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[afro-nets] Rolling Back a Malaria Epidemic in South Africa

Rolling Back a Malaria Epidemic in South Africa
-----------------------------------------------

Mosquito Control and ACT Are Both Likely Contributors to the Re-
duction of Malaria in KwaZulu-Natal

This is an interesting article for those of us discussing ma-
laria control in Africa.

Mizan Siddiqi
mailto:msiddiqi@voxiva.net


--
Rolling Back a Malaria Epidemic in South Africa
By Patrick E. Duffy, Theonest K. Mutabingwa

The authors discuss the success in malaria control in KwaZulu-
Natal (reported by Barnes and colleagues), and its implications
for the rest of Africa.

PLoS Med 2(11): e368
http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10%2E1371%2Fjournal%2Epmed%2E0020368


Amid the dire statistics showing a deadly resurgence of malaria,
a notable success has been scored in South Africa. In KwaZulu-
Natal province, malaria cases increased from about 600 in 1991-
1992 to more than 30,000 by 1999-2000 [1]. Then, after household
spraying with DDT was implemented, and the new antimalarial com-
bination artemether-lumefantrine (AL) was widely deployed (Fig-
ure 1), cases declined by more than 99% over the next three
years. A paper in PLoS Medicine by Barnes et al. [2] examines
the implementation and efficacy of AL during the KwaZulu-Natal
crisis. They conclude that vector control and widespread use of
artemisinin-based combination therapy (ACT) such as AL may con-
fer similar benefits in other African countries. Could the adop-
tion of these policies salvage the Roll Back Malaria Initiative
that was formed in 1999 to halve malaria deaths by 2010 [3], but
which was recently lamented as "dysfunctional" for its inaction
in the face of rising malaria morbidity and mortality rates [4]?

Artemisinins to the Rescue

Artemisinin derivatives such as artemether have several advan-
tages- they act rapidly, cause few side effects, and have not
yet acquired resistant parasites [5].Artemisinins also prevent
parasite transmission by inactivating or killing gametocytes
[6]. In northwestern Thailand malaria incidence declined after
the ACT artesunate-mefloquine was introduced, and its effective-
ness has been sustained over several years, possibly due to ga-
metocytocidal effects [7]. In a study recently published in PLoS
Medicine [6], gametocytes from Gambian children treated with AL
were less likely than those from children treated with a chloro-
quine and sulfadoxine-pyrimethamine (SP) combination to infect
mosquitoes. These reports have led many to expect that ACTs will
dramatically improve case management, and reduce malaria trans-
mission in Africa.

KwaZulu-Natal-A Special Case?

Caution is warranted, however. KwaZulu-Natal is more similar to
Thailand than to most sub-Saharan countries in ways that may af-
fect the influence of ACTs. The economic strength of South Af-
rica supported effective vector control measures and a health-
care infrastructure that facilitated prompt diagnosis and treat-
ment. Poorer sub-Saharan countries are unable to support similar
programs in the absence of additional financial resources. Non-
economic issues may also limit the effect of ACTs on malaria in-
cidence and case management in Africa. Malaria transmission and,
therefore, immunity are low in both Thailand and KwaZulu-Natal.
Thais and South Africans typically get sick when they are in-
fected, and seek treatment. In African countries where malaria
transmission is high, semi-immune individuals often do not feel
sick enough to seek treatment, and act as a reservoir for con-
tinued transmission. Additionally, African children often pre-
sent with high-density parasitemia, making it more likely that
parasites will be temporarily suppressed but then recrudesce af-
ter artemisinin therapy[8,9].

ACTs will improve treatment outcomes in areas of sub-Saharan Af-
rica where resistant parasites have rendered the current fi rst-
line drugs nearly useless. Drug resistance has probably played a
key role in the rising malaria mortality rates among African
children [10], so ministries of health are optimistic that ACTs
will reverse this awful trend. However, the longterm effective-
ness of ACTs in high endemicity areas has not been proven, and
many operational questions remain unanswered.

ACT Alternatives

Are ACTs the most effective new antimalarial combination? In the
July issue of PLoS Medicine, Dorsey and colleagues reported that
the nonartemisinin combination of SP and amodiaquine (AQ) was as
effective or better (and cheaper) than the combination of ar-
tesunate and AQ for treating Ugandan children, when both recru-
descent and new infections were considered [11]. Resistance to
both SP and AQ is spreading in Africa, and this will limit the
sustainability of the combination. Furthermore, because recru-
descent parasites are more likely to be drug-resistant [12], and
recrudescences were more common after SP-AQ, this combination
may accelerate the spread of resistant parasites. Nevertheless,
the combination should be considered as a short-term strategy in
areas where the parasite remains sensitive. The results also
caution that the benefits of ACTs may be limited in high en-
demicity areas unless re-infections are promptly treated.

Is AL the Best ACT for Africa?

AL is the only co-formulated ACT, which improves compliance.
Furthermore, a dramatic rollback of malaria has been achieved in
KwaZulu-Natal where AL was deployed. These have been strong fac-
tors in the selection of AL as first-line therapy by many Afri-
can countries. However, the sharp decline in malaria in KwaZulu-
Natal commenced after DDT spraying of households was initiated
and before AL was deployed; therefore, the relative contribution
of AL remains unclear. Sustained success with ACTs in Thailand
has been achieved with artemether-mefloquine. The long-term ef-
fectiveness of AL remains unproven. The extended half-life of
lumefantrine and the short half-life of artesunate mean that
many reinfections in Africa will be exposed to lumefantrine
alone, increasing the odds that resistant parasites will be se-
lected. Worrying reports from Zanzibar suggest that lumefantrine
resistance may already be emerging there, not long after AL was
introduced as second-line therapy [13]. Future studies should
compare different artemisinin and nonartemisinin combination
therapies for their long-term effectiveness. Finally, the huge
new market for AL in Africa has outstripped the available sup-
plies, delaying the launch of ACTs in some countries, and it re-
mains uncertain when these supply problems will be fully re-
solved.

Learning from Success

Will ACTs "roll back malaria"? TheBarnes et al. paper focuses on
the effi cacy and implementation of AL in KwaZulu-Natal, but ac-
tive surveillance and treatment for asymptomatic carriers [1],
as well as residual spraying, contributed to the success. Barnes
et al. argue for an effective vector control program and ACT im-
plementation in the context of a well-developed rural primary
health-care infrastructure. While the cost of executing these
programs throughout Africa may seem great, the cost of not doing
so is likely to be greater, especially if resistance to ACTs
emerges as a consequence. In any case, the widespread expecta-
tion that ACTs alone will turn the tide in the fight against ma-
laria may be unrealistic.


References

1. Craig MH, Kleinschmidt I, Le Sueur D, SharpBL (2004) Explor-
ing 30 years of malaria case data in KwaZulu-Natal, South Af-
rica: Part II. The impact of non-climatic factors. Trop Med Int
Health 9: 1258-1266.

2. Barnes KI, Durrheim DN, Little F, Jackson A, Mehta U, et al.
(2005) Effect of artemetherlumefantrine policy and improved vec-
tor control on malaria burden in KwaZulu-Natal, South Africa.
PLoS Med 2: e330. DOI: 10.1371/journal.pmed.0020330

3. Nabarro D (1999) Roll Back Malaria. Parassitologia 41: 501-
504.

4. [Anonymous] (2005) Reversing the failures ofRoll Back Ma-
laria. Lancet 365: 1439.

5. White NJ (2004) Antimalarial drug resistance. JClin Invest
113: 1084-1092.

6. Sutherland CJ, Ord R, Dunyo S, Jawara M,Drakeley C, et al.
(2005) Reduction of malaria transmission to anopheles mosquitoes
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10.1371/journal.pmed.0020092

7. Nosten F, van Vugt M, Price R, Luxemburger C, Thway KL, et
al. (2000) Effects of artesunatemefl oquine combination on inci-
dence of Plasmodium falciparum malaria and mefl oquineresistance
in western Thailand: A prospective study. Lancet 356: 297-302.

8. Tanariya P, Tippawangkoso P, Karbwang J, Na-Bangchang K,
Wernsdorfer WH (2000) In vitro sensitivity of Plasmodium falci-
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artemether. Br J Clin Pharmacol 49: 437-444.

9. Ittarat W, Pickard AL, Rattanasinganchan P, Wilairatana P,
Looareesuwan S, et al. (2003) Recrudescence in artesunate-
treated patients with falciparum malaria is dependent on para-
site burden not on parasite factors. Am J Trop Med Hyg 68: 147-
152.

10. Snow RW, Trape JF, Marsh K (2001) Thepast, present and fu-
ture of childhood malaria mortality in Africa. Trends Parasitol
17: 593-597.

11. Yeka A, Banek K, Bakyaita N, Staedke SG,Kamya MR, et al.
(2005) Artemisinin versus nonartemisinin combination therapy for
uncomplicated malaria: Randomized clinicaltrials from four sites
in Uganda. PLoS Med 2:e190. DOI: 10.1371/journal.pmed.0020190

12. Mutabingwa T, Nzila A, Mberu E, Nduati E, Winstanley P, et
al. (2001) Chlorproguanildapsone for treatment of drug-resistant
falciparum malaria in Tanzania. Lancet 358:1218-1223.

13. Sisowath C, Stromberg J, Martensson A,Msellum M, Obondo C,
et al. (2005) In vivo selection of Plasmodium falciparum pfmdr1
86N coding alleles by artemether-lumefantrine (Coartem). J In-
fect Dis 191: 1014-1017. November 2005 | Volume 2 | Issue 11 |
e368

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