Posts Tagged ‘bird flu’

Clinical Syndromes, Laboratory Diagnosis and Treatment of Orthomyxoviruses

February 12, 2012 3 comments

Clinical Syndromes

Depending on the degree of immunity to the infecting strain of virus and other factors, infection may range from asymptomatic to severe. Patients with underlying cardiorespiratory disease, people with immune deficiency (even that associated with pregnancy), the elderly, and smokers are more prone to have a severe case.

After an incubation period of 1 to 4 days, the “flu syndrome” begins with a brief prodrome of malaise and headache lasting a few hours. The prodrome is followed by the abrupt onset of fever, chills, severe myalgias, loss of appetite, weakness and fatigue, sore throat, and usually a nonproductive cough. The fever persists for 3 to 8 days, and unless a complication occurs, recovery is complete within 7 to 10 days. Influenza in young children (under 3 years) resembles other severe respiratory tract infections, causing bronchiolitis, croup, otitis media, vomiting, and abdominal pain, accompanied rarely by febrile convulsions (Table 1). Complications of influenza include bacterial pneumonia, myositis, and Reye syndrome. The central nervous system can also be involved. Influenza B disease is similar to influenza A disease.

Influenza may directly cause pneumonia, but it more commonly promotes a secondary bacterial superinfection that leads to bronchitis or pneumonia. The tissue damage caused by progressive influenza virus infection of alveoli can be extensive, leading to hypoxia and bilateral pneumonia. Secondary bacterial infection usually involves Streptococcus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus. In these infections, sputum usually is produced and becomes purulent.

Although the infection generally is limited to the lung, some strains of influenza can spread to other sites in certain people. For example, myositis (inflammation of muscle) may occur in children. Encephalopathy, although rare, may accompany an acute influenza illness and can be fatal. Postinfluenza encephalitis occurs 2 to 3 weeks after recovery from influenza. It is associated with evidence of inflammation but is rarely fatal.

Reye syndrome is an acute encephalitis that affects children and occurs after a variety of acute febrile viral infections, including varicella and influenza B and A diseases. Children given salicylates (aspirin) are at increased risk for this syndrome. In addition to encephalopathy, hepatic dysfunction is present. The mortality rate may be as high as 40%.

Laboratory Diagnosis

The diagnosis of influenza is usually based on the characteristic symptoms, the season, and the presence of the virus in the community. Laboratory methods that distinguish influenza from other respiratory viruses and identify its type and strain confirm the diagnosis (Table 2).

Influenza viruses are obtained from respiratory secretions. The virus is generally isolated in primary monkey kidney cell cultures or the Madin-Darby canine kidney cell line. Nonspecific cytopathologic effects are often difficult to distinguish but may be noted within as few as 2 days (average, 4 days). Before the cytopathologic effects develop, the addition of guinea pig erythrocytes may reveal hemadsorption (the adherence of these erythrocytes to HA-expressing infected cells). The addition of influenza virus-containing media to erythrocytes promotes the formation of a gel-like aggregate due to hemagglutination. Hemagglutination and hemadsorption are not specific to influenza viruses, however; parainfluenza and other viruses also exhibit these properties.

More rapid techniques detect and identify the influenza genome or antigens of the virus. Rapid antigen assays (less than 30 min) can detect and distinguish influenza A and B. Reverse transcriptase polymerase chain reaction (RT-PCR) using generic influenza primers can be used to detect and distinguish influenza A and B, and more specific primers can be used to distinguish the different strains, such as H5N1. Enzyme immunoassay or immunofluorescence can be used to detect viral antigen in exfoliated cells, respiratory secretions, or cell culture and are more sensitive assays. Immunofluorescence or inhibition of hemadsorption or hemagglutination (hemagglutination inhibition [HI]) with specific antibody can also detect and distinguish different influenza strains. Laboratory studies are primarily used for epidemiologic purposes.

To read more click on this link to the full article: Clinical Syndromes, Laboratory Diagnosis and Treatment of Orthomyxoviruses


Pathogenesis and Epidemiology of Orthomyxoviruses

February 3, 2012 Leave a comment

Pathogenesis and Immunity

Influenza initially establishes a local upper respiratory tract infection. To do so, the virus first targets and kills mucus-secreting, ciliated, and other epithelial cells, causing the loss of this primary defense system. NA facilitates the development of the infection by cleaving sialic acid residues of the mucus, thereby providing access to tissue. Preferential release of the virus at the apical surface of epithelial cells and into the lung promotes cell-to-cell spread and transmission to other hosts. If the virus spreads to the lower respiratory tract, the infection can cause severe desquamation (shedding) of bronchial or alveolar epithelium down to a single-cell basal layer or to the basement membrane.

In addition to compromising the natural defenses of the respiratory tract, influenza infection promotes bacterial adhesion to the epithelial cells. Pneumonia may result from a viral pathogenesis or from a secondary bacterial infection. Influenza may also cause a transient or low-level viremia but rarely involves tissues other than the lung.

Histologically, influenza infection leads to an inflammatory cell response of the mucosal membrane, which consists primarily of monocytes and lymphocytes and few neutrophils. Submucosal edema is present. Lung tissue may reveal hyaline membrane disease, alveolar emphysema, and necrosis of the alveolar walls

Interferon and cytokine responses peak at almost the same time as virus in nasal washes and are concomitant with the febrile phase of disease. T-cell responses are important for effecting recovery and immunopathogenesis. However, influenza infection depresses macrophage and T-cell function, hindering immune resolution. Interestingly, recovery often precedes detection of antibody in serum or secretions.

Protection against reinfection is primarily associated with the development of antibodies to HA, but antibodies to NA are also protective. The antibody response is specific for each strain of influenza, but the cell-mediated immune response is more general and is capable of reacting to influenza strains of the same type (influenza A or B virus). Antigenic targets for T-cell responses include peptides from HA but also from the nucleocapsid proteins (NP, PB2) and M1 protein. The NP, PB2, and M1 proteins differ considerably for influenza A and B but not between strains of these viruses; hence T-cell memory may provide future protection against infection by different strains of either influenza A or B.

The symptoms and time course of the disease are determined by interferon and T-cell responses and the extent of epithelial tissue loss. Influenza is normally a self-limited disease that rarely involves organs other than the lung.Many of the classic “flu” symptoms (e.g., fever, malaise, headache, and myalgia) are associated with interferon induction. Repair of the compromised tissue is initiated within 3 to 5 days of the start of symptoms but may take as long as a month or more, especially for elderly people.

To read more click on this link to the full article: Pathogenesis and Epidemiology of Orthomyxoviruses

Structure and Replication of Orthomyxoviruses

January 31, 2012 1 comment


Influenza A, B, and C viruses are the only members of the Orthomyxoviridae family, and only influenza A and B viruses cause significant human disease. The orthomyxoviruses are enveloped and have a segmented negative-sense RNA genome. The segmented genome of these viruses facilitates the development of new strains through the mutation and reassortment of the gene segments among different human and animal (influenza A) strains of virus. This genetic instability is responsible for the annual epidemics (mutation: drift) and periodic pandemics (reassortment: shift) of influenza infection worldwide.

Influenza is one of the most prevalent and significant viral infections. There are even descriptions of influenza epidemics (local dissemination) that occurred in ancient times. Probably the most famous influenza pandemic (worldwide) is the Spanish influenza that swept the world in 1918 to 1919, killing 20 to 40 million people. In fact, more people died of influenza during that time than in the battles of World War I. Pandemics caused by novel influenza viruses occurred in 1918, 1947, 1957, 1968, and 1977, but fortunately none have occurred since. New virus strains have been detected since the last pandemic, including an outbreak of avian influenza first noted in Hong Kong in 1997, which has caused some human disease and fatalities. Fortunately, prophylaxis in the form of vaccines and antiviral drugs is now available for people at risk for serious outcomes.

To read more click on this link to the full article: Structure and Replication of Orthomyxoviruses.

Top 10 Infectious Diseases That Have Killed Millions of People

The discovery of the antibiotics by the middle of the 20th century seemed to have doomed the human pathogens. They proved effective against many bacteria and fungi causing hospital infections, like meningitis, pneumonia and scarlet fever, which before were deadly. But antibiotics cannot attack viruses, like HIV or flu virus; many cause allergies and kill many beneficial microorganisms.

The under use of antibiotics (when a patient does not complete treatment because he/she feels better) cause the emergence of resistant strains, as not all the bacteria are killed. Their abuse is also harmful. In livestock they induce an accelerated growth, and this cause an increase in the microbial resistance. This can leave us without antibiotics.

Massive vaccination campaigns eliminated to the end of the 20th century smallpox and today polio leave paralyzed less than 1,000 children annually (in 1988 more than 1,000 per day), and has remained active in less than 10 countries. Sanitation has eliminated cholera, whose bacterium is transmitted through infested water, from many places. Better food, life style, medical care and laws controlling food manipulation have reduced infection diseases in many places.

In the 21st century, there are still infections against which we are defenseless and which, despite all the medical advances, bringing advantages more to developed nations, still kill millions of people every year. Poverty, war, hunger, lack of health infrastructure and sanitation, immigration, trade, globalization contribute to the spread of the diseases. In the last years, outbreaks of ebola, cholera, pest, meningitis, SARS and bird flu have been witnessed. These are infectious diseases that have produced and produce a lot of victims around the world.


1.Black Plague

(also called bubonic plague) outbroke in Europe in 1347, when a boat coming from Crimea docked at Mesina, Sicily. Besides its load, the ship transported the pest, which soon spread throughout whole Italy. It was like the end of the days for Europe. In four years, this bacterium killed 20 to 30 million Europeans, about one third of the continent’s population. Even the remote Iceland was struck. In the Extreme East, China dwindled from 123 million inhabitants at the beginning of the 13th century to just 65 million during the 14th century, because of the pest and the hunger.

The pest bacterium is transmitted by fleas and usually, the infection jump from rats to humans.

This catastrophe has not match in the human history. 25 to 50 % of the inhabitants of Europe, North Africa and certain Asian areas died then.

Knowing the cause of the pandemic helped: in 1907 an outbreak of bubonic plague in San Francisco produced just several victims, as the authorities started a massive campaign for exterminating the rats, while in 1896 an outbreak in India caused 10 million dead in 12 years, as the cause was not known.


2. Smallpox

Americas escaped of the Black Death because of the isolation. But when discovered, the smallpox struck. In 1518 an outbreak of smallpox in the Haiti island left just 1,000 of the Native Indians. 100 years after the discovery of America by Columbus, 90 % of its native population have died of smallpox. Mexico passed from 30 million to 3 million inhabitants, Peru from 8 million to 1 million.

About 1,600, when the first European colonists reached Massachusetts, found it practically uninhabited, as smallpox had killed almost all local Indians.

It is believed that along the history, smallpox killed more humans that all the wars of the 20th century together. Since 1914 to 1977 smallpox killed 300 to 500 million people. By 1970, smallpox still killed 2 million people annually, but OMS managed to eradicate the diseases through vaccination and in the last case was found in Somalia, in 1977. This was possible because smallpox transmits only from human to human. At the time of eradication, no effective cure was known against smallpox.

The first ever vaccine was created in 1798 by Edward Jenner and was against smallpox.

3. Leishmaniosis

infects 2 million people annually and about 12 million diseased are found worldwide, mostly adult men. It is produced by a protozoa (Leishmania) that spreads through the bite of the sand flies (Phlebotomus).

The most severe type is “kala azar” (“black fever” in Hindu), which infects 0.5 million people, and incubation lasts some weeks. The parasite induces skin ulcers which extend all over the body and can produce obstructions or nasal hemorrhage.

It causes severe lesions on the legs and a temporary or definitive physical disability.

Kala azar swells the spleen and the liver and attacks the bony marrow and linph nodules. Without treatment, the parasite kills 75-95 % of the patients.

It is found mainly in Africa, China, India, Latin America, and outbreaks occur sometimes in Mexico and the US.

The best drug is Pentostam. Intravenous Amphotericin B is effective, like the Pendamidine, but there is no vaccine yet.


4. Malaria

is found in 500 million people (!) and is caused by a protozoa spread by the female of the Anopheles mosquito. 300 million of these cases are severe. In the east African villages, children are bitten by the Anopheles mosquitoes carrying malaria 50-80 times a month.

It triggers fever, shivering, abundant sweating, articulation pains, severe headache, vomit and extreme weakness, so that the diseased cannot even cry.

Annually, 1.5 million people die of malaria (one million in Africa South of Sahara), a child every 30 seconds. About 120 million people died of malaria since 1914, and the disease is endemic in 101 countries, mainly tropical, in Africa, Asia and America.

It spreads during the rainy season, when the mosquitoes breed. Quinine extracted from the bark of the South American cinchona tree saved millions of malaria diseased. Many treatments have been developed (mefloquine, Halofantrine, Artemisia products) but none has a total effectiveness, as the parasite constantly mutates, and there is no vaccine.


5. Gonorrhea and syphilis

are triggered by two bacteria (Neisseria and Treponema pallida) and are transmitted sexually.

62 million people worldwide are affected, aged mainly 15 to 29 years, all over the planet, especially in urban areas and of low socioeconomic level.

In man, gonorrhea produces urinary incontinence, urethra pain, reddening, penis burning sensation and testicle inflammation. In women, it induces severe pain which reaches the trumps and uterus.

Syphilis induces ulcered lesion (syphilis chancre) at the entrance site. After that, it triggers skin eruptions, fever, hair loss, less severe hepatitis and gential condilloms, but if untreated, the lesions extend to the nervous system, leading to death.

The treatment consists in extremely powerful antibiotics (ceftriaxone, Cefixime, and others) which are also extremely costly.


6. Pneumonia

affects 1 % of the planet’s population and can be produced by viruses or bacteria (like Aeromonas hydrophila).

It produces fever, shiver, sweating, cough with expectoration, muscle, head and thoracic pain, appetite loss, weakness.

This is the main cause of mortality in the world: it kills 3.5 million people each year. It attacks especially patients with severe immunodepression, those that follow chemotherapy, people who are older than 75, asthmatics, smokers, alcoholics, those with renal insufficiency and children under 2 years of age. It affects especially the poor countries.

Antibiotics work in the case of the bacteria. Therapy includes oxygen, liquids, and physiotherapy.

Patients with a simple pneumonia can cure in 2-3 weeks, but elders or those with debilitating diseases can die of respiratory or cardiorespiratory failure.

The vaccine trimetropin sulfamethoxazole is effective against the most frequent complications.


7. Sleeping sickness

is triggered by the Tripanosoma gambiense and T. rhodesiense, protozoans spread by the tse-tse fly (Glossina). The American variant, T cruzi, is spread by biting bugs and cause the disease called chagas.

The toxins of the parasites affect especially the central nervous system and the heart muscle. It manifests through fever, edemas, sleepiness, and meningitis.

It affects 60 million people, but only 4 million receive treatment, and it kills 150,000 people yearly.

It affects the livestock, being deadly or inducing low fertility, weight and productivity, with severe economical losses. It is found in the habitat of the tse-tse fly: over 10 million square km in 36 African countries. Chagas is found in certain areas of Central and South America.

DFMO, the effective drug, is already not produced. Currently, melarsoprol with arsenic are employed, fact that induces the death of up to 10 % of the patients. Vaccine exists only for the carrying livestock. There are also efforts to eliminate the flies in some areas.


8. Tuberculosis

is caused by the Koch bacterium. It is as old as the humankind. TBC was found even in mummies coming from the ancient Egypt and Peru. 2 million people die annually of tuberculosis. About 150 million people are estimated to have died of TBC since 1914.

One third of the people carry the Koch bacterium, which spreads through the air and affects all the body, especially the lungs. It induces prolonged coughing, fever, shivering, bloody expectoration, weight loss, sweating, tiresome, and glossy eyes.

It infects one third of the world population and each year another new 8 million cases appear. Each second a person dies of tuberculosis. It is more aggressive in women and persons between 15 and 45 years old. Mutant strains are resistant to almost all drugs and kill about 50 % of the patients.

It is worldwide spread, but its advance is rampant in Bangladesh, China, Indonesia, Philippines, India and Pakistan, with over half of the new cases.

TBC has a treatment, but it cannot be eradicated because of the emergence of multiresistant strains if the long and costly treatment, of over 6 months, is interrupted sooner than it should. 3-5 % of the new cases are coinfected with HIV.

The vaccine is effective in children, but useless in adults. Current employed drugs are isoniazid, ethambutol and Rifapentin.



is estimated to be found in 46-60 million people and it’s produced by the human immunodeficiency virus (HIV), spread through blood, semen, and vaginal fluids. Some say the virus is still in an early stage.

The symptoms come rather late and start with exhaustion and fever. After that, ganglion inflammation appears along with persistent diarrhea, pneumonia and weight loss. In the final stage, the patient’s state is profoundly altered.

Each minute, five new persons get infected with HIV, and the virus kills young people, found in their productive period. It has killed 25 million people since 1981 and about 3.3 million people with HIV die annually. 68 million people could die between 2000-2020. Africa has lost 20 % of its labor power. Lifespan in Sub-Saharian Africa is now of 47 years old; without the AIDS it would have been 62.

In developed world, 58 % of the new cases are drug addicts who share syringes and 33 % through unprotected sexual contacts, but in undeveloped countries is mainly through unprotected sex and blood transfusions.

28 million of the HIV infected are found in Africa, and 0.5 million in West Europe; 300,000 in Eastern Europe, 600,000 in Eastern Asia and Oceania; 2.6 million in America (mostly South America).

Antiretrovirals can improve the immunity but its price is too costly for about 95 % of the infected. Only 4 % of the patients in the developing countries receive treatments. This treatment can cost 6-18,000 Euro ($ 8-25,000) and the virus will get resistance to drugs if the treatment is interrupted.

In pregnant women, antiretrovirals during the second and third trimesters of the pregnancy can avoid the child’s infection.

There is no vaccine, and the combination of up to four different drugs is the main principle in stopping the disease. These drugs keep the blood lymphocytes at normal levels, maintaining the virus latent but without its deadly ability.


10.Spanish flu

hit the world in 1918-1919 and killed over 30 million persons, soon after the First World War. Not even the bubonic plague had ever killed so rapidly so many persons. Typhus outbreaks use to accompany war conflicts. A huge typhus pandemic outbroke during the First World War in the eastern Europe. Since 1914, over 20 million people died of typhus.