Anna Giulia Cattaneo, M.D.
DBSF, Università dell'Insubria, Via J-H. Dunant,
3 - 21100 Varese
The trend of increasing prevalence of active cases of tuberculosis
(TBC) in global populations is a health-threatening problem
that reduces the possibilities of control of the disease and
imposes specific tuberculosis surveillance measures to organisms
for public health.
It is partly due to unusual or multidrug-resistant (MDR)
strains of Mycobacteria, reinfection and/or reactivation,
and spreading conditions affecting immune competence, like
When aged people are on concern, a number of considerations
should be done. In the Western world, old and oldest individuals
often spent a part of their life in decades of last centuries
in which TBC was a quite common diseases, many of them being
survivors to infection. On the other hand, a portion of this
population is living in communities, suffers from chronic
diseases affecting respiratory functions and immunocompetence,
and could represent an under-diagnosed reserve of infection.
Attention paid to tuberculosis surveillance and epidemiological
studies on TBC in aged persons is sporadic, and generally
limited to considerations inter- or extrapolated from studies
devoted to general populations.
In this Editorial, focused on description of TBC diffusion
in aged people inhabiting Western countries and East Europe,
the following points should be discussed:
1. Incidence and prevalence of TBC
2. Diagnostic problems and elusive cases
3. Characterization of the infectious agent: species, strains
4. Spread of infection or reactivation of old cases
6. Preventive measures.
Special attention is paid to the situation in Italy.
Incidence and prevalence of TBC
Different trends can be carried out comparing the notification
rate in 32 European countries from 1995 to 2002 (http://www.eurotb.org/).
When only two groups of age are taken into account, namely
45-64 years and >64 years, it seems to be evident that
higher prevalence of TBC is registered in older individuals.
This is true in the majority of countries, with the exception
of Romania, Ukraine, Russia and Estonia, where adult are more
often affected than aged individuals. In these countries,
as in Bosnia Herzegovina, the notification rate is higher
than in the other European countries ( 50 up to > 200 x105
in comparison with 10 to 30-50 x105), and rates are increasing.
With minor differences, all other countries in Europe and
in USA (http://www.cdc.gov/nchstp/tb/)
show a lower notification rate, while higher in older age,
a negative trend (reduction of the rate in recent years),
or invariant values, especially when very low rates are registered.
Italy presents a quite good situation, with negative trend
and values between 4 and 9 x105 in adults, and between 12
and 17 x 105 in people aged more than 64, better than in Germany,
France UK and Switzerland. In a near future some differences
could be expected, due to the earlier peak of prevalence in
resident born out from Europe, as shown in several studies
(Journal of Clinical Microbiology, May 2001, p. 1802-1807,
Vol. 39, No. 5, http://www.eurotb.org/).
Sex bound differences have been described, with general higher
prevalence in males. In a small sample of patient resident
in Lombardy higher rates of cases appeared to be located in
the 4th decade in females and in the 6th decade in males (Journal
of Clinical Microbiology, June 2001, p. 2213-2218, Vol. 39,
- Diagnostic problems and elusive cases.
Elusive cases of tubercular infection are especially frequent
in frail organisms, in which symptoms and localizations are
often unusual. The strain of Mycobacterium responsible for
infection is also a cause of misdiagnosis.
Epidemiological data permit to approximate the prevalence
- Pulmonary TBC is by far the commonest infection, responsible
for 70-75% of cases.
- Extra pulmonary disease (no more than 20% of all cases)
can be localized in the lymphatic apparatus (43%), pleura
(18%), bone (11%) peritoneum (6%), and genitourinary apparatus
(5%). Miliary TBC, defined as pulmonary and extra pulmonary
co infection, represents about 9% of all cases.
Retarded diagnosis could be quite common in older individuals
living alone, or with relatives not trained to take care
of the oldest. On the contrary, a large statistics carried
out in 2003 in US reports a percentage near to 100% of correct
diagnosed cases in residents in long-term care facilities.
Need for an early and correct diagnosis could be improved
by adopting adequate measures for clinical, instrumental
and etiological diagnosis, for risk evaluation, and notification
of all newly diagnosed cases and "at risk- individuals.
Associated risks include alcohol abuse, unemployment in
the past 24 months and homeless state and residence in metropolitan
areas associated to psychosocial or medical frailty. HIV
seems to be associated to TBC infection, but at the present
it is by far more frequent in young people, aged 25-44 years.
- Characterization of the infectious agent: species, strains
TBC causative agents are included in the Mycobacterium tuberculosis
complex, represented by five mycobacterial species: M. tuberculosis,
M. bovis, M. africanum, M. microti, and M.canetti, almost
identical in DNA homology studies and in terms of their ability
to cause clinical disease and to be transmissible from person
to person. Therefore, diseases caused by any of the five organisms
are classified as tuberculosis, with the only exception of
the BCG (Bacillus of Calmette-Guerin) strain M. bovis, whose
transmission is usually jatrogenic, following cancer immunotherapy.
Infections with Mycobacteria other than those cited before
(as M. avium, M.intracellulare, M. kansasii, M. marinum and
other) are more appropriately included in "atypical mycobacterium,
or NTM (Non Tuberculosis Mycobacteria) infections- . They
are different from TBC both clinically and epidemiologically.
Molecular biology methods can improve diagnosis.
- Re-infection or reactivation of old cases
A consistent portion of people ageing at the present time,
and even more those reaching oldest age, survived in their
youth a tubercular infection. The 70% of a large sample considering
90% of all population affected by TBC in Norway was distributed
in two decades, between 70 and 89 years of age.
Analysis of infection clustering (multiple isolates with an
identical DNA pattern) can be done by the restriction fragment
length polymorphism technique: a cluster identifies an infective
outbreak, while diversity states instead reactivation of latent
TBC. The situation seems to be very similar in a number of
countries with low prevalence of infection, included Italy
(15% of clustering, Eur. J. Epidemiol. 1997, 13:845-851; 16%,
Journal of Clinical Microbiology, 2001, 39: 2213-2218), Norway
(11%, Journal of Clinical Microbiology, 2001, 39: 1802-1807),
and Switzerland (17%, Eur. Respir. J. 1998, 11:804-808), in
which relapse due to reinfection seems to be the rule, and
transmission possible but only in marginal cases. Unexpectedly,
in Denmark the prevalence of cluster is by far higher (49%),
and large cluster are present, documenting a wide spread of
infection (J. Clin. Microbiol. 1998, 36:305-308). The rather
higher frequency of TBC, and even of multiresistant strains,
in recent immigrates from high prevalence countries does not
seems a threatening for spreading of new infections among
population in countries like Norway, in which the control
is good (Eur. J. Epidemiol. 2000, 13:845-851). On the contrary,
a half of all new cases of TBC seems to be transmitted from
foreign to native individuals in the Netherlands (Am. J. Epidemiol.
1998, 147:187-195). In a large study carried out in Great
Vancouver, Canada, age was not found to be linearly associated
to clustering, but clusters were significantly more frequent
in groups in which higher prevalence of TBC is usually found:
aged individuals, non-Aboriginal, or Aboriginal in their adulthood
appeared to be clustered, and this fact suggests a possible
role played by these subjects in transmission on tuberculosis.
(CMAJ. 2002 August 20; 167 (4): 349-352).
- Single- and Multi-Drug-resistance (SDR and MDR)
This health threatening problems includes old and new phenomena.
The resistance developed by Mycobacteria to Streptomycin and
that more recent to Isoniazid are in fact well-known and frequent
phenomena, to which the newly developed resistance to other
antitubercular drugs has been added. An evaluation of the
phenomenon on a worldwide scale has shown a prevalence of
6,6% SDR and of 1,4% of MDR in all cases of primary developed
resistance. Mean prevalence for SDR if 12.2% and that for
MDR is 13.0% of all cases of acquired resistance. These last
show a lower frequency in population than primary developed
resistance. In its all, resistance phenomena are more frequent
in patients treated more than once, and in those affected
by AIDS, in which acquired resistance is greater. Great differences
in trend between different countries have been found; Italy
was not evaluated (NEJM, 1998, 338:1641-1649).
- Preventive measures.
The first prevention seems to be an early diagnosis of new
cases and new epidemics: this concept is not so obsolete as
it could seem. In fact, a recent study carried out in London
shows a diagnostic delay ranging from 14 and 104 days, with
different trend in relation to age, sex, social and racial
provenience of subjects. No selected data obtained in older
people are shown in this study, age being only considered
as more or less than 40 years (BMJ. 2003, 326(7395): 909-910.)
Other important preventive measures should principally remove
risk factors (mainly social frailty, physical decline due
to not unavoidable conditions, like poverty or careless, AIDS
infection - rare in person aged at the present, but growing
in future generations -, and alcoholism), errors in drug assumption
and early abandonment of therapy, in addition to general hygienic
measures for isolation of active cases.
Improving notification, diagnostics and epidemiological knowledges
also in the oldest layers of populations seems to be a good
purpose for the future.
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