Disease	Estimated deaths (annual)
Acute lower respiratory infection	3.5 million
HIV/AIDS	2 million
Tuberculosis	2 million
Diarrhoeal disease	1.8 million
Malaria	1 million
Measles	350 000
Whooping cough	301 000
Tetanus	292 000
Meningitis	175 000
Leishmaniasis	51 000
Trypanosomiasis	10 000

The WHO has set eight Millennium Development Goals (MDGs), to be achieved by 2015: these include combating HIV/AIDS, malaria and other diseases. Currently, nine African and 29 non-African countries are on course to meet the malaria targets and the global incidence of TB is slowly falling. New HIV infections fell by 16% between 2000 and 2008 and antiretroviral treatment provision in low and middle income countries increased 10-fold between 2003 and 2008. A public/private partnership, the Global Fund, was established to combat AIDS, tuberculosis and malaria and has achieved much by providing the means for treatment for TB, insecticide-treated bed nets for malaria and antivirals for HIV. Several other funding streams (governmental, non-governmental and charitable) have also contributed to the fight against infection.

The impact of global warming on the spread of infection remains uncertain but may be significant. Both natural climatic events and the gradual global change in weather conditions can affect the spread and transmission of infectious diseases. Changes in temperature may directly influence the behaviour of insect vectors, while changes in rainfall may have an effect on water-borne disease. Climate change may also trigger population movement and migration, indirectly affecting infection transmission.

FURTHER READING

Byass P, Graham WJ. Grappling with uncertainties along the MDG trail. Lancet 2011; 378:1119–1120.

Infectious agents

The causative agents of infectious diseases can be divided into four groups:

Prions are the most recently recognized and the simplest infectious agents, consisting of a single protein molecule. They contain no nucleic acid and therefore no genetic information: their ability to propagate within a host relies on inducing the conversion of endogenous prion protein PrP^c into an abnormal protease-resistant isoform referred to as PrP^Sc.

Viruses contain both protein and nucleic acid and so carry the genetic information for their own reproduction. However, they lack the apparatus to replicate autonomously, relying instead on ‘hijacking’ the cellular machinery of the host. They are small (usually less than 250 nanometres (nm) in diameter) and each virus possesses only one species of nucleic acid (either RNA or DNA).

Bacteria are usually, though not always, larger than viruses. Unlike the latter they have both DNA and RNA, with the genome encoded by DNA. They are enclosed by a cell membrane and even bacteria which have adopted an intracellular existence remain enclosed within their own cell wall. Bacteria are capable of fully autonomous reproduction and the majority are not dependent on host cells.

Eukaryotes are the most sophisticated infectious organisms, displaying subcellular compartmentalization. Different cellular functions are restricted to specific organelles, e.g. photosynthesis takes place in the chloroplasts, DNA transcription in the nucleus and respiration in the mitochondria. Eukaryotic pathogens include unicellular protozoa, fungi (which can be unicellular or filamentous) and multicellular parasitic worms.

Other higher classes, notably the insects and the arachnids, also contain species which can parasitize man and cause disease: these are discussed in more detail on page 160.

Host–organism interactions

Each of us is colonized with huge numbers of microorganisms (10¹⁴ bacteria, plus viruses, fungi, protozoa and worms) with which we co-exist. The relationship with some of these organisms is symbiotic, in which both partners benefit, while others are commensals, living on the host without causing harm. Infection and illness may be due to these normally harmless commensals and symbiotes evading the body’s defences and penetrating into abnormal sites. Alternatively, disease may be caused by exposure to exogenous pathogenic organisms which are not part of our normal flora.

The symptoms and signs of infection are a result of the interaction between host and pathogen. In some cases, such as the early stages of influenza, symptoms are almost entirely due to killing of host cells by the invading organism. Usually, however, the harmful effects of infection are due to a combination of direct microbial pathogenicity and the body’s response to infection. In meningococcal septicaemia, for example, much of the tissue damage is caused by cytokines released in an attempt to fight the bacteria. The molecular mechanisms underlying host-pathogen interactions are discussed in more detail on page 78.

Sources of infection

The endogenous skin and bowel commensals can cause disease in the host, either because they have been transferred to an inappropriate site (e.g. bowel coliforms causing urinary tract infection) or because host immunity has been attenuated (e.g. candidiasis in an immunocompromised host). Many infections are acquired from other people, who may be symptomatic themselves or be asymptomatic carriers. Some bacteria, like the meningococcus, are common transient commensals, but cause invasive disease in a small minority of those colonized. Infection with other organisms, such as the hepatitis B virus, can be followed in some cases by an asymptomatic but potentially infectious carrier state.

Zoonoses are infections that can be transmitted from wild or domestic animals to man. Infection can be acquired in a number of ways: direct contact with the animal, ingestion of meat or animal products, contact with animal urine or faeces, aerosol inhalation, via an arthropod vector or by inoculation of saliva in a bite wound. Many zoonoses can also be transmitted from person to person. Some zoonoses are listed in Table 4.2.

Table 4.2 Zoonotic infections

Most microorganisms do not have a vertebrate or arthropod host but are free-living in the environment. The vast majority of these environmental organisms are non-pathogenic, but a few can cause human disease (Table 4.3). Person-to-person transmission of these infections is rare. Some parasites may have a stage of their life cycle which is environmental (e.g. the free-living larval stage of Strongyloides stercoralis and the hookworms), even though the adult worm requires a vertebrate host. Other pathogens can survive for periods in water or soil and be transmitted from host to host via this route (see below): these should not be confused with true environmental organisms.

Table 4.3 Environmental organisms which can cause human infection

Organism	Disease (most common presentations)
Bacteria
Burkholderia pseudomallei	Melioidosis
Burkholderia cepacia	Lung infection in cystic fibrosis
Pseudomonas spp.	Various
Legionella pneumophila	Legionnaires’ disease (pneumonia)
Bacillus cereus	Gastroenteritis
Listeria monocytogenes	Various
Clostridium tetani	Tetanus
Clostridium perfringens	Gangrene, septicaemia
Mycobacteria other than tuberculosis (MOTT)	Pulmonary infections
Fungi
Candida spp.	Local and disseminated infection
Cryptococcus neoformans	Meningitis, pulmonary infection
Histoplasma capsulatum	Pulmonary infection
Coccidioides immitis	Pulmonary infection
Mucor spp.	Mucormycosis (rhinocerebral, cutaneous)
Sporothrix schenckii	Lymphocutaneous sporotrichosis
Blastomyces dermatitidis	Pulmonary infection
Aspergillus fumigatus	Pulmonary infections

Routes of transmission

Endogenous infection

The body’s own endogenous flora can cause infection if the organism gains access to an inappropriate area of the body. This can happen by simple mechanical transfer, e.g. colonic bacteria entering the female urinary tract. The nonspecific host defences may be breached, for example, by cutting or scratching the skin and allowing surface commensals to gain access to deeper tissues; this is frequently the aetiology of cellulitis. There may be more serious defects in host immunity owing to disease or chemotherapy, allowing normally harmless skin and bowel flora to produce invasive disease.

Air-borne spread

Many respiratory tract pathogens are spread from person to person by aerosol or droplet transmission. Secretions containing the infectious agent are coughed, sneezed or breathed out and are then inhaled by a new victim. Some enteric viral infections may also be spread by aerosols of faeces or vomit. Environmental pathogens such as Legionella pneumophila and zoonoses such as psittacosis, are also acquired by aerosol inhalation, while rabies virus may be inhaled in the dust from bat droppings.

Faeco-oral spread

Transmission of organisms by the faeco-oral route can occur by direct transfer (usually in small children), by contamination of clothing or household items (usually in institutions or conditions of poor hygiene) or most commonly via contaminated food or water. Human and animal faecal pathogens can get into the food supply at any stage. Raw sewage is used as fertilizer in many parts of the world, contaminating growing vegetables and fruit. Poor personal hygiene can result in contamination during production, packaging, preparation, or serving of foodstuffs. In the western world, the centralization of food supply and increased processing of food has allowed the potential for relatively minor episodes of contamination to cause widely disseminated outbreaks of food-borne infection.

Water-borne faeco-oral spread is usually the result of inadequate access to clean water and safe sewage disposal and is common throughout the developing world. Worldwide, 1.1 billion people have no access to clean water and 2.6 billion do not have basic sanitation.

Vector-borne disease

Many tropical infections, including malaria, are spread from person to person or from animal to person by an arthropod vector. Vector-borne diseases are also found in temperate climates, but are relatively uncommon. In most cases part of the parasite life cycle takes place within the body of the arthropod and each parasite species requires a specific vector. Simple mechanical transfer of infective organisms from one host to another can occur, but is rare. Some vector-borne diseases are shown in Table 4.4.

Table 4.4 Infections transmitted by arthropod vectors

Vector	Disease	Microorganism
Mosquito	Malaria	Plasmodium spp.
	Lymphatic filariasis	Wuchereria bancrofti, Brugia malayi
	Yellow fever	Flavivirus
	West Nile fever	Flavivirus
	Dengue	Flavivirus
Sandfly	Leishmaniasis	Leishmania spp.
Blackfly	Onchocerciasis	Onchocerca volvulus
Tsetse fly	Sleeping sickness	Trypanosoma brucei
Flea	Plague	Yersinia pestis
	Endemic typhus	Rickettsia typhi
	Carrion’s disease	Bartonella bacilliformis
Reduviid bug	Chagas’ disease	Trypanosoma cruzi
Louse	Epidemic typhus	Rickettsia prowazekii
Louse	Louse-borne relapsing fever	Borrelia recurrentis
Hard tick	Lyme disease	Borrelia burgdorferi
	Typhus (spotted fever group)	Rickettsia spp.
	Babesiosis	Babesia spp.
	Tick-borne relapsing fever	Borrelia duttonii
	Tick-borne encephalitis	Flavivirus
	Congo-Crimean haemorrhagic fever	Nairovirus (Bunyavirus)