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Drug-resistant HIV case remains controversial
Newsdesk
Vietnamese cases suggest avian flu has been underestimated Isolation of influenza H5N1 virus from faecal specimens of a 4-year-old boy in Vietnam has raised the possibility that the number of cases of avian influenza worldwide may have been underestimated, according to new research (N Engl J Med 2005; 352: 686–91). “Awareness of the full clinical spectrum of influenza H5N1 is essential”, but until now clinical surveillance of influenza H5N1 has focused only on respiratory illnesses, Menno de Jong (Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam) told TLID. The boy had severe diarrhoea and no respiratory symptoms at presentation, but developed coma, which proved fatal. 2 weeks earlier, his sister had died from similar symptoms. The team is now investigating whether H5N1 can cause milder respiratory illnesses in addition to the often fatal severe pneumonias reported so far. Intriguingly, Jong and colleagues report that encephalitis is a common manifestation of influenza H5N1 virus infection in poultry and several animals. “The important next step . . . is to find out how often the neurological disease manifestation occurs in humans. It may well be that, just as for infection with the regular human influenza strains (eg, H3N2, H1N1, influenza B), neurological manifestations of influenza H5N1 are very rare”, he said. According to Michael Perdue of the WHO Global Influenza Programme, while classic faecal–oral transmission
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
AP Photo/Sakchai Lalit
See Leading Edge page191
A Thai official sprays poultry cages with disinfectant
of influenza viruses is unlikely, direct contact of mucosal membranes with contaminated material could indeed result in infection, so environmental contamination with influenza viruses could still pose a substantial risk. “We cannot yet extrapolate the findings into an alteration of the case definition for H5N1 infection based on just a single confirmed case such as this. So it is likewise not possible to make a statement on the possibility of missed cases”, he said. In a related development, Thailand’s Prime Minister, Thaksin Shinawatra, is revisiting his government’s plans concerning the handling of free-range ducks, which are a way of life for several thousand people in the country. Which aspects of the plans are being revisited is not clear, but last month’s
decision by the government to cull around 3 million free-range ducks has prompted concerns from Free-Range Duck Traders and Producers Club. William Aldis, the WHO’s representative in Thailand, believes that a major cause of worry is that the virus is still circulating in poultry. “Cases of outbreak in poultry are being reported in the country [more] sporadically and less frequently when compared with earlier outbreaks, but so far, no human cases have been detected”, he said. According to Aldis, the Thai Ministry of Public Health has been working hard to put a strong surveillance system in place, which involves people from the village level— the village health volunteers.
Khabir Ahmad
Drug-resistant HIV case remains controversial The announcement of an unusually aggressive and highly drug-resistant strain of HIV has ignited a storm of criticism and disagreement from AIDS experts and activists. But at the recent 12th Conference on Retroviruses and Opportunistic Infections, David Ho— 200
head of the Aaron Diamond AIDS Research Center in New York—defended his decision to alert publichealth officials about a patient who had shown a rapid progression to full-blown AIDS, and whose viral strain was resistant to three of four classes of HIV drugs.
“Given the lack of scientific clarity, we believed that, from a publichealth perspective, the most prudent thing to do was to notify the New York Department of Health and Mental Hygiene”, Ho said in a special session devoted to this case. “And http://infection.thelancet.com Vol 5 April 2005
Newsdesk
that is the decision we stand by today.” But because this was only a single patient, critics have questioned the wisdom of making a public announcement before all of the data have been assembled and analysed. Similar case studies have also been reported, including two Canadian patients with drug-resistant and rapidly progressing HIV strains. (AIDS 2003; 17: 1256–58) “The case in New York seems to be an extension of what we previously reported”, said Julio Montaner (University of British Columbia, Vancouver, BC, Canada), who treated both patients. “The patient in New York has more resistance and has progressed within a shorter period of time.”
Montaner points out that a small percentage of patients infected with wild-type virus can have very rapid progression, while a small percentage can have very slow progression. “So it’s not clear right now if the cases that we are starting to see truly represent the beginning of a new epidemic, or a supervirus as such.” Ho stated that it has been known for a number of years that the transmission of multidrug-resistant (MDR) virus is possible, as is rapid progression following acute infection. In this case, there appeared to be a convergence of the MDR virus and rapid progression in a person who has had many high-risk sexual contacts and who used metham-
phetamine. “We cannot conclude if this is due to an aggressive virus or a genetic predisposition”, said Ho. “We do not know if this is a single isolated event or if there are additional cases out there.” The viral sequence is now being compared with those in the database at the Los Alamos National Laboratory, with the hope of finding a closely related HIV-1 strain that might provide an epidemiological linkage to this case. Thus far, the patient does not appear to have any predisposing genetic markers, but testing is still underway.
Roxanne Nelson
Researchers at the New York University School of Medicine (NY, USA) may have found a way to treat latent Kaposi’s sarcoma-associated herpesvirus (KSHV, also known as HHV8) infections. Ornella Flore and colleagues report that glycyrrhizic acid (GA)—a compound isolated from liquorice that inhibits the lytic replication of other herpesviruses—terminates KSHV latent infection of B lymphocytes (J Clin Invest 2005; 115: 642–52). “This is the first time we have found anything that targets latent gene expression in herpesvirus-infected cells”, says Flore, “but it is too soon to say whether GA will be effective against other latent herpesviruses or suitable for clinical use against KSHV”. The treatment of infections caused by herpesvirus is complicated by their ability to establish latent infections. Herpesviruses can hide within their host cells, making only the few proteins needed to maintain latency, and emerges at a later date to cause overt disease. No currently available drugs directly attack latent herpesviruses, although latent Epstein–Barr virus can be reactivated, thus allowing treatment with standard antiviral drugs. http://infection.thelancet.com Vol 5 April 2005
Flore’s team reports that GA disrupts latent KSHV infection of B lymphocytes in culture by downregulating the expression of latency-associated nuclear antigen and upregulating viral cyclin expression, resulting in the selective death of KSHV-infected cells. The next step, explains Flore, “is to see whether GA can inhibit the growth of KSHV-induced human tumours transplanted into mice. GA is already used clinically in Japan to treat hepatitis, so this lead is definitely worth following.” “GA is the first antiviral to have an effect on latently KSHV-infected lymphoma cells”, says KSHV expert Ethel Cesarman (Weill Medical College of Cornell University, New York, USA). But, she notes, “we don’t know yet the sites of KSHV infection in immunocompetent individuals and which (if any) viral genes are expressed, so it is difficult to predict whether GA might clear KSHV completely from the body”. Jindrich Cinatl (University Hospital Medical School, Frankfurt, Germany), who is studying GA treatment of severe acute respiratory syndrome, also finds Flore’s results intriguing. However, he warns that the GA concentrations needed to terminate latent KSHV infec-
ABPL/Sam Stowell
Liquorice compound beats latent herpesvirus
Sweet solution to latent infection?
tion in B lymphocytes are higher than those used to treat hepatitis and may cause unacceptable side-effects. Therefore, chemical modification of GA might be required before it can be used to treat latent herpesvirus infections.
Jane Bradbury 201
Vietnamese cases suggest avian flu has been underestimated Isolation of influenza H5N1 virus from faecal specimens of a 4-year-old boy in Vietnam has raised the possibility that the number of cases of avian influenza worldwide may have been underestimated, according to new research (N Engl J Med 2005; 352: 686–91). “Awareness of the full clinical spectrum of influenza H5N1 is essential”, but until now clinical surveillance of influenza H5N1 has focused only on respiratory illnesses, Menno de Jong (Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam) told TLID. The boy had severe diarrhoea and no respiratory symptoms at presentation, but developed coma, which proved fatal. 2 weeks earlier, his sister had died from similar symptoms. The team is now investigating whether H5N1 can cause milder respiratory illnesses in addition to the often fatal severe pneumonias reported so far. Intriguingly, Jong and colleagues report that encephalitis is a common manifestation of influenza H5N1 virus infection in poultry and several animals. “The important next step . . . is to find out how often the neurological disease manifestation occurs in humans. It may well be that, just as for infection with the regular human influenza strains (eg, H3N2, H1N1, influenza B), neurological manifestations of influenza H5N1 are very rare”, he said. According to Michael Perdue of the WHO Global Influenza Programme, while classic faecal–oral transmission
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
AP Photo/Sakchai Lalit
See Leading Edge page191
A Thai official sprays poultry cages with disinfectant
of influenza viruses is unlikely, direct contact of mucosal membranes with contaminated material could indeed result in infection, so environmental contamination with influenza viruses could still pose a substantial risk. “We cannot yet extrapolate the findings into an alteration of the case definition for H5N1 infection based on just a single confirmed case such as this. So it is likewise not possible to make a statement on the possibility of missed cases”, he said. In a related development, Thailand’s Prime Minister, Thaksin Shinawatra, is revisiting his government’s plans concerning the handling of free-range ducks, which are a way of life for several thousand people in the country. Which aspects of the plans are being revisited is not clear, but last month’s
decision by the government to cull around 3 million free-range ducks has prompted concerns from Free-Range Duck Traders and Producers Club. William Aldis, the WHO’s representative in Thailand, believes that a major cause of worry is that the virus is still circulating in poultry. “Cases of outbreak in poultry are being reported in the country [more] sporadically and less frequently when compared with earlier outbreaks, but so far, no human cases have been detected”, he said. According to Aldis, the Thai Ministry of Public Health has been working hard to put a strong surveillance system in place, which involves people from the village level— the village health volunteers.
Khabir Ahmad
Drug-resistant HIV case remains controversial The announcement of an unusually aggressive and highly drug-resistant strain of HIV has ignited a storm of criticism and disagreement from AIDS experts and activists. But at the recent 12th Conference on Retroviruses and Opportunistic Infections, David Ho— 200
head of the Aaron Diamond AIDS Research Center in New York—defended his decision to alert publichealth officials about a patient who had shown a rapid progression to full-blown AIDS, and whose viral strain was resistant to three of four classes of HIV drugs.
“Given the lack of scientific clarity, we believed that, from a publichealth perspective, the most prudent thing to do was to notify the New York Department of Health and Mental Hygiene”, Ho said in a special session devoted to this case. “And http://infection.thelancet.com Vol 5 April 2005
Newsdesk
that is the decision we stand by today.” But because this was only a single patient, critics have questioned the wisdom of making a public announcement before all of the data have been assembled and analysed. Similar case studies have also been reported, including two Canadian patients with drug-resistant and rapidly progressing HIV strains. (AIDS 2003; 17: 1256–58) “The case in New York seems to be an extension of what we previously reported”, said Julio Montaner (University of British Columbia, Vancouver, BC, Canada), who treated both patients. “The patient in New York has more resistance and has progressed within a shorter period of time.”
Montaner points out that a small percentage of patients infected with wild-type virus can have very rapid progression, while a small percentage can have very slow progression. “So it’s not clear right now if the cases that we are starting to see truly represent the beginning of a new epidemic, or a supervirus as such.” Ho stated that it has been known for a number of years that the transmission of multidrug-resistant (MDR) virus is possible, as is rapid progression following acute infection. In this case, there appeared to be a convergence of the MDR virus and rapid progression in a person who has had many high-risk sexual contacts and who used metham-
phetamine. “We cannot conclude if this is due to an aggressive virus or a genetic predisposition”, said Ho. “We do not know if this is a single isolated event or if there are additional cases out there.” The viral sequence is now being compared with those in the database at the Los Alamos National Laboratory, with the hope of finding a closely related HIV-1 strain that might provide an epidemiological linkage to this case. Thus far, the patient does not appear to have any predisposing genetic markers, but testing is still underway.
Roxanne Nelson
Researchers at the New York University School of Medicine (NY, USA) may have found a way to treat latent Kaposi’s sarcoma-associated herpesvirus (KSHV, also known as HHV8) infections. Ornella Flore and colleagues report that glycyrrhizic acid (GA)—a compound isolated from liquorice that inhibits the lytic replication of other herpesviruses—terminates KSHV latent infection of B lymphocytes (J Clin Invest 2005; 115: 642–52). “This is the first time we have found anything that targets latent gene expression in herpesvirus-infected cells”, says Flore, “but it is too soon to say whether GA will be effective against other latent herpesviruses or suitable for clinical use against KSHV”. The treatment of infections caused by herpesvirus is complicated by their ability to establish latent infections. Herpesviruses can hide within their host cells, making only the few proteins needed to maintain latency, and emerges at a later date to cause overt disease. No currently available drugs directly attack latent herpesviruses, although latent Epstein–Barr virus can be reactivated, thus allowing treatment with standard antiviral drugs. http://infection.thelancet.com Vol 5 April 2005
Flore’s team reports that GA disrupts latent KSHV infection of B lymphocytes in culture by downregulating the expression of latency-associated nuclear antigen and upregulating viral cyclin expression, resulting in the selective death of KSHV-infected cells. The next step, explains Flore, “is to see whether GA can inhibit the growth of KSHV-induced human tumours transplanted into mice. GA is already used clinically in Japan to treat hepatitis, so this lead is definitely worth following.” “GA is the first antiviral to have an effect on latently KSHV-infected lymphoma cells”, says KSHV expert Ethel Cesarman (Weill Medical College of Cornell University, New York, USA). But, she notes, “we don’t know yet the sites of KSHV infection in immunocompetent individuals and which (if any) viral genes are expressed, so it is difficult to predict whether GA might clear KSHV completely from the body”. Jindrich Cinatl (University Hospital Medical School, Frankfurt, Germany), who is studying GA treatment of severe acute respiratory syndrome, also finds Flore’s results intriguing. However, he warns that the GA concentrations needed to terminate latent KSHV infec-
ABPL/Sam Stowell
Liquorice compound beats latent herpesvirus
Sweet solution to latent infection?
tion in B lymphocytes are higher than those used to treat hepatitis and may cause unacceptable side-effects. Therefore, chemical modification of GA might be required before it can be used to treat latent herpesvirus infections.
Jane Bradbury 201