Indonesia Human Cases - April 9, 2008 - 20th June 2008

[kent nickell]

Re: Indonesia Human Cases - April 9, 2008+

Commonground, I agree completely with your analysis (post 339). Dengue and typhus are difficult to diagnose by lab methods and we see almost nothing on what tests they are using to make these diagnoses. Trying to sort out the cause of acute febrile illness by clinical symptoms is problematic due to overlap of symptoms and 'political correctness'.

WHO, Promed and other official sources seem too ready to accept implausible causes of these infections. I think it's important that we try and keep track of these clusters which seem to be logically linked to confirmed H5N1 cases.

Some recent news reporting out of Indonesia and other places seems encouraging in that they are addressing these problems of trying to be more discriminatory in making a proper diagnosis. (What person in what country would not want their disease properly diagnosed so that it could be properly treated?)

It would also be useful to have more information on confirmatory tests of cases of mild disease for which tamiflu appears to be useful. We are losing a lot of valuable information here is we can't do the basics of linking together what type of medical treatment is working for what specific disease. And in the case of H5N1 what type of treatment is working relative to changes in the sequence data.

[sharon sanders]

Re: Indonesia Human Cases - April 9, 2008+

Yes. But in Indonesia more than 80% of the case's presentation were influenza-like illness, pneumonia and severe influenza. It is not impossible to accept the reality of co-morbidity in some of recent cases. Don't restrict your view, people!
In fact Indonesian live amidst endemic Dengue Fever (and Dengue Haemorrhagic Fever), Malaria, Tubercolosis, severe malnoutrition conditions, viral hepatitis, infectious gastroenteric diseases... Nothing new, since the early cases of bird flu in humans presented with GI symptoms, septic shock with hemorrhages.
Again, nothing precludes to co-morbid presentation of human birdflu infections.

Thanks IOH. I agree, co-infection is highly likely in many cases. This data simply points out the diagnosis at the onset of illness.

This is why complete visibility is essential. Many of these diseases are endemic in Indonesia.

International Organizations have a difficult mission as they are "invited" into member countries.......or not.

[HenryN]

Re: Indonesia Human Cases - April 9, 2008+

Commonground, I agree completely with your analysis (post 339). Dengue and typhus are difficult to diagnose by lab methods and we see almost nothing on what tests they are using to make these diagnoses. Trying to sort out the cause of acute febrile illness by clinical symptoms is problematic due to overlap of symptoms and 'political correctness'.

WHO, Promed and other official sources seem too ready to accept implausible causes of these infections. I think it's important that we try and keep track of these clusters which seem to be logically linked to confirmed H5N1 cases.

Some recent news reporting out of Indonesia and other places seems encouraging in that they are addressing these problems of trying to be more discriminatory in making a proper diagnosis. (What person in what country would not want their disease properly diagnosed so that it could be properly treated?)

It would also be useful to have more information on confirmatory tests of cases of mild disease for which tamiflu appears to be useful. We are losing a lot of valuable information here is we can't do the basics of linking together what type of medical treatment is working for what specific disease. And in the case of H5N1 what type of treatment is working relative to changes in the sequence data.

I think much of the diagnosis is based on what is most common. I don't think that either dengue ot typhoid diagnosis are based on any specific lab tests, which is why the positive H5N1 in a family member is the appropriate guide for diagnosing other family members with identical symtoms, especially since all of these index cases are fatal (if the patient survived, antibody tests could be run, but these highly suspect diagnosis are for FATAL cases).

These clusters really are not that complex and don't require highly unlikely co-infections, expecially when there are no specific lab tests to support dengue fever, typhus, or "lung inflammation".

[HenryN]

Re: Indonesia Human Cases - April 9, 2008+

Commonground, I agree completely with your analysis (post 339). Dengue and typhus are difficult to diagnose by lab methods and we see almost nothing on what tests they are using to make these diagnoses. Trying to sort out the cause of acute febrile illness by clinical symptoms is problematic due to overlap of symptoms and 'political correctness'.

WHO, Promed and other official sources seem too ready to accept implausible causes of these infections. I think it's important that we try and keep track of these clusters which seem to be logically linked to confirmed H5N1 cases.

Some recent news reporting out of Indonesia and other places seems encouraging in that they are addressing these problems of trying to be more discriminatory in making a proper diagnosis. (What person in what country would not want their disease properly diagnosed so that it could be properly treated?)

It would also be useful to have more information on confirmatory tests of cases of mild disease for which tamiflu appears to be useful. We are losing a lot of valuable information here is we can't do the basics of linking together what type of medical treatment is working for what specific disease. And in the case of H5N1 what type of treatment is working relative to changes in the sequence data.

Dengue fever is a relatively common problem in Indonesia and periodically reaches epidemic proportions in Jakarta and other parts of Indonesia, usually every 4-5 years. Rarely fatal in fit adults, the patient is often left debilitated and requires considerable time for convalescence. Dengue Fever is most common during the rainy season (November - May) as the mosquito requires clean standing water to reproduce.
Dengue occurs due to infection by a flavivirus which is transmitted by the bite of the Aedes mosquito. (Unlike malaria, this disease occurs in greater Jakarta - urban dengue occurs in nearly all tropical countries).
SYMPTOMS

Certainly in the first stages of illness, dengue fever is difficult if not impossible to clinically distinguish from the many other possible causes of similar symptoms and signs.
IN ADULTS:
Following the deposit of the dengue virus in the skin by the bite, there is a an incubation period of 2 - 14 (usually 4 - 8) days.
Thereafter onset of symptoms is usually abrupt, coinciding with viremia (the virus multiplying in the bloodstream) with chills, headache, backache, weakness, pain behind the eyes, flushing of the face, muscle and joint pain, and lassitude. The joint and back pains can be very bad indeed; hence the older name 'breakbone fever'.
The temperature rapidly rises, often to 40°C (104°F), and there is a low heart rate (compared to the degree of, and other causes of, high fever). The blood pressure is often low also. A transient rash which blanches under pressure may be seen during the first 24 hours of fever.
During the 2<SUP>nd</SUP> to 6<SUP>th</SUP> day of fever, nausea and even vomiting may occur, and the patient may develop one or more of the following; skin hypersensitivity, generalized swelling of regional lymph nodes, swelling of the palms, changes in taste sensation, loss of appetite, constipation, anxiety and depression.
Within 2 to 4 days a temporary improvement can occur with a sudden drop in temperature and subjective improvement - for 24 hours until there is a second rapid temperature rise. A generalized morbilliform (“measles-like”) rash appears a characteristic rash on the trunk, limbs, palms and soles especially. (This second febrile phase does not invariably occur). This rash usually disappears in 1-5 days, the skin in these areas turns bright red and may peel. The temperature should fall back to normal and the infectious episode is effectively over.
Epistaxis (“nose bleeds”), petechiae (“red skin spots”) and purpuric skin lesions (“purple skin spots / bruises”) can occur at any stage of the disease, varying with age, sex, and type of dengue virus. Bleeding from the gastrointestinal tract, and excessive vaginal bleeding if menstruating can also occur, but do not usually occur in the majority of cases.
IN CHILDREN:
A fever occurs in nearly all dengue infections in children; the other most common symptoms are a red throat, a (usually mild) runny nose, cough, and mild gastrointestinal symptoms which of course may present similar to pharyngitis, influenza, and upper respiratory infections.
The presentation of dengue in the younger child is much less characteristic than in the older child and adult as above.
CONFIRMING THE DIAGNOSIS

There are no immediately useful tests for dengue fever which are unequivocally accurate. However the laboratory can be used to aid confirmation of a clinically suspicious case:

• The white cell count is often low unlike in bacterial causes of fever.
• The dengue blot test can give both false positive and false negative results, especially in the first week of the disease.
• The diagnosis will in a large proportion of cases be based on clinical presentation and a characteristic
  drop of platelets in the blood (platelets are often low - normal is 150,000 - 400,000).

Definite confirmation of the diagnosis of dengue infection can be made by sophisticated tests, but the results are not available for two weeks or more after the onset of the illness (because two separate blood samples need to be tested (by the same lab) for dengue antibody levels, the first as soon as possible after the onset of the illness, the second 10-14 days later).
Convalescence can take weeks, and bed rest and antipyretics and analgesics are required. An attack produces immunity for a year or more, but only to the one of the four flavivirus strains responsible for the intial illness.
DENGUE HAEMORRHAGIC FEVER / DENGUE SHOCK SYNDROME

A rare complication of dengue fever, dengue haemorrhagic fever, can occur, most often in small children and elderly adults. This can sometimes be a serious illness. If DHF / DSS occurs it will usually do so by day 3-5 of the fever.
IN CHILDREN
In children, the progression of disease is not always characteristic. A relatively mild first phase with an abrupt onset of fever, malaise, vomiting, headache anorexia and cough is succeeded 2-5 days later by weakness and, sometimes, physical collapse. Frequently, spots appear on the forehead, arms and legs, along with spontaneous bruises and bleeding from punctures where blood was taken. The more ill child may breathe rapidly and often effortfully; the pulse may be weak, rapid, and thready. Almost always patients have a positive “tourniquet test” (where a tourniquet i.e. a blood pressure cuff is applied and the skin demonstrates petechiae and / or bruising).
The WHO criteria for DHF are a platelet count of less than 100,000 and a haematocrit 20&#37; greater then normal. Such children need to be hospitalized and watched for potential DSS. Such shock can be a mortal illness and requires rapid and careful in-hospital management with assiduous correction and replacement of fluid, electrolytes, plasma and sometimes fresh blood / platelet transfusions. The most useful laboratory test in suspected DHF is estimation of thrombocytes (platelets) which will be very low. In contrast to uncomplicated dengue fever the white cell count is more often high. Mortality ranges from 5 - 30% (in untreated native populations) and the highest risk is to infants under 1 year.
TREATMENT

There is no specific treatment for the infectious cause - the dengue virus - in either dengue fever or DHF / DSS. The symptoms can and should be treated, and in the rare cases of DSS, treatment for shock as well as a low platelet count is both essential and available - including fresh blood and / or platelet transfusion -but there is no medicine or vaccine anywhere available that can act specifically against the virus.
It has been suggested that DHF is more likely if the patient has previously had an attack of dengue within the last calendar year (generally within the last 8-12 months), and that the occurrence of DHF relates to this previous "sensitization". Previous exposure may raise the incidence of subsequent DHF, presumably (as experiments have shown) by the antibody elicited in response to the first infection, being capable of enhancing the infection due to the virus found in the second episode.
Uncontrolled bleeding distinguishes this from uncomplicated dengue fever. Bleeding can occur from the gums, nose, intestine, or under the skin as bruises or spots of blood especially under a tourniquet - this test should be employed if there is any suspicion. The liver is often enlarged.

http://www.expat.or.id/medical/dengue.html

[kent nickell]

Re: Indonesia Human Cases - April 9, 2008+

Thanks Henry, these problems can make it especially difficult to pull out the mild cases of H5N1. Typhus appear to be in the same category of difficulty to make an accurate lab diagnosis. Also a lot of patients therefore just get empiric treatment which now likely includes tamiflu. Would be interesting to know how well tamiflu use is tied to any sort of lab diagnosis of H5N1.

http://www.emedicine.com/MED/topic2332.htm

Typhus

Typhus refers to a group of infectious diseases that are caused by rickettsial organisms and result in an acute febrile illness. Arthropod vectors transmit the etiologic agents to humans. The principle diseases of this group are epidemic or louse-borne typhus and its recrudescent form known as Brill-Zinser disease, murine typhus, and scrub typhus.

Epidemic typhus occurs in Central and South America, Africa, northern China, and certain regions of the Himalayas. Outbreaks may occur when conditions arise that favor the propagation and transmission of lice. Brill-Zinsser disease may occur in approximately 15% of people with a history of primary epidemic typhus.

Murine typhus occurs in most parts of the world, particularly in subtropical and temperate coastal regions. It occurs mainly in sporadic cases, and incidence is probably greatly underestimated in the more endemic regions. Rats, mice, and cats, which are hosts for the disease, are particularly common along coastal port regions. Temperate climates may have a rise in the flea vector and a subsequent rise in the incidence of murine typhus in the summer months. Prior infection with R typhi provides immunity to subsequent reinfection.

Scrub typhus occurs in the western Pacific region, northern Australia, and the Indian subcontinent. Incidence of scrub typhus is largely unknown. Many cases are undiagnosed because of its nonspecific manifestations and the lack of laboratory diagnostic testing in endemic areas. However, a report of incidence of scrub typhus in Malaysia was approximately 3% per month, and multiple infections in the same individual may occur because of a lack of cross-immunity among the various strains of Orientia tsutsugamushi.

Epidemic typhus has the most severe clinical presentation of the typhus group of rickettsial infections. In severe disease, gangrene may occur and lead to loss of digits, limbs, or other appendages. The vasculitic process may also lead to CNS dysfunction, ranging from dullness of mentation to coma, multiorgan system failure, and death. The mortality rate in untreated persons may be as low as 20% in healthy individuals and as high as 60% in elderly or debilitated persons.

Since the advent of widely available antibiotic treatment, mortality rates have fallen to approximately 3-4%. The mortality rate for treated patients with murine typhus is 1-4% and less than 1% for scrub typhus.

Laboratory studies are not particularly helpful in confirming a diagnosis of typhus. These studies assist the clinician in assessing the degree of severity of the illness and in helping exclude other diseases in the differential diagnosis.

http://www.ajtmh.org/cgi/content/abstract/57/1/91

Seroepidemiologic Evidence for Murine and Scrub Typhus in Malang, Indonesia

Indonesian military personnel stationed in Malang, East Java were among troops deployed to central Cambodia as part of the United Nations' Transition Authority Cambodia peace-keeping operation in 1992. Predeployment blood samples obtained from a cohort of Indonesian soldiers indicated a high prevalence of antibodies to antigens of Rickettsia typhi or Orientia (formerly Rickettsia) tsutsugamushi, the etiologic agents for murine and scrub typhus, respectively.

[Sally Furniss]

Re: Indonesia Human Cases - April 9, 2008+

New Thread

http://www.flutrackers.com/forum/showthread.php?p=164793#post164793