Boelaert, Marleen

Chappuis, François

De Weggheleire, Anja

Depoortere, Evelyn

Hasker, Epco

Kambo, Charles

Kande, Victor

Lutumba, Pascal

Potet, Julien

Pécoul, Bernard

PubMed

Epco Hasker

Pascal Lutumba

François Chappuis

Victor Kande

Julien Potet

Anja De Weggheleire

Charles Kambo

Evelyn Depoortere

Bernard Pécoul

Marleen Boelaert

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Human African trypanosomiasis in the Democratic Republic of the Congo: a looming emergency?

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Human African Trypanosomiasis in the Democratic Republic of the Congo: A Looming Emergency?

Hasker, E

Lutumba, P

Chappuis, F

Kande, V

Potet, J

De Weggheleire, A

Kambo, C

Depoortere, E

Pécoul, B

Boelaert, M

MSF Field Research

Viewpoints
Human African Trypanosomiasis in the Democratic
Republic of the Congo: A Looming Emergency?
Epco Hasker
1, Pascal Lutumba
2, Franc ¸ois Chappuis
3, Victor Kande
4, Julien Potet
5, Anja De Weggheleire
6,
Charles Kambo
7, Evelyn Depoortere
1, Bernard Pe ´coul
8*, Marleen Boelaert
1
1Institute of Tropical Medicine, Antwerp, Belgium, 2University of Kinshasa, Kinshasa, Democratic Republic of the Congo, 3Division of International and Humanitarian
Medicine, Geneva University Hospitals & University of Geneva, Geneva, Switzerland, 4Programme National de Lutte contre la Trypanosomiase Humaine Africaine,
Kinshasa, Democratic Republic of Congo, 5Me ´decins Sans Frontie `res - Access Campaign, Paris, France, 6Me ´decins Sans Frontie `res, Kinshasa, Democratic Republic of the
Congo, 7CDI Bwamanda, Democratic Republic of the Congo, 8Drugs for Neglected Diseases initiative, Geneva, Switzerland
Human African trypanosomiasis
(HAT), also known as ‘‘sleeping sickness’’,
is a parasitic disease that is fatal if left
untreated. The disease is transmitted by
the tsetse fly and is endemic to sub-
Saharan Africa, where it mainly affects
impoverished rural communities. There
are two forms of HAT; the West African
variant caused by Trypanosoma brucei gam-
biense is the most common and accounts
for over 90% of the current case load. The
disease occurs in two stages, the haemato-
lymphatic stage (stage 1) with no or few
specific symptoms, followed by the me-
ningo-encephalitic stage (stage 2), which
occurs when the parasite has crossed the
blood-brain barrier. This second stage is
characterized by neurological signs and
personality changes; damage to the hypo-
thalamus can lead to disturbances of the
normal sleep/wake cycle, hence the name
‘‘sleeping sickness’’ [1].
The ominous reputation of HAT is
linked to a history of devastating epidem-
ics, controlled with sometimes draconian
measures, only to re-emerge again once
control measures were abandoned. At the
turn of the 20
th century, an estimated
300,000 to 500,000 people died from
HAT; another major epidemic occurred
in the 1920s–’30s [2]. By the mid-1960s,
the disease was almost eliminated, but 30
years later incidence levels were back to
where they had been in the 1920s [3]. This
is illustrated by data from the Democratic
Republic of the Congo (DRC), the worst
affected country (Figure 1). After indepen-
dence in 1960, the strict and costly HAT
control measures put in place by the
colonial authorities were relaxed and the
number of HAT cases gradually increased.
Operations of the national sleeping sick-
ness control programme (Programme Na-
tional de Lutte contre la Trypanosomiase
Humaine Africaine, PNLTHA) continued
to be funded mainly by the Belgian
government. When in 1991 all Belgian
bilateral aid, including the support to the
PNLTHA, was suspended because of
international sanctions against the Mobutu
regime, the epidemiological situation soon
became dramatic.
In 1998, a total of 40,000 cases were
reported worldwide, 66% of which (26,318
cases) in the DRC. The WHO estimates
that 300,000 cases remained undetected
and therefore untreated [4]. An emergen-
cy HAT control program was launched
and followed up by the current program,
which is largely funded through bilateral
cooperation with Belgium. Active screen-
ing was resumed, reaching up to 3 million
persons per year, at an annual cost of 2.8
million US$. However, in the perspective
of this external funding being phased out,
and with no alternative funding sources
identified as of yet, the PNLTHA has been
forced to gradually scale down active case
finding campaigns.
In 2009, T.b. gambiense HAT was still
focally endemic in 24 Sub-Saharan Afri-
can countries, but out of the 9,688 cases
reported globally, 7,326 (76%) occurred in
the DRC [5]. The provinces of Bandundu
and Kasai Oriental remain heavily affect-
ed; the situation in Province Orientale is
unclear, because on-going armed conflict
interferes with screening campaigns, but
more than 3,000 cases have been diag-
nosed over the last 5 years [6].
Averting a Looming Emergency
The recent evolution of HAT control
activities in the DRC calls for urgent
action to prevent a new resurgence.
Similar considerations apply to the other
countries where HAT is endemic.
Continuity of Control Efforts
Because humans are assumed to be the
sole reservoir for T.b.gambiense HAT, active
population screening combined with treat-
ment of cases has since long been the
backbone of HAT control. When control
efforts are scaled down in response to low
prevalence, increasing numbers of infected
persons are not identified and do not
receive treatment, making transmission of
the parasite possible [7]. It is only a matter
of time before prevalence goes up again to
reach epidemic levels [8]. This is exactly
what is at risk of happening in the DRC at
the moment. Control efforts of the past
decade have paid off, and disease trans-
mission is under control in most, but
certainly not in all provinces. Abandoning
control measures at this stage, while
transmission is still on-going, guarantees
a progressive increase of prevalence in the
coming years.
It would be a wasteful use of resources
to let that happen. The investments made
in the past decade by the Congolese
national control program, building the
expertise to ensure the complex screening,
diagnostic and curative activities, in addi-
tion to ensuring the demanding logistic
support, all risk being lost. In the provinces
of Bandundu, Kasai Oriental and Orien-
tale, the disease is not under control yet
and reinforcement of the control measures
is needed. In order to avoid re-emergence
Citation: Hasker E, Lutumba P, Chappuis F, Kande V, Potet J, et al. (2012) Human African Trypanosomiasis in
the Democratic Republic of the Congo: A Looming Emergency? PLoS Negl Trop Dis 6(12): e1950. doi:10.1371/
journal.pntd.0001950
Editor: Joseph Mathu Ndung’u, Foundation for Innovative New Diagnostics (FIND), Switzerland
Published December 13, 2012
Copyright:  2012 Hasker et al. This is an open-access article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium,
provided the original author and source are credited.
Funding: The authors received no funding for this work.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: bpecoul@dndi.org
PLOS Neglected Tropical Diseases | www.plosntds.org 1 December 2012 | Volume 6 | Issue 12 | e1950of HAT in other areas, the available
expertise needs to be maintained and
mobilized in the most appropriate way.
Integration of HAT Control
In a context of substantial decrease of
case notifications and reduced budgets for
active screening, integration of HAT con-
trol into general primary healthcare seems
a logical nextstep. Efforts to integrate HAT
control services have been on-going since
2008, but a number of issues related to the
disease and to the health system represent
serious constraints to this integration effort.
To date there is no simple diagnostic test
available that can be applied routinely in a
rural health centre in sub-Saharan Africa.
HAT diagnosis usually involves a two-step
procedure, using the Card Agglutination
Test for Trypanosomiasis (CATT), fol-
lowed by a parasitological confirmation test
[9,10]. The CATT test is easy to perform
but requires a battery-powered rotator, as
well as a cold chain; parasitological confir-
mation tests require at least a functional
microscope. Because the treatment regi-
men depends on disease stage, a lumbar
puncture for stage determination is neces-
sary. Current treatment regimens for HAT
are complex, requiring one week of daily
intramuscular injections for patients in
stage 1 or twice daily intravenous perfu-
sions for patients in stage 2.
The local health system is ill equipped to
deal with a rare disease with a non-specific
early clinical presentation that requires
complex diagnostics and treatment. Passive
case finding has been shown to entail long
delays and missed diagnoses [11,12]. The
mean duration of stage 1 and 2 is estimated
at 526 and 500 days, respectively [13].
Since most patients detected passively are
diagnosed only when in stage 2, they have
been infectious to the vector (and therefore
sustaining transmission) for at least one or
two years. Moreover, patients diagnosed in
stage 2 are at higher risk for irreversible
sequelæ and require a more complex
treatment [14]. Despite efforts aimed at
integration, the proportion of cases detect-
ed through passive screening in the DRC
have remained relatively stable over the
past four years, apparently not compensat-
ing for the decrease in active screening.
Even if problems related to diagnostic
and treatment procedures could be over-
come, one more constraint to the integra-
tion of HAT control activities remains. In
the DRC, the average annual attendance
rate of health services is estimated at 0.15
per inhabitant [15]. Unless a significant
effort is made to further develop health
services and increase their utilization, it is
an illusion to think the current health
system is sufficient to control HAT or to
detect resurgence at an early stage. Until
then, some form of active surveillance will
continue to be required.
Control in Low Prevalence Contexts
Once prevalence levels go down, pop-
ulations in HAT endemic areas no longer
perceive the disease as a threat. Under
such circumstances, people are no longer
prepared to participate in the screening
campaigns because these are time con-
suming, have little respect for privacy, and
because people fear the side effects of
HAT treatment [16]. In addition, in a low
prevalence context, screening activities
become less efficient. The province of
Equateur in the DRC was the focus of a
major epidemic in the 1990s. In 2011,
only 219 HAT cases were diagnosed in
this province, of which 62 by mobile
screening teams; yet during that year, 5
mobile screening units made up of 33 staff
members in total, had screened 144,281
persons (personal communication Dr.
Christian Roberti).
A poor yield should not be a pretext for
abandoning active screening activities, but
rather serve as a call for innovative
screening methods to be developed and
field tested. Laveissie `re described in 1998
how health workers going from house to
house collecting blood samples on filter
papers that were later processed in labo-
ratories, were able to reach more people at
a lower cost when compared to mobile
teams [17]. Difficulties in communicating
test results and in tracing back HAT
suspects have until now been the main
reasons for keeping with the mobile team
approach. Nowadays, modern communi-
cation technology has penetrated the most
distant corners of rural Africa and geo-
graphic positioning systems (GPS) that
were once unaffordable can be bought
Figure 1. Annual case notification of HAT in DRC, 1926–2011. Source: PNLTHA.
doi:10.1371/journal.pntd.0001950.g001
PLOS Neglected Tropical Diseases | www.plosntds.org 2 December 2012 | Volume 6 | Issue 12 | e1950for less than 100 USD. Using a rapid test
currently undergoing phase III evaluation
would allow the immediate communica-
tion of the screening test result, while still
in the village. A Loop-mediated isothermal
Amplification (LAMP) test that can pro-
vide direct evidence of the presence of T.b.
gambiense DNA in a sample is currently
under development [18]. This test can be
performed on samples collected on filter
paper and can be carried out with
equipment that is automatized to such a
degree that it can be used at the level of a
district laboratory. If the diagnostic accu-
racy of this new test can be confirmed, the
combination of rapid tests and LAMP with
the use of GPS technology would make it
possible to locate and map all those
probably infected with T.b. gambiense in a
very efficient manner. Those individuals
could then be invited for a further
diagnostic workup in the privacy of a
consultation room in a larger health center
or district hospital, where they could also
be started on treatment.
A new treatment regimen based on 10
days of once daily oral administration of
fexinidazole is currently entering phase II
clinical trials. If these trials are successful,
fexinidazole could allow the diagnostic
threshold to be lowered, because it is easy
to administer and expected to be less toxic.
This drug passes the blood brain barrier
and would be suitable for both stage 1 and
stage 2 patients, thus obviating the need
for a lumbar puncture [19].
Conclusion
After a major upsurge in the 1990s,
HAT is now under control in most
endemic regions. To prevent resurgence
from re-occurring, which we know will
happen if control efforts are relaxed, the
continuation of control activities is crucial.
In the DRC the knowledge, expertise and
capacity are in place; continued funding of
the national HAT control programme
would allow for these to be utilized and
the epidemiological situation to be kept
under control.
With new, easy to perform diagnostic
tests and an oral treatment regimen in the
pipeline, integration of HAT control into
general healthcare services can be consid-
ered. However, integration will not be
sufficient to prevent HAT resurgence in
the longer term. Continued strong surveil-
lance, covering at least the historically
known HAT foci, is crucial, and cannot
rely on passive case finding alone. At the
same time, under the current circumstanc-
es of lowering prevalence, active surveil-
lance using mobile teams is neither
effective nor sustainable. Possible alterna-
tive approaches to surveillance have been
identified but still need to be field tested
and optimized.
HAT is listed by the WHO as one of the
diseases requiring ‘‘Innovative and Inten-
sified Disease Management’’ [20]. In the
coming years, a gradual and well-managed
integration of the HAT control activities in
the general health services can be envis-
aged, but this will require further research
to identify the best strategies in low
prevalence contexts. A minimal vertical
approach to control the disease is likely to
remain necessary. Finally, a regional
control strategy, coordinated between
countries where HAT is prevalent, should
be actively explored.
References
1. Van den Enden E (2010) Illustrated lecture notes on
tropical medicine [e-learning program]. Institute of
Tropical Medicine. Available: http://content-e.itg.
be/content-e/pub_ITG/Illustrated_lecture_notes_
on_Tropical_Medicine_1169817124568/index.
htm. Accessed 11September 2012.
2. Malvy D, Chappuis F (2011) Sleeping sickness.
Clin Microbiol Infect 17: 986–995. doi:10.1111/
j.1469-0691.2011.03536.x.
3. Barrett MP (1999) The fall and rise of sleeping
sickness. Lancet 353: 1113–1114. doi:10.1016/
S0140-6736(98)00416-4.
4. WHO (2012) Human African trypanosomiasis
(sleeping sickness). Fact sheet Nu259. Available:
http://www.who.int/mediacentre/factsheets/
fs259/en/. Accessed 11September 2012.
5. Simarro PP, Cecchi G, Paone M, Franco JR,
Diarra A, et al. (2010) The atlas of human African
trypanosomiasis: a contribution to global map-
ping of neglected tropical diseases. Int J Health
Geogr 9: 57. doi:10.1186/1476-072X-9-57.
6. Chappuis F, Lima MA, Flevaud L, Ritmeijer K
(2010) Human African trypanosomiasis in areas
without surveillance. Emerg Infect Dis 16: 354–
356.
7. Lutumba P, Robays J, Miaka mia Bilenge C,
Mesu VK, Molisho D, et al. (2005) Trypanoso-
miasis control, Democratic Republic of Congo,
1993–2003. Emerg Infect Dis 11: 1382–1388.
doi:10.3201/eid1602.090967.
8. Van Nieuwenhove S, Betu-Ku-Mesu VK, Dia-
bakana PM, Declercq J, Bilenge CM (2001)
Sleeping sickness resurgence in the DRC: the
past decade. Trop Med Int Health 6: 335–341.
9. Magnus E, Vervoort T, Van Meirvenne N (1978)
A card-agglutination test with stained trypano-
somes (C.A.T.T.) for the serological diagnosis of
T. B. gambiense trypanosomiasis. Ann Soc Belg
Med Trop 58: 169–176.
10. Robays J, Bilengue MM, Van der SP, Boelaert M
(2004) The effectiveness of active population
screening and treatment for sleeping sickness
control in the Democratic Republic of Congo.
Trop Med Int Health 9: 542–550.
11. Debrouwere V, Pangu KA (1989) [The flexibility
of an integrated health service in the campaign
against Trypanosoma brucei gambiense trypano-
somiasis]. Ann Soc Belg Med Trop 69 Suppl 1:
221–229.
12. Hasker E, Lumbala C, Mbo F, Mpanya A, Kande
V, Lutumba P, Boelaert M (2011) Health care-
seeking behaviour and diagnostic delays for
Human African trypanosomiasis in the Demo-
cratic Republic of the Congo. Trop Med Int
Health 16: 869–874. doi:10.1111/j.1365-
3156.2011.02772.x.
13. Checchi F, Filipe JA, Haydon DT, Chandramo-
han D, Chappuis F (2008) Estimates of the
duration of the early and late stage of gambiense
sleeping sickness. BMC Infect Dis 8: 16.
doi:10.1186/1471-2334-8-16.
14. Priotto G, Kasparian S, Mutombo W, Ngouama
D, Ghorashian S, et al. (2009) Nifurtimox-
eflornithine combination therapy for second-stage
African Trypanosoma brucei gambiense trypano-
somiasis: a multicentre, randomised, phase III,
non-inferiority trial. Lancet 374: 56–64.
15. Wembonyama S, Mpaka S, Tshilolo L (2007)
[Medicine and health in the Democratic Republic
of Congo: from Independence to the Third
Republic]. Med Trop (Mars) 67: 447–457.
16. Robays J, Lefevre P, Lutumba P, Lubanza S,
Kande BetuKu MesuV,etal.(2007) Drugtoxicity
and cost as barriers to community participation in
HAT control in the Democratic Republic of
Congo. Trop Med Int Health 12: 290–298.
doi:10.1111/j.1365-3156.2006.01768.x.
17. Laveissiere C, Meda AH, Doua F, Sane B (1998)
[Detecting sleeping sickness: comparative efficacy
of mobile teams and community health workers].
Bull World Health Organ 76: 559–564.
18. FIND (2011) Loop-mediated isothermal amplifi-
cation (LAMP). Available: http://www.
finddiagnostics.org/programs/hat-ond/hat/
molecular_diagnosis.html. Accessed 11 Septem-
ber 2012.
19. Torreele E, Bourdin TB, Tweats D, Kaiser M,
Brun R, et al. (2010) Fexinidazole–a new oral
nitroimidazole drug candidate entering clinical
development for the treatment of sleeping sick-
ness. PLoS Negl Trop Dis 4: e923. doi:10.1371/
journal.pntd.0000923.
20. WHO. Innovative and intensified disease man-
agement (IDM). Available: http://www.who.int/
neglected_diseases/disease_management/en/.
Accessed 11 September 2012.
PLOS Neglected Tropical Diseases | www.plosntds.org 3 December 2012 | Volume 6 | Issue 12 | e1950

English

[Detecting sleeping sickness: comparative efficacy of mobile teams and community health workers].

[Medicine and health in the Democratic Republic of Congo: from Independence to the Third Republic]. Med Trop (Mars)

[The flexibility of an integrated health service in the campaign against Trypanosoma brucei gambiense trypanosomiasis].

A card-agglutination test with stained trypanosomes (C.A.T.T.) for the serological diagnosis of T. B. gambiense trypanosomiasis.

Drug toxicity and cost as barriers to community participation in HAT control in the Democratic Republic of Congo.

Estimates of the duration of the early and late stage of gambiense sleeping sickness.

Fexinidazole–a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS Negl Trop Dis 4: e923. doi:10.1371/ journal.pntd.0000923.

Health careseeking behaviour and diagnostic delays for Human African trypanosomiasis in the Democratic Republic of the Congo.

Human African trypanosomiasis (sleeping sickness). Fact sheet Nu259. Available: http://www.who.int/mediacentre/factsheets/ fs259/en/. Accessed

Human African trypanosomiasis in areas without surveillance.

Illustrated lecture notes on tropical medicine [e-learning program].

Innovative and intensified disease management (IDM). Available: http://www.who.int/ neglected_diseases/disease_management/en/.

Loop-mediated isothermal amplification (LAMP). Available: http://www. finddiagnostics.org/programs/hat-ond/hat/ molecular_diagnosis.html.

Nifurtimoxeflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial.

Sleeping sickness resurgence in the DRC: the past decade.

Sleeping sickness.

The atlas of human African trypanosomiasis: a contribution to global mapping of neglected tropical diseases.

The effectiveness of active population screening and treatment for sleeping sickness control in the Democratic Republic of Congo.

The fall and rise of sleeping sickness.

Human african trypanosomiasis in the democratic republic of the congo: a looming emergency?

Human African Trypanosomiasis in the Democratic Republic of the Congo: A Looming Emergency?

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