Contagious bovine pleuropneumonia is a directly transmitted disease. Closeness of contact, intensity of infection and the number of susceptible animals determine the rate of spread of the disease. Large numbers of MmmSC are present in bronchial secretions, nasal discharges and exhaled air and are transmitted to susceptible animals in close contact by droplets emanating from either cattle with clinical disease or subclinical carriers that are actively excreting the organism. Closely stabled or trucked animals are therefore most prone to infection. However, aerosols containing infected droplets may spread the disease over distances of 20 m or more. In extensive sub-Saharan African farming conditions spread of the disease may nevertheless be rapid, facilitated by the common practice of penning the animals at night, and when large numbers of animals mingle at places such as watering points or live markets.

Transmission depends upon direct contact between infected and susceptible animals, with fomites apparently playing no role in the spread of the disease. Healthy animals introduced into crushes, sales yards or vehicles that have previously been occupied by infected animals do not become infected. Transmission does not occur through ingestion of contaminated feed or direct exposure to the organs of animals that have died of CBPP. Since the organisms may be excreted in the urine of severely diseased cattle, inhalation of aerosol droplets of infected urine may cause infection. The organism has also been isolated from semen but venereal transmission requires further investigation.

Apart from shedding of MmmSC by clinically ill animals, there are other sources of infection. Cattle in the incubatory phase of the disease may harbour MmmSC in their nasal passages for 40 days prior to developing clinical signs or antibodies and are considered to be a potent source of infection. It has also been postulated that recovered animals with sequestra in their lungs might pose a risk for infection, since viable MmmSC has been isolated from sequestra for up to 12 months. As long as the bacteria remain encapsulated by fibrous tissue in the intact sequestrum the animal will not be infective, but it is postulated that sequestra might rupture and permit shedding of the bacteria and consequent transmission of the disease. This is obviously difficult to reproduce. Most of the support for the contention that these animals play a role in transmission is based on attempts to explain outbreaks that have occurred when no obvious source of introduction could be identified and on models based on assumptions of infectivity, but limited experimental work suggested that carriers, if infectious at all, would only occasionally transmit the disease.

The intensity of infection is determined by the concentration of infective organisms in a herd at a given time. It is highest during an acute outbreak but low intensities of infection, which may occur in the early stages of an outbreak and result in slower spread, are more complicated for control and account for the insidious nature of CBPP. Low intensities of infection also result later in an outbreak when only the clinically sick animals in a herd are treated with antimicrobials.

Not all cattle within a herd are equally susceptible to CBPP, and from 10 to 60 per cent of the cattle may be naturally resistant to it, and an even lower number of animals may develop clinical signs. Animals that survive outbreaks have substantial resistance, and in a closed herd, although it may take a long time, the disease may disappear completely, leaving only the young, new calves susceptible. However, studies in pastoral cattle in East Africa suggest that CBPP would persist indefinitely even in an isolated herd of the size typical for the area. In Africa herds are rarely closed, with considerable between-herd movement and contact, and new introductions are therefore probably common. It was observed that young calves that were infected developed arthritis, particularly of the carpal and tarsal joints and it was believed that they did not develop pneumonia. However, in the 1995 Botswana outbreak, which occurred in fully naïve cattle, calves aged three to six months developed severe lung lesions, and it is probable that calves in endemic situations are protected by colostral immunity that slowly wanes. In mixed crop-livestock systems in East Africa it was also observed that the calves are generally kept away from the rest of the herd except when suckling and therefore are at lower risk of exposure.

There is no evidence that MmmSC causes clinical disease in any species other than cattle under natural conditions. The disease is abortive in water buffaloes although seroconversion occurs, and transmission to cattle from this species has not been demonstrated. Natural infection has been demonstrated in goats by recovery of the agent from their lungs but experimental inoculation suggested that their susceptibility to the disease is low, and the fact that CBPP was eradicated from Botswana by culling only the cattle, although large numbers of goats are present in the affected area, suggests that they do not serve as a reservoir for the disease. Surveillance for CBPP in goats in countries free of the disease has, however, been suggested based largely on the resurgence of CBPP in southern Europe in the 1980s and 90s from a source that has never been identified. Molecular genetic characterization of the mycoplasmas isolated during those outbreaks demonstrated conclusively that the disease was not introduced from Africa or Asia and must therefore have originated from one or more unknown reservoirs of infection in the affected area. The disease has never been recorded in wild ruminants and it is believed that positive serology from various wild species using the complement fixation test (CFT) was due to cross reactions with other mycoplasmas. Two African buffaloes experimentally infected with MmmSC died after seroconverting with high antibody titres but did not develop lesions of CBPP so that the cause of death was questionable.