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There are effective anti-malaria drugs and the W.H.O. emphasizes
early diagnosis and prompt treatment of malaria. However, there are
major problems of drug resistance, particularly to chloroquine which
has been the mainstay of malaria treatment, especially in Africa,
because of its low cost and relative freedom from side effects. There is much interest in the development of malaria vaccines, but
the only one which has been extensively field tested only gave a
limited degree of protection (Alonso et al., 1994). Between the 1940s and 1960s malaria eradication was achieved in
the USA, USSR, southern Europe and most Caribbean Islands mainly by
vector control. Much progress was also made in the Indian
subcontinent and parts of South America. Now in the 1990s emphasis
needs once again to be placed on vector control. The vectors of human malaria all belong to the genus Anopheles whose adults (Figure 1) are recognized by their "tail in the air" posture, dappled wings in most tropical species and long pair of palps beside the proboscis in the female.
Figure 2. Anopheles larva As in other mosquitoes only the females bite and they use the proteins from a blood meal to produce a batch of eggs. These are laid in relatively clean water, such as in marshes, puddles, irrigation water etc. Unlike other mosquito larvae, those of Anopheles float parallel to the water surface (Figure 2). They develop through 4 larval instars to a short lived, motile pupal stage. The whole process from egg to emergence of the adult from the pupa takes little more than a week at tropical temperatures.
Figure 3. Plasmodium oocysts on the outside of a mosquito's midgut. Soon after emergence the adults mate and the female goes in search
of its first blood meal. If this contains gametocytes of malaria
parasites (which belong to the genus Plasmodium), male and
female gametes of the parasite undergo fertilization in the
mosquito's stomach, the zygotes develop into oocysts on the outer
surface of the stomach wall (Figure 3) and sporozoites develop in the
oocysts, over a period of about 12 days, before populating the
mosquito's salivary glands. During subsequent feeds the injection of
saliva into the host carries sporozoites, which may establish a new
malaria infection in the host. During the approximately 12 days
required for sporozoite development, a member of most female tropical
anopheline mosquito species would be expected, if it survives, to
re-visit houses 3 or 4 times to take bloodmeals and thus initiate new
cycles of egg development. If the mosquito can be killed at any one
of those 3 or 4 house visits it can never develop sporozoites and
become a disease vector. It is this fact which is the key to most
successful malaria vector control programs which aim to increase the
dangers of house visits for adult mosquitoes. Larval control also
contributes to some malaria vector control programs, especially where
larval sites are limited in extent and are definable - e.g. wells and
water tanks in Indian urban areas. In rural areas in the wet tropics
Anopheles may breed in every water filled foot- and hoof-print
and larval control is an almost hopeless undertaking.
Figure 4. A sprayman at work inside a
house. The main method of attacking adult mosquitoes in houses is
spraying the inside surfaces of the walls and roof or ceiling with a
residual insecticide (Figure 4). This requires teams of trained spray
operatives equipped with hand operated spray pumps. The teams must be
transported to the villages when they are needed, with adequate
supplies of insecticide. The intention of house spraying is that
mosquitoes will rest on the insecticide deposit before or after
biting and remain long enough to pick up a lethal dose. The insecticide most widely used for house spraying has been DDT,
which has continued to be recommended for this purpose long after it
was banned for agricultural use in the USA and many other countries.
It has been recommended because of its cheapness per unit weight and
its durability, which allows programs to be based on spraying twice a
year, or only once in areas with a short annual malaria mosquito
season. Arguments about DDT applied to field crops accumulating in
food chains are considered inapplicable to DDT sprayed inside houses.
However, unfortunately in low income countries it is almost
impossible to prevent illicit diversion of insecticides intended for
anti-malaria use to farmers. The consequent insecticidal residues in
crops at levels unacceptable for the export trade have been an
important factor in recent bans of DDT for malaria control in several
tropical countries (Curtis, 1994). Some of the claims in the 1960s
and 70s about supposed effects of DDT on human health were almost
certainly ill-founded. DDT residues in human breast milk have been
repeatedly observed, but usually attributed to earlier intake with
contaminated food. However, there is recent evidence from South
Africa (cited by Curtis, 1994) that, in areas of anti-malaria use of
DDT, breast milk contains much higher residues than other areas and
in the former areas the intake by a breast-fed baby would greatly
exceed the Allowable Daily Intake (which is defined by the WHO and
FAO on a lifetime intake basis and so is not readily related to a
baby's intake of milk). There is also some evidence (cited by Curtis,
1994) for neurological abnormalities in babies taking in relatively
high DDT residues with their milk. DDT has already been replaced by organophosphate or carbamate insecticides such as malathion or bendiocarb where DDT resistance has been detected, e.g. in Sri Lanka, parts of India, Pakistan, Turkey and Central America. However, these compounds are considerably more expensive to use than DDT, and malathion does not persist well on mud walls. Pyrethroids such as deltamethrin and lambdacyhalothrin are
effective at far lower doses than DDT (c.25 mg/sq. metre compared
with 2 gm/sq. metre). Although more expensive per unit weight, these
pyrethroids are not much more expensive per house protected per year
(Curtis, 1994). They are also much more acceptable to householders
because they leave no visible deposit on walls and because they kill
nuisance insects such as cockroaches. Therefore rates of refusal of
spraying by householders are lower with pyrethroids than with DDT and
therefore there is a much better chance of reaching a level of
coverage at which the vectorial capacity of the mosquito population
will be lowered to a point at which malaria transmission will be
interrupted. Contrary to fears based on experience with other insects such as
House Flies, genes for DDT resistance in Anopheles do not
generally give cross resistance to pyrethroids. Resistance has been
selected to pyrethroids in a few Anopheles populations but so
far has not been a major problem in the field. Like DDT, pyrethroids
tend to irritate mosquitoes so that they do not rest on deposits for
long. However, the pyrethroids paralyze the nervous system so fast
that contact for a few minutes is enough to kill, whereas much longer
contact is required with DDT and mosquitoes may escape it without
picking up a lethal dose. For these reasons, when comparisons have
been Control of Malaria Vectors in Africa and Asia made, better
malaria control has generally been achieved with pyrethroids than
with DDT. An increasingly popular application of pyrethroids is in the
impregnation of bednets (Curtis, 1991). Nets have long been
appreciated as a protection against night biting mosquitoes including
malaria vectors. However, nets are often torn or hung is such a way
that mosquitoes can enter or bite through them. The initial motive
for impregnating them with an insecticide, which was safe for close
human contact, was to add a chemical barrier to the imperfect
physical barrier presented by the net. Studies in experimental huts
have proved that pyrethroid impregnation of holed nets makes them
function much better in preventing biting of a sleeper than do
untreated holed nets. This apparently arises because a treated net
kills or irritates and drives away mosquitoes before they have found
a hole in the net and entered it. An additional argument for treating bednets is that they are a
rational place in which to deploy a residual insecticide because
mosquitoes are attracted to them by the carbon dioxide and body odor
emitted by the sleeper. Thus the net acts like a baited trap. In
comparison with spraying a family's house, the amount of insecticide
needed to treat their nets is much less and synthetic netting is a
more favorable substrate for a residual insecticide than is a mud
wall. Furthermore bednets intercept mosquitoes in their search for a
human host, whereas house spraying pre-supposes that the mosquitoes
will rest inside a house before or after feeding, which is not the
habit of some Anopheles species, An.dirus Peyton &
Harrison. In Hainan Island, China, impregnated bednets were shown to
be effective against severe malaria due to Plasmodium
falciparum Welch transmitted by An.dirus where DDT
spraying was ineffective. Surprisingly, only now is a direct
comparison being made between a pyrethroid used for house spraying
and for bednet impregnation. Many of the arguments for impregnation of bednets apply to
impregnation of curtains over eaves, windows and doors. The latter
method may have the advantages of:- (i) smaller areas of fabric to treat; (ii) possibility of using more toxic insecticides which would not
be acceptable for intimate contact with people's beds; (iii) protection of people when they are indoors but before they
go to bed. On the other hand, in rural tropical houses it is difficult to fix
curtains (especially eave curtains where roofs are of galvanized
iron) so as to make as effective a barrier against mosquito entry as
is provided by a bednet. Also bednets can be readily carried by
travelers or nomads and can be used over beds or sleeping mats out of
doors, as often used by people in very hot countries. In the world's largest treated bednet program, that in Sichuan
Province, China, up to 2.25 million bednets have been treated
annually by spraying deltamethrin (Chen et al., 1995). This has been
associated with a remarkable decline in the already relatively low
level of malaria due to P. vivax (Grassi & Feletti) which
is the less serious of the two main species causing human
malaria.
Figure 5. Woman in a Tanzanian village re-dipping bednets in a
pyrethroid emulsion after they have been in use for 6 months. In most other projects, bednets are impregnated by dipping in an
emulsion of a pyrethroid (Figure 5), drying and re-hanging them. This
needs to be done every 6-12 months, or more frequently if the nets
are frequently washed. The dipping method is very simple and does not
require spray pumps or trained operatives as are required for a house
spraying program. Thus, in The Gambia (W. Africa) a National Bednet
Impregnation Program has been initiated based on the efforts of
village health workers. Monitoring of the first year's results in a
sample of the villages showed a 25% reduction in child mortality from
all causes (D'Allessandro et al., 1995). Trials are in progress in
three other African countries to determine if this result is
repeatable. It remains questionable, however, whether this or other
forms of vector control will work adequately or sustainably in the
heartland of tropical African malaria where transmission rates are
much higher than in The Gambia and where large reductions in
infective biting rates may still leave the population "saturated"
with malaria and where naturally acquired immunity might be expected
to fade and counterbalance any benefits of achievable levels of
vector control. In such areas integration of vector control with the
hoped-for vaccine may be necessary for real progress - the vaccine
should aim to replace immunity acquired the hard way via malaria
attacks, and the vector control should aim to reduce the level of
transmission to a level with which the vaccine can cope. It is a cause for concern that large scale use of pyrethroid
impregnated nets may select for pyrethroid resistance of a
physiological kind or may change mosquito behavior so that they bite
out of doors before people go indoors to go to bed. There have so far
been one or two such reports but the large and sustained projects in
China do not appear have produced such problems. Where Anopheles breeding is sufficiently limited in extent
and definable, larval control can make a significant contribution to
malaria control. However, it should be recognized that it only works
by reducing the density of local vector populations and not by
reducing their chances of survival to the dangerous age at which they
can carry sporozoites. Furthermore, the effect of localized larval
control is easily swamped by immigration from outside the area of
control. Thus a high percentage of all productive breeding sites
within flight range of the community which it is intended to protect
must be found and effectively dealt with. A variety of ways of
dealing with them are possible (see Curtis, 1991) :- (i) They can be drained or filled so as permanently to remove them
as breeding sites. This approach has been applied in industrialized
areas in India (Dua et al., 1988). (ii) Breeding in water tanks can be prevented by screening them -
this is legally compulsory in Bombay, India. (iii) Under some conditions irrigation can be carried out
according to a carefully regulated intermittent schedule so that
fields are dried once a week and thus larval life cycles cannot be
completed. (iv) The organophosphate insecticide temephos ("Abate") can be
applied. This can safely be done even to potable water and there are
few places in the world where Anopheles mosquitoes are
resistant to it. (v) The breeding sites may be stocked with larvivorous fish. These
are to some extent self-propagating, but sites need to be checked at
intervals and those where the fish have died out need to be
re-stocked from a fish rearing facility. In some parts of Asia, Grass
Carp (Ctenopharyngodon idella) have been used in rice fields
which provide a crop of edible fish as well as mosquito control and
improvement of rice yields. (vi) The bacterial toxin from Bacillus thuringiensis
israelensis (Bti) can be sprayed into breeding sites as a
highly specific agent against mosquito larvae. This is extensively
used against larvae of nuisance mosquitoes in Germany and the USA.
Unfortunately the toxin is not self-propagating or long lasting in
natural breeding sites and frequent re-treatment is unaffordable in
most low income countries where the malaria problem exists. There is considerable interest among biologists, including
molecular biologists, in the idea of rendering mosquito populations
genetically harmless by introduction of genes which make them
non-susceptible to Plasmodium (Collins and Paskewitz, 1994) or
divert them from being strongly attracted to biting humans (as is the
world's most dangerous malaria vector An.gambiae Giles in
Africa) to biting animals. Strains have already been selected which
are non-susceptible to Plasmodium and An.gambiae has a
sibling species, An.quadriannulatus (Theobald), with which it
is inter-crossable in the laboratory and which only bites animals and
therefore is not a vector of human malaria. The real problem with these concepts is not so much producing
harmless strains, but propagating their genes extensively given that
the capital expenditure to allow mass release from large insect
factories would probably only be invested to protect cash crops, such
as cattle from the Screw Worm Fly (Cochliomyia hominovorax),
whereas protection of the children of the rural poor is not seen as
an economically worthwhile activity by those who control economic and
political power in the world. Thus if desirable genes are to be
spread in Anopheles populations, genetic systems will have to
be developed which will reliably cause genes to spread from a small
"seeding" of a wild population. Possible candidates for this are
transposable elements or the intracellular symbiont
Wolbachia. The idea of creating genes for harmless Anopheles has
attracted much attention from laboratory based biologists and this is
welcome. However, it is important that this work does not divert
resources from the further development and application of methods
which already are demonstrably effective at saving lives now,
especially the extension of the benefits of impregnated bednets to
the hundreds of millions at risk from malaria. References: Alonso, P., Smith, T., Armstrong Schellenberg, J.R.M., Masanja,
H., Mwankusye, S., Urassa, H., Bastos de Azevedo, I., Chongela, J.,
Kobero, S., Menendez, C., Hurt, N., Thomas, M.C., Lyimo, E., Weiss,
N.A., Hayes, R., Kitua, A.Y., Lopez, M.C., Kilama, W.L., Teuscher, T.
& Tanner, M. (1994) Randomized trial of efficacy of SPf66 vaccine
against Plasmodium falciparum malaria in children in southern
Tanzania. Lancet 344, 1175-1181. Chen Hualiu, Yang Wen, Kang Wuanmin & Liu Chongyi (1995) Large
scale spraying of bednets to control mosquito vectors and malaria in
Sichuan, China. Bulletin of the World Health Organization 73,
321-328. Collins, F.H. & Paskewitz, S.M. (1995) Malaria: current and
future prospects for control. Annual Review of Entomology 40,
195-219. Curtis, C.F. ed. (1991) Control of Disease Vectors in the
Community. Wolfe, London. Curtis, C.F. (1994) Should DDT continue to be recommended for
malaria vector control? Medical & Veterinary Entomology 8,
107-112. Dua, V.K., Sharma, V.P. & Sharma, S.K. (1988)
Bio-environmental control of malaria in an industrial complex at
Hardwar (U.P.), India. Journal of the American Mosquito
Association 4, 426-430. D'Alessandro, U., Olaleye, B.O., McGuire, W., Langerock, P.,
Bennett, S., Aikins, M.K., Thomson, M.C., Cham, B.A. & Greenwood,
B.M. (1995) Mortality and morbidity from malaria in Gambian children
after introduction of an impregnated bednet program. Lancet
345, 479-483. Gilles, H.M. and Warrell, D.A. (1993) Bruce-Chwatt's Essential
Malariology, 3rd edition, Edward Arnold, London For additional information on malaria see the following WWW sites:
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