Tuberculosis in Tropical Areas and Immigrants

Abstract

About 95% of cases and 98% of deaths due to tuberculosis (TB) occur in tropical countries while, in temperate low incidence countries, a disproportionate portion of TB cases is diagnosed in immigrants.
Urbanization, poverty, poor housing conditions and ventilation, poor nutritional status, low education level, the HIV co-epidemic, the growing impact of chronic conditions such as diabetes are the main determinants of the current TB epidemiology in tropical areas. TB care in these contests is complicated by several barriers such as geographical accessibility, educational, cultural, sociopsychological and gender issues. High quality microbiological and radiological facilities are not widely available, and erratic supply of anti-TB drugs may affect tropical areas from time to time. Nevertheless in recent years, TB control programs reached major achievements in tropical countries as demonstrated by several indicators.
Migrants have a high risk of acquire TB before migration. Moreover, after migration, they are exposed to additional risk factors for acquiring or reactivating TB infection, such as poverty, stressful living conditions, social inequalities, overcrowded housing, malnutrition, substance abuse, and limited access to health care. TB mass screening programs for migrants have been implemented in low endemic countries but present several limitations. Screening programs should not represent a stand-alone intervention, but a component of a wider approach integrated with other healthcare activities to ensure the health of migrants.

Full text

Mediterr J Hematol Infect Dis 2014; 6; Open Journal System
MEDITERRANEAN JOURNAL OF HEMATOLOGY AND INFECTIOUS DISEASES
www.mjhid.org ISSN 2035-3006
Review Article
Tuberculosis in Tropical Areas and Immigrants
Lorenzo Zammarchi1, Filippo Bartalesi2 and Alessandro Bartoloni1,2
1 Infectious Diseases Unit, Department of Experimental & Clinical Medicine, University of Florence School of
Medicine, Florence, Italy
2 SOD Malattie Infettive e Tropicali, AOU Careggi, Firenze, Italy
Correspondance to: Alessandro Bartoloni. E-mail: alessandro.bartoloni@unifi.it
Competing interests: The authors have declared that no competing interests exist.
Published: June 1, 2014
Received: April 11, 2014
Accepted: April 16, 2014
Citation: Mediterr J Hematol Infect Dis 2014, 6(1): e2014043, DOI: 10.4084/MJHID.2014.043
This article is available from: http://www.mjhid.org/article/view/13235
This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.
Abstract. About 95% of cases and 98% of deaths due to tuberculosis (TB) occur in tropical
countries while, in temperate low incidence countries, a disproportionate portion of TB cases is
diagnosed in immigrants.
Urbanization, poverty, poor housing conditions and ventilation, poor nutritional status, low
education level, the HIV co-epidemic, the growing impact of chronic conditions such as diabetes are
the main determinants of the current TB epidemiology in tropical areas. TB care in these contests is
complicated by several barriers such as geographical accessibility, educational, cultural,
sociopsychological and gender issues. High quality microbiological and radiological facilities are
not widely available, and erratic supply of anti-TB drugs may affect tropical areas from time to
time. Nevertheless in recent years, TB control programs reached major achievements in tropical
countries as demonstrated by several indicators.
Migrants have a high risk of acquire TB before migration. Moreover, after migration, they are
exposed to additional risk factors for acquiring or reactivating TB infection, such as poverty,
stressful living conditions, social inequalities, overcrowded housing, malnutrition, substance abuse,
and limited access to health care. TB mass screening programs for migrants have been
implemented in low endemic countries but present several limitations. Screening programs should
not represent a stand-alone intervention, but a component of a wider approach integrated with
other healthcare activities to ensure the health of migrants.
Introduction. Despite encouraging progress, the
burden of tuberculosis (TB) remains enormous with
about one third of the World population latently
infected with the etiologic agent Mycobacterium
tuberculosis,1 8.7 million new cases of active disease
and 1.4 million people died in 2011.2 Some authors
state that 95% of all cases and 98% of deaths due to
TB, occurs in tropical countries.3 In the matter of facts
among the 22 high burden countries that account for
more than 80% of the worldwide incident cases of the
disease, 19 have territories geographically located, at
least in part, within the tropics (Table 1), indicating
tropical areas as the most affected by TB in the World.
In high income industrialized countries, the majority of

Mediterr J Hematol Infect Dis 2014; 6: Open Journal System
Table 1. High burden countries with territories located within the tropics and estimated incidence.2
High burden country in the tropics
Estimated incidence
(rate per 100,000 population)
Estimated number of cases
(number in thousands)
Estimated portion respect
to the global burden
Bangladesh
225
340
4%
Brazil
42
83
1%
Cambodia
424
61
0.7%
China
75
1000
11.5%
Democratic Republic of the Congo
327
220
2.5%
Ethiopia
258
220
2.5%
India
181
2200
25%
Indonesia
187
450
5.2%
Kenya
288
120
1.4%
Mozambique
548
130
1.5%
Myanmar
381
180
2%
Nigeria
118
190
2.2%
Philippines
270
260
3%
South Africa
993
500
5.7%
Thailand
124
86
1%
Uganda
193
67
0.8%
United Republic of Tanzania
169
78
0.9%
Viet Nam
199
180
2%
Zimbabwe
603
77
0.9%
Afghanistan, Pakistan and Russian Federation are considered high burden countries but they have not territories located within the tropics.
which are located outside the tropics, the overall TB
incidence is low, as expected given the inverse
correlation between economic development of the
country and its TB diffusion.4 A disproportionate and
growing portion of subjects affected by TB in
industrialized countries are migrants from tropical
countries,5,6 configuring this group of subjects as a TB
vulnerable population in low endemic areas.
The aim of this review is to give an overview on the
historical, epidemiological, clinical and
microbiological characteristics and recent control
strategies of TB in tropical countries and migrant
populations.
History of TB in Tropical Areas and Migration.
Current evidence supports the so called "Out-of-and-
back-to-Africa" scenario in explaining the origin and
global spread of human TB.7 Human M. tuberculosis
complex probably originated in Africa and
accompanied the Out-of-Africa migrations of modern
humans approximately 70,000 years ago.7 The three
phylogenetically ‘modern’ lineages of M. tuberculosis
complex (namely the East Asian, the Central
Asian/Delhi and the Euro-American lineage) seeded in
China, India and Europe, respectively where human
population strongly grew during the last few centuries.7
As overcrowding conditions and the urbanization
increased, TB expanded in these areas and
concomitantly spread globally through waves of human
migrations.7 Through European colonization, the Euro-
American lineage of M. tuberculosis complex reached
other regions such as the Americas in the mid
nineteenth century and sub-Saharan Africa at the
beginning of the twentieth century.7,8 Historians and
paleopathologists, supported by the detection of
mycobacterial DNA in pre-Columbian human remains,
suggests that TB was already present in pre-Columbian
America. Today most TB in the Americas is caused by
the Euro-American lineage, but in the pre-Columbian
period, the etiologic agent may have been Asian forms,
as would be expected given the original human
colonization of the Americas via the Bering Strait.
Alternatively, pre-Columbian TB might have been
caused by mycobacterial lineages which are now
extinct perhaps because they were outcompeted by the
Euro-American lineage following the massive influx of
Europeans into the Americas between the early
eighteenth and early twentieth century.7
Epidemiology and Determinants of Tuberculosis in
Tropical Areas. The majority of the known risk
factors for acquiring TB infection and for progress to
TB disease after the infection are widespread and
responsible for the high burden of TB in tropical areas.
About 59% of new estimated TB cases occur in
South East Asia and the Western Pacific Regions,2
where some of the most populated countries (India,
China, Indonesia) and some of the most crowded cities
of the World are located.9 Urbanization and the
consequent overcrowded living conditions, through the
increase of shared airspace between individuals, are
among the well-known risk factors to acquire TB.10
Urbanization is a relatively new, but growing
phenomenon in Africa, which is substantially less
populated than Asian regions.9 However, countries of
the African Region account for 26% of the World's TB

Mediterr J Hematol Infect Dis 2014; 6: Open Journal System
cases and they have the highest incidence rate of cases
and death per capita.2 In Africa, the TB epidemic is
overlapped and strongly driven by HIV infection which
is the most powerful risk factor for developing active
TB disease in subjects infected with M. tuberculosis.11
In this region, 46% of subjects who develop active TB
are estimated to be co-infected with HIV (ranging from
8% in Ethiopia to 77% in Swaziland).2 In extreme
settings, such as gold-mining workforce in South
Africa, the annual incidence reaches value of 2,000-
3,000 per 100,000 population due to the high rate of
HIV co-infection (up to 80% among subjects with
active TB) and silicosis.12
Concerning countries of the region of Americas,
only Brazil, is considered a high burden country given
its relevant contribution to the absolute number of TB
cases, despite a relatively low overall incidence rate
(less than 50 per 100,000 population). However, the
burden of TB in Brazil is not uniformly distributed in
the national territories with more 70% of cases
concentrated in 315 over 5,564 municípios
corresponding to those hosting the large metropolitan
cities where overcrowding and extreme poverty is more
frequent.13 In some districts of São Paolo (Brazil)
where the Human Development Index is particularly
low, TB incidence is 167 per 100,000 population.14
Some tropical countries such as Haiti, Peru, Bolivia
and Suriname have the highest incidence of TB in the
Americas (between 100 and 200 per 100,000
population).15 HIV co-epidemic is probably one of the
most important determinant of the high incidence
found in Sub-Saharan Africa, as well in Brazil and
Haiti, where about 20% of incident TB cases is HIV
co-infected.15
Re-infection of subjects with previous latent
tuberculosis infection (LTBI), which account for up to
40% of the general population in countries like India,16
may play an important role. Even if people with LTBI,
have a markedly lower risk of developing TB disease
after a re-infection if compared with previously
uninfected subjects,17 in endemic areas the contribution
of re-infection may account up to 70% of TB relapse
cases.18
A very important, even if distal, determinant of TB
in tropical areas is poverty that affects housing
conditions, ventilation, nutritional status, education and
the access to health care system.19 In some areas of
India, for example, the amount of monthly earning as
well as the schooling degree have been correlated to
TB prevalence.19 About two third of cases are
diagnosed between 15-44 years of age in countries
such as South Africa and India. The impact on the
health status of young adults in their most
economically active years makes that not only does
poverty predispose one to TB, but also TB can increase
poverty.19 In India three to four months of work time,
the equivalent to 20–30 per cent of annual household
income, are typically lost because of TB.19
A growing role of emergent risk factors for
progression from latent to active TB, such as certain
chronic conditions, have been observed more recently
in tropical areas. Smoking doubles the risk of TB and
might account for up to half of all deaths in men with
TB in India.20 Diabetes is associated with an about
three-times increase in TB risk accounting for about
20% of smear-positive tuberculosis cases in India in
2000.20 Helminthic infestations that are endemic in
tropical countries are strongly suspected to negatively
impact on TB diseases inducing immunological
alterations including alternatively activation of
macrophages and Th1-lymphocytes response
impairment.21 In a cohort of HIV-infected Ugandan
adults, Schistosoma mansoni infestation was associated
with an increased risk of TB progression.22 Finally,
according to a recent review of the literature on racial
difference in susceptibility to infection by M.
tuberculosis, black skin people may have consistently
higher susceptibility to TB if compared to whites skin
peoples due to environmental, immunologic, and
genetic factors.23
Epidemiology and Determinants of Tuberculosis in
Immigrants. TB is a well-known phenomenon linked
to migration. By the time of the Italian migration to
America between the XX and the XXI century, Italian
migrants, resettled in New York city, worked in the
factories of the metropolis in very poor housing and
living conditions. In this setting, Italian migrants
experienced a very high number of TB cases with tens
of cases per household and the block where they lived
was named “lung’s block”.24
Today, migration is a global social phenomenon
that may be defined as a movement of people within
and among countries as a consequence of wealth
disparity, poverty, wars, natural disasters and political
persecution.19,25 To date there are an estimated 740
million internal migrants and 200 million of
international migrants (Figure 1),26 without
considering irregular migrants of which it is difficult to
make an affordable estimate.
Many migrants originate from countries where TB
have a high incidence, such as tropical countries, and
resettle in higher income countries, such as Unites
States, Canada, Australia, New Zealand and western
Europe, where TB incidence is now very low (less than
10 per 100,000 population) (Table 2).25
In the United States (US), TB cases in foreign-born
persons accounted for 62% of total TB cases in 2011
with Asians accounting for 29% and Hispanics/Latinos
for 21% of all cases.6 Considering the countries

Mediterr J Hematol Infect Dis 2014; 6: Open Journal System
Figure 1. The pattern of inter- and intra-regional migrant movements. [United Nations Development Programme, Summary. Human
Development Report 2009. Overcoming barriers: Human mobility and development, United Nations Development Program, (2009).
Reproduced with permission]
belonging to the European Economic Area (EEA),
foreign origin persons represented 26% of cases
diagnosed in 2011.5 However, this percentage rises to
more than 40% in the western European countries
holding the highest proportions of migrants in Europe
(Table 2).5 In the EEA the majority of foreign origin
subjects diagnosed with TB in 2009 originated from
Asia (34.2%), Africa (28.6%) and other European
countries (19.9%).27
Immigration is playing an important role in the
epidemiology of TB in certain high burden countries
with emerging economies. In some districts of São
Paolo (Brazil), the portion of TB cases diagnosed in
Bolivian migrants grew up to 53% of total cases in the
period 1998-2008,14 while migrant workers from rural
areas of China resettled in the district of Shanghai
accounted for 67.4% of cases diagnosed in 2006-
2008.28
It is clear that migrants currently play an important
role in determining the current epidemiology of TB in
countries where they settled. However reports from
different high income countries with well-performing
screening and treatment systems have shown that
foreign-born TB patients do not contribute importantly
to TB transmission in the native population.25,29,30
Based on genotyping analysis, a variable portion of TB
cases in native populations (ranging from 2% to 17%)
has been attributed to transmission from foreign-born
subjects.31,32 In more recent study, performed in
Denmark, transmission from Danes to migrants
occurred 2.5 times more frequently than vice-versa.30
Migrants are exposed in their country of origin to
several risk factors for TB infection and progression as
already explained in the above paragraph.
The incidence in the countries of origin is the
strongest predictor of TB incidence in migrants
according to some authors.33 However in other studies
the TB incidence in selected migrant communities was
found to be lower or higher if compared with the
incidence in the country of origin according to the
degree of socio-economical integration of the
community.34,35 After migration, foreign born people
are exposed to a series of additional factors that have
been associated with an increasing risk of acquiring or
reactivating TB infection such as poverty, stressful
living condition, material deprivation, social
inequalities, unemployment, fewer educational
opportunities, overcrowded housing, malnutrition,
substance abuse, and limited access to health care.36
TB in migrants may occur as a consequence of a
reactivation of a LTBI acquired in the country of
origin, but also because of a new infection acquired in
the host country after resettlement or during travel in
the country of origin. Molecular epidemiology
studies have helped to understand the relevance of

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Table 2. Number and portion of cases of active tuberculosis in
foreign origin people diagnosed in countries of the European
Economic Area and selected low TB incidence countries.5,6,39,93,94
Country
Number of TB cases
diagnosed in foreign
origin subjects
Portion of TB cases
diagnosed in foreign
origin subjects
European
Economic Area*
Austria
326
47.5%
Belgium
544
52.1%
Bulgaria
9
0.4%
Cyprus
45
83.3%
Czech Republic
112
18.7%
Denmark
235
61.7%
Estonia
48
14.1%
Finland
79
24.3%
France
2,456
49.7%
Germany
2,025
46.9%
Greece
216
44.2%
Hungary
27
1.9%
Ireland
179
42.1%
Italy
1,677
47.6%
Latvia
59
6.7%
Lithuania
44
2.3%
Luxemburg
21
80.8%
Malta
28
84.8%
Netherland
710
70.5%
Poland
38
0.4%
Portugal
385
15.2%
Romania
50
0.3%
Slovakia
3
0.8%
Slovenia
57
29.7%
Spain
2,138
31.6%
Sweden
524
89.4%
United Kingdom
6,287
70.1%
Iceland
7
77.8%
Liechtenstain
-
-
Norway
317
87.8%
United States*
6,510
62%
Canada°
~1,040
66%
Australia^
1,141
88%
New Zealand*
227
75.4%
*Data referred to 2011 ° Data referred to 2010; ^ Data referred to
2009
LTBI reactivation in the pathogenesis of TB in
migrants. In these studies, clustered cases (defined as
two or more cases with clonally related TB strains) are
assumed to belong to a chain of recent transmission,
while cases whose M. tuberculosis isolates display
unique patterns are regarded as sporadic and assumed
to be caused by reactivation.35 According to the
different studies, 10%-45% of TB cases diagnosed in
foreign-born patients are clustered,35,37,38 this means
that a relevant proportion of active TB cases is
probably caused in immigrants by new infection
acquired after migration, even if the majority of cases
are due to LTBI reactivation acquired before migration.
As well known a considerable portion (23-53%) of
TB cases in migrants is diagnosed in the first years (2-
4) after resettlement in the host country.6,39-41 However,
the reasons for this phenomenon are not completely
clear. Some authors suggest that the stressful and
socioeconomically disadvantaged living conditions in
the first years after migration could contribute to the
reactivation of TB early after arrival.36 However, the
risk of TB in migrants was found to persist for their life
time.42 For example, in one study, one third of TB
cases in Australia migrants were diagnosed 10 years
after arrival, and this interval was larger when
considering European migrants only.43
An increased risk of TB is still present in second
generation migrants in which a link to endemic
countries persists after migration through social
networks or travel in the country of origin of their
ethnic minority group.44,45 In United Kingdom (UK),
for example, the highest incidence rates in UK born
subjects are in ethnic minority groups.46 The role of
travel to visit friends and relatives on the risk of TB
infection during an international travel is not exactly
known. However the risk for an international traveler
approximates the risk of transmission in the local
population of the country of destination,47 and it is
associated with duration of travel.48 Among travelers,
immigrant visiting friends and relatives, especially
children, are likely to represent a group at higher risk,
perhaps due to their closer contact with the local
population as shown by several studies that report an
association between TST positivity and return to the
country of origin.49
TB Diagnosis and Management in Tropical Areas.
The most common symptom of pulmonary TB is a
productive cough for more than 2 weeks, which may be
accompanied by other respiratory symptoms (shortness
of breath, chest pains, hemoptysis) and/or
constitutional symptoms (loss of appetite, weight loss,
fever, night sweats, and fatigue).50 The presence of
those symptoms are enough to met the definition of
suspected TB case according to the World Health
Organization (WHO).50
For a patient living in a remote tropical village that
has cough for more than 2 weeks, the way to achieve
the correct diagnosis of TB, to start anti-tubercular
treatment and to complete it successfully may be very
long and full of hurdles. According to a systematic
review, in resource limited countries the average
patient delay (time from the onset of symptoms until
the patient see the first health care practices) and
average health system delay (time from the first health
care seeking for diagnosis until the diagnosis made) are
31.7 days and 28.5 days, respectively.51
Low educational level, low awareness and
knowledge about TB and sociopsychological barriers,
gender inequalities, are the first bottlenecks for the
initial health access.52 Believing TB incurable or
caused by evil spirit, possible social exclusion

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following the diagnosis of TB (stigma), fear of
revealing HIV status to neighbors, since TB is closely
related to HIV in tropical areas, are some the factors
conditioning health seeking behaviors and the
diagnostic delay in tropical countries.52
Rural residence and other geographical barriers are
further limiting factors in the diagnostic path. Ideally a
health facility able to start the clinical management of a
suspected TB case should be within 1-day walking
distance as many patients have limited access to
motorized vehicles.52 However, in 2011 the WHO
estimates that only 15 of the 22 high TB burden
countries met the target of having 1 microscopy centre
per 100,000 population and 17 of the 36 countries with
a high burden of TB and multidrug-resistant (MDR)
TB have the recommended capacity of 1 laboratory to
perform culture and drug susceptibility test (DST) per
5 million population.2
Initial visit to a governmental low-level healthcare
facility, initial visit to traditional or unqualified
practitioner or even a visit to a private practitioner are
factors associated with further diagnostic delay.52 The
delay in diagnosis from this point forward reflects a
lack of effective diagnostic tools and follow-up
routines since a correct diagnosis requires both good
training and available diagnostic facilities.52 Table 3
reports the list of the most important factors associated
with diagnostic delay according to a systematic
review.52
Diagnosis of TB is a challenge not only in tropical
countries, but anywhere resources are limited.
Conventional microbiological methodology such as
direct microscopy and culture, when available, have
intrinsic limitation that have constrained TB care and
control up to now.2 Smear microscopy has a low
sensitivity (about 64%),53 which is even lower in HIV
positive patients54 and in children.55 Culture is
considered the gold standard but requires some weeks
to give a positive result and even new liquid culture
techniques, which are more sensitive and allow a faster
grown of mycobacteria, are seldom available in
resource-constrained settings largely because of cost.56
Radiology has an important role in the diagnosis of TB
but the equipment is expensive to obtain, maintain,
operate and experienced radiologist are required in
order to interpret the often non-specific radiological
signs of TB.3 Few years ago, the situation of
radiological manpower and facilities in sub-Saharan
Africa was reported to show a desperate shortage of
radiologists, radiographers and equipment, with most
of services located in the capital with few at rural
hospital and CT scanners or high resolution ultrasound
machines available only in 40% of these countries.57
In view of the paucity of diagnostic tools available,
the challenge of TB diagnosis in the tropics may be
Table 3. Risk factors for TB diagnostic delay (adapted from Storla
DG et al).52
Coexistence of chronic cough and/or other lung diseases
Negative sputum smear
Extrapulmonary TB
Rural residence
Low access to healthcare
(geographical or socio-psychological barriers)
Initial visit to government low-level healthcare facility
Initial visit to traditional or unqualified practitioner
Initial visit to private practitioner
Initial visit to tertiary-level services/hospital
Old age
Poverty
Female sex
Alcoholism or substance abuse
History of immigration
Low educational level and/
or low awareness and knowledge about TB
Generally poor health
Smoking
Coexistence of sexually transmitted diseases
Less severe and indifferent symptoms
No hemoptysis
Married
Single
Large family size
Farmer
White (vs. aboriginal)
Muslim
Belonging to an indigenous group
No insurance
Beliefs about TB (not curable, caused by evil spirits, etc.)
Stigma
Self-treatment
The study by Storla DG et al. was a systematic review that includes
58 articles in the final analysis. Thirty eight studies (65%) were
carried out in countries with incidence >40 per 100,000 population
(the majority of which tropical), while 20 studies (35%) were
carried out in non-tropical lower incidence countries.
"HIV" and "Initial visit to tertiary-level services/hospital" have
been removed from the original table because they were negatively
associated with diagnostic delay according to the majority of the
studies.
related to problems of differential diagnosis. In the
tropics, pulmonary TB must be distinguished from
other rare endemic and ubiquitous conditions such
bacterial pneumonia, histoplasmosis,
paracoccidioidomycosis, coccidioidomycosis,
melioidosis, actinomycosis, paragonimiasis,
echinococcosis, nocardial and aspergillus mycetoma,
dirofilariosis, neoplasm, sarcoidosis,58,59 which could
be a hard task, given the limited diagnostic resources
available.
Hopefully, the recent availability of new rapid tests
could revolutionize TB care in endemic and tropical
countries. The new test Xpert MTB/RIF, which has
been endorsed by WHO in December 2010, is a
cartridge-based automated diagnostic test that has three
main advantages if compared with older tests: 1) it
enables simultaneous detection of M. tuberculosis

Mediterr J Hematol Infect Dis 2014; 6: Open Journal System
complex and rifampicin-resistant associated genotype;
2) provides accurate results in less than two hours so
that patients can be offered proper treatment on the
same day; 3) has minimal bio-safety requirements,
training, and can be housed in non-conventional
laboratories.60 According to a meta-analysis, the pooled
sensitivity was 98.7% for pulmonary sputum positive
TB and 75% for sputum negative TB with an overall
specificity of 98.4%, while the sensitivity on non-
respiratory clinical samples resulted to be 80.4%.61, 62
Xpert MTB/RIF showed dramatic cut of the time
needed to start treatment, especially in smear negative
cases, and to obtain rifampicin susceptibility result. 63
With the introduction of Xpert MTB/RIF, there has
been also an increase of the number of
microbiologically confirmed TB in children,62 and an
increase of the number of pulmonary TB cases detected
in HIV positive patients when compared with
microscopy.62 Between its endorsement by WHO and
the end of June 2012, 1.1 million test cartridges were
procured in 67 (46%) of the 145 countries eligible to
purchase them at initial concessional prices (9.98 $ per
test from August 2012).62 Currently, WHO strongly
recommends the use of Xpert MTB/RIF for use, as the
primary diagnostic test, in individuals suspected of
having MDR or HIV-associated TB and in testing
cerebrospinal fluid specimens from patients presumed
to have TB meningitis; furthermore, WHO provides
“conditional recommendations” for its use in other
settings.64 However, several weakness of this new tool
have already been highlighted, including elevated cost
of the platform (17,000$), the sophisticated hardware
needing calibration and maintenance, need of
continuous electrical power supply and air
conditioning, short shelf life of cartridges needing good
procurement system, need for cartridges storage at 2-
28°C and system for disposal after use.62 Concerning
other relatively recent diagnostic tools such as
interferon gamma release assays (IGRA) and
serological test for TB, WHO recommended against
their use in middle and low income countries for the
diagnosis of both active and LTBI.2
Directly Observed Treatment (DOT) of TB reduces
TB related death, disability and transmission, and it is
highly cost-effective intervention even in the lowest
income countries.2 Treatment of a drug-sensitive TB,
case, takes 6 months, while treatment for MDR TB
case takes 18-20 months according to the WHO
recommendations.2 The target of 85% of treatment
success for new TB cases has been achieved at global
level, but it is still under the goal threshold in African
(73%), Americas (74%) and European Regions (74%),
with the lowest rate (53%, possibly underestimated)
reached by South Africa.2
Concerning patients with MDR-TB, that represent a
growing portion of cases, only 44% to 58% completed
treatment successfully according to different Regions.2
In Africa, 19% of patients with MDR-TB is not able to
complete the treatment because of death.2
TB and HIV are strictly related, and the
management of the two conditions must go hand in
hand. To date only 40% of patients with TB are tested
for HIV, with the African Region performing better
than all other regions (69%).2 However only 56% of
people eligible for antiretroviral therapy is receiving it
in Africa.65 The assessment of the HIV status in a
patient with TB is essential since the timely start of
antiretroviral therapy has been demonstrated to reduce
significantly the mortality of the patient.66-68 Treatment
success of TB is hampered by several problems that
may be amplified especially in tropical areas, such as
problematic access to health care facilities, poor
adherence to treatment, availability of quality drugs,
high rate of MDR cases, and HIV co-infection.
Treatment default implies persistence of infection
source, increased mortality, increased relapse rates and
increased risk of the development of resistant strains.
In different case control studies, frequently
identified risk factors associated with a default of the
patients under TB treatment in tropical areas were
inadequate knowledge on TB,69,70 illiteracy or low
education level,70,71 herbal medication use,69 low
income,69 alcohol abuse,69-71 HIV co-infection,69,71 male
gender69 poor patient-provider interaction,70 side
effects to anti TB drugs.70
The erratic supply of drugs that may affect some
areas is another relevant problem. A survey carried out
in Ethiopia in 2008 showed that the first line drugs for
TB treatment were not available in about 20% of 48
health facilities that were supposed to have.72 Doctors
without Borders recently reported a drug supply crisis
in Mthatha (South Africa) started in 2013.73 During a
survey done in May 2013 in the area, still 40% of
facilities suffered stock-outs of antiretroviral drugs
and/or TB drugs with a median duration for reported
stock-outs of 45 days.73
TB Diagnosis and Management in Immigrants. The
access to health system, including TB diagnostic and
treatment services is lower in migrant populations
compared to native subjects. Migrants have a longer
patient diagnostic delay for TB (defined as the time
elapsed from the onset of symptoms and the first
medical consultation), while natives have a longer
health care diagnostic delay (defined as the time
elapsed between the first medical consultation and the
initiation of treatment).74,75 The increased patient delay
is possibly due to a combination of reasons that hinder
migrants of using the available TB services. Among

Mediterr J Hematol Infect Dis 2014; 6: Open Journal System
those factors, there are language barriers, possible lack
of medical insurance, fear of deportation (for illegal
migrants) or discontinuation of their employment74,75
and competing socio-economic priorities may prevail
over health issues. Even if in most of countries TB
diagnosis and treatment are provided for free at
government health facilities to all migrants, including
illegal migrants, additional costs of transport and the
time needed to perform medical consultations may
represent significant obstacles for access to health
system for migrants on low wages.76 The longer health
care diagnostic delay in native subjects can be
explained by the lower TB incidence among native
subjects in low endemic countries, that leads
physicians to reduce their index of suspicion regarding
the possibility of TB diagnosis and ordering other tests
rather than TB-diagnostic tests.74,75
TB treatment in migrant populations can be
challenging due to lower adherence to treatment.77-79
According to a recent study, loss to follow-up in TB
cases in UK appears to occur primarily in young male
adults and in subjects born outside the UK, particularly
those who migrated within the 2 years prior to
diagnosis.77 Moreover, this study showed that lost to
follow-up patients were more frequently infected with
a resistant M. tuberculosis strain compared to patients
who completed or were still on treatment (11% vs.
7.4%), highlighting the vicious circle among poor
compliance to treatment and resistance to
antitubercular drugs.77 Higher therapeutic abandonment
has been recently found also in foreign born patients if
compared to natives in Granada (Spain)79 and in
Chinese internal migrants if compared to permanent
residents.78
Another challenging issue in the management of TB
in migrants, in low endemic countries, is the high
frequency of MDR-TB in this population if compared
to natives (Table 4). The majority of European and
other low prevalence countries, excluding some of the
high priority countries in the WHO European Region
(such as Latvia, Lithuania, Bulgaria and Estonia),
report higher prevalence of MDR-TB cases in migrants
if compared to the native population.80 This is probably
due to the high prevalence of MDR-TB in migrants
countries of origin and possibly to the low compliance
to treatment that characterizes migrants and leads to
acquire drug resistance.
Given the epidemiological importance of migrant
subjects in determining the epidemiology of TB in
industrialized countries, many of those countries
implemented different control measures for TB,
including mass screening programs. The rationale of
these programs is the early detection and treatment of
active and then contagious TB cases, in order to
prevent M. tuberculosis transmission within the host
Table 4. Prevalence of Multi Drug Resistance in native and foreign
origin subjects diagnosed with tuberculosis in countries of the
European Economic Area and selected low TB incidence
countries.5,6,39,93,94
Country
MDR prevalence in subject with TB (%)
Native
Foreign origin
European
Economic Area*
Austria
0
8.9
Belgium
0
3.7
Bulgaria
7.5
0
Cyprus
0
3
Czech Republic
0.6
6.2
Denmark
0
1.8
Estonia
30.3
25.8
Finland
1.3
4.4
France
-
-
Germany
0.6
3.4
Greece
0
5.6
Hungary
1.3
10
Ireland
0
1.7
Italy
1.4
4.2
Latvia
14.9
13.3
Lithuania
20.9
29.4
Luxemburg
0
13.3
Malta
0
0
Netherland
0
2.8
Poland
0.8
3.8
Portugal
1.1
5.4
Romania
8.8
14.3
Slovakia
1.6
0
Slovenia
0
0
Spain
-
-
Sweden
0
3.9
United Kingdom
0.3
2.1
Iceland
-
0
Liechtenstain
-
-
Norway
0
1.7
United States*#
0.6
1.7
Canada
-
-
Australia
-
-
New Zealand*
0
1.1
Footnotes: *Data referred to 2011; # Data referred to cases without
previous diagnosis of TB.
country.81 Indeed screening for active TB may decrease
the period of infectiousness by as much as 33%.82
Secondary benefits of immigration screening are
reduced transmission of TB in the country of origin and
during travel.81
A recent survey showed that high-income
industrialized countries have widely different
approaches to the screening of migrants arriving in
their territories.83 In the majority (23 of 25, 92%) of
cases, screening is performed after the arrival, while
only 36% (9 of 25) and 20% (5 of 25) of countries
perform also pre-arrival and at-arrival screening
respectively, according to the different type of
immigrants.83 The majority of countries (25, 86.2%)
screens for active TB and most commonly (76% of
cases) the screening is compulsory.83 The most
commonly used tool for screening for active TB in

Mediterr J Hematol Infect Dis 2014; 6: Open Journal System
adult migrants is a chest radiograph, which is used by
22 of 25 (88%) industrialized countries alone or in
combination with clinical examination and less
commonly, with tuberculin skin test (TST).83 However,
screening protocols based on chest x-ray only are
unable to detect cases of extrapulmonary TB, which
represent a not negligible portion of TB cases in
migrant patients (24% of cases diagnosed in non US
born patient in US).84 Moreover, concerning pulmonary
TB, chest x-ray shows a sensitivity of 86-97% and a
specificity of 75-89% according to the different criteria
used for imaging interpretation.85 The median yield of
screening for TB disease (portion of patients with
active TB among those screened) has been found quite
low (0.18%) in the EEA.86
Only 16 of 29 (55.2%) countries, inquired in the
above survey, screens for LTBI by using TST in 68.8%
of cases or TST plus a confirmatory IGRA in 25% or
an IGRA alone in 18.8%.83 Some authors strongly
support the implementation of screening for LTBI
based on the evidence that the majority of active TB
cases, diagnosed in migrants, are due to a LTBI
reactivation acquired in the country of origin38 and on
the findings of cost-effectiveness analysis.87,88
According to a cost-effectiveness study, the most
suitable strategy would be to screen with an IGRA (in
particular QuantiFERON-TB Gold In-Tube. Carnegie,
Cellestis, Australia) test all migrants coming in UK
from countries with an incidence of more than 250
cases per 100,000 (incremental cost-effectiveness ratio
[ICER] of £ 21,565 per prevented case of TB) without
port of arrival chest x-ray.88 However these results are
opposite to those of a previous study done in Canada
that found chest radiograph the most and Quantiferon
the least cost-effective strategy to screen migrants.89
The discordance of the findings are probably explained
by the different assumptions done in the models such
as high rates of acceptance and completion of
chemoprophylaxis assumed in the English study and
low prevalence of latent infection in new immigrants
assumed in the Canadian study.
While the attention of the different governmental
programs and several scientists seems to focus on mass
screening programs for active TB and/or LTBI, this
kind of interventions should not represent a stand-alone
intervention, but a component of a wider approach.86
The six points proposed by the STOP TB strategy
(Table 5),80 which address the activities to deal with
TB at global level, could be a useful paradigm for
drawing a more comprehensive approach for TB
control in migrant populations.
Table 5: The six components of the STOP TB strategy.80
1) Pursue high-quality DOTS expansion and enhancement
2) Address TB-HIV, MDR-TB, and the needs of poor and
vulnerable populations
3) Contribute to health system strengthening based on primary
health care
4) Engage all care providers
5) Empower people with TB, and communities through partnership
6) Enable and promote research
Implementing DOT in low endemic areas or newer
socially and culturally acceptable programs to sustain
treatment adherence, address MDR-TB, contributing to
health systems strengthening with the presence of peer
educators and culturally-oriented health staff, engaging
all care providers including members of Non
Governmental Organizations and voluntary
associations, empowering migrants communities and
promoting research to find new possible operational
solutions and tools for TB care and prevention could
likely be of benefit for future TB control programs in
migrants.90
In conclusion TB care should be offered and
integrated with other healthcare activities within the
context of a holistic approach to ensure the health and
wellbeing of new entrant migrants.76,91,92
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