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OCR for page 190
15
Expenmental Control of Malaria
in West Africa
Epidemiology encompasses a sophisticated field of ecological knowl-
edge, and complex mathematical models are available to describe and
predict patterns of disease incidence in space and time. The Garki project
in Nigeria began in 1970 to provide detailed information on all factors in
the transmission of malaria and to test hypotheses about the dynamics of
malaria. The project was based on epidemiological models of proven
value, it was carefully planned, and it had appropriate controls. It was
viewed as a prototype for more extensive malaria control projects else-
where in Africa.
Although the project was carefully designed and executed in an inte-
grated way over several years and data were gathered on the basis of a
realistic mathematical model of malaria transmission, it failed to produce
the predicted results, because incorrect assumptions were made about the
biology of the mosquito vectors. In particular, it was assumed that all
mosquitoes behave alike, whereas resting behavior actually varied in such
a way that a large fraction of the mosquitoes did not land inside buildings,
where they would have been exposed to the contact insecticide used. This
case study highlights the importance of accurate and detailed natural his-
tory in the design of effective control strategies and the effect of initial
assumptions on the results of using even sophisticated models.
190
OCR for page 191
Case Stucly
ROBERT M. MAY, Department of Biology, Princeton University
INTRODUCTION
Malaria might well be the most important public health problem in
tropical Africa. The intensity of malaria transmission is so high that control
is very difficult, and many malariologists have suggested that humans
should not interfere with the established natural immunity in the popu-
lation, inasmuch as intervention could increase the severity of the clinical
manifestations of malaria and the mortality caused by it in older children
and adults. Largely for that reason- and because the public health infra-
structure was inadequate theory predicted that available programs to
control malaria would not work, and Africa was not included in the global
malaria eradication program launched by the World Health Organization
(WHO) in the 1950s.
However, spraying houses with DDT was locally effective in inter-
rupting malaria transmission, and the results of later pilot projects in
various African countries suggested that malaria transmission could be
interrupted, particularly in forested areas, if insecticide coverage were
total and were followed by full surveillance. But in none of these pilot
projects were quantitative epidemiological data collected. In view of this
background, WHO decided to begin a field research project, carefully
designed to provide information on all the factors involved in malaria
maintenance and transmission. The northern part of Nigeria, specifically
the Garki district, was selected for this project.
The designers of the project decided to put more resources than usual
into collection of baseline data and into evaluation of the impact of spraying
houses with an effective residual insecticide (either alone or in combination
with mass administration of drugs). As part of this effort to understand
the dynamics of malaria transmission, a mathematical model was devel-
oped and tested against data. The model was developed in an attempt to
simulate malaria transmission realistically, in the hopes of understanding
the various factors involved and improving the planning of control pro-
grams. The Garki project was also designed to study an array of seroim-
munological tests administered before, during, and after the application
of control measures.
The project is described in detail in The Garki Project, edited by Mol-
ineaux and Gramiccia (19801.
191
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192
SELECTED CASE STUDIES
THE ENVIRONMENTAL PROBLEMS
Malaria is caused by the multiplication of parasitic protozoa of the
family Plasmodiidae in the blood cells or other tissues of the vertebrate
host; the clinical symptoms in humans arise from multiplication of the
blood stages of the parasite. The several genera of malarial parasites are
associated with different hosts. Four main species of Plasmodium are
found in humans: P. falciparum, P. vivax, P. malariae, and P. ovale
(comparatively rare); P. falciparum is the most common in tropical regions
and is of greatest concern in the Garki region. and P. vivax is most common
in temperate zones.
Infection of a human host begins with the bite of a female anopheline
mosquito and the injection of sporozoite stages of the parasite into the blood-
stream. These stages are carried to the liver, where they develop in the
parenchymal cells. After an incubation period of several days (or months,
as some researchers have argued for P. vivax), these exoery~rocytic stages
(i.e., from outside the red cells) grow, divide, and release merozoites into
the bloodstream. The merozoites penetrate red cells, where they grow and
subdivide to produce more merozoites, which rupture the host cells and
invade other red cells. At some ill-understood point in this process, some of
the merozoites develop into sexual stages, the gametocytes. Only the ga-
metocytes are infective to the mosquito. When a vector mosquito bites a
human and ingests male and female gametocytes, these are freed from the
ingested blood cell, and the female gamete is fertilized and develops into an
oocyst on the wall of the mosquito's gut. After about 10 days (the devel-
opment time depends on temperature), immature sporozoites migrate from
the ruptured oocyst to the mosquito's salivary glands and mature to infectivity,
and the cycle is ready to repeat itself.
Thus, the overall cycle of the malaria parasite involves transmission
both from mosquito to human and from human to mosquito. One method
of control or eradication of malaria, therefore, is to reduce the mosquito
population sufficiently to keep the parasite cycle from maintaining itself.
After World War II, DDT was effective in reducing mosquito populations
and the incidence of malaria in many parts of the world (more in Asia
than in Africa, where transmission rates have always been very high).
The pesticide chosen in the Garki project was propoxur, which is more
specifically targeted against anopheline mosquitoes than are broad-spec-
trum insecticides, such as DDT.
Malaria is commonly believed to be responsible for more deaths than
any other infectious disease, both today and throughout history. It is listed
as the principal cause of morbidity and mortality by most African countries
(notably by Nigeria, the most populous). In Latin America, respiratory
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EXPERIMENTAL CONTROL OF MAI~RIA IN WEST AFRICA
193
tract infection tends to be listed as the most common cause of morbidity
and mortality, followed by malaria and then measles; malaria ranks first
in Brazil and Colombia. In Asia, gastrointestinal infection is the most
common, followed by respiratory infection, with malaria ranking third as
a source of morbidity; malaria ranks first in Malaysia. In short, malaria
is a very serious public health problem throughout the tropical world
(which is largely coincident with the developing world), and it is of
especial importance in tropical Africa.
GENERAL APPROACH
The general approach of the Garki project was formulated on the basis
of earlier pilot studies in Africa and elsewhere, all of which were quali-
tative, rather than quantitative. In contrast with the earlier studies, the
Garki project had clearly formulated quantitative objectives. The main
objectives were as follows (Molineaux and Gramiccia, 1980, p. 211:
· "To study the epidemiology of malaria in the lowland rural Sudan
savanna. This means in particular a concentration of the study on the
measurement of entomological, parasitological and seroimmunological
variables and on their relationships. Also included were some meteoro-
logical, demographic and clinical variables, and the study of the prevalence
of abnormal haemoglobins in the population."
· To measure the effect of specified activities directed toward inter-
rupting transmission. Such intervention included spraying with a residual
insecticide, propoxur, alone and in combination with mass administration
of drugs.
· To undertake control measures in conjunction with the construction
and testing of a mathematical model of malaria transmission. The general
aim was to develop such a model into a planning tool that permitted
comparison of the expected effects of different control strategies. Specif-
ically, the model was developed to link entomological variables with
parasitological variables (particularly the prevalence and transmissibility
of P. falciparum) and to calculate the expected parasitological effect of
defined changes in mosquito population density. The model also sought
to permit evaluation of the effects of specific schemes for the mass ad-
ministration of drugs, including the estimated role of immunity.
DEVELOPMENT OF THE PROJECT
Boundaries
In the preparatory phase, from September 1969 through September
1970, preliminary entomological and parasitological surveys were made,
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SELECTED CASE STUDIES
and specific areas and clusters of villages were chosen for detailed study.
Protocols, forms, and operation manuals were drafted, and field and lab-
oratory methods were tested. The boundaries of the study were, in effect,
defined as specific villages in the Garki region.
Study Strategy anal Monitoring
Drawing on experience gained in earlier, qualitative pilot projects in
Africa and elsewhere, the designers of the Garki project produced a study
strategy that divided the operation into three main phases of data collection
and monitoring.
In the baseline phase, from October 1970 through March 1972 (which
included a dry season, a wet season, and a second dry season), baseline
epidemiological and parasitological data were collected in the clusters of
villages that had been selected for followup. The preliminary insecticide
and drug trials were also run.
In the intervention phase, from April 1972 through October 1973 (which
included a wet season, a dry season, and a second wet season), the
intervention strategies and the monitoring of epidemiological variables in
the treated and untreated clusters of villages were implemented. The length
of this phase of the project was not fixed in advance, but rather was left
open to be guided by accumulated knowledge. In February 1972, a review
of the results obtained up to then suggested that the additional information
likely to be gained from a third year of intervention and monitoring would
not justify the expense and the expected additional loss of population
immunity (as discussed in the introduction of this case study).
In the postintervention phase, from November 1973 to the termination
of the project in February 1976, selective administration of drugs in the
villages covered during the intervention phase was continued, as was
epidemiological monitoring in the villages treated with the most intensive
strategies and in one cluster of untreated (control) villages.
The antimosquito insecticide propoxur was sprayed, primarily inside
buildings, in 164 villages, distributed over roughly 1,000 km2 a total
of around 30,000 huts that housed a total population of some 50,000
persons. Propoxur is a contact chemical, so a mosquito must land on a
sprayed surface if it is to pick up the insecticide. It remains active against
mosquitoes on sprayed surfaces long after application. The coverage with
insecticide, expressed as a proportion of huts sprayed, averaged about
99%. This coverage was estimated immediately after each spraying; the
true coverage must have been somewhat lower, owing to building and
repair activities between rounds of insecticide application.
A combination of the antimalarial drugs sulfalene and pyrimethamine
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EXPERIMENTAL CONTROL OF MALARIA IN WEST AFRICA
195
was given to about 16,000 people in 60 of the sprayed villages. Infants
were excluded, but visitors were included. The proportion of the total
population given the drugs averaged about 85~o (higher in the wet season,
lower in the dry season).
USES OF KNOWLEDGE
The relevant ecological facts pertaining to the dynamics of malaria
transmission are conveniently discussed under two headings: the mosquito
and the malaria parasite. Human immunology, although extensively stud-
ied (Molineaux and Gramiccia, 1980), did not yield any findings partic-
ularly relevant to the overall design of control programs and is not treated
here.
The Mosquito
The extent of contact between mosquitoes and humans in the Sudan
savanna is very high indeed: the biting rates of Anopheles gambiae sensu
lato and A. funestus were found to attain seasonal peaks of 174 and 94
bites per person per night, respectively (in studies that averaged more than
8 nights). The vectorial capacity, defined as the rate of contact between
human hosts via the mosquito vectors, reached a seasonal peak of about
40, which is some 2,000 times the critical value for maintaining endemic
malaria. The cumulative inoculation rate by mosquitoes reached a max-
imum of 145 sporozoite-positive bites per person in l year (of which 132
were in the wet season).
The mosquito density, and hence the extent of malaria transmission, in
the Sudan savanna varies widely with season, year, and locale, according
to Molineaux and Gramiccia (1980), who write:
In most villages, the vectorial capacity drops below its critical level for about half of
the year (this does not necessarily prevent transmission, given the large reservoir of
parasites), while in some it remains well above the critical level throughout the year.
The variations from year to year are relatively important; over a period of 3 years,
these variations followed the variations in total rainfall in the case of A. funestus but
not in the case of A. gambiae s.l. Villages, even when not obviously different on
inspection and located only a few kilometres apart, differ in vector density, anopheline
fauna (A. funestus has a very uneven distribution) and probably in vector behaviour
and karyotypes. Among 8 villages, the cumulative inoculation rate ranged from 18
to 145 sporozoite-positive bites in one year. The local and yearly variations stress the
need for adequate baseline and comparison (control) data for a correct evaluation of
the impact of control measures.
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196
SELECTED CASE STUDIES
The Malaria Parasite
In general, the baseline prevalence of malaria parasitemia was high,
and the age-specific curves of both prevalence and density of infection
were typical of a high rate of transmission with a high level of acquired
immunity. The findings were the same on each of the three parasites (P.
falciparum, P. malariae, and P. ovate). There was relatively little variation
among villages or between years.
The rate at which infants acquired malaria and the rate of onset of
episodes of patent parasitemia (with fever, etc.) in the general population
both testified to the high rate of transmission. The marked increase in the
rate at which patent parasitemia disappeared with increasing age and the
high ratio (nearly 1:1) of the entomological inoculation rate to the infant
conversion rate (the ineffectiveness of sporozoite-positive bites) confirmed
the high level of population immunity.
The combination of propoxur spraying and mass administration of sul-
falene and pyrimethamine every 10 weeks reduced the prevalence of P.
falciparum to a very low point in the dry season, but it did not significantly
interrupt malaria transmission. Nor did it prevent an increase in prevalence
in the wet season, when natural conditions favored mosquito breeding. A
new equilibrium, with incidence oscillating between wet and dry seasons,
was reached rapidly, and continuation of the intervention program would
probably not have affected this result significantly. It was concluded that
mobility of the human population, which was relatively pronounced, was
unlikely to be the main cause of the maintenance of transmission. As
discussed at length below, the main limiting factor was probably the
exophily of some of the mosquitoes i.e., their preference for resting
outdoors.
When propoxur was sprayed and drugs administered more often (every
2 weeks in the wet season, every 10 weeks in the dry season), the prev-
alence of P. falciparum decreased to around 1% in the dry season and to
5% or less in the wet season. But transmission was still not interrupted
greatly. As with the lower-frequency intervention, a new oscillating equi-
librium was fairly rapidly attained, and it seems unlikely that continuation
of the intervention would have modified the result. Again, it was concluded
that exophily of the mosquitoes was the main cause, rather than population
mobility.
As expected, mass application of the drugs at high frequencies for 1.5
years caused a temporary loss of immunity against P. falciparum, which
was reflected in the resurgence of malaria in the postintervention phase
of the project.
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EXPERIMENTAL CONTROL OF MAI~RIA IN WEST AFRICA
GENERAL THEORY
197
The basic model for malaria was first set out by Ross (1911, 1916) and
later refined by MacDonald (1952, 1957, 1973), who included the latent,
infected-but-not-yet-infectious period for the mosquito. If we divide the
human host population into those who are susceptible and those who are
infected and divide the female mosquito population into the susceptible
and the infected, we can construct a pair of differential equations to
describe the essentials of the dynamics of infection.
dxldt = (abMlN)y(1 -x)-rx,
dyldt = ax(1 - y)- by,
where
(1)
(2)
x 1S
y 1S
N is
M is
the proportion of the human population infected,
the proportion of the female mosquito population
the size of the human population,
the size of the female mosquito population,
a is the rate of biting on a human by a single mosquito (number
of bites per unit time),
b is the proportion of infected bites on humans that produce an
infection,
r is the per capita rate of recovery for humans (fir is the average
duration of infection in a human host), and
is the per capita mortality rate for female mosquitoes (lid is the
average lifetime of a mosquito).
infected.
In this simplest model, the total populations of both humans and female
mosquitoes are assumed to be unchanging (N and M constant), so the
dynamic variables are the proportions infected in the two populations (x
and y). Equation 1 describes changes in the proportion of humans infected.
New infections are acquired at a rate that depends on the number of
mosquito bites per person per unit time (aMlN), on the probabilities that
the biting mosquito is infected (y) and that a bitten human is not already
infected (1 -x), and on the chance that an uninfected person bitten by
an infected mosquito will become infected (b); and infections are lost by
the return of infected people to the uninfected class, at a characteristic
recovery rate (rx). Equation 2 describes changes in the proportion of
mosquitoes infected. The gain term is proportional to the number of bites
per mosquito per unit time (a) and to the probabilities that the biting
mosquito is uninfected (1 - y) and that the bitten human is infected
already (x); the loss term arises from the death of infected mosquitoes (y).
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198
SELECTED CASE STUDIES
More formally, the loss terms for infected humans and for infected mos-
quitoes both involve death and recovery. But for human hosts the recovery
rate is typically greater than the death rate (by 1-2 orders of magnitude),
whereas for mosquitoes the opposite is typically the case; the above for-
mulation is therefore a sensible approximation.
This model is, of course, highly simplified. One of its glaring flaws is
the failure to disarticulate the "infected" categories of human and mosquito
hosts to take account of the various developmental stages of the parasite.
For instance, the model does not incorporate the incubation period of Me
parasite in the mosquito (during which no sporozoites are present in Me
salivary glands of the "infected" mosquitoes), even though this incubation
period is comparable with the mean life span of the mosquito. We pursue
this complication below. Likewise, the model does not distinguish between
the pathological asexual merozoite blood stages and the infectious gametocyte
sexual stages in the human. Encounters between biting mosquitoes and the
humans they bite are assumed to be random.
Notwithstanding those shortcomings, the simple model defined by
Equations 1 and 2 is useful in laying bare the essentials of the transmission
process and in elucidating patterns in the diverse array of epidemiological
data on different geographical regions. In particular, the model makes
plain the significance of the "basic reproductive rate" of the parasite, in
this context conventionally called z0 (MacDonald, 1952, 19571. The basic
reproductive rate is essentially the number of secondary infections gen-
erated by one infected individual in a population of susceptibles. If this
number is, on the average, less than unity, the disease will be unable to
maintain itself; if it equals or exceeds unity, the disease will be able to
maintain itself. In general, the larger the basic reproductive rate, the greater
the resistance of the disease to eradication. In this simple model,
z0 = ma2bl,ur,
.
where m Is the number of female mosquitoes per human host (MIN).
This result is intuitively understandable: the mosquito biting rate, a,
enters twice in the cycle (hence, ah; transmission is helped by large
numbers of mosquitoes per human host (large m) and by large b; and
transmission is hindered by a high mosquito death rate or by fast recovery
(large ,u and r, respectively).
To be more accurate, we should recognize that a latent period of duration
T must elapse before an infected mosquito becomes infectious. This in-
troduces an additional factor, exp(- of), into Equation 3 to represent the
probability that an infected mosquito will survive the latent period to
(3)
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EXPERIMENTAL CONTROL OF MALARIA IN WEST AFRICA
199
become a transmitter of infection. The resulting expression for z0 (as first
derived by MacDonald, 1952, 1957) is then
z0 = ma2b expt-~T)I~r.
A SPECIFIC MODEL
(4)
Dietz et al. (1974) developed a more realistic modification of the above
model, which is presented in detail in Molineaux and Gramiccia (1980,
Ch. 101. The essentials of the model are indicated schematically in Figure
1. There are two classes of people: one class has a low rate of recovery
from malana, and all infections can be detected; the other class has a high
recovery rate, and infections have only a 70% chance of being detected
(owing to the low densities of parasites). Members of both classes re-
peatedly are exposed, become infected, and recover, remaining within
their own class except for a fixed rate of transition from the relatively
susceptible class to the relatively immune class (the transition rate is
determined by fitting the model to the data). The model thus takes into
account the basic characteristics of immunity to malaria.
Within the framework of this model, it is possible to calculate the
prevalence of P. falciparum as a function of the vectorial capacity and of
its spontaneous and man-induced changes. It is also possible to calculate
the effect of mass administration of drugs on the prevalence of malaria.
The model gave a good account of the basic dynamics of the interactions
among humans, mosquitoes, and malaria. But the effects of insecticide
~ 1
NONINFECTIOUS
NEGATIVE l l l l I I SLOW RECOVERY
X3 ~X4
Y3
I ~NON I N F ECTI OUS
FAST RECOVERY
.
FIGURE 1 Schematic illustration of malaria model of Dietz et al. (1974~. As dis-
cussed more fully in text, diagram shows various categories of individuals considered
in model and possible transitions between categories.
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200
SELECTED CASE STUDIES
on mosquito longevity were not accurately estimated by treating the mos-
quito population as homogeneous and as all resting indoors. Accurate
prediction of the effects of insecticide on mosquito mortality, and on
overall transmission dynamics, required an appreciation of the heteroge-
neity of the environment, which was not built into the original model.
The study concluded that the specific model described above does indeed
simulate the epidemiology of P. falciparum infections with acceptable
realism and that it can be used both for planning malaria control and for
teaching the epidemiology and control of malaria. But important compli-
cations enter into the estimation of the parameters in the model, particularly
the estimation of the effects of insecticides on mosquito mortality rates.
These complications in many ways constitute the most interesting of the
lessons learned in this case.
CONCLUSION: THE CASE STUDY AND
ECOLOGICAL KNOWLEDGE
It will be seen that the Dietz et al. model does not discriminate among
different classes of mosquito vectors. A substantial complication, how-
ever, arises from inhomogeneities in the effects of insecticides. In the
Garki project, an insecticide was applied to interior surfaces of houses
and was therefore more effective against mosquitoes that rest indoors after
a blood meal. If insecticides do not affect all mosquitoes equally, mea-
surements of the average biting rate and of average longevity might be
severely distorted (Molineaux et al., 19791. Suppose that after spraying
there are in effect two mosquito populations: a minority (initially pi =
0.2) that rest outdoors (exophilous) and are consequently relatively un-
affected by the spraying, and a majority (initially P2 = 0.8) that rest
indoors (endophilous) and suffer greater mortality. Let al = 1 bite per
day and act = 0.05 per day for the exophilic mosquitoes, and a2 = 2
and ~2 = 0.5 for the endophilic ones. Let the latent period, T. equal 10
days for all mosquitoes. The correct way to calculate the effective index,
a expt-/, which determines the transmission rate from infected
mosquitoes to human hosts and is therefore relevant to evaluating the
effects of intervention, is to take the appropriate arithmetic average of the
separate indexes:
peat exp(- ~l~l,u~ + p2a2 expf-~2T)/112 = 2.5.
But if the endophilic and exophilic categories are not properly distin-
guished, then the above index is likely to be estimated with average values
of a and of ,u: a expt-,ul~l,u = 0.073 (where a = plan + p2a2 = 1.8
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EXPERIMENTAL CONTROL OF MALARIA IN WEST AFRICA
201
and ~ = Pled + P2~2 = 0 41) Molineaux et al. (1979) analyzed the
consequences of this aggregation phenomenon in considerable detail and
emphasized that aggregating the groups will always underestimate the
biting capacity of the mosquito population and hence will always under-
estimate the basic reproductive rate, zO, and overestimate the impact of
insecticides. As the above example makes clear, these incorrect estimates
can lead to seriously wrong conclusions.
The above discussion captures the essentials of the most important
surprise found in the Garki project. It was known from the outset that the
intensity of transmission of malaria in these parts of Africa was very high.
Indeed, the study showed the basic reproductive rate of the infection to
be about 1,000; in other words, the transmission rate, or "vectorial ca-
pacity of the mosquito," was about 1,000 times the critical value required
for the maintenance of endemic malaria. This very high transmission rate
put malaria in tropical Africa in a category of its own and constituted one
reason that a control program like that tried in the Garki project was not
attempted earlier. Against this background, however, it was not understood
that heterogeneities in the environmental setting of the mosquitoes might
invalidate simple estimates of the efficacy of insecticide application, which
were based on assumptions that the mosquito population was effectively
homogeneous and that most mosquitoes rested indoors much of the time.
Thus, it was found that spraying with the residual insecticide propoxur
did not have the expected effect on the prevalence of malaria, although
coverage was as nearly complete as possible and the insecticide was very
effective against the mosquito vectors (it produced a high mortality rate
even at the beginning of the third wet season after the last application).
Immigration of vectors or humans from unsprayed villages did not appear
to be a significant factor. The decisive factor appears to have been the
exophily of a substantial fraction of the mosquito vectors. The combination
of exophily with a high biting rate maintained a high transmission rate.
Thus, although the insecticide program was supplemented by administra-
tion of drugs at high frequency and with high coverage and it reduced
malaria to a very low incidence, it failed to interrupt transmission.
In more detail, it was found that the effect of residual spraying in
reducing A. gambiae s.l. populations, and hence malaria transmission,
varied significantly among villages. The variation was probably related
not to variations in spraying coverage or to distance from unsprayed
villages, but to variation in the amount of exophily. The amount of ex-
ophily appeared to be a relatively stable characteristic of particular villages,
and it also appeared to be associated with genetic differences within species
of the A. gambiae complex. The vector population attached to a village
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202
SELECTED CASE STUDIES
appeared to be relatively isolated genetically most of the time. This was
also in accord with the observation that the effect of spraying was influ-
enced little by the size of the sprayed area.
As to the possible genetic mechanisms underlying the behavioral dif-
ferences between endophilic and exophilic mosquitoes, Molineaux and
Gramiccia (1980) stated:
A. gambiae s.l. in the study area is composed of A. gambiae s.s. and A. arabiensis.
The dominant species is usually A. arabiensis but the relative abundance of the 2
species varies between times and places in ways which are not explained. A. gambiae
s.s. is the more anthropophilic and has higher sporozoite rates; no clear-cut difference
was demonstrated regarding exophily or effectiveness of propoxur. The vectorial
capacity was estimated as if A. gambiae s.l. were a single species; appropriate sim-
ulations show that this is unlikely to have introduced a large error in the estimate.
The cytogenetic investigations of Coluzzi suggest that resting behaviour and exposure
to propoxur are related less to the relative abundance of the 2 species than to the
intraspecific frequency of certain chromosomal inversions, some of which may be
associated with a relatively stable behaviour pattern of the individual.
In short, the essential conclusion of the Garki study, which was not
anticipated in the early planning, was that,
if the resting behavior of a mosquito species is genetically determined, exophily will
be a stable characteristic of individual vectors, and the usual method of interpreting
the impact of residual insecticides on longevity, which tacitly assumes uniform bet
haviour, is overoptimistic.
From the parasitological point of view, the study was interesting, in
that its longitudinal nature permitted it to demonstrate that almost everyone
was infected early in life, not only by P. falciparum, but very probably
also by P. malariae and even by P. ovale, which is commonly regarded
as a "rare" parasite. In addition, early demonstration of the effect of
parasitism on immunity confirmed that a degree of immunity is evoked
by malarial infection and that continual reinfection is necessary to maintain
such immunity over the long term. Other clinical studies showed inter-
esting relationships between body temperature and parasitemia and showed
a significant effect of malaria control on frequency of fever and on an-
thropometric indicators of the nutritional status of children.
In another conclusion, Molineaux and Gramiccia (1980) stated that "the
new mathematical model, painstakingly tested against hard facts, allows
much more realistic simulations of the epidemiology of malaria, both
before and after the application of control measures, than was previously
possible." Cohen and Singer (1979) developed the model further, incor-
porating additional elements of realism (such as infection with more than
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EXPERIMENTAL CONTROL OF MALARIA IN WEST AFRICA
203
one species of malaria and a more accurate description of immune re
sponses in human hosts) while retaining an essential understanding of the
process of malaria transmission.
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Aron, J. L., and R. M. May. 1982. The population dynamics of malana. Pp. 139-179 in
R. M. Anderson, ed. Population Dynamics of Infectious Diseases. Chapman and Hall,
London.
Cohen, J. E., and B. Singer. 1979. Malana in Nigeria: Constrained continuous-time Markov
models for discrete-time longitudinal data on human mixed-species infections. Pp. 69-
133 in S. A. Levin, ed. Lectures on Mathematics in the Life Sciences. Vol. 12. Some
Mathematical Questions in Biology. American Mathematical Society, Providence, R.I.
Dietz, K., L. Molineaux, and A. Thomas. 1974. A malaria model tested in the African
Savannah. Bull. WHO 50:347-357.
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Committee Comment
In general, the interactions between hosts and parasites are examples
of prey-predator associations that have some simplifying features espe-
cially for human host-parasite systems, in which the population size of
the human host is usually determined by other factors and much infor-
mation on transmission and maintenance of the parasite is often available.
Many public health studies can be viewed as examples of the interaction
of environmental problems (broadly defined) with ecological principles.
The Garki project is notable in that it was very thoughtfully designed,
was maintained in an integrated way over several years, and carefully
interdigitated the data gathered with a relatively realistic mathematical
model. Moreover, the mathematical model, based on hard data and tested
against data gathered in the course of the study, could be thought of as a
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204 SELECTED CASE STUDIES
paradigm for a prey-predator model. It was successful in explaining the
patterns of prevalence before, during, and after the intervention program.
Interestingly, during construction of the basic model, no thought had
been given to the possible effects of genetic and behavioral heterogeneity
in the vector mosquito population. Such effects turned out to be the most
important factor working against control. That a large fraction of the
mosquitoes were exophilic meant that simple preliminary estimates of the
overall transmission rate and of the likely effect of insecticides were
incorrect.
This story illustrates the need for careful design in the gathering of data
(and the extent to which a thoughtful mathematical model can guide the
process) and shows that, no matter how carefully these things are thought
through, unexpected complications are likely. Beyond these platitudes,
the story also illustrates a specific theme found in much contemporary
ecological theory. It seems increasingly likely that spatial heterogeneity,
with different dynamic processes going on in separate patches, will be the
most important factor in the overall persistence of many natural prey-
predator or host-parasite associations (Hassell and May, 19851. The Garki
project is certainly one example: behavioral heterogeneity in the mosquito
population was, on the one hand, the most important factor in maintaining
infection in the presence of an intervention program and, on the other
hand, a factor not initially reckoned with (in a preliminary analysis drawn
from the conventional traditions of ecological theory, which too often treat
the world as homogeneous).
Reference
Hassell, M. P., and R. M. May. 1985. From individual behaviour to population dynamics.
Pp. 3-32 in R. Sibly and R. Smith, eds. Behavioural Ecology. Blackwell, Oxford, Eng.
Representative terms from entire chapter:
malaria transmission
