Globalization and Health BioMed Central

Review Open Access

A review of co-morbidity between infectious and chronic disease in
Sub Saharan Africa: TB and Diabetes Mellitus, HIV and Metabolic
Syndrome, and the impact of globalization
Fiona Young*, Julia A Critchley, Lucy K Johnstone and Nigel C Unwin

Address: Institute of Health and Society, 4th Floor William Leech Building, Medical School, University of Newcastle upon Tyne, Newcastle upon
Tyne, NE2 4HH, UK
Email: Fiona Young* - fiona.young@ncl.ac.uk; Julia A Critchley - Julia.critchley@ncl.ac.uk; Lucy K Johnstone - L.KJohnstone@ncl.ac.uk;
Nigel C Unwin - N.C.Unwin@ncl.ac.uk
* Corresponding author

Published: 14 September 2009 Received: 18 March 2009

Accepted: 14 September 2009
Globalization and Health 2009, 5:9 doi:10.1186/1744-8603-5-9
This article is available from: http://www.globalizationandhealth.com/content/5/1/9
© 2009 Young et al; licensee BioMed Central Ltd.
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
Background: Africa is facing a rapidly growing chronic non-communicable disease burden whilst
at the same time experiencing continual high rates of infectious disease. It is well known that some
infections increase the risk of certain chronic diseases and the converse. With an increasing dual
burden of disease in Sub Saharan Africa the associations between diseases and our understanding
of them will become of increased public health importance.
Aims: In this review we explore the relationships reported between tuberculosis and diabetes
mellitus, human immunodeficiency virus, its treatment and metabolic risk. We aimed to address the
important issues surrounding these associations within a Sub Saharan African setting and to
describe the impact of globalization upon them.
Findings: Diabetes has been associated with a 3-fold incident risk of tuberculosis and it is
hypothesised that tuberculosis may also increase the risk of developing diabetes. During co-morbid
presentation of tuberculosis and diabetes both tuberculosis and diabetes outcomes are reported
to worsen. Antiretroviral therapy for HIV has been associated with an increased risk of developing
metabolic syndrome and HIV has been linked with an increased risk of developing both diabetes
and cardiovascular disease. Globalization is clearly related to an increased risk of diabetes and
cardiovascular disease. It may be exerting other negative and positive impacts upon infectious and
chronic non-communicable disease associations but at present reporting upon these is sparse.
Conclusion: The impact of these co-morbidities in Sub Saharan Africa is likely to be large. An
increasing prevalence of diabetes may hinder efforts at tuberculosis control, increasing the number
of susceptible individuals in populations where tuberculosis is endemic, and making successful
treatment harder. Roll out of anti-retroviral treatment coverage within Sub Saharan Africa is an
essential response to the HIV epidemic however it is likely to lead to a growing number of
individuals suffering adverse metabolic consequences. One of the impacts of globalization is to
create environments that increase both diabetes and cardiovascular risk but further work is needed
to elucidate other potential impacts. Research is also needed to develop effective approaches to
reducing the frequency and health impact of the co-morbidities described here.

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Introduction treat individuals with concomitant disease which were

In Sub-Saharan Africa (SSA) infectious diseases still cause reported to improve outcomes[20,21]. However, until
the majority of mortality (69% of deaths). Chronic non- recent years there was a lack of good evidence on the
communicable diseases such as cardiovascular disease, strength and nature of the association between TB and
diabetes mellitus (DM), chronic respiratory disease and DM. At present recognition of the association between
cancers, contribute around a quarter of deaths[1]. This diabetes and TB is low. The link goes unmentioned in
picture is changing as SSA undergoes an epidemiological many national and global TB control strategies even
transition with a rapidly increasing burden of, and associ- though it is plausible that diabetes is a major threat to
ated mortality from, chronic non-communicable diseases. effective TB control and the attainment of the TB Millen-
nium Development Goals as well as other national and
It has long been recognised that infective agents may pre- global targets [22-26].
dispose to, or trigger, some chronic non-communicable
diseases with examples including infective contributions Studies have shown an increased risk of TB infection in
to cervical, liver and stomach cancers, and possible infec- individuals with both type 1 and type 2 diabetes although
tive triggers for some types of diabetes[2,3]. In addition it measures of the strength of the association do
is becoming clear that two of the most common infectious vary[10,12,27-31]. Recently a meta-analysis of 3 studies
diseases in Africa, tuberculosis (TB) and human immuno- carried out by Murray and Jeon showed that having diabe-
deficiency virus (HIV)/acquired immune deficiency syn- tes was associated with a relative risk (RR) of 3.11 for con-
drome (AIDS), may also be closely related to chronic non- tracting TB[10]. Stevenson et al carried out a systematic
communicable diseases [4-13]. Diabetes predisposes to review of the subject finding that diabetes has been esti-
tuberculosis with some evidence that TB may also predis- mated to increase the risk of TB infection from 1.5 in one
pose to diabetes[10,14-16]. Antiretroviral therapy for HIV study up to 7.8 times in an other[12]. Stevenson et al also
may increase the risk of metabolic syndrome (the cluster- looked at the reported effects of age, gender and ethnicity
ing of abdominal obesity, hyperglycaemia, dyslipidaemia upon the strength of the association between TB and DM.
and hypertension) and thus predispose to type 2 diabetes Reporting that gender did not seem to affect the RR for TB
and cardiovascular disease[6,7,9,11,17,18]. amongst individuals with DM, but that age did. The RR
seems to be highest at younger ages and shows a decline
In this article we discuss the evidence on the relationships as age increases, although this finding is not replicated in
between TB and DM, and the possible mechanisms all studies, some show no association between the RR of
through which this link may be caused, we then discuss TB amongst individuals with DM and of older age[12].
the link between antiretroviral therapy (ART), metabolic The increased risk of contracting TB for DM patients has
syndrome (MS) and cardiovascular disease (CVD). We been demonstrated in many different study populations.
also address the potential public health importance of One study reports a difference in the association between
these relationships within SSA and describe the possible TB and DM in different ethnic groups[28]. The study
impact of globalization upon these associations. In order reports that DM is not a risk factor for TB in 'Black Hispan-
to review these areas we have considered matters from ics' but is amongst 'White Americans' and 'Hispanics'. The
biological, medical and social science perspectives where cause of this finding is unclear; the investigators state that
needed. it may be due to unidentified HIV infection among 'black'
controls which could attenuate any association found
This article is based on detailed literature searches under- between diabetes and tuberculosis[28]. In order to gain a
taken by the authors for articles published since 1950. better awareness of the effect of ethnicity upon the
Searches were undertaken in MEDLINE and EMBASE, plus strength of the RR of individuals with DM for contracting
screening of reference lists in identified articles. Poten- TB further investigation is needed.
tially relevant reports, bulletins and guidelines were also
screened, including ones from the United Nations (UN), Estimates of the population attributable risk (PAR) for TB
World Health Organization (WHO), International Diabe- from diabetes illustrate the potential importance of this
tes Federation (IDF) and UK Department of Health relationship. PAR is dependent upon the prevalence of the
(DoH). risk factor (diabetes) and the strength of its relationship to
the outcome (TB) and provides, given certain assump-
Diabetes Mellitus (DM) and Tuberculosis (TB) tions, an estimate of the proportion of the outcome that is
Diabetes increases the risk of TB directly caused by the risk factor. Stevenson et al estimated
An association between DM and TB has long been cited. that diabetes accounts for approximately 14.8% of inci-
In around 1000 A.D. Avicenna noted that 'phthisis', tuber- dent Pulmonary Tuberculosis (PTB) in India, and a
culosis, often complicated diabetes[19]. In the UK, in the slightly higher amount of TB infection has been found to
1950's, some joint TB and diabetes clinics were set up to be attributable to DM (25%) in a Mexican setting[16,30].

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Can TB increase the risk of diabetes? tially explain the increased risk of lung infection for
Although the majority of studies identify and discuss the individuals with DM as well as the altered presentation of
presence of diabetes as a risk factor for TB, the relationship TB during co-morbidity[43]. Deficiencies in vitamins A, C
between DM and TB is posited to be bidirectional. Early and D are linked both with an increased risk of DM and
studies by Engelbach et al and Nichols et al reported that TB. It has been hypothesised that there is a pathway upon
not only could having diabetes increase an individuals which they act that dictates susceptibility to both diseases
likelihood of developing TB but that having TB could lead [44-47].
to the presentation of diabetes[32,33]. Work carried out
by Karachunskii et al showed that individuals with TB can As afore mentioned some TB medications such as Isoni-
develop changes in carbohydrate metabolism such as azid have been shown to have hyperglycaemic effects giv-
insulin deficiency and persistent hyperglycaemia[34]. ing plausible mechanisms as to why glucose control is
Impaired glucose tolerance (IGT) and increased rates of impaired in TB patients[35]. Inflammation caused by IL6
DM have been found amongst TB patients in an African and TNFα whilst modulating a response to TB infection
setting. A Tanzanian study found TB patients to have could cause an increase in insulin resistance thus decreas-
increased rates of IGT and a Nigerian study found an ing insulin production causing an increase in blood glu-
increased level of IGT and DM amongst TB patients. These cose[48]. Although no singular mechanism has been
results have been interpreted as an indication that TB can identified as the cause of the associations between TB and
cause DM[14,15]. However, given the cross sectional DM many plausible causal pathways have been suggested.
rather than longitudinal design of these studies, their
results are also compatible with undetected DM and IGT Effect on health outcomes when TB and DM are
being present prior to the onset of TB. It is well known concomitant
that in most populations a large proportion of those with An associated deterioration of both conditions occurs dur-
DM or intermediate hyperglycaemia are undiagnosed and ing co-morbidity with TB and DM. It is known that diabe-
only detected upon blood glucose testing. tes makes TB management more difficult and that chronic
stimulation of the inflammatory system by TB may affect
Although uncertainty remains around whether TB is a risk diabetes management and outcomes. In a study carried
factor for DM it is clear that tuberculosis, as with other out in Mumbai, a higher mortality rate for tuberculosis
infections, complicates diabetes management and that when complicated with diabetes was seen. This increased
some of the TB treatment regimes, including Isoniazid, mortality rate has been found elsewhere[49,50]. Co-pres-
have hyperglycaemic effects[35]. entation of TB and DM was associated with increased dia-
betes related complications in a recent study and poorer
Reported mechanisms causing the association blood glucose control[13,28]. Tight blood glucose control
DM is known to impair immune function[36,37]. Specif- is thought to reduce the risk of TB infection in an individ-
ically DM hinders cell mediated immunity and has been ual with DM[13,28].
associated with low levels of leucocytes, polymorphonu-
clear neutrophils (PMNs) and a decreased T-helper1 Co-presentation with TB and DM has also been associated
cytokine response to TB [36,38,39] (PMNs produce with more severe TB symptoms and clinical presentation;
cytokines and carry out phagocytosis[40]). T-helper 1 increased lung cavitations, and longer periods of smear
(Th1) type cytokines are vital in the control and inhibi- positivity[51,52]. In co-morbid patients the involvement
tion of TB, for example, Interferon Gamma (IFN-γ) is of the lower lung field is more common, Sosman and
important for combating microbial infection and both Steidl found multilobular cavitary TB was more common
IFN-γ and Tumor Necrosis Factor alpha (TNFα, another in people with diabetes[52]. However, there are relatively
Th1 cytokine) attack TB via the activation of macrophages few studies that look at the lung pathology of co-infected
[38-41]. Activated macrophages release reactive oxygen DM-TB patients, data is sparse and sometimes contradic-
species (ROS) and free radicals such as Nitric Oxide which tory, and as such it should be considered cautiously. In
are essential for infection control, including TB infec- Nijmegen researchers monitored TB patients both with
tion[38,40]. Not only are macrophages the primary site of and without diabetes while they received treatment, they
TB infection but they also instigate the main immune found that co-morbid individuals were more likely to
response to TB[12,41]. Macrophage function is inhibited have positive sputum results after six months of TB treat-
in individuals with diabetes, the production of ROS, and ment, 22.2% compared with only 9.5% of the non-com-
phagocytic and chemotactic abilities are impaired. All of plicated TB cases. This suggests TB bacterial clearance
which are important for TB clearance[38,39,42]. takes a longer time in DM patients. Animal models have
Depressed immunity in DM patients would plausibly shown that hyperglycaemia causes higher TB bacterial
cause a higher risk of developing TB. Pulmonary microan- loads than you would see in animals with normal blood
giopathy occurs as a complication of DM and could par- glucose, this implies that infectivity is greater during

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hyperglycaemia which has implications for DM patients and mortality. Once someone starts ART they will remain
and could relate to the increased clearance times seen[53]. upon it for life.

Data upon the effect co-morbidity has on the likelihood HIV and ART causing Metabolic Syndrome
of the TB infection being multi-drug resistant is inconsist- The range of potential adverse consequences of ART is
ent. In a study carried out on the Texas border population wide and includes gastro-intestinal disturbance, hepato-
it was found that multi-drug resistant TB (MDR-TB) was toxicity, pancreatitis, peripheral neuropathy, mitochon-
associated with DM with an Odds Ratio of 2.1[42]. Other drial toxicity and anaemia[59]. Risk associations between
studies have shown no increased association between DM HIV, its treatment, and various features of MS have been
and MDR-TB. Incompletion of TB treatment is a major reported. It is during the treatment of HIV with ART that
cause of primary drug resistance. DM patients are thought metabolic syndrome can be induced. The mechanism for
to have impaired gastrointestinal drug absorption due to this is unknown but it is thought to either be due to the
gastroparesis which may affect treatments. A study by Nij- infectious, inflammatory, process of HIV itself, a form of
land et al reported that Rifampicin is not absorbed as drug induced toxicity or perhaps through indirect effects.
effectively in TB-DM patients, this could again be due to Two classes of ART, nucleoside reverse transcriptase inhib-
poor gastrointestinal uptake, or due to differences in itors (NRTIs) and protease inhibitors (PIs) have been
metabolism, excretion and body weight[54]. This poor associated with inducing MS[18,60,61]. HIV treatment
intake of anti-TB drugs by DM patients could be a possible with protease inhibitors has not only been associated with
mechanism that leads to the development of drug resist- hyperglycaemia, but the development of insulin resist-
ance. ance (a feature of MS and precursor to DM), increased lev-
els of cholesterol and triglycerides, lipodystrophy, and the
HIV, Metabolic Syndrome, and Heart Disease onset or complication of diabetes[18,60].
Metabolic Syndrome
Metabolic abnormalities such as; glucose intolerance, We will discuss further the association seen between HIV
Insulin resistance, abdominal adiposity high BP, and low and three major components of MS, dyslipidemia, lipod-
HDL cholesterol and raised triglycerides tend to cluster, ystrophy and insulin resistance. Although these three fea-
and it is the presence of these clustered abnormalities tures of MS are clearly inter-related the nature of these
which are referred to as Metabolic Syndrome (MS). There relationships are not yet fully understood, so, in order to
is no universally accepted definition for MS but the 3 most describe their association with MS as noted in the litera-
often used are those as set out by the World Health Organ- ture we will do so separately.
isation (WHO), International Diabetes Federation (IDF)
and National Cholesterol Education Program Adult Treat- Risk of HIV Lipodystrophy (HIV-LD) in HIV+ patients
ment Panel 3 (NCEPATPIII) [55-57]. Probably the most HIV Lipodystrophy (HIV-LD) is seen in long term survi-
relevant to be used within an African setting due to its vors of HIV infection, most of whom are receiving ART.
clinical accessibility is that of the IDF which requires for HIV-LD is a complex syndrome thought to occur due to
the diagnosis of MS central obesity, plus two of the fol- the secondary effects of HIV infection, direct drug-induced
lowing four additional factors: raised triglycerides, toxicities and, or, the indirect effects of changes in body
reduced high density lipoprotein cholesterol, raised blood composition on lipid metabolism[62]. The syndrome
pressure, or raised fasting plasma glucose[57]. consists of both metabolic abnormalities (hyperlipidae-
mia and IR) and body fat redistribution (central adiposity
Anti Retroviral Treatment and peripheral fat wasting). Central adiposity is manifest
Anti-retroviral treatment (ART) is the main management by the accumulation of visceral fat in the intra-abdominal
regimen for HIV/AIDS, it consists of a number of drugs space (abdominal obesity), dorsocervical spine (buffalo
that suppress viral replication and decrease viral load[58]. hump) and the breasts. Peripheral wasting describes loss
HAART (highly active antiretroviral therapy) is the gold of subcutaneous adipose tissue (lipoatrophy) in the
standard for treatment where three or more drugs are limbs, face and buttocks in a generalised fashion. Both
combined in order to prevent the development of drug central adiposity and peripheral wasting can occur
resistance. There are currently five classes of ART drug cat- together but the underlying processes typically take place
egorised on the basis by which they suppress HIV infec- independently so that most often one feature is present
tion; Protease inhibitors (PIs), Nucleoside or nucleotide alone[8]. The risk of central adiposity and peripheral
reverse transcriptase inhibitors (NRTI), Non nucleoside wasting is greatly increased in HIV+ patients on ART. In the
reverse transcriptase inhibitors (NNRTI), fusion inhibi- Lancet, in 1997, the first report on body fat redistribution
tors and integrase inhibitors[58]. Widespread use of ART in an HIV+ person associated with PI-treatment was pub-
in high-income countries has profoundly changed the lished[60]. The following year, 1998, Carr et al designed a
outlook for HIV+ individuals, reducing both morbidity cross-sectional study to characterise the syndrome that

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was leading to this observed body fat redistribution and to which is accompanied by impaired insulin sensitivity[17].
determine if it was seen in association with all PI use or It has been shown that ART regimens impair glucose tol-
only in HIV patients using PIs. Healthy individuals, PI erance in one of two ways; induction of peripheral IR in
naïve HIV+ patients and HIV+ patients on PIs, were com- skeletal muscle and adipose tissue and impairment of
pared[18]. It was already known that Protease Inhibitors pancreatic beta cells to compensate[17]. It has also been
cause certain metabolic abnormalities such as hypergly- reported that PIs bind to and block the insulin sensitive
caemia but, this publication was the first to report that glucose transporter GLUT4[68]. Less is known about the
HIV patients on PIs had an increased risk of developing a mechanisms involved in the NRTIs effect on insulin sensi-
syndrome of lipodystrophy with hyperlipidaemia and IR. tivity[11]. It has been well documented that IR is related
It is now accepted that PI and other ART use in HIV+ indi- to abdominal obesity, hypertriglyceridaemia and is asso-
viduals are associated with fat redistribution. Studies on ciated with type 2 DM[18] There is much controversy as to
nevirapine [63] (an NNRTI) and stavudine, and lamivu- whether it is changes in body composition that reflect
dine [59,64] (NRTIs) have all shown an association underlying metabolic changes or vice versa[69]. In a
between usage and changes in fat deposition. All ART tri- recently published study in which ART-naïve patients
als that have included objective body shape evaluation were randomised to receive either an NRTI-regimen or an
have consistently found an increased risk of abdominal NRTI-sparing regimen, glucose and insulin were assessed
fat in HIV patients regardless of which ART is used. How- before and approximately three months after initiation of
ever it is unknown which ARTs cause the most severe accu- therapy. The researchers reported that there was a reduc-
mulation of visceral fat[65]. tion in peripheral insulin sensitivity without significant
changes in body fat distribution in the NRTI group but not
Risk of Dyslipidemia in HIV+ patients the NRTI-sparing group[70]. These findings indicate the
Dyslipidaemia is characterised by hypertriglyceridaemia, changes are not mediated by alteration in body composi-
hypercholesterolaemia and low serum high density lipo- tion but that the risk is associated with NRTI usage.
protein (HDL) cholesterol, features of defective lipopro-
tein metabolism[6]. Although abnormal lipid profiles are Risk of Heart Disease in HIV+ patients
reported in HIV+ individuals before the onset of ART, Magula and Mayosi (2003) looked at cardiac involvement
hypertriglyceridaemia becomes both more prevalent and in HIV patients and showed that abnormalities are com-
severe during treatment[66]. Sullivan et al in 1998 moner in HIV patients. Approximately half of hospitalised
reported a case in which serum triglycerides markedly HIV patients and a high number of out-patients were
increased after 5 months of treatment with ritonavir (a found to develop cardiac abnormalities[71]. The DAD
PI). In the same patient there was also an increase in cho- study (Data Collection on Adverse Events of Anti-HIV
lesterol, both concentrations returned to baseline 5 weeks Drugs) assessed the risk of Myocardial Infarction (MI) in
after discontinuing ritonavir showing the association to HIV patients by measuring the incidence of MI in terms of
be treatment rather than infection led[67]. duration of HAART. The relative risk of an MI for an HIV
patient on HAART was shown to be raised and to increase
Hypertriglyceridaemia and hypercholesterolaemia have over time[7]. In another study cardiovascular disease risk
been reported to occur with long term usage of drugs from was found to be significantly higher in HIV patients with
the three main classes of ART, however, the association MS in comparison to HIV patients with only abnormal
seems most common place with the use of PIs. Chen et al body fat redistribution. This shows that MS increases the
report prevalence of dyslipidaemia (defined as hypertrig- risk of MI more severely than body fat changes alone.
lyceridaemia, hypercholesterolaemia and low HDL) in Based on the Framingham criteria [72] the researchers
HIV+ individuals being treated with HAART as 70-80% report median percentage of cardiovascular disease risk at
and state that it can be associated with all available PIs[6]. ten years for those with the MS and those without to be 10
It has also been reported that severe hypertriglyceridaemia and 5 respectively. It is not known how the traditional car-
associated with PI therapy can lead to acute pancreati- diovascular risk factors (e.g. smoking) modulate risk in
tis[67]. the HIV population[66].

Risk of Insulin Resistance in HIV+ patients Importance of these associations in a Sub-

It is also known that HIV+ people are at increased risk of Saharan African setting and the impact of
IR due to the pro-inflammatory process of HIV, the direct globalization upon them
effects of ARTs and also, indirect effects as consequences Importance of both associations within Sub Saharan Africa
of ART (for example body fat distribution changes). The Although much research is needed before we fully under-
pathogenesis of ART-induced IR has been the focus of stand the biological pathways and effect on disease rates
much discussion. Evidence suggests that body fat distribu- of the associations between the chronic and infectious dis-
tion changes cause increased fat deposition in muscle eases discussed in this paper it is clear that they could

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potentially have a large public health impact within Sub- were receiving it by December 2005[75]. The G8 nations
Saharan Africa. In 2004 the WHO estimated there were and the UN national assembly agreed to working with
8.9 million new cases of tuberculosis, of which only half WHO and UNAIDS to continue developing an essential
were reported to public-health authorities and, or, package of HIV prevention, treatment and care with the
WHO[73]. The WHO African region has the highest esti- aim of moving as close as possible to universal access to
mated incident TB rate (356 per 100, 000 population per treatment by 2010. The treatment of HIV with ARTs is a
year) [73]. A large proportion of the increase in incident huge and greatly needed advance decreasing morbidity
tuberculosis seen in Africa is attributable to the spread of and mortality from HIV substantially but it has some
HIV. In 2004 34% of newly diagnosed TB cases in Africa unintended consequences that require either preventive
were estimated to be infected with HIV[73]. Diabetes Mel- efforts or appropriate treatment. If the goal of universal
litus is a large cause of morbidity and mortality in Sub- ART treatment within SSA is met then a substantial rise in
Saharan Africa. The IDF has estimated that the prevalence metabolic syndrome, diabetes and heart disease may be
of diabetes in SSA as a whole for 2006 was approximately seen. More research is needed to know how important this
10.8 million, and they predict that this will rise by up to relationship will be globally and within SSA.
80% by 2025 giving a prevalence of 18.7 million[74].
Could the large estimated rises in diabetes prevalence The impact of globalization upon both associations within
impact upon the future prevalence of TB, due to the asso- Sub-Saharan Africa and beyond
ciation between the two diseases, as the rises in HIV have Globalization, which can be defined as a process in which
already been seen to? regions are becoming increasingly interconnected via the
growing movement of people, goods, capital and ideas
As previously stated Stevenson et al estimated that Diabe- has both positive and negative impacts on health[76].
tes accounts for approximately 14.8% of incident Pulmo- One of the major processes indicative of globalization
nary Tuberculosis (PTB) in India, and a higher proportion currently ongoing in SSA is urbanisation, resulting from a
of TB infection has been found to be attributable to DM combination of natural population increase, reclassifica-
(25%) in a Mexican setting[16,29,30]. These findings flag tion of areas formerly considered rural, and rural to urban
the potential public health importance of the association migration[77]. It is estimated that by 2020 the total urban
in Africa, although it must be noted that these estimates population in SSA will double so that 487 million indi-
were not carried out within high HIV settings. As the num- viduals will be living in urban areas. Growth of the urban
bers of individuals with DM rise it is plausible that there populations within Sub Saharan African countries is
will be associated rises in the incidence of TB. The 2006 occurring presently at an average rate of 4.5% per
United Nations Joint Programme on HIV/AIDS year[78]. Urbanisation in SSA, as in other less developed
(UNAIDS) report estimated that 63% (24.7 million) of all parts of the world, is strongly associated with increased
people infected with HIV worldwide resided in Sub-Saha- levels of obesity, diabetes and cardiovascular disease[79].
ran Africa and that the majority of deaths globally In urban SSA obesity levels now equal those of the
occurred here (72%, 2.8 million). All Southern African west[80]. Lower levels of physical activity [81] and an
countries with the exception of Angola have an estimated increasing calorie rich diet are key drivers of these
adult HIV prevalence above 10%. In Botswana, Lesotho, increased rates. The production of processed foods has
Swaziland, and Zimbabwe, the estimated adult HIV prev- high profit margins and transnational food corporations
alence exceeds 20%[75]. Effective treatment of HIV infec- are amongst the largest sources of foreign direct invest-
tion with antiretroviral therapy (ART) is now available ment in many countries of Sub Saharan Africa[82].
even in countries with limited resources and in Africa the Indeed, it has been appreciated for many years that the
number of individuals receiving treatment has been global availability and marketing of cheap vegetable oils
greatly increased by the 3' by 5' campaign[75]. The large and fats is leading to increasing fat consumption in less
increase that has occurred in the number of people on developed countries[83]. Obesity is the major risk factor
ART has meant the number of people living with AIDS as for Type 2 diabetes, which accounts for over 90% of all
a chronic condition has massively increased. diabetes[74], and rural-urban comparisons of diabetes in
SSA find 2 to 5 fold higher prevalence in urban
The WHO and UNAIDS 3' by 5' initiative, aimed to pro- areas[81,84,85]. As an increase in diabetes prevalence
vide treatment to 3 million people in low and middle occurs alongside rapid urbanisation, it is reasonable given
income countries by 2005. By December 2005, 18 coun- the evidence reviewed here to suggest that this will make
tries had met their 3' by 5' target and 1.3 million individ- TB control more difficult, and may even lead to a rise in
uals were receiving ART. In Sub-Saharan Africa, the TB incidence. It is expected that numbers of individuals
number of people receiving HIV treatment increased more affected by the co-morbidities of diabetes and TB will rise.
than eight-fold to 810,000 from 100,000. Despite these There are at least two million people who were born in
increases in ART, only 20% of those in need of treatment Sub Saharan Africa now living in North America or West-

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ern Europe[86]. They have moved from a region of high The literature reports a clear association between DM and
risk for TB and HIV to countries with a lower risk of these TB and also discusses the possibility of this link being bi-
conditions, meaning that they tend to be disproportion- directional. Although the underlying mechanisms for the
ately represented in their host countries amongst those association are not yet definite many possible pathways of
with TB and HIV. For example, according to the UK action have been reported. The link between TB and DM
Health Protection Agency, there were over 1500 new cases will pose a serious threat to public health in SSA as DM
of TB in the UK amongst people born in Africa in 2007, prevalence rises. There are also published studies report-
which is an annual rate of more than 300 per 100,000 ing an association between HIV, its treatment and many
compared to less than 10 per 100,000 in the white UK various features of metabolic syndrome. Although associ-
born population. In addition, people of African origin liv- ations between HIV, its treatment using ART and HIV-LD,
ing in the UK, and other richer countries, tend to be at insulin resistance, dyslipidemia and heart disease are now
higher risk of diabetes, 2 to 4 fold higher, than the major- accepted as occurring in western environments the mech-
ity white population[74]. It is therefore highly plausible, anisms through which these occur are still under debate.
but currently unknown, that international migrants from More research is needed in low income countries in order
Africa to richer parts of the world are at much greater risk to find the extent to which these issues will be a problem
of the adverse combination of TB and diabetes. The poten- in SSA.
tial importance of the relationships in international
migrants, moving from Africa to richer parts of the world, An awareness of the problems that occur due to the asso-
is poorly researched and requires further attention. ciations seen between chronic and infectious disease
Labour migration patterns in Africa are considered one of should allow us to deal with them more efficiently. More
the underlying determinants of the spread and distribu- research however is needed upon the mechanisms of
tion of HIV infection[87], which in turn is also linked to action for these risk associations in order for effective pre-
the spread of TB infection. Economic globalization is vention or treatment of them to occur and more research
identified as one of the drivers of labour migration within needs to be carried out before we truly understand how
Africa, both within and between countries, and particu- globalization is impacting upon the associations.
larly from rural to urban areas[88]. Thus an interaction is
occurring between globalization, the risk of HIV infection Abbreviations
and exposure to "obesogenic" urban environments. It is AIDS: Acquired Immune Deficiency Syndrome; ART:
only with wider availability of ART that this combination Antiretroviral Therapy; CVD: Cardiovascular Disease;
becomes of public health importance giving a further DAD study: Data Collection on Adverse Events of Anti-
increased risk to HIV positive people on ARTs of develop- HIV Drugs study; DM: Diabetes Mellitus; HAART: Highly
ing metabolic syndrome, diabetes and cardiovascular dis- Active Antiretroviral Therapy; HIV: Human Immunodefi-
ease. Even with the afore mentioned side effects ART is the ciency Virus; HIV-LD: HIV Lipodystrophy; IDF: Interna-
most essential response to the HIV/AIDs epidemic but the tional Diabetes Federation; IFNγ: Interferon Gamma; IGT:
potential health effects of its prolonged use need to be Impaired Glucose Tolerance; IL-4: Interleukin 4; IL-6:
addressed. Positive impacts of globalization are also seen. Interleukin 6; IL-12: Interleukin 12; MDR-TB: Multi-Drug
As the world becomes increasingly interconnected it has Resistant TB; MI: Myocardial Infarction; MS: Metabolic
become easier to implement treatment in areas where dis- Syndrome; NCEPATPIII: National Cholesterol Education
ease is endemic and globalization, as represented through Program Adult Trial Participants 3; NRTI: Nucleotide
the activities of international organisations such as the Reverse Transcriptase Inhibitor; NNRTI: Non-Nucleotide
United Nations/WHO, has played a large role in the Reverse Transcriptase Inhibitor; PI: Protease Inhibitor;
increased access individuals within SSA now have to ART. PMNs: Polymorphonuclear Neutrophils; PTB: Pulmonary
Reduction in prices of ARTs for use within SSA by interna- TB; ROS: Reactive Oxygen Species; RR: Relative Risk; SSA:
tional drug corporations and the pledges from private Sub-Saharan Africa; TB: Tuberculosisy; Th1: T-Cell helper
donors have also contributed to this increased accessibil- one; TNFα: Tumor Necrosis Factor Alpha; UNAIDS: The
ity. United Nations Joint Programme on HIV/AIDS; WHO:
World Health Organisation.
Conclusion
SSA is currently seeing a very large change in the major Competing interests
health problems it faces. The link between chronic and The authors declare that they have no competing interests,
infectious diseases becomes more important as the epide- that there are no conflicts of interest and/or financial dis-
miological transition in SSA progresses against a backdrop closures where any of this work is identified. All authors
of globalization. In this review we reported upon the asso- have read and approved the final manuscript.
ciations seen between two examples of chronic and infec-
tious disease.

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