Malaria affects more people, more persistently, throughout more of the world than any other insect- borne disease. Some 120 million new cases arise each year. The World Health Organization calculated that malaria control during the period 1950–72 reduced the proportion of the world’s (excluding China’s) population exposed to malaria from 64% to 38%. Since then, however, exposure rates to malaria in many countries have risen towards the rates of half a century ago, as a result of concern over the unwanted side-effects of dichlorodiphenyl-trichloroethane (DDT), resistance of insects to modern pesticides and of malaria parasites to antimalarial drugs, and civil unrest and poverty in a number of countries. Even in countries such as Australia, in which there is no transmission of malaria, the disease is on the increase among travelers, as demonstrated by the number of cases having risen from 199 in 1970, to 629 in 1980, and 700–900 in the 1990s with 1–5 deaths per annum.
The parasitic protists that cause malaria are sporozoans, belonging to the genus Plasmodium. Four species are responsible for the human malarias, with others described from, but not necessarily causing diseases in, primates, some other mammals, birds, and lizards. There is developing molecular evidence that at least some of these species of Plasmodium may not be restricted to humans, but are shared (under different names) with other primates. The vectors of mammalian malaria are always Anopheles mosquitoes, with other genera involved in bird plasmodial transmission.
The disease follows a course of a prepatent period between infective bite and patenty, the first appearance of parasites (sporozoites; see Box 15.1) in the erythrocytes (red blood cells). The first clinical symptoms define the end of an incubation period, some nine (P. falciparum) to 18–40 (P. malariae) days after infection. Periods of fever followed by severe sweating recur cyclically and follow several hours after synchronous rupture of infected erythrocytes (see below). The spleen is characteristically enlarged. The four malaria parasites each induce rather different symptoms:
- Plasmodium falciparum, or malignant tertian malaria, kills many untreated sufferers through, for example, cerebral malaria or renal failure. Fever recurrence is at 48 h intervals (tertian is Latin for third day, the name for the disease being derived from the sufferer having a fever on day one, normal on day two, with fever recurrent on the third day). P. falciparum is limited by a minimum 20°C isotherm and is thus most common in the warmest areas of the world.
- Plasmodium vivax, or benign tertian malaria, is a less serious disease that rarely kills. However, it is more widespread than P. falciparum, and has a wider temperature tolerance, extending as far as the 16°C summer isotherm. Recurrence of fever is every 48 h, and the disease may persist for up to eight years with relapses some months apart.
- Plasmodium malariae is known as quartan malaria, and is a more widespread, but rarer parasite than P. falciparum or P. vivax. If allowed to persist for an extended period, death occurs through chronic renal failure. Recurrence of fever is at 72 h, hence the name quartan (fever on day one, recurrence on the fourth day). It is persistent, with relapses occurring up to half a century after the initial attack.
- Plasmodium ovale is a rare tertian malaria with limited pathogenicity and a very long incubation period, with relapses at three-monthly intervals.
Malaria exists in many parts of the world but the incidence varies from place to place. As with other diseases, malaria is said to be endemic in an area when it occurs at a relatively constant incidence by natural transmission over successive years. Categories of endemicity have been recognized based on the incidence and severity of symptoms (spleen enlargement) in both adults and children. An epidemic occurs when the incidence in an endemic area rises or a number of cases of the dis- ease occur in a new area. Malaria is said to be in a stable state when there is little seasonal or annual variation in the disease incidence, and it is predominantly trans- mitted by a strongly anthropophilic (human-loving) Anopheles vector species. Stable malaria is found in the warmer areas of the world where conditions encourage rapid sporogeny and usually is associated with the P. falciparum pathogen. In contrast, unstable malaria is associated with sporadic epidemics, often with a short-lived and more zoophilic (preferring other animals to humans) vector that may occur in massive numbers. Often ambient temperatures are lower than for areas with stable malaria, sporogeny is slower, and the pathogen is more often P. vivax.
Disease transmission can be understood only in relation to the potential of each vector to transmit the particular disease. This involves the variously complex relationship between:
- vector distribution;
- vector abundance;
- life expectancy (survivorship) of the vector;
- predilection of the vector to feed on humans (anthropophily);
- feeding rate of the vector;
- vector competence.
With reference to Anopheles and malaria, these factors can be detailed as follows.
Vector distribution Anopheles mosquitoes occur almost worldwide, with the exception of cold temperate areas, and there are over 400 known species. However, the four species of human pathogenic Plasmodium are transmitted significantly in nature only by some 30 species of Anopheles. Some species have very local significance, others can be infected experimentally but have no natural role, and perhaps 75% of Anopheles species are rather refractory (intolerant) to malaria. Of the vectorial species, a handful are important in stable malaria, whereas others become involved only in epidemic spread of unstable malaria. Vectorial status can vary across the range of a taxon, an observation that may be due to the hidden presence of sibling species that lack morphological differentiation, but differ slightly in biology and may have substantially different epidemiological significance, as in the An. gambiae complex (Box 15.2).
Vector abundance Anopheles development is temperature dependent, as in Aedes aegypti (Box 6.2), with one or two generations per year in areas where winter temperatures force hibernation of adult females, but with generation times of perhaps six weeks at 16°C and as short as 10 days in tropical conditions. Under optimal conditions, with batches of over 100 eggs laid every two to three days, and a development time of 10 days, 100-fold increases in adult Anopheles can take place within 14 days.
As Anopheles larvae develop in water, rainfall significantly governs numbers. The dominant African malaria vector, An. gambiae (in the restricted sense; Box 15.2), breeds in short-lived pools that require replenishment; increased rainfall obviously increases the number of Anopheles breeding sites. On the other hand, rivers where other Anopheles species develop in lateral pools or streambed pools during a low- or no-flow period will be scoured out by excessive wet season rainfall. Adult survivorship clearly is related to elevated humidity and, for the female, availability of blood meals and a source of carbohydrate.
Vector survival rate
The duration of the adult life of the female infective Anopheles mosquito is of great significance in its effectiveness as a disease transmitter. If a mosquito dies within eight or nine days of an initial infected blood meal, no sporozoites will have become available and no malaria is transmitted. The age of a mosquito can be calculated by finding the physiological age based on the ovarian “relicts” left by each ovarian cycle (section 6.9.2). With knowledge of this physiological age and the duration of the sporogonic cycle (Box 15.1), the proportion of each Anopheles vector population of sufficient age to be infective can be calculated. In African An. gambiae (in the restricted sense; Box 15.2), three ovarian cycles are completed before infectivity is detected. Maximum transmission of P. falciparum to humans occurs in An. gambiae that has completed four to six ovarian cycles. Despite these old individuals forming only 16% of the population, they constitute 73% of infective individuals. Clearly, adult life expectancy (demography) is important in epidemiological calculations. Raised humidity prolongs adult life and the most important cause of mortality is desiccation.
Anthropophily of the vector
To act as a vector, a female Anopheles mosquito must feed at least twice; once to gain the pathogenic Plasmodium and a second time to transmit the disease. Host preference is the term for the propensity of a vector mosquito to feed on a particular host species. In malaria, the host preference for humans (anthropophily) rather than alternative hosts (zoophily) is crucial to human malaria epidemiology. Stable malaria is associated with strongly anthropophilic vectors that may never feed on other hosts. In these circumstances the probability of two consecutive meals being taken from a human is very high, and disease transmission can take place even when mosquito densities are low. In contrast, if the vector has a low rate of anthropophily (a low probability of human feeding) the probability of consecutive blood meals being taken from humans is slight and human malarial transmission by this particular vector is correspondingly low. Transmission will take place only when the vector is very numerous, as in epidemics of unstable malaria.
The frequency of feeding of the female Anopheles vector is important in disease transmission. This frequency can be estimated from mark—release—recapture data or from survey of the ovarian-age classes of indoor resting mosquitoes. Although it is assumed that one blood meal is needed to mature each batch of eggs, some mosquitoes may mature a first egg batch without a meal, and some anophelines require two meals. Already-infected vectors may experience difficulty in feeding to satiation at one meal, because of blockage of the feeding apparatus by parasites, and may probe many times. This, as well as disturbance during feeding by an irritated host, may lead to feeding on more than one host.
Even if an uninfected Anopheles feeds on an infectious host, either the mosquito may not acquire a viable infection, or the Plasmodium parasite may fail to replicate within the vector. Furthermore, the mosquito may not transmit the infection onwards at a subsequent meal. Thus, there is scope for substantial variation, both within and between species, in the competence to act as a disease vector. Allowance must also be made for the density, infective condition, and age profiles of the human population, as human immunity to malaria increases with age.
The vectorial capacity of a given Anopheles vector to transmit malaria in a circumscribed human population can be modeled. This involves a relationship between the:
- number of female mosquitoes per person;
- daily biting rate on humans;
- daily mosquito survival rate;
- time between mosquito infection and sporozoite production in the salivary glands;
- vectoral competence;
- some factor expressing the human recovery rate from infection.
This vectorial capacity must be related to some estimate concerning the biology and prevalence of the parasite when modeling disease transmission, and in monitoring disease control programs. In malarial studies, the infantile conversion rate (ICR), the rate at which young children develop antibodies to malaria, may be used. In Nigeria (West Africa), the Garki Malaria Project found that over 60% of the variation in the ICR derived from the human-biting rate of the two dominant Anopheles species. Only 2.2% of the remaining variation is explained by all other components of vectorial capacity, casting some doubt on the value of any measurements other than human-biting rate. This was particularly reinforced by the difficulties and biases involved in obtaining reasonably accurate estimates of many of the vectorial factors listed above.