Arrested development is an important feature of the
life cycles of a number of nematode species. It is of particular importance in the order
Strongylida especially the Trichostrongyles of grazing ruminants, the small strongyles of
horses and the hookworms of dogs and humans.
Synonyms include the terms hypobiosis, larval
inhibition, inhibited larval development and arrested larval development
Arrested development may be defined as a
temporary halt in the parasitic phase of development at a specific point in the nematode
Under normal circumstances when a host is infected
with a nematode, parasitic development begins immediately and continues through to adult
males and females in the normal prepatent period characteristic of the species. However,
under certain circumstances larval development will be halted or arrested at a specific
stage (usually L3 or L4) and the prepatent period is prolonged sometimes for weeks or
|This image shows a histological section of
an abomasum with an arrested larva (early L4) of Ostertagia ostertagi contained within a
Arrested larvae not only fail to grow but also
their metabolic rate decreases significantly and they stop moving. In this state they can
survive for weeks or months before resuming development and may also be resistant to some
anthelmintics at doses that are usually lethal to adults and normally developing larval
Arrested development can only be diagnosed by
examining the population of worms in a host animal at necropsy. If arrested stages are
present, the worm population will show the following characteristics.
1. A significant percentage
of larvae will be at the same stage of development.
2. The sizes of recovered worms will show a
bimodal distribution. The smaller group will be arrested larvae, and the larger group will
be mature adults. (In the case of Ostertagia
ostertagi, the nematode population will include adult males (~ 7 mm
long & 0.12 mm wide) , adult females (~ 10 mm long and 0.14 mm wide)
larvae in the early L4 stage (~ 1 mm long & 0.03 mm wide). The image
Image courtesy of Dr. Jorge
Guerrero, Merial Inc
the relative sizes of an arrested L4 and a mature adult male).
3. The most recent exposure of the host
animal to infection will be at least prior to the prepatent periods of the nematode
Initiating factors in arrested development
Epidemiological and experimental evidence has
identified three factors responsible for the initiation of arrested development.
Seasonal influences on infective larvae on
Host immune responses inhibiting the normal
development of the parasitic phase of the life cycle.
An overcrowding effect whereby the presence of
adult worms causes the "feedback" inhibition of incoming infective larvae which
go into arrest until the adult worm population decreases in number or is eliminated.
Hypobiosis is the term most often used for arrested
development that has a seasonal basis. It is a biologically important feature since
it seems to be of particular importance in nematodes with relatively short adult life
spans. In these species hypobiosis is initiated by an environmental signal received by
free-living L3s. When these L3s subsequently infect a host, they do not develop
continuously through to adults but instead arrest in host tissues either as exsheathed L3s
or as early L4s.
In other words hypobiosis occurs inside the
definitive host but results from environmental signals received by free-living infective
larvae. It is a mechanism for nematodes to survive a period of harsh climatic conditions,
hostile to survival of their progeny, by arresting as immature stages until conditions
improve to the point where free-living larval stages can again grow and develop to the
In regions of the northern hemisphere with cool,
temperate climates and pronounced seasonal changes, arrested larvae accumulate inside
grazing animals during the fall/autumn, with the onset of falling temperatures signaling
the approach of winter, a season that is usually threatening to the survival of
free-living stages on pasture.
The resumption of development of these hypobiotic
larvae occurs in late winter or early spring when environmental conditions are, once
again, conducive to survival and development of free-living preparasitic stages.
In warm temperate regions of the northern
hemisphere, hypobiosis appears to be linked to the onset of a dry season since dry
conditions also threaten both the survival and development of free-living stages. In the
southern United States, for example, Ostertagia ostertagi arrests during spring and
remains arrested during the following hot, dry summer. Hypobiosis in Spring thus allows
Ostertagia to survive within the host, as early L4's, protected from the inhospitable
external environment. Similarly, hypobiosis occurs in Spring in regions of the southern
hemisphere where summers are also hot and dry. These regions include parts of Australia
(coastal and adjoining tablelands), Chile, Peru, Brazil, Argentina and South Africa.
In tropical regions, hypobiosis has been recorded at
the onset of dry seasons. In Northern Nigeria, for example, with a six-month dry season,
hypobiosis occurs in Haemonchus contortus and Cooperia species in cattle. Resumption of
development begins at the onset of the rainy season when the environment is, once again,
hospitable to the survival and development of free-living stages. In contrast, hypobiosis
is much less important in Southern Nigeria and Southern Ghana where the dry season is
Hypobiosis is clearly genetically controlled but is
not an "all or none" phenomenon. In cold temperate climates such as are found in
Maine and Eastern Canada, the great majority of trichostrongyle larvae ingested by grazing
ruminants, in late fall (autumn), will undergo hypobiosis. In milder climates, for example
southern England, only a proportion of such ingested larvae (usually no more than 60%)
will arrest since England's milder winters will often allow preparasitic stages to survive
on pasture. Several studies have shown that the propensity for hypobiosis is genetically
based. For example, cattle from Ohio, infected with a "winter-arresting" strain
of Ostertagia ostertagi were moved to Louisiana ( a region where hypobiosis occurs in
Spring) and grazed on Ostertagia-free pastures thus contaminating them with free-living
stages of the "winter-arresting" strain. Calves grazed on this newly
contaminated pasture were subsequently shown to contain hypobiotic larvae in the fall
(autumn), the season for hypobiosis in their original Ohio environment rather than Spring,
the time for hypobiosis in their new environment. The converse was also true, i.e.
Ostertagia in cattle transferred from Louisiana to Ohio continued to show hypobiosis in
the Spring. This evidence confirmed other observations that several different strains
exist in populations of nematodes where hypobiosis is a significant feature of the life
The resumption of development (to adults) of these
arrested larvae occurs once the environment is, again, suitable for preparasitic
development of the next generation of eggs and larvae. The triggering mechanisms
responsible for ending hypobiosis and allowing larvae to resume development, are not
really known. However, it has been hypothesized that seasonally arrested larvae are in a
similar state to diapause in insects. If so, then some type of genetically programmed
clock would trigger the ending of hypobiosis at a set time after induction. Evidence for
this comes from New Zealand studies where it was found that hypobiotic larvae mature at
the same rate as they undergo arrest leading to the conclusion that arrested larvae resume
their development at a set time after they become arrested in the host. For example, we
can assume that hypobiotic larvae begin to accumulate in September in cattle grazing
pastures in cool temperate regions of the northern hemisphere and this accumulation ends
when these cattle are housed for the winter at the end of November. If we further assume
that these larvae will remain arrested for 4 months then resumption of development
will begin in January and continue until the end of March.
It appears that seasonal hypobiosis is an important
option for the life cycles of a number of nematodes of grazing animals, particularly
ruminants. This is particularly true of the Trichostrongyles such as Ostertagia,
Haemonchus, Trichostrongylus, Cooperia and Dictyocaulus as well as Oesophagostomum and,
also, the small strongyles of horses.
Another form of arrested development is also recognized and is due to the
influence of the immune response. As animals graze, they continually ingest infective
third stage larvae which develop to adults in the normal prepatent period. As the grazing
season progresses these animals develop a strong immune response to nematode infections
and one of the manifestations of the immune response is the inhibition of larvae inside
the host. Larvae infecting a host are more likely to arrest if there is already an
established population of adult worms in that host. In sheep, goats and pigs
maturation of these immunologically arrested larvae appears to be linked with parturition.
An inhibition of the immune response, specifically associated with gut-dwelling nematodes,
is related to serum levels of prolactin. Immune competence is restored when prolactin
levels drop, at weaning, and worm burdens are usually expelled as a consequence of the
restored immune response.
Hypobiosis and immunological arrest of parasitic larvae should be
distinguished from other forms of developmental arrest seen in paratenic and intermediate
hosts during the life cycles of many nematodes, particularly the ascarids and spirurids.
This form of arrested development is often called quiescence since it is an intrinsic part
of the life cycle, is not an option and is not triggered by extraneous influences.
Biological importance of arrested development
Whatever the triggering mechanisms are that initiate developmental arrest
and induce resumption of development, the phenomenon has considerable biological
importance to nematodes that incorporate it into their life cycle options. It also has
considerable epidemiological implications to nematode hosts and must be considered when
devising methods for prevention and control of nematode infections and disease.
There are several reasons why arrested development is important.
1. Arrested development ensures survival of
nematodes during times when conditions are hostile to their survival in the external
2. Resumption of development of large
numbers of larvae in a host may produce serious outbreaks of disease.
3. Development of adults from arrested
larvae will produce significant contamination of pastures with nematode eggs at a time
when environmental conditions are, once again, favorable for development of preparasitic
stages to infective larvae. This contamination which begins at the start of the grazing
season and reaches a peak several weeks later is particularly dangerous for young,
immunologically naive animals grazing pastures for the first time.
4. Hypobiotic larvae are depressed
metabolically and hence may be less susceptible to some anthelmintics. Clearly the choice
of drugs to be used in a nematode control program will be influenced by the role of
arrested development in specific nematode life cycles and by the susceptibility of
arrested larvae to the range of available anthelmintics.