Romain Micol

Philippe Buchy

Julie Galimand

Duong Veasna

Laurent Ferradini

Suna Balkan

Philippe Jean Guerin

Pierre-Régis Martin

Arnaud Fontanet

Olivier Lortholary

Christine Rouzioux

Marianne Leruez-Ville

Astriti

Bhattarakosol

Cermelli

Chhin

Gautheret-Dejean

Irving

Leruez-Ville

Micol

Qavi

Senya

Ward

English

Micol, Romain

Buchy, Philippe

Galimand, Julie

Veasna, Duong

Ferradini, Laurent

Balkan, Suna

Guerin, Philippe Jean

Martin, Pierre-Régis

Fontanet, Arnaud

Lortholary, Olivier

Rouzioux, Christine

Leruez-Ville, Marianne

MSF Field Research

JMM Correspondence
No association between human herpesvirus 6 reactivation and
cryptococcosis in human immunodeficiency virus-infected patients
Human herpesvirus 6 (HHV-6) is a part of
the virus subfamily betaherpes. A recent in
vitro study suggested that HHV-6 may
dysregulate monocyte-mediated anti-
cryptococcal defences with an overall pro-
cryptococcus result (Cermelli et al., 2006).
Briefly, co-cultures of THP1/JJHAN cell
lines were tested for anti-cryptococcal
activity by c.f.u. inhibition assay. THP1/
JJHANmock and THP1/JJHANHHV-6 co-
cultures were exposed to Cryptococcus
neoformans for 2, 3, 4 and 6 h. The co-
cultures showed negative levels of anti-
cryptococcal activity that were more
marked for THP1/JJHANHHV-6 at 6 h. The
results demonstrated that macrophages
exposed to HHV-6 have reduced anti-
cryptococcal activity.
Cryptococcosis is a major cause of
opportunistic infections in Cambodian
human immunodeficiency virus (HIV)-
infected patients with severe
immunodepression (Chhin et al., 2004;
Senya et al., 2003). Indeed, the prevalence
of cryptococcal infection among HIV-
infected patients with a CD4
+ count ,200
cells mm
23 was 18.0% (59/327) in a recent
Cambodian study (Micol et al., 2007).
The HHV-6 seroprevalence is up to 90%
in children less than 2 years old in
industrialized countries (Irving &
Cunningham, 1990). No data are available
concerning the HHV-6 seroprevalence in
the Cambodian population. However, in
Thailand the seroprevalence of HHV-6 was
88.1% (185/210) in children under 12
years old (Bhattarakosol et al., 2001).
HHV-6 reactivation has been observed in
HIV-infected individuals (Astriti et al.,
2006; Qavi et al., 1995). Thus, we
compared the prevalence of HHV-6
reactivation among 53 cases of
cryptococcal infection and 105 controls
without cryptococcal infection to validate
or not in vivo data obtained in vitro by
Cermelli et al. (2006).
In 2007, stored sera (Institut Pasteur du
Cambodge) were used for HHV-6 and
cytomegalovirus (CMV) DNA detection by
quantitative PCR. DNA was extracted from
200 ml serum with the MagNA Pure
Compact (Roche) following the MagNA
Pure Compact nucleic acid isolation kit I
protocol. We used the HHV-6 quantitative
in-house PCR from the Virology
Laboratory of the Pitie ´ Salpe ˆtrie `re Hospital
(Paris, France) (Gautheret-Dejean et al.,
2002). The CMV real-time PCR was
conducted according to the protocol used
in the Unite ´ de Virologie of the Ho ˆpital
Necker-Enfants Malades since 2001
(Leruez-Ville et al., 2003). HHV-6
replication was defined as the presence of
HHV-6 DNA in serum. Cryptococcal
infection was defined by a positive
cryptococcal polysaccharide agglutination
test [in serum or cerebrospinal fluid (CSF)]
and/or positive C. neoformans culture
(blood, CSF or urine), or positive India ink
direct examination of CSF. Continuous
variables were presented with their median
and interquartile range (IQR). Variables
were compared between groups using the
Mann–Whitney U test for continuous
variables, and the chi-square or Fischer’s
exact test for categorical variables.
The median (IQR) age of patients was 34
years (31–37 years). The median CD4
+
count (IQR) was 14 cells mm
23 (6–32 cells
mm
23). The two groups presented no
difference in age (median 35 versus 34
years), gender (males/females 34/19 versus
62/43) and CD4
+ count [14 cells mm
23
(IQR 6–24 cells mm
23) versus 15 cells
mm
23 (IQR 6–47 cells mm
23)]. The
prevalence of positive HHV-6 PCR was
3.8% (2/53) in the cryptococcal infection
group and 0% in controls (Fisher exact
test P50.1). The CMV DNAaemia
prevalence was 56.6% (30/53) and 55.2%
(58/105) in cases and controls, respectively
(P50.9). The viral loads of the two HHV-6
positive sera were high (5.4 and 6.0 log
copies ml
21) suggesting either reactivation
with high replication or a possible
chromosomal integration (Ward et al.,
2006). In addition there was no more
CMV replication among patients with
cryptococcal infection than among those
without infection.
In conclusion, there was no in vivo
association between HHV-6 replication
and cryptococcal infection in Cambodian
HIV-infected patients. Severely
immunodepressed HIV-infected patients
with HHV-6 or CMV DNA in their serum
do not present an increased risk of
developing cryptococcosis than
appropriate controls.
Acknowledgements
The authors thank Anne Badrichani for scient-
ific discussion about this manuscript and Dawn
Gaither for reviewing the manuscript.
Romain Micol,
1 Philippe Buchy,
2
Julie Galimand,
1 Duong Veasna,
2
Laurent Ferradini,
3 Suna Balkan,
4
Philippe Jean Guerin,
5
Pierre-Re ´gis Martin,
6
Arnaud Fontanet,
7 Olivier Lortholary,
8
Christine Rouzioux
1
and Marianne Leruez-Ville
1
1Unite ´ de Virologie, Ho ˆpital Necker-
Enfants Malades, Universite ´ Rene ´
Descartes, EA 36-20, Paris, France
2Unite ´ de Virologie, Institut Pasteur du
Cambodge, Phnom Penh, Cambodia
3Me ´decins Sans Frontie `res, Ho ˆpital Pre ´a
Bath Norodom Sihanouk, Phnom Penh,
Cambodia
4Me ´decins Sans Frontie `res, Paris, France
5Epicentre, Paris, France
6Me ´decins Du Monde, Ho ˆpital Kosamak,
Phnom Penh, Cambodia
7Unite ´ d’Epide ´miologie des Maladies
Emergentes, Institut Pasteur, Paris, France
8Service des Maladies Infectieuses et
Tropicales, Universite ´ Rene ´ Descartes,
Ho ˆpital Necker-Enfants Malades, Centre
d’Infectiologie Necker-Pasteur, Paris,
France
276 DOI 10.1099/jmm.0.000992-0 G 2009 SGM Printed in Great BritainCorrespondence: Romain Micol
(romain.micol@gmail.com)
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Correspondence
http://jmm.sgmjournals.org 277

No association between human herpesvirus 6 reactivation and cryptococcosis in human immunodeficiency virus-infected patients

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No association between human herpesvirus 6 reactivation and cryptococcosis in human immunodeficiency virus-infected patients.

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No association between human herpesvirus 6 reactivation and cryptococcosis in human immunodeficiency virus-infected patients

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