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Annals of Tropical Medicine & Parasitology, Vol. 96, Supplement No.

2, S143–S152 (2002)

Limitation and facilitation in the vectors and other aspects

of the dynamics of Ž larial transmission: the need for
vector control against Anopheles-transmitted Ž lariasis*
Institut de Recherche pour le Développement ( IRD), Laboratoire d’Informatique Appliquée,
32 Avenue Henri Varagnat, 93143 Bondy Cedex, France

Received and accepted 16 July 2002

In certain Ž laria–mosquito combinations, the number of infective, third-stage larvae (L3 ) that develop in a
mosquito is not proportional to the number of microŽ lariae (mV ) ingested by that mosquito. As the number of
mV ingested increases, the yield of L3 per microŽ laria may either increase (in a process known as ‘facilitation’)
or decrease (in a process known as ‘limitation’). Each ingested microŽ laria that is successful (in terms of reaching
the haemocoel) increases (facilitation) or decreases (limitation) the ‘permeability’ of the stomach wall for the next
microŽ laria. Limitation is seen in some culicine mosquitoes, especially the Aedes spp. that transmit Wuchereria
bancrofti, which, in consequence, become relatively more eYcient as vectors as they ingest fewer mV. This
phenomenon makes the interruption of Ž larial transmission by Aedes spp. particularly diYcult.
As the survival of anopheline mosquitoes is adversely aVected by Ž larial infection, the use of mass drug
administrations (MDA) to reduce the prevalence and intensity of microŽ laraemias may increase the mean life-
span of some of the local Anopheles species. If these same species also act as vectors of malarial parasites, eVective,
drug-based control of W. bancrofti may worsen the problem posed by malaria. Therefore, wherever malaria and
bancroftian Ž lariasis are co-endemic and caused by parasites transmitted by the same species of mosquito, MDA
should be augmented by interventions (use of bednets or house-spraying ) against adult Anopheles.

Although there may be practical and eco- MODES OF PARASITE

nomic reasons why the control of lymphatic TRANSMISSION
Ž lariasis (LF) using mass drug admini-
strations (MDA) is to be preferred to control In at least some of the mosquito vectors
of the disease via vector control (VC), either of the parasites causing LF, the parasitic
intervention, if eVective, could interrupt the yield — the number of human-infective,
transmission of the parasites that cause the third-stage larvae (L3 ) developing from each
disease. The choice of whether to use MDA, microŽ laria ingested — is not constant. It
VC or both in a particular setting depends
may increase as the number of microŽ lariae
partly on the vector–parasite combinations
(mV ) ingested increases (in a phenomenon
involved and whether the Ž larial vectors also
known as ‘facilitation’) or it may decrease
transmit any other human pathogens, such
(in a phenomenon known as ‘limitation’; Bain,
as Plasmodium spp.
1971; Brengues and Bain, 1972). Facilitation
and limitation aVect the epidemiology and
Reprint requests to: G. Pichon. control of LF, via the transmission dynamics
E-mail:; fax 33 148 47 30 88.
of the Ž larial parasites causing the disease
*This is a revised working paper originally prepared for
the WHO (2002) informal consultation on the vectors (Pichon, 1974a, b). Limitation (negative
of lymphatic Ž lariasis. density-dependence) occurs in some culicine
© 2002 The Liverpool School of Tropical Medicine
DOI: 10.1179/000349802125002509

vectors (Pichon, 1974a, b; Subramanian et al., ing/mosquito, and H is the inverse of the
1989, 1998) whereas facilitation ( positive regression slope coeYcient for yield ( y/x),
density-dependence) occurs in some of in the case of limitation, or for failure
the anopheline vectors (Pichon, 1974a, b; [1­ ( y/x) ], in the case of facilitation. The
Southgate and Bryan, 1992). Both phen- H parameter is a measure of the ‘reciprocal
omena can be described mathematically adaptation’ for a particular vector–parasite
(Fig. 1), limitation as the equation: combination. The combinations giving high
values of H, such as the 20 estimated for Ae.
y=Hx/(x+H ) polynesiensis infected with W. bancrofti var.
paciŽ ca, probably represent very ancient
and facilitation as:
adaptations (see Table). Pichon (1981) used
y =x­ [Hx/(x+H )] this assumption, and the results of other
studies on subperiodicity, to develop the
where x is the number of mV ingested/ hypothesis that W. bancrofti speciation might
mosquito, y the number of L 3 [or, in some have accompanied the ethnogenesis of the
analyses, of Ž rst-stage larvae (L1 )] develop- Polynesians.

FIG. 1. A diagrammatic representation of limitation (L) and facilitation (F), here shown for the production of
Ž rst-stage larvae (L1 ) from ingested microŽ lariae. H, the inverse of the regression slope coeYcient b, allows for
measurement of the ‘reciprocal adaptation’ for a particular vector–parasite combination.
TABLE. QuantiŽ cation of the limitation (H) in some of the culicine vectors of Ž lariae and of the facilitation (H¾ ) in some of the anopheline vectors

Vector Parasite Locality Filarial larval stage H/H¾ Reference

Aedes polynesiensis Sub-periodic Wuchereria bancrofti Tahiti L1 H=20 Rosen (1955)
L3 H=20 Prod’hon et al. (1980)
Ae. aegypti* Sub-periodic W. bancrofti Tahiti L1 H=10² Prod’hon et al. (1980)
L3 H=0 Prod’hon et al. (1980)
Ae. aegypti* Setaria labiato-papillosa Burkina Faso L1 H=3.5² Brengues and Bain (1972)
Culex quinquefasciatus* Sub-periodic W. bancrofti Tahiti L1 H=68² Prod’hon et al. (1980)
L3 H=0.3 Rosen (1955)
Cx. quinquefasciatus Periodic W. bancrofti Tanzania L3 H=3 Jordan and Goatly (1962)
Cx. quinquefasciatus Periodic W. bancrofti India L3 H=7 Subramanian et al. (1998)
Mansonia longipalpis Sub-periodic Brugia malayi Malaya L1 H=35² Wharton (1957b)
Anopheles gambiae Periodic W. bancrofti Burkina Faso L1 H¾ =78 Brengues and Bain (1972)
L3 H¾ =78 Brengues and Bain (1972)
An. gambiae Periodic W. bancrofti Gambia L1 H¾ =120 Southgate and Bryan (1992)
An. arabiensis Periodic W. bancrofti Gambia L1 H¾ =42 Southgate and Bryan (1992)
An. melas Periodic W. bancrofti Gambia L1 H¾ =3.6 Southgate and Bryan(1992)

* Not a natural vector of the Ž laria.

For the reduction in parasite numbers after the parasites leave the stomach of the vector.

Limitation Polynesian island where humans and the

In Ž larial transmission, as in many physical vector species of mosquito co-exist, and
systems, negative density-dependence (i.e. intensive MDA using diethylcarbamazine
limitation) helps to produce stability. Where (DEC) and some VC, all carried out by the
limitation occurs, such as in the transmission Institut Louis Malardé ( ) in an
of W. bancrofti by Aedes in Polynesia or by exemplary fashion for more than 50 years,
Culex in India (Subramanian et al., 1998), failed to eliminate LF from any island com-
East Africa ( Jordan and Goatly, 1962) and munity. This failure is associated with the
the Americas (WHO, 2002), the total inter- amazing eYciency of Ae. polynesiensis as a
ruption of transmission (the ultimate goal of vector, itself a consequence, in part, of the
LF-control programmes) is not only hard to limitation phenomenon. On the Polynesian
reach but also unstable [Fig. 2(a) ]. Despite islands of Moorea and Maupiti, the preval-
the island distribution of W. bancrofti trans- ence of LF was reduced from 30%–35% to
mitted by Ae. polynesiensis in Polynesia, there 3%–6% within a few years but several more
appears to a surprising stability in the LF decades of control interventions then failed
in this region. The rather homogeneous to reduce prevalence any further (Esterre
geographical distribution of LF endemicity et al., 2001). The elimination of the residual
in Polynesia contrasts markedly with the infections appeared impossible and this could
patchy endemicity of anopheline-transmitted not be attributed to the resistance of the
W. bancrofti across West Africa. In Polynesia, parasite or the reluctance of the population
sub-periodic W. bancrofti is present in every to participate in the MDA. Interruption of
MDA in another island was followed by a
return to the high prevalences observed
pre-intervention within 5 years. As recently
discussed by Burkot and Ichimori (2002),
Burkot et al. (2002) and Lardeux et al.
(2002), new tools are needed to control the
diurnally active Ae. polynesiensis and the other
eYcient vectors of sub-periodic W. bancrofti
in Polynesia.
Limitation also occurs in the W. bancrofti–
Cx. quinquefasciatus combination, within the
mosquito’s stomach (i.e. in the development
of L1 from mV ) and also in the develop-
ment of L3 from L1 . In the study in Tahiti
by Prod’hon et al. (1980), for example, the
development of W. bancrofti L1 from the mV
ingested by Cx. quinquefasciatus was found
to carry an H-value of >60, whereas the
corresponding H-value for the development
FIG. 2. Representation of limitation in culicine trans- of the L3 was only 0.3. Pichon et al. (1976)
mission (a) and of facilitation in anopheline transmission
(b), assuming there is Ž laria-attributable mortality in
found that the same phenomenon seems to
the vectors. The curves run above or below the line occur in the development of Brugia malayi in
of adult-worm mortality (P) — assumed to follow a Mansonia longipalpis (=Ma. dives) (Wharton,
negative-exponential — except at the points of stable 1957a, b). Although Cx. quinquefasciatus is
equilibrium (E) or Webber’s critical point (W). The fortunately not an eYcient vector of the sub-
arrows indicate the direction in which the size of the
parasite population is likely to go, spontaneously, as
periodic W. bancrofti found in Polynesia, it
the result of control interventions. After Pichon et al. can transmit a Caribbean strain of periodic
(1974). W. bancrofti (Rosen, 1955).

Facilitation and Thresholds been estimated. For An. farauti-transmitted

The transmission of W. bancrofti by anopheline W. bancrofti in the Solomon Islands, Webber
mosquitoes is characterized by facilitation and Southgate (1981) showed that there
(Brengues and Bain, 1972). Pichon et al. was a critical biting rate (0.66/human-hour,
(1974) suggested that this mechanism could or about eight bites per person each
cause instability in the parasite population, night) necessary for continued transmission.
and explain the patchy distribution of LF For An. sinensis-transmitted B. malayi in
endemicity in areas where W. bancrofti is China, Zang et al. (1991) considered that, if
transmitted by Anopheles. In this case, there no individual carried >200 mV /ml blood,
is a threshold point — which, to honour human infection would invariably die out
Roger Webber (who was once confronted if its prevalence fell below a threshold of
with the same questions about LF as the 1.55%–2.23%.
author, albeit at a diVerent extremity of There may be no such threshold in
the PaciŽ c Ocean), is here named Webber’s areas such Polynesia, where limitation, not
critical point (W) — that is relatively far facilitation is the rule. Knowing why eradica-
from eradication and close to the stable tion is so diYcult in these circumstances
equilibrium [Fig. 2(b) ]. Below this point, may be some comfort to those involved in
the parasite population dies out spon- the local control campaigns. In fact, even in
taneously. The re-establishment of a stable vector–parasite combinations complicated
parasite population in an area in which trans- by limitation, another threshold does exist.
mission has been interrupted and infection It occurs when the probability that two
eradicated would then necessitate the intro- worms diVering in sex meet in the same host
duction of many parasites (in humans and/or is too low. Unfortunately, this threshold will
mosquitoes). Local eradications could have be very much lower than Webber’s point
occurred in historical or recent times, either and close to zero. Whether it is attainable is
spontaneously or following human inter- still unknown.
vention, such as the spraying of houses with Disease control (based on VC, MDA
DDT during the World Health Organ- or both) should be relatively eYcient in
ization’s Malaria Eradication Campaign in regions with anopheline transmission, such
the 1950s. It now seems clear that house- as West Africa. Once the interventions take
spraying to control malaria inadvertently the disease below Webber’s point, the Ž larial
caused the Ž rst, well documented, local population should steadily decrease to the
eradication of LF. This occurred in 1979 in point of stable eradication.
Choiseul (one of the Solomon Islands),
where W. bancrofti was transmitted by An.
farauti (Webber, 1977, 1979, 1991). The DIFFERENTIAL VECTOR
results of a parasitological survey of Choiseul MORTALITY CAUSED BY FILARIAL
in 1996–1997 ( J. Leafasia, unpubl. obs.) PARASITES
and an immunological survey in 1998–1999
(S. Randell, unpubl. obs.) indicated that, In the early, laboratory studies (Adams-
20 years after the eradication, the island Chapman, 1965; Brengues and Coz, 1972),
remained LF-free. heavy W. bancrofti infections were found to
The evidence for a threshold in a model cause only slight additional mortality in a
of host–parasite relationship is not only pool of Ae. polynesiensis and An. gambiae s.l.
interesting theoretically. In operational terms, (and, curiously, the mortality of the non-
the quantiŽ cation of a target threshold to infected controls was signiŽ cantly higher
break transmission should motivate the than that of mosquitoes carrying light
staV involved in control/eradication cam- infections). In the Ž eld, however, Brengues
paigns. Two thresholds have, in fact, already et al. (1975) detected strong mortality among

An. gambiae s.l. and An. funestus caused by If there is signiŽ cant Ž laria-attributable mor-
the Ž rst-stage and second-stage larvae (L1 tality in the potential vectors of W. bancrofti,
and L2 ) of W. bancrofti. He found that the Ž larial infection may limit the size of the
mean intensity of infection with the L1 or L2 population of these mosquitoes, especially
was signiŽ cantly higher in the mosquitoes in areas where bancroftian Ž lariasis is hyper-
coming to bite at night than in those cap- endemic. The reduction of the parasite
tured, while resting (in the same houses), population by MDA may thus produce an
on the following morning. Since the parasite increase in the numbers of the vector species.
load in these vector species only reduces
when parasites cross the stomach wall and
enter the haemocoel, the observed decrease
in Ž larial load from night to morning could OTHER FACTORS
only be attributed to diVerential mortality
caused by the Ž lariae in the infected In many areas, an MDA-induced increase
mosquitoes. in the mosquito biting rate may be a ‘price
Using a model of negative-exponential
worth paying’ to control LF. In some areas,
survival dependent on the parasite load
however, Ž larial parasites are transmitted to
(Dietz, 1975; May, 1977; Pichon et al.,
the human population by the same Anopheles
1976, 1980b), Pichon et al. (1980b) found
spp. that transmit malarial parasites. For
that, if a mosquito contains one L1 , taking
a new bloodmeal decreases its probability of example, malarial parasites can be transmitted
survival to the next morning by a factor (h) to humans by the vectors of nocturnally
equal to 0.95. If the mosquito contains 10 periodic W. bancrofti in West Africa (An.
L 1 , its diVerential probability of survival funestus and the An. gambiae complex) and
during the next few hours is close to h10 Papua New Guinea (An. farauti and other
(=0.5). During the parasite’s development members of the An. punctulatus group) and
from L1 to L2 , the corresponding survival the vectors of nocturnally periodic B. malayi
coeYcient (h) is 0.84 for a burden of one in Malaysia (such as An. campestris and An.
larva, and 0.17 for a burden of 10 larvae. donaldi).
It is believed that the presence of Ž larial Many factors will have to be considered
parasites in the thoracic muscles (which are if a realistic estimate of the impact of anti-
used for locomotion) slows down the speed Ž larial MDA on malaria transmission is
of take-oV and of  ight of the mosquito. In to be made: facilitation; diVerential vector
captivity, this phenomenon may be beneŽ cial mortality; frequency of bloodmeals; level
to the mosquitoes, as it may reduce the risk of anthropophily; and the frequency distri-
of being wounded against the netting of the bution of infection intensities in the vectors
cage or from drowning in the water of biting an individual (Pichon et al., 1980a).
the oviposition container. However, under
The theoretical distribution of the parasites
natural conditions, an inability to respond
in each vector species of mosquito is a
quickly to the threat of predation (by ants,
zero-truncated negative binomial with para-
spiders, lizards etc.) is a serious handicap to
an infected mosquito. This could explain, at meter k =0.3 (Pichon et al., 1979; Grenfell
least in part, why the L 3 burdens observed et al., 1990;
in the Ž eld are generally much smaller than The potential impact of the MDA-based
those seen after experimental infections in eradication of microŽ laraemia on the survival
the laboratory. Most estimates of the Ž laria- of a cohort of 100,000 female Anopheles
attributable mortality in mosquitoes are has been simulated (Fig. 3) using the Para-
probably under-estimates, as they take no Dis ‘freeware’ (
account of any mortality caused while the paradis/parad2.html). It is estimated that, in
parasites are L3 . Tingrela, in Burkina Faso (a highly endemic

FIG. 3. Potential impact of the clearance of microŽ laraemia (using mass drug administrations) on the survival
of 100,000 potential vectors of human malaria. The two graphs indicate (a) the diVerential survival of a cohort
of Anopheles exposed to high microŽ laraemias, and (b) the survival of An. gambiae s.l. in the presence (d ) or
absence (s ) of microŽ laraemias. The arrows indicate periods of ‘post-prandial’ mortality attributable to the Ž larial
development in the infected mosquitoes.

focus of LF; Brengues et al., 1975), the sup- Even if the true value is slightly higher than
pression of microŽ laraemia caused by MDA 233, it would still be too low to indicate that
would result in 233 potentially malaria- antiŽ larial MDA (in areas where malaria and
infective mosquitoes for every 100 that there LF are co-endemic) would have an immense
would have been in the absence of MDA. impact on the prevalence of malaria or the
The value of 233 is almost certainly an under- level of malaria-attributable morbidity. (The
estimate as it takes no account of any Ž laria- survival of most Ž laria-positive mosquitoes
attributable mortality that may occur more is not markedly aVected by the infections
than 12 days after the ingestion of the mV. because the intensity of the infections is

FIG. 4. The hypothetical relative durations of the malaria-transmission season (MTS) in areas where Wuchereria
bancrofti is hyper-endemic (h ) or absent (j ). Only in the Ž laria-free area are the numbers of potential vectors of
malaria [surviving long enough to be infective (i.e. 12 days) ] high enough in June and October to support
signiŽ cant malaria transmission in these months.

generally low.) In a highly endemic focus cularly of members of the An. gambiae com-
of LF in which each resident is bitten plex, can be estimated. Such mortality will
400 times a year by mosquitoes carrying have to be considered if the prevalence of
Plasmodium falciparum sporozoites, elimi- microŽ laraemia is to be accurately estimated
nation of the LF might increase the annual by xenomonitoring (Chadee et al., 2002;
number of malaria-infective bites to 900/ Ramzy, 2002; WHO, 2002).
resident. Although the impact of the MDA
on malaria may be slight, it may well be long
lasting. Moreover, in climates with a short
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