Biology Reference
In-Depth Information
refining treatment strategies (such as the use of combination therapies) in
the face of declining single-dose drug efficacy.
11
Currently there is no
evidence for anthelmintic (benzimidazole) resistant A.
lumbricoides,
although this is not the case for human hookworms,
222
and a single
nucleotide polymorphism (SNP) in parasite
associated with
widespread benzimidazole resistance in nematode species of veterinary
importance
223
b
-tubulin
e
has recently been shown to occur at high frequency in
T. trichiura-infected people repeatedly treated with benzimidazoles in
Panama.
224
For transmission models to be most useful they need to be parame-
terized using data on the phenotypic manifestations (increased drug
tolerance of worms, potential fitness costs) and genetic basis of resistance
(how many loci would be involved, whether or not these are linked,
whether anthelmintic resistance is conferred by recessive alleles) which
should be collected as part of control program monitoring and evaluation
activities.
225
It is also likely that individual-based, stochastic models will
be necessary on the basis of modeling work in veterinary animals,
demonstrating that the mode of infection (trickle or clumped) signifi-
cantly influences the rate of spread of anthelmintic resistance.
226,227
e
Elimination
In certain circumscribed foci, intervention efforts are moving from
morbidity control to transmission interruption and elimination of STHs,
including A. lumbricoides.
228
Experiences from Japan,
229
the Republic of
Korea
230
and most recently from the People's Republic of China
231
suggest that such ambitious targets will only be achieved using integrated
control approaches, encompassing a consolidation of MDA combined
with socio-economic improvements, particularly improved access to
sanitation.
72,232
Similar conclusions have been reached frommathematical
models; the theoretical transmission breakpoint densities for
A. lumbricoides and other STHs are extremely low,
16,203
meaning that mass
treatments alone would need to be administered at a prohibitively high
coverage and frequency.
20
Despite this, in low endemicity settings or where combined control
initiatives have resulted in prolonged heavy suppression of transmission,
models may be warranted that are suitable for assessing the feasibility of
elimination under specific conditions that reflect the reality of a control
program. In such circumstances, individual-based stochastic modeling
approaches become necessary, in essence because at low parasite densities
the probability of stochastic population fade-out (extinction) becomes
important, a phenomenon which is omitted from mean-based (mass
action) deterministic constructs. The output from multiple runs of
stochastic models can be used to construct probabilistic statements about
the chance of elimination under specified control conditions.
