Final Issue: Volume 16 Number 51	Published on: 21 December 2006	Final Issue in PDF PDF format (283 Kb)

News Archives

Last updated: Volume 15, No.8 (PDF file, 673 KB)

Archives | News Archives 2006: Page 1| 24 February 2005

News Archives: | 2006 | 2005 | 2004 | 2003

• Multidrug resistant HIV and rapid progression of disease: a single case in New York
• Atypical presentation of avian influenza in Vietnam, February 2004
• Influenza A outbreak in a community hospital in south east Wales where few healthcare workers had received   immunisation, February 2005

  Multidrug resistant HIV and rapid progression of disease: a single case in New York

 

A single case of a highly drug-resistant strain of rapidly progressive human immunodeficiency virus (HIV) infection has been diagnosed in a New York City resident, who had not previously undergone antiviral drug treatment. This was reported by the New York City Department of Health and Mental Hygiene (1). The individual was infected within the previous 20 months, and this represents a transmitted drug-resistant virus, which has reduced susceptibility to drugs in three of the four available classes currently available. In addition, the infection appears to have a very short the interval between HIV infection and the onset of AIDS. No other cases of this particular strain of transmitted virus have been documented in New York. There is, however, very limited surveillance of this type currently undertaken in New York City.

This case is noteworthy for two reasons. Firstly, transmission of HIV-1 resistant to drugs within three of the four available classes of antiretroviral drugs occured recently, and secondly, a very rapid disease progression is inferred from the supposed time of infection. Although each of these occurrences is rare, they are both previously documented in the literature, and may be independent of each other.

The prevalence of transmitted HIV-1 drug resistance in the United Kingdom (UK) and the rest of Europe is assessed by surveillance of resistance in drug-naive individuals, and also in those individuals with recent infection (more comparable to the case described above).The UK HIV Resistance Database demonstrates a prevalence of any form of transmitted resistance of 18% within 2410 drug-naive individuals studied between 1996 and 2003, with 3% infected with three-class resistant virus in 2002 (2). A similar dataset from the Europe-wide CATCH study identifies 10% (of a population of 1633) with any form of resistance between 1998 and 2002 (3). The largest dataset from individuals with recent infection (thus allowing more accurate estimation of time trends for transmitted resistance) comes from the Concerted Action on Seroconversion to AIDS and Death in Europe (CASCADE), a large collaboration of seroconverter cohorts. Of 453 such individuals known to have been infected from 1987 to 2003, 12% had any form of resistance at diagnosis, with a peak of 19% in 1999. Only 0.5% were infected with three-class resistant HIV (4). Since such cohorts allow follow-up of recruited individuals with a known time of infection, it is possible to explore the impact of transmitted resistance on CD4 decline (natural history/disease progression), in the absence of therapy. Such analysis of the UK Register of HIV Seroconverters shows no difference in disease progression between those infected with resistance and those without resistant virus, over a five year follow-up period (5). This suggests that the characteristics of the recent New York case are not necessarily due to the resistance pattern of the infecting virus strain.

Taken together, these datasets show that transmission of drug resistance is evident in the United Kingdom (UK) and Europe as a whole. Although infection with such strains will compromise response to first line antiretroviral therapy, there is little evidence, to date, that such transmission is, in itself, associated with increased pathogenicity or faster disease progression. Nevertheless, there exists a myriad of forms of HIV resistance, reflecting varying degrees of drug resistance. The possibility that particular resistant variants, currently at low frequency in the population, are more transmissible than others or are more damaging, cannot be excluded. In view of the ongoing transmission of HIV within the UK, such a possibility must be considered (6).

It is important to maintain large scale population-based surveillance of transmitted resistant viruses. In particular, linking such data to clinical cohort follow-up will be essential for the early detection of viruses, which respond poorly to antiretroviral therapy and/or cause rapid disease progression.

References

1.New York City Department of Health and Mental Hygiene. New York City resident diagnosed with rare strain of multi-drug resistant HIV that rapidly progresses to AIDS (press release). New York, United States: New York City Department of Health and Mental Hygiene, 11 February 2005 [cited 21 February 2005]. Available at: <http://www.nyc.gov/html/doh/html/public/press05/pr016-05.html>.

 

2.Health Protection Agency. An update on HIV drug resistance in the United Kingdom. Commun Dies Rep Wkly [serial online] 25 November 2004 [cited 21 February 2005]; 14 (48): HIV/STIs. Available at: <http://wwww.hpa.org.uk/cdr/archives/2004/cdr4804.pdf>.

 

3.Wensing AMJ, van de Vijver DAM C, Asjo B, Balotta C, Camacho R, de Luca A, et al. The CATCH Study: Combined analysis of resistance transmission over time of chronically and acutely infected patients in Europe. The 2nd IAS Conference on Pathogenesis and Treatment, 2003 July 13-17, Paris, France. Abstract LB01. Available at: <http://www.ias2003.org/admin/images/upload/195.PDF>.

 

4.Masquelier B, Pillay D, van der Hoek L, Prins M, Balestre E, Nielsen C, et al. Changes in Prevalence and Characteristics of Transmitted Resistance over Time among European Seroconverter Cohort. Program and abstracts of the 11th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2004; San Francisco, California. Abstract 683.

 

5.Bhaskaran K, Pillay D, Walker AS, Fisher M, Hawkins D, Gilson R, et al. Do patients who are infected with drug-resistant HIV have a different CD4 cell decline after seroconversion? An exploratory analysis in the UK Register of HIV Seroconverters. AIDS 2004; 18(10):1471-3.

 

6.Murphy G, Charlett A, Jordan LF, Osner N, Gill ON, Parry JV. HIV incidence appears constant in men who have sex with men despite widespread use of effective antiretroviral therapy. AIDS 2004; 18(2): 265-72

 

Atypical presentation of avian influenza in Viet Nam, February 2004

 

A recently published report describes the case of a 4 year old boy who presented with fever, headache, vomiting and severe diarrhoea, followed by seizures and coma (gastroenteritis and encephalitis) in Viet Nam in February 2004 (1). The child had no respiratory symptoms and chest radiography was initially normal. The illness progressed rapidly and the child died, despite intensive care. Although some respiratory signs developed late on in the illness (bilateral mild crackles and wheezes and radiographic evidence of infiltrates) and respiratory failure eventually ensued, doctors treating the child did not consider respiratory problems to be the most relevant clinical problem for most of the duration of the illness. An enteric fever was initially diagnosed and the patient was treated accordingly.

As part of an ongoing encephalitis study, however, an avian influenza virus (A/H5N1) was eventually isolated from cerebrospinal fluid, faecal, throat, and serum specimens from the patient in October 2004, confirming a (postmortem) diagnosis of influenza H5N1 infection. It emerged that the patient’s older sister had developed a similar illness 11 days earlier and had also died, but no specimens were available.

Epidemiological investigations could not confirm that either child had a clear exposure to ill poultry. Both children regularly washed (and the girl regularly swam) in a canal that was also used by ducks, which excrete large quantities of virus when infected. Human-to-human transmission is virtually ruled out because of the time interval between the two cases.

Although encephalitis and encephalopathy are well recognised as rare complications of influenza, this is only the second time that H5N1 infection has been reported as presenting initially with fever and diarrhoea, but without respiratory symptoms. The first case with this presentation was also in 2004 and also fatal (the case occurred March 2004, in Thailand, and was reported in July 2004), but did not attract the same media attention (2).

There are a number of immediate implications:

1. The clinical spectrum of H5N1 disease might be wider than initially thought; further information is required to establish whether similar cases might have been missed in south east Asia.

2. As H5N1 virus was identified in faeces, a possible and hitherto unsuspected route of transmission of the H5N1 virus may exist, with implications for infection control.

3. Surveillance for possible rare imported cases of H5N1 infection may have to be adjusted to capture individuals with this presentation. Until further information on the likelihood of other missed cases is available, it is currently not recommend that surveillance algorithms for avian influenza (3) be extended to detect and investigate large numbers of travellers returning from south east Asia with fever and diarrhoea.

References

 

1.De Jong MD, Bach VC, Phan TQ, Vo MH, Tran TT, Nguyen BH, et al. Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. N Engl J Med. 2005 17 February; 352(7):686-91. (abstract available at <http://content.nejm.org/cgi/content/abstract/352/7/686>.

 

2.Apisarnthanarak A, Kitphati R, Thongphubeth K, Patoomanunt P, Anthanont P, Auwanit W, et al. Atypical avian influenza (H5N1). Emerg Infect Dis. 2004 10 July; 10(7):1321-4. <http://www.cdc.gov/ncidod/EID/vol10no7/pdfs/04-0415.pdf>.

3.Health Protection Agency. [online]. Sars and avian influenza (H5N1) algorithim: recognition, investigation, and initial management of potential cases. London, HPA, December 2004 [cited 24 February 2005], Available at:
<http://www.hpa.org.uk/infections/topics_az/avianinfluenza/pdfs/Algorithm.pdf>.

 

 

Influenza A outbreak in a community hospital in south east Wales where few healthcare workers had received   immunisation, February 2005

 

On the morning of 1 February 2005, the local infection control team in the Pontypridd and Rhondda NHS Trust (local health authority) in south east Wales were notified of 13 patients and five healthcare workers (HCW) with fever and respiratory symptoms on an orthopaedic convalescent ward of a community hospital. The average age of the patients was 83 years (range: 74 to 96 years) (figure).

Figure Epidemic curve, influenza A outbreak in a district general hospital, Wales, January – February 2005

The infection control nurse visited the ward that afternoon to assess the situation and institute control measures to prevent further spread of the infection. The ICT limited patient and HCW movements, discouraged visitors, and reinforced standard precautions (eg, use of alcohol gel for handwashing) and use of masks for procedures involving close patient contact. All relevant parties (hospital, bed and nursing management, clinical and other support services) were informed of the outbreak. The ward was reopened on 7 February.

The index case was in a HCW whose symptoms had begun on 29 January. She had been in contact with 46 people in the hospital (25 other HCWs and 21 patients) during the three days that she was symptomatic. During and immediately after this period, 23 people (seven HCWs and 16 patients) became ill. Two HCWs had been on sick leave since 30 January, one day after being in contact with the index case. Follow-up on 2 February identified four new cases in three patients and one HCW. At the subsequent follow-up on 4 February, only one further case was identified, in a HCW. Almost all the cases suffered from high fever, cough, and myalgia.

Nose and throat dry swabs and swabs in virus transport medium were taken from 14 patients. Influenza A infection was diagnosed by PCR in 11 swabs 24 hours after sample collection.

Treatment with antivirals was not recommended because this was the first confirmation of circulation of influenza A virus in the health district, and virological confirmation was therefore needed before antivirals could be used. If subsequent outbreaks occur in this district during the 2004-2005 influenza season, the use of antivirals should be considered on clinical grounds (1). The use of antivirals as prophylaxis was not considered because of the high attack rate occurring at the time of notification.

All of the 24 people affected had been eligible to receive influenza vaccine in the autumn of 2004, because they were either aged over 65 years, suffering from a chronic disease (five patients with diabetes), or because they were HCWs.

Of the 21 patients exposed to the index case, 5 (24%) had received influenza vaccine in October 2004. This vaccine included both influenza A and B strains. Two patients (40% of those vaccinated) developed virologically confirmed influenza A and other three did not. Of the 25 HCWs exposed, only four (16%) had received influenza vaccine.

Discussion and lessons learned
This outbreak highlights the importance of early detection of influenza cases in patients and HCWs, as well as the need to improve vaccine uptake and compliance with working restrictions during illness.

A knowledge of the circulation of influenza A in the community would have allowed consideration of use of antivirals in line with the national guidelines (2).

A circular on the 2004-2005 Welsh immunisation programme (3) was distributed to public health officials, hospitals, and general practitioners throughout Wales. This placed special emphasis on the proactive role of general practitioners in achieving good influenza immunisation rates in the community, particularly in people aged 65 years and over, living in long-stay care homes, or in a high risk category (ie, with chronic heart, respiratory, renal disease, diabetes, or immune-suppression)

Most of the patients in the affected ward were in a high risk category, and the reasons for the low influenza vaccine uptake among patients should be investigated. Patients with chronic illnesses being treated in hospitals are at risk of contracting influenza if they have not been previously vaccinated.

The reasons for the low vaccine uptake in HCWs should also be investigated, and the hospital’s practices of offering influenza immunisation to its HCWs should be reviewed. In the autumn of 2004, a memo was circulated to clinical managers and a general notice was sent to all departments offering influenza vaccination through the occupational health department, but this does not seem to have been effective. Only 83 out of 1900 nurses (4%), eight out of 100 consultants (8%), and none of the 200 other medical staff (0%) (including junior hospital doctors and specialist registrars [qualified trainees]) received influenza vaccine during this season. Junior doctors move between wards more than nurses do, and may be a potential source of infection while symptomatic. A better targeted offer of influenza vaccine for all medical staff might improve vaccine uptake in future.


References

 

1.Health Protection Agency [online]. Algorithm for prescribing oseltamivir for prophylaxis against influenza - (update: Feb 2005). London: HPA, February 2005 [cited 18 February 2005]. Available at: <http://www.hpa.org.uk/infections/topics_az/influenza/pdfs/Prophylaxisflowchart.pdf>.

 

2.Health Protection Agency. Algorithm for prescribing oseltamivir or zanamivir for treatment of influenza-like illness - (update: Feb 2005). London : HPA, February 2005 [cited February 2005]. Available at:
<http://www.hpa.org.uk/infections/topics_az/influenza/pdfs/Prophylaxisflowchart.pdf>.

3.Welsh Assembly Government (Chief medical officer Wales ). 2004-05 influenza immunisation programme ; Welsh Health Circular. Cardiff : Welsh Assembly Government, 7 September 2004. Available at:<http://www.cmo.wales.gov.uk/content/communications/welsh-health-circulars/63-04-flu-immunisation-e.pd>.