many of the human WNV cases are being confirmed by the CDC
laboratories?

A. When WNV was first found in the United States in 1999, the CDC reference laboratory confirmed all human cases of WNV. Through a comprehensive, CDC-sponsored laboratory training program, most states now have the ability to perform the initial blood tests to identify IgM-antibody in the blood or CSF of suspect human WNV infections. Mosquito control efforts are often implemented on the basis of a positive result in this initial test. Many of the state laboratories have also developed the capability to perform the PRNT. Because of this, the CDC reference lab is called upon for confirmatory testing by fewer and fewer states; however, the increased activity of WNV in 2002 still requires that many tests be performed at the CDC reference laboratory. An exact calculation of the percentage of human cases confirmed at the CDC reference laboratory will not be available until the final 2002 case counts are completed.

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Resources

(1) Center for Disease Control and Prevention. <http://www.cdc.gov>

(2) Human Virology, Second Edition 2000. Collier, L. and Oxford, John. Oxford University Press.

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