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Signs and symptoms of Dengue fever

Dengue fever and dengue hemorrhagic fever (DHF) are acute febrile diseases, found in the tropics and Africa, and caused by four closely related virus serotypes of the genus Flavivirus, family Flaviviridae. The geographical spread is similar to malaria, but unlike malaria, dengue is often found in urban areas of tropical nations, including Puerto Rico,Singapore,Malaysia, Taiwan, Indonesia, Philippines, India and Brazil. Each serotype is sufficiently different that there is no cross-protection and epidemics caused by multiple serotypes (hyperendemicity) can occur. Dengue is transmitted to humans by the Aedes aegypti (rarely Aedes albopictus) mosquito, which feeds during the day.

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This infectious disease is manifested by a sudden onset of fever, with severe headache, muscle and joint pains (myalgias and arthralgias-severe pain gives it the name break-bone fever or bonecrusher disease) and rashes. The dengue rash is characteristically bright red petechiae and usually appears first on the lower limbs and the chest; in some patients, it spreads to cover most of the body. There may also be gastritis with some combination of associated abdominal pain, nausea, vomiting or diarrhea.

Other symptoms include:

fever;

bladder problems;

constant headaches;

severe dizziness; and,

loss of appetite.

uncontrollable laughing,

extreme constipation

Some cases develop much milder symptoms which can, when no rash is present, be misdiagnosed as influenza or other viral infection. Thus travelers from tropical areas may inadvertently pass on dengue in their home countries, having not been properly diagnosed at the height of their illness. Patients with dengue can pass on the infection only through mosquitoes or blood products and only while they are still febrile.

The classic dengue fever lasts about six to seven days, with a smaller peak of fever at the trailing end of the disease (the so-called "biphasic pattern"). Clinically, the platelet count will drop until the patient's temperature is normal.

Cases of DHF also show higher fever, haemorrhagic phenomena, thrombocytopenia, and haemoconcentration. A small proportion of cases lead to dengue shock syndrome (DSS) which has a high mortality rate.

Diagnosis: The diagnosis of dengue is usually made clinically. The classic picture is high fever with no localising source of infection, a petechial rash with thrombocytopenia and relative leukopenia.

The WHO definition of dengue haemorrhagic fever has been in use since 1975; all four criteria must be fulfilled:

Fever, bladder problem, constant headaches, severe dizziness and loss of appetite.

Hemorrhagic tendency (positive tourniquet test, spontaneous bruising, bleeding from mucosa, gingiva, injection sites, etc.; vomiting blood, or bloody diarrhea)

Thrombocytopenia (<100,000 platelets per mm³ or estimated as less than 3 platelets per high power field)

Evidence of plasma leakage (hematocrit more than 20% higher than expected, or drop in haematocrit of 20% or more from baseline following IV fluid, pleural effusion, ascites, hypoproteinemia)

Dengue shock syndrome is defined as dengue hemorrhagic fever plus:

Weak rapid pulse,

Narrow pulse pressure (less than 20 mm Hg) or,

Cold, clammy skin and restlessness.

Serology and polymerase chain reaction (PCR) studies are available to confirm the diagnosis of dengue if clinically indicated.

Treatment: The mainstay of treatment is supportive therapy. Increased oral fluid intake is recommended to prevent dehydration. Supplementation with intravenous fluids may be necessary to prevent dehydration and significant concentration of the blood if the patient is unable to maintain oral intake. A platelet transfusion is indicated in rare cases if the platelet level drops significantly (below 20,000) or if there is significant bleeding.

The presence of melena may indicate internal gastrointestinal bleeding requiring platelet and/or red blood cell transfusion.

Aspirin and non-steroidal anti-inflammatory drugs should be avoided as these drugs may worsen the bleeding tendency associated with some of these infections. Patients may receive paracetamol preparations to deal with these symptoms if dengue is suspected.

Emerging treatments: Emerging evidence suggests that mycophenolic acid and ribavirin inhibit dengue replication. Initial experiments showed a fivefold increase in defective viral RNA production by cells treated with each drug. In vivo studies, however, have not yet been done.

Epidemiology: World-wide dengue distribution, 2006. Red: Epidemic dengue. Blue: Aedes aegypti.

World-wide dengue distribution, 2000The first epidemics occurred almost simultaneously in Asia, Africa, and North America in the 1780s. The disease was identified and named in 1779. A global pandemic began in Southeast Asia in the 1950s and by 1975 DHF had become a leading cause of death among children in many countries in that region. Epidemic dengue has become more common since the 1980s. By the late 1990s, dengue was the most important mosquito-borne disease affecting humans after malaria, there being around 40 million cases of dengue fever and several hundred thousand cases of dengue hemorrhagic fever each year. There was a serious outbreak in Rio de Janeiro in February 2002 affecting around one million people and killing sixteen.

On March 20, 2008, the secretary of health of the state of Rio de Janeiro, Sérgio Côrtes, announced that 23,555 cases of dengue, including 30 deaths, had been recorded in the state in less than three months. Côrtes said, "I am treating this as an epidemic because the number of cases is extremely high." Federal Minister of Health José Gomes Temporão also announced that he was forming a panel to respond to the situation. Cesar Maia, mayor of the city of Rio de Janeiro, denied that there was serious cause for concern, saying that the incidence of cases was in fact declining from a peak at the beginning of February. By April 3, 2008, the number of cases reported rose to 55,000

Significant outbreaks of dengue fever tend to occur every five or six months. The cyclicity in numbers of dengue cases is thought to be the result of seasonal cycles interacting with a short-lived cross-immunity for all four strains, in people who have had dengue (Wearing and Rohani 2006). When the cross-immunity wears off, the population is then more susceptible to transmission whenever the next seasonal peak occurs. Thus in the longer term of several years, there tend to remain large numbers of susceptible people in the population despite previous outbreaks because there are four different strains of the dengue virus and because of new susceptible individuals entering the target population, either through childbirth or immigration.

There is significant evidence, originally suggested by S.B. Halstead in the 1970s, that dengue hemorrhagic fever is more likely to occur in patients who have secondary infections by serotypes different from the primary infection. One model to explain this process is known as antibody-dependent enhancement (ADE), which allows for increased uptake and virion replication during a secondary infection with a different strain. Through an immunological phenomenon, known as original antigenic sin, the immune system is not able to adequately respond to the stronger infection, and the secondary infection becomes far more serious. This process is also known as superinfection (Nowak and May 1994; Levin and Pimentel 1981).

In Singapore, there are about 4,000-5,000 reported cases of dengue fever or dengue haemorrhagic fever every year. In the year 2003, there were six deaths from dengue shock syndrome.[citation needed] It is believed that the reported cases of dengue are an underrepresentation of all the cases of dengue as it would ignore subclinical cases and cases where the patient did not present for medical treatment. With proper medical treatment, the mortality rate for dengue can therefore be brought down to less than 1 in 1000.[citation needed]

Vaccine development: There is no commercially available vaccine for the dengue flavivirus. However, one of the many ongoing vaccine development programs is the Pediatric Dengue Vaccine Initiative which was set up in 2003 with the aim of accelerating the development and introduction of dengue vaccine(s) that are affordable and accessible to poor children in endemic countries. Thai researchers are testing a dengue fever vaccine on 3,000-5,000 human volunteers after having successfully conducted tests on animals and a small group of human volunteers. A number of other vaccine candidates are entering phase I or II testing.

Mosquito control: A field technician looking for larvae in standing water containers during the 1965 Aedes aegypti eradication program in Miami, Florida. In the 1960s, a major effort was made to eradicate the principal urban vector mosquito of dengue and yellow fever viruses, Aedes aegypti, from southeast United States. Courtesy: Centers for Disease Control and Prevention Public Health Image LibraryPrimary prevention of dengue mainly resides in mosquito control. There are two primary methods: larval control and adult mosquito control. In urban areas, Aedes mosquitos breed on water collections in artificial containers such as plastic cups, used tires, broken bottles, flower pots, etc. Continued and sustained artificial container reduction or periodic draining of artificial containers is the most effective way of reducing the larva and thereby the aedes mosquito load in the community. For reducing the adult mosquito load, fogging with insecticide is somewhat effective.

Prevention of mosquito bites is another way of preventing disease. This can be achieved either by personal protection or by using mosquito nets. In 1998, scientists from the Queensland Institute of Research in Australia and Vietnam's Ministry of Health introduced a scheme that encouraged children to place a water bug, the crustacean Mesocyclops, in water tanks and discarded containers where the Aedes aegypti mosquito was known to thrive. This method is viewed as being more cost-effective and more environmentally friendly than pesticides, though not as effective, and requires the ongoing participation of the community.

Personal protection: Personal prevention consists of the use of mosquito nets, repellents containing NNDB or DEET, covering exposed skin, use of DEET-impregnated bednets, and avoiding endemic areas.

Potential antiviral approaches: In cell culture experiments and mice Morpholino antisense oligos have shown specific activity against Dengue virus.

The yellow fever vaccine (YF-17D) is a related Flavivirus, thus the chimeric replacement of yellow fever vaccine with dengue has been often suggested[clarify] but no full scale studies have been conducted to date.

In 2006, a group of Argentine scientists discovered the molecular replication mechanism of the virus, which could be attacked by disruption of the polymerase's work.

Water contaminated with feces causes Typhoid

Typhoid fever, also known as enteric fever, bilious fever or Yellow Jack, is an illness caused by the bacterium Salmonella enterica serovar Typhi. Common worldwide, it is transmitted by the ingestion of food or water contaminated with feces from an infected person. The bacteria then multiply in the blood stream of the infected person and are absorbed into the digestive tract and eliminated with the waste. The organism is a Gram-negative short bacillus that is motile due to its peritrichous flagella. The bacteria grows best at 37°C (human body temperature).

Symptoms: Typhoid fever is characterized by a sustained fever as high as 40°C (104°F), profuse sweating, gastroenteritis, and nonbloody diarrhea. Less commonly a rash of flat, rose-colored spots may appear.

Classically, the course of untreated typhoid fever is divided into four individual stages, each lasting approximately one week. In the first week, there is a slowly rising temperature with relative bradycardia, malaise, headache and cough. Epistaxis is seen in a quarter of cases and abdominal pain is also possible. There is leukopenia with eosinopenia and relative lymphocytosis, a positive diazo reaction and blood cultures are positive for Salmonella Typhi or Paratyphi. The classic Widal test is negative in the first week.

In the second week of the infection, the patient lies prostrated with high fever in plateau around 104°F (40°C) and bradycardia (Sphygmo-thermic dissociation), classically with a dicrotic pulse wave. Delirium is frequent, frequently calm, but sometimes agitated. This delirium gives to typhoid the nickname of "nervous fever". Rose spots appear on the lower chest and abdomen in around 1/3 patients. There are rhonchi in lung bases. The abdomen is distended and painful in the right lower quadrant where borborygmi can be heard. Diarrhea can occur in this stage: six to eight stools in a day, green with a characteristic smell, comparable to pea-soup. However, constipation is also frequent. The spleen and liver are enlarged (hepatosplenomegaly) and tender and there is elevation of liver transaminases. The Widal reaction is strongly positive with antiO and antiH antibodies. Blood cultures are sometimes still positive at this stage.

In the third week of typhoid fever a number of complications can occur:

Intestinal hemorrhage due to bleeding in congested Peyer's patches; this can be very serious but is usually non-fatal.

Intestinal perforation in distal ileum: this is a very serious complication and is frequently fatal. It may occur without alarming symptoms until septicaemia or diffuse peritonitis sets in.

Encephalitis : Metastatic abscesses, cholecystitis, endocarditis and osteitis

The fever is still very high and oscillates very little over 24 hours. Dehydration ensues and the patient is delirious (typhoid state). By the end of third week defervescence commences that prolongs itself in the fourth week. Diagnosis: Diagnosis is made by blood, bone marrow or stool cultures and with the Widal test (demonstration of salmonella antibodies against antigens O-somatic and H-flagellar). In epidemics and less wealthy countries, after excluding malaria, dysentery or pneumonia, a therapeutic trial time with chloramphenicol is generally undertaken while awaiting the results of Widal test and blood cultures.

Treatment: Doctor administering a typhoid vaccination at a school in San Augustine County, Texas. Photograph by John Vachon, April 1943.Typhoid fever in most cases is not fatal. Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and ciprofloxacin, have been commonly used to treat typhoid fever in developed countries. Prompt treatment of the disease with antibiotics reduces the case-fatality rate to approximately 1%. When untreated, typhoid fever persists for three weeks to a month. Death occurs in between 10% and 30% of untreated cases.

Resistance: Resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole and streptomycin is now common, and these agents have not been used as first line treatment now for almost 20 years. Typhoid that is resistant to these agents is known as multidrug-resistant typhoid (MDR typhoid).

Ciprofloxacin resistance is an increasing problem, especially in the Indian subcontinent and Southeast Asia. Many centres are therefore moving away from using ciprofloxacin as first line for treating suspected typhoid originating in India, Pakistan, Bangladesh, Thailand or Vietnam. For these patients, the recommended first line treatment is ceftriaxone.

There is a separate problem with laboratory testing for reduced susceptibility to ciprofloxacin: current recommendations are that isolates should be tested simultaneously against ciprofloxacin (CIP) and against nalidixic acid (NAL), and that isolates that are sensitive to both CIP and NAL should be reported as "sensitive to ciprofloxacin", but that isolates testing sensitive to CIP but not to NAL should be reported as "reduced sensitivity to ciprofloxacin". However, an analysis of 271 isolates showed that around 18% of isolates with a reduced susceptibility to ciprofloxacin (MIC 0.125-1.0 mg/l) would not be picked up by this method. It not certain how this problem can be solved, because most laboratories around the world (including the West) are dependent disc testing and cannot test for MICs.

Prevention: Sanitation and hygiene are the critical measures that can be taken to prevent typhoid. Typhoid does not affect animals and therefore transmission is only from human to human. Typhoid can only spread in environments where human faeces or urine are able to come into contact with food or drinking water. Careful food preparation and washing of hands are therefore crucial to preventing typhoid. There are two vaccines currently recommended by the World Health Organisation for the prevention of typhoid: these are the live, oral Ty21a vaccine (sold as Vivotif Berna) and the injectable Vi capsular polysaccharide vaccine (sold as Typhim Vi). Both are between 50 to 80% protective and are recommended for travellers to areas where typhoid is endemic. There exists an older killed whole-cell vaccine that is still used in countries where the newer preparations are not available, but this vaccine is no longer recommended for use, because it has a higher rate of side effects (mainly pain and inflammation at the site of the injection). Transmission: Death rates for Typhoid Fever in the U.S. 1906-1960Flying insects feeding on feces may occasionally transfer the bacteria through poor hygiene habits and public sanitation conditions. Public education campaigns encouraging people to wash their hands after toileting and before handling food are an important component in controlling spread of the disease. According to statistics from the United States Center for Disease Control, the chlorination of drinking water has led to dramatic decreases in the transmission of typhoid fever in the U.S.

A person may become an asymptomatic carrier of typhoid fever, suffering no symptoms, but capable of infecting others. According to the Centers for Disease Control approximately 5% of people who contract typhoid continue to carry the disease after they recover. The most famous asymptomatic carrier was Typhoid Mary. She was a young cook that was responsible for infecting about 47 people during her lifetime, killing three of the infected. This was the first time a perfectly healthy person was known to be responsible for an "epidemic".

Epidemiology: With an estimated 16-33 million cases of annually resulting in 500,000 to 600,000 deaths in endemic areas, the World Health Organisation identifies typhoid as a serious public health problem. Its incidence is highest in children between 5 and 19 years old.[8]

Heterozygous advantage: It is thought that cystic fibrosis may have risen to its present levels (1 in 1600 in UK) due to the heterozygous advantage that it confers against typhoid fever. The CFTR protein is present in both the lungs and the intestinal epithelium, and the mutant cystic fibrosis form of the CFTR protein prevents entry of the typhoid bacterium into the body through the intestinal epithelium.

History: Around 430-426 B.C., a devastating plague, which some believe to have been typhoid fever, killed one third of the population of Athens, including their leader Pericles. The balance of power shifted from Athens to Sparta, ending the Golden Age of Pericles that had marked Athenian dominance in the ancient world. Ancient historian Thucydides also contracted the disease, but he survived to write about the plague. His writings are the primary source on this outbreak. The cause of the plague has long been disputed, with modern academics and medical scientists considering epidemic typhus the most likely cause. However, a 2006 study detected DNA sequences similar to those of the bacterium responsible for typhoid fever.[9] Other scientists have disputed the findings, citing serious methodologic flaws in the dental pulp-derived DNA study. The disease is most commonly transmitted through poor hygiene habits and public sanitation conditions; during the period in question, the whole population of Attica was besieged within the Long Walls and lived in tents.

In the late 19th century, typhoid fever mortality rate in Chicago averaged 65 per 100,000 people a year. The worst year was 1891, when the typhoid death rate was 174 per 100,000 persons. The most notorious carrier of typhoid fever-but by no means the most destructive-was Mary Mallon, also known as Typhoid Mary. In 1907, she became the first American carrier to be identified and traced. She was a cook in New York; some believe she was the source of infection for several hundred people. She is closely associated with forty-seven cases and three deaths. Public health authorities told Mary to give up working as a cook or have her gall bladder removed. Mary quit her job but returned later under a false name. She was detained and quarantined after another typhoid outbreak. She died of pneumonia after 26 years in quarantine.

In 1897, Almroth Edward Wright developed an effective vaccine.

Most developed countries saw declining rates of typhoid fever throughout first half of 20th century due to vaccinations and advances in public sanitation and hygiene. Antibiotics were introduced in clinical practice in 1942, greatly reducing mortality. At the present time, incidence of typhoid fever in developed countries is around 5 cases per 1,000,000 people per year.

An outbreak in the Democratic Republic of Congo in 2004-05 recorded more than 42,000 cases and 214 deaths.

China’s quake victims suffer mental trauma

As many as 10 percent of those affected by the earthquake in southwest China will need long-term mental health care, the World Health Organisation said on Friday, adding the region had a chance to build a better healthcare system.

Health services should include more capacity for psychological care, as well as rehabilitation facilities for the huge numbers who lost limbs when the 7.9 magnitude quake struck on May 12.

"What we know is that everyone who has gone through something like this will have some kind of need of psychological support," Hans Troedsson, the WHO's China representative, told a news conference.

Much of that support could be provided within the community as schools resume classes and lives begin to get back to normal.

"We also know that usually up to 10 percent will need more professional mental health services," he said. "It is an area that has sometimes not gotten the attention it requires."

Hospitals were overwhelmed by sheer numbers in the days following the quake that killed at least 70,000, but for those who managed to reach medical help, the fatality rate was low, Troedsson said,

In the weeks following, there have been no major outbreaks of disease.

The WHO was also in the process of consulting with the Chinese government on rebuilding hospitals to withstand future natural disasters.

The process should add only 2 to 5 percent to the cost of a new building, but it was vital such safety measures be incorporated into the design to be effective, officials said.

"These are not add-ons, they are fundamental decisions to be made at the start of the design," said Tony Gibbs, an engineering consultant to the WHO.

Rebuilding Sichuan's healthcare offered an opportunity to address some of the issues plaguing China's medical system, which include a lack of trained healthcare workers in rural areas, the WHO officials said.

- Reuters, Beijing