Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 75
7
TB and Drug-Resistant TB in
Vulnerable Populations
Key Messages
• ediatric TB is generally underreported since children can be
P
difficult to diagnose and are often overlooked or slighted in TB
statistics.
• reatment of children calls for quality-assured pediatric formula-
T
tions with standard regimens.
• nterventions in the lives of TB patients who suffer from alcohol or
I
drug dependence can greatly reduce treatment default rates and
the spread of drug-resistant strains.
• espite an increase in HIV infection rates, the number of active
D
TB patients in Russian prisons has fallen by more than half over
the past decade, in part because of more effective diagnostic and
treatment programs.
Speakers at the workshop addressed TB and drug-resistant TB among
three particularly vulnerable populations: children, people with drug and
alcohol dependencies, and the incarcerated.
75
OCR for page 76
76 DRUG-RESISTANT TUBERCULOSIS IN RUSSIA
DRUG-RESISTANT TB IN CHILDREN: THE HIDDEN EPIDEMIC1
Pérez-Vélez has been studying TB in the port city of Buenaventura,
Colombia, since 2006. According to Pérez-Vélez, drug-susceptible and
drug-resistant TB in children is underdiagnosed and underreported, and
efforts to combat it are therefore underfunded. TB in children is a “hid-
den epidemic” and a major neglected child health problem he suggested,
especially in communities that are ill equipped to address the problem
adequately.
Data typically include only microbiologically confirmed and mainly
smear-positive cases, yet children frequently have extrapulmonary TB,
which can be difficult to diagnose clinically and confirm bacteriologically
and carries its own set of complications. There are two additional reasons
why accurate information on the epidemiology of TB in children is limited:
(1) the criteria for defining a case of TB in a child vary, and (2) of the four
WHO criteria for diagnosing TB in children, two (PPD-tuberculin test and
radiography) often are not available in resource-limited settings—those
with the highest burden of TB.
Furthermore, until 2007 WHO typically grouped all children in one
age category—ages 0–14—rather than analyzing them in more precise
subgroups. Even today, WHO reports results only for ages 0–4 and 5−14,
even though children aged 5−10 tend to develop TB at much lower rates,
thus confounding the latter grouping. In countries with an intermediate
burden of TB, including many Latin American nations, many regions have
high-burden pockets of TB; when averaged with the TB notifications from
low-burden regions, however, the high-burden areas effectively disappear
and consequently receive little attention. Native Indians (Amerindians)
are an example of a highly vulnerable population, with some reservations
having incidence rates as high as 1,000 per 100,000 population and high
mortality. Another group underrepresented in surveillance reports consists
of peasants, including many children, displaced by civil wars and often
living in camps.
Children also have traditionally been excluded from surveillance of TB
drug resistance. In the report series Anti-Tuberculosis Drug Resistance in
the World (WHO, 2008), children originally were not included, and when
they were, age groups between 0 and 14 were combined. In many health
policy meetings and clinical training courses, pediatric TB is not even on
the agenda.
Pérez-Vélez suggested that children be divided into different age groups
and that a strong effort be made to eliminate underreporting. To advocate
1 This section is based on the presentations of Carlos Pérez-Vélez, National Jewish Health
and University of Colorado School of Medicine, Denver, Colorado; Dr. Shin; and Gary
Reubenson, Rahima Moosa Mother and Child Hospital, South Africa.
OCR for page 77
77
DRUG-RESISTANT TB IN VULNERABLE POPULATIONS
effectively for policy changes, supporting data must be available to decision
makers. In addition, Pérez-Vélez noted, quality-assured pediatric formula-
érez-Vélez
rez-Vélez
élez
lez formula-
tions of both first-line and second-line anti-TB medications are needed for
standard regimens.
Drug-Resistant TB in Children in Colombia
Limited data from several Latin American countries reveal widely vary-
ing pediatric resistance rates (Table 7-1). Bogota, the capital of Colombia,
has 8 to 10 million inhabitants. The incidence of TB is reported as 25
per 100,000 population, compared with an estimated 200 per 100,000 in
Buenaventura (which is near Cali, the center of the Colombian drug trade).
According to data gathered from 2001 to 2009 in Colombia, about 70
percent of children have pulmonary TB, and about a quarter have extra-
pulmonary TB. These pediatric patients also have a variety of TB clinical
syndromes, including pulmonary, central nervous system, and lymph node
diseases. Pérez-Vélez shared a current pediatric case he is treating, a 2-year-
old girl with MDR TB adopted from China. The girl’s strain of TB is resis-
tant to a total of six drugs (although her case does not qualify as XDR TB).
She has disseminated TB, including pulmonary disease (bronchopneumonia,
endobronchial disease, bronchiectasis), with associated massive mediastinal
TABLE 7-1 Varying MDR TB Rates Revealed by Surveys of Anti-TB
Drug Resistance in South American Children, 2001−2009
Any Isoniazid
Patients Resistance Resistance MDR
Country Year(s) of Survey Tested (%) (%) (%)
Argentina 2005 N = 683 10.0 5.7 2.2
P = 136 25.0 18.4 15.4
Colombia 2001−2009 N = 26 20.8 12.0 3.2
P=3 0.8 0.8 0.8
Paraguay 2001 N = 235 11.1 6.4 2.1
P = 51 19.6 11.8 3.9
Peru 2006 N = 1,809 23.2 11.6 5.3
P = 360 41.7 30.3 23.6
Uruguay 2005 N = 335 2.1 1.2 0
P = 33 9.1 6.1 6.1
NOTE: N = new TB cases; P = previously treated TB cases.
SOURCES: Llerena et al., 2010; Wright et al., 2009.
OCR for page 78
78 DRUG-RESISTANT TUBERCULOSIS IN RUSSIA
lympohadenopathy (complicated by external compression of the trachea),
two cervical lymphadenitis lesions, Pott’s spinal disease, and severe fail-
ure to thrive. The armamentarium for treating this child is, as one would
expect, quite limited, said Pérez-Vélez.
In Colombia in 2007, 593 cases of TB were reported in children below
age 15, representing just 5.3 percent of the total number of cases in the
country. This is a low number for an intermediate-burden country and
should probably be closer to 10 percent, Pérez-Vélez noted. As a general
rule, said Pérez-Vélez, 5−10 percent of the caseload in low-burden coun-
érez-Vélez,
rez-Vélez,
élez,
lez, coun-
tries would be children, 10−20 percent in intermediate-burden countries,
and 20–40 percent in high-burden countries, although these proportions
are gross estimates based on epidemiological studies that carried out both
passive and active case finding. In Buenaventura, a high-burden TB set-
ting, the pediatric caseload was almost zero in 2006 and is now at 23
percent (personal communication, Cesar A. Moreira, TB Controller of
Buenaventura). Also, about 45 percent of pediatric cases in Colombia were
smear positive, which suggests a late diagnosis since children are generally
paucibacillary and therefore smear negative and culture negative. This find-
ing also suggests a dependency on smear microscopy-based, as opposed to
culture-based, diagnosis, which is quite common in developing countries.
In some countries, children diagnosed with TB (i.e., fulfilling the recom-
mended WHO criteria) are not treated because of the misconception that
they, like adults, require bacteriological confirmation. Pérez-Vélez sug-
érez-Vélez sug-
rez-Vélez
élez
lez
gested that a solely smear-based program is inadequate for bacteriological
confirmation in children and that a strengthening of laboratory capacity
(especially for mycobacterial cultures and associated drug susceptibility
testing) is necessary.
Of 128 pediatric TB cases in Colombia from 2001 to 2009—although
this clearly is an underreported number, said Pérez-Vélez—3 had been
treated previously, and 125 were new cases. Of the new cases, 99 were
drug-susceptible, 14 exhibited monoresistance, 8 exhibited polyresistance,
and 4 were MDR TB. The accuracy of these results depends on having both
accurate bacteriological tests and good-quality samples, Pérez-Vélez empha-
érez-Vélez empha-
rez-Vélez
élez
lez
sized. Even in very young children (including infants), who cannot undergo
the conventional specimen collection method of gastric aspiration/lavage,
bacteriological confirmation (and subsequent drug susceptibility testing)
can be carried out through nasopharyngeal aspiration after sputum induc-
tion. Pérez-Vélez’s research group (Grupo Tuberculosis Valle-Colorado) is
evaluating the bacteriological yield of alternative specimens to the gastric
aspirate, including induced sputum, as well as a highly absorbent nylon
string that absorbs the sputum swallowed by the pediatric patient over
many hours while asleep or awake (known as the “string test”). Pérez-Vélez
also stressed the importance of reducing the time elapsed between diagnos-
OCR for page 79
79
DRUG-RESISTANT TB IN VULNERABLE POPULATIONS
ing TB in children and obtaining results of drug susceptibility testing to
guide the clinician in selecting an effective regimen of anti-TB medications.
Pediatric Drug-Resistant TB in Peru
Shin stated that in pediatric populations, patterns of drug resistance
are often different from those in adults because pediatric TB infections are
primary (i.e., transmitted from person to person). In these cases, excess
morbidity and mortality are likely due to underdiagnosis. In Peru, a study
examined 38 children with a median age of 11 who had experienced an
average of more than 6 months from first TB diagnosis to MDR TB treat-
ment. Rates of adverse events were much lower than for adults, and the
children tolerated treatment very well despite the use of aggressive therapy.
The median number of drugs in the regimen was six, and cure rates were
94 percent.
Pediatric Drug-Resistant TB in South Africa
An estimated 1 million cases of pediatric TB occur annually worldwide,
three-quarters of which are in 22 high-burden countries, said Reubenson.
Since the vast majority of these cases are smear negative, this figure is likely
an underestimate. Pediatric TB has traditionally been neglected, suggested
Reubenson. TB in children is difficult to diagnose and confirm, and from
a public health perspective, children are less likely to transmit the disease.
However, there is increasing awareness of the problem.
Children are especially important in assessing drug-resistant TB through
surveillance programs because they represent patients that have recently
been infected and therefore reflect circulating strains and prevalent drug
susceptibility patterns. Yet international data on pediatric TB are extremely
limited. In unpublished 2008 data, among 140 culture-confirmed pediatric
cases in two Johannesburg academic hospitals, 49 percent were infected
with HIV, 14.2 percent showed resistance to isoniazid, and 8.8 percent had
MDR TB. Among this latter group, 85 percent had received no previous
TB treatment, none had a history of contact with an adult with MDR TB,
30 percent had a history of contact with an adult with TB, 54 percent were
infected with HIV, and the mortality rate was 30 percent (with a quarter
of these deaths occurring prior to confirmation of MDR TB). Notably,
none of those with confirmed MDR TB had a history of an adult MDR
TB contact, and 85 percent had received no previous TB treatment. “These
are the things we are taught to look for when trying to diagnose pediatric
MDR TB,” said Reubenson, “and they would not have been helpful in
these situations.”
Reubenson said he was aware of two confirmed cases of pediatric XDR
OCR for page 80
80 DRUG-RESISTANT TUBERCULOSIS IN RUSSIA
TB in Gauteng Province, where he works. Both had undergone multiple
previous courses of TB therapy, and both were HIV-infected. One died, and
one has had consistently negative sputa and is, it is hoped, cured.
Each South African province has its own treatment center for MDR TB,
where cases are treated predominantly as inpatients. Isolates are tested for
susceptibility to the second-line drugs ethambutol, ethionamide, streptomy-
cin, amikacin, ofloxacin, and kanamycin, but not para-aminosalycylic acid,
capreomycin, pyrazinamide, terizidone, or other quinolones. This series of
tests largely follows national MDR TB treatment guidelines, but the Sizwe
Hospital in Guateng Province does individualize therapy according to the
specific isolates. Additional drugs used occasionally include high-dose iso-
niazid, clarithromycin, augmentin, moxifloxacin, para-aminosalycylic acid,
and capreomycin. All HIV-infected children with drug-resistant TB receive
ART, irrespective of clinical or immunological staging.
Almost no data are available on outcomes, although anecdotal expe-
rience indicates that outcomes are fairly good. As Reubenson suggested,
however, patients who come to the hospital have in a sense “preselected”
themselves for survival, so their prognosis would be expected to be better
than that for the overall cohort.
MDR TB TREATMENT FOR PEOPLE WITH
DRUG AND ALCOHOL DEPENDENCIES2
According to Shin, people who abuse alcohol have a higher risk of con-
tracting TB, having drug-resistant TB, and experiencing excess morbidity
and mortality. Researchers have looked at the ethnography of alcohol abuse
in different settings, the role of alcohol in causes of death, and the effect of
alcohol interventions on TB and alcohol dependency outcomes. One objec-
tive of these studies has been to integrate care for alcohol dependency into
TB programs so that it is a part of TB management.
Shin noted that many patients who abuse alcohol are eager for treat-
ment, despite the stereotype that they resist assistance. For example, two-
thirds of eligible patients enrolled in a study of naltrexone therapy and
counseling in Tomsk, even though the researchers initially suspected that
alcoholic patients might not be willing or wish to receive care. Shin elabo-
rated that these patients generally cannot afford counseling services through
the private sector and are happy for the opportunity to receive treatment for
their alcohol dependency during TB treatment. She suggested that, instead
of viewing this population as untreatable, treatment programs must raise
2 This section is based on the presentations of Dr. Shin and Piotr Golubchikov, Tomsk Re-
gional Tubercular Clinic.
OCR for page 81
81
DRUG-RESISTANT TB IN VULNERABLE POPULATIONS
the level of support for these patients and become more aggressive in diag-
nosing and treating them.
Golubchikov presented a case study of treatment for patients with TB
and alcohol dependency. Tomsk Oblast lies within the Siberian Federal
District of the Russian Federation. It has a population of about 1 million
living in an area of 317,000 square kilometers. The DOTS program was
piloted in the Tomsk region of Russia in 1994 to treat drug-susceptible
TB, and in 2000 the DOTS-Plus program was launched to treat MDR TB.
Beginning in 2000, Partners In Health began working in Tomsk Oblast, and
in 2004 the region received a grant from the Global Fund to Fight AIDS,
Tuberculosis, and Malaria.
With financial support from Partners In Health, a cohort of patients
was enlisted in MDR TB treatment from 2000 to 2002. Of 244 patients,
191 were cured, 16 failed, 12 died, and 25 defaulted. When 75 patients
were enrolled in a second cohort for treatment in 2004−2005, the results
were much worse (Figure 7-1). According to Golubchikov, the main rea-
sons for the high failure and default rates in the second cohort were higher
rates of alcoholism and drug addiction. This is especially unfortunate, said
Golubchikov, because these patients tend to leave treatment facilities and
infect others.
78%
80 69%
70
57%
60
50
Percent
32%
40
30 18% 15%
20 1%
7%
10
0
Cured Failure Default Alcoholics and
Drug Addiction
2000–2002 2004–2005
FIGURE 7-1 The 2004−2005 cohort had worse outcomes than the 2000−2002
cohort, largely because of alcoholism and7-1.eps
Figure drug addiction.
SOURCE: Golubchikov et al., 2010.
OCR for page 82
82 DRUG-RESISTANT TUBERCULOSIS IN RUSSIA
Golubchikov and his colleagues work mainly in the areas of alcohol
harm reduction, narcotics harm reduction, social support for patients,
development of patient-centered approaches, and training programs for
staff and patients. All patients are tested for alcohol and drug dependence
before beginning treatment.
If alcohol dependence is detected, patients receive counseling from a
substance abuse professional and psychologist before they begin treatment,
and this counseling is available throughout the course of therapy. The treat-
ment program has been participating in research on the effectiveness of
naltrexone to counter alcohol dependence. In addition, it provides separate
counseling rooms for the substance abuse professional and the psycholo-
gist. Long-term communication with the psychologist is important to the
treatment program, said Golubchikov.
For those dependent on drugs, counseling is available from a substance
abuse professional and psychologist throughout the course of therapy.
Outreach workers from Nasha Klinika, a nongovernmental organization,
encourage intravenous drug users and MDR TB patients to receive treat-
ment, and arrangements are made for patients to visit a drug abuse clinic
to address their addiction or reduce their doses of drugs.
Patients receive a weekly distribution of food and other necessities,
clothes, free travel to outpatient facilities, hot meals at local TB day-patient
facilities, and the assistance of social workers for such tasks as applying
for disability benefits. The development of patient-centered approaches
included the expansion of day-patient facilities, with two hot meals served
daily; home care for 60 patients; treatment at village health centers; and
expansion of a network of volunteers in remote districts. The “Sputnik”
program involves the provision of home visits for persistent or potential
defaulters from TB treatment, with medical and psychological intervention
and social support.
The Tomsk Oblast TB Service also has taken several administrative
measures to counter MDR TB. A mobile default team visits the homes of
patients who have missed their morning dose that day. A default committee
consisting of a deputy head doctor, psychologist, substance abuse profes-
sional, and social worker meets to discuss patients who have missed their
treatment for more than 3 days. A substance abuse professional, psycholo-
gist, and social worker conduct home visits. Improved case management
and psychological support in the TB hospital have led to a decrease in early
discharges of high-risk patients from inpatient clinics.
Health professionals receive training for clinical management of MDR
TB, for detection and treatment of side effects, and for working with
patients with alcohol and drug dependencies. Patients undergo their own
health training, receive talks on TB, and have access to the management
staff of TB facilities. Specialists from Alcoholics Anonymous and the Rus-
OCR for page 83
83
DRUG-RESISTANT TB IN VULNERABLE POPULATIONS
sian Orthodox Church are involved in the program to support TB patients.
Also, patients who have successfully completed TB treatment programs talk
with current patients.
These efforts have had a dramatic effect on the outcomes of MDR TB
patients, said Golubchikov. In 2005, the year after the Global Fund grant
was launched in Tomsk, defaults among civilian patients in the DOTS-Plus
program dropped from 28.8 percent to 13.9 percent, and this percentage
has continued to fall since then (Figure 7-2). The percentage of MDR TB
among new bacteriologically proven cases of pulmonary TB investigated
for drug susceptibility has fallen from a high of 16.8 percent earlier in the
decade to slightly more than 13 percent. The level of XDR TB among all
positive susceptibility tests has fallen from a high of 3.5 percent in 2006
to about 2.5 percent currently. TB mortality has declined more in Tomsk
Oblast than in the Siberian Federal District and the Russian Federation
(Figure 7-3). And the estimated reservoir of infectious MDR TB cases
among the civilian sector has fallen from a high of more than 800 people
in 2002 to fewer than 400 in 2009.
28.9% 28.8%
16.7%
16.1% 13.9%
11.1% 9.7% 8.7%
GF grant
2001 2002 2003 2004 2005 2006 2007 2008
Year
FIGURE 7-2 Default percentages among MDR TB patients dropped substantially
after initiation of the DOTS-Plus program through a Global Fund grant.
Figure 7-2.eps
SOURCE: Golubchikov et al., 2010.
OCR for page 84
84 DRUG-RESISTANT TUBERCULOSIS IN RUSSIA
40
35
33.8
33.3
35
31.5
30.5
29.9 29.3
28.6 29.1
28.6
30
26
25 22.6 21.9 21.9
21.8 21.3
Percent
19.8 19.7
18.4
20 16.9 17.9
20.6
20 16.4
18.3 17.9 17.8
17.7
15
15.4
13.5 12.6 12.2
10
10.4
9.4
DOTS Plus
5
0
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
Year
Tomsk Obl. Sib FD Russia
FIGURE 7-3 TB mortality in Tomsk Oblast has fallen at a greater rate than in the
Siberian Federal District or the Russian Federation.
SOURCE: Golubchikov et al., 2010.Figure 7-3.eps
TB IN THE PRISON SYSTEM OF THE RUSSIAN FEDERATION3
Safonova reported that the number of active TB patients in Russia’s
penal institutions has fallen by more than half over the past decade (Figure
7-4). Even greater reductions have occurred in TB incidence and mortality
in Russia’s penal institutions. This decrease is due in part to shorter prison
sentences following changes in criminal law, but it is also due to programs
designed to detect and treat TB in the prison system. Financing from the
Global Fund and The World Bank were used in part to create a laboratory
network in the prison system, and 90 laboratories have been established.
Drug sensitivity testing has allowed the detection of MDR TB cases fol-
lowed by the introduction of second-line drugs. As a result, said Safonova,
diagnostics are now quite good, with coverage rates of more than 97 per-
cent, and prisons in 70 territories are now covered by second-line treatment.
During this same period, the number of HIV-infected patients in Rus-
sia’s penal institutions has increased, as has the number of prisoners coin-
fected with HIV and M.tb. (Figure 7-5). The number of drug-resistant and
MDR TB patients in Russia’s penal institutions also has risen. In 2009, 54.4
3 This
section is based on the presentation of Svetlana Safonova, Russia’s Federal Correc-
tion Service.
OCR for page 85
85
DRUG-RESISTANT TB IN VULNERABLE POPULATIONS
98,767
79,431
Number of Active TB Patients
70,100
50,915
48,370 47,431
44,704
42,346 40,765
2001 2002 2003 2004 2005 2006 2007 2008 2009
Year
FIGURE 7-4 The number of active TB patients in Russia’s penal institutions has
declined over the past decade. Figure 7-4.eps
SOURCE: Safonova, 2010.
percent of patients exhibited drug resistance, and 21.9 percent had MDR
TB. Among relapse TB patients, these percentages were much higher—82.9
and 49.9 percent, respectively. Among those TB patients in Russia’s penal
institutions that excreted M.tb., 2.5 percent of new cases and 7.2 percent
of relapse cases in 2009 were XDR TB.
Many new cases of TB are discovered only in penal institutions, mean-
ing that the patients would not have known they were infected with TB if
they had not been incarcerated. Of all new TB cases appearing in Russia,
only 12 percent appear in penal institutions. About 90 percent of those
TB patients diagnosed in penitentiaries did not know about their infection
prior to arrest.
About 68 percent of these cases are occupants of urban areas, and
only about 2 percent are homeless, contrary to a common stereotype, said
Safonova. Among these new cases, 76 percent are aged 20−29, and the
majority are employed. About 80 percent are unmarried, and 41 percent
of those sick were convicted for the first time.
OCR for page 86
86 DRUG-RESISTANT TUBERCULOSIS IN RUSSIA
Total
55,964
HIV
HIV+TB 49,213
42,164
40,429
36,414
35,217 35,317
30,904
4,870
3,912
3,542
3,054
2,566
2,947 2,547 2,560
2002 2003 2004 2005 2006 2007 2008 2009
Year
FIGURE 7-5 The number of patients infected with HIV and coinfected with HIV
and M.tb. in Russia’s penal institutions has risen since 2004.
Figure 7-5.eps
SOURCE: Safonova, 2010.
The Russian penitentiary service has several priorities, said Safonova:
• e
arly diagnosis of TB through x-ray and microbiological
investigation,
• c
ontinued development of the prison service’s laboratories and
bacteriological investigation of all categories of TB patients,
• i
nternal and external quality control of laboratories,
• c
ontinued development of the expertise of medical staff and provi-
sion of training, and
• c
ontinuing international cooperation.
