Infectious diseases, tropical medicine and sexually transmitted infections

Chapter 4 Infectious diseases, tropical medicine and sexually transmitted infections




INFECTION AND INFECTIOUS DISEASE 











VIRAL INFECTIONS 


















































SEXUALLY TRANSMITTED INFECTIONS 













Infection and infectious disease


‘Infection’ is defined as the process of foreign organisms invading and multiplying in or on a host. In practice, the term is usually reserved for situations in which this results in harm, rather than an infectious agent simply colonizing the host without ill effect. Infectious diseases remain the main cause of morbidity and mortality in man, particularly in developing areas where they are associated with poverty and overcrowding.


In the developed world increasing prosperity, universal immunization and antibiotics have reduced the prevalence of infectious disease. However, antibiotic-resistant strains of microorganisms and diseases such as human immunodeficiency virus (HIV) infection, variant Creutzfeldt–Jakob disease (vCJD), avian influenza and pandemic H1N1 influenza have emerged. There is increased global mobility, both enforced (as a result of war, civil unrest and natural disaster) and voluntary (for tourism and economic benefit). This has aided the spread of infectious disease and allowed previously localized pathogens such as dengue and West Nile virus to establish themselves across much wider territories. An increase in the movement of livestock and animals has enabled the spread of zoonotic diseases like monkeypox, while changes in farming and food-processing methods have contributed to an increase in the incidence of food- and water-borne diseases. Deteriorating social conditions in the inner city areas of our major conurbations have facilitated the resurgence of tuberculosis and other infections. Prisons and refugee camps, where large numbers of people are forced to live in close proximity, often in poor conditions, are providing a breeding ground for devastating epidemics of infectious disease. There are new concerns about the deliberate release of infectious agents such as smallpox or anthrax by terrorist groups or national governments.


In the developing world successes such as the eradication of smallpox have been balanced or outweighed by the new plagues. Infectious diseases cause nearly 25% of all human deaths (Table 4.1), rising to more than 50% in low income countries. Two billion people – one-third of the world’s population – are infected with tuberculosis (TB), up to 400 million people catch malaria every year and 200 million are infected with schistosomiasis. Some 500 million people are chronically infected with a hepatitis virus (either HBV or HCV) and 34 million people are living with HIV/AIDS, with 2.6 million new HIV infections in 2008 (65% in sub-Saharan Africa). Infections are often multiple and there is synergy both between different infections and between infection and other factors such as malnutrition. Many of the infectious diseases affecting developing countries are preventable or treatable, but continue to thrive owing to lack of money and political will.


Table 4.1 Worldwide mortality from infectious diseases







































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.






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 PrPc into an abnormal protease-resistant isoform referred to as PrPSc.


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.




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












Prevention and control


Methods of preventing infection depend upon the source and route of transmission, as described above.



image Infection control measures. Poor infection control practice in hospitals and other healthcare environments can cause the transfer of infection from person to person. This may be air-borne, via fomites or a direct contact route. It is essential that all healthcare workers wash or clean their hands before and after patient contact and whenever necessary they should wear gloves, aprons and other protective equipment. This is particularly necessary when performing invasive procedures, or manipulating indwelling devices such as cannulae.



image Eradication of reservoir. In a few diseases, for which man is the only natural reservoir of infection, it may be possible to eliminate disease by an intensive programme of case finding, treatment and immunization. This has been achieved in the case of smallpox. If there is an animal or environmental reservoir, complete eradication is unlikely, but local control methods may decrease the risk of human infection (e.g. killing of rodents to control plague, leptospirosis and other diseases).









image Immunization (see p. 94).




Healthcare-associated infections (HCAI)

In recent years, the burden of morbidity, mortality and cost attributed to healthcare-associated infection has been highlighted in many developed countries. Although data from low income countries are lacking the impact of HCAI is likely to be even greater. Clostridium difficile, Staphylococcus aureus (especially MRSA), vancomycin-resistant enterococci and multiresistant Gram-negative organisms are all strongly associated with healthcare contact and are an increasing problem in hospitals worldwide. In the UK, the Department of Health estimates the risk of acquiring HCAI in a healthcare facility to be 6–10%, with HCAIs costing the NHS up to £1 billion per year. The response to HCAIs needs to be multifaceted. High standards of basic infection control (isolation, barrier precautions, hand hygiene and cleaning) need to be combined with decreased use of invasive devices such as vascular cannulae and urinary catheters, with better insertion and care standards when these are used. Antibiotic stewardship, with reduced overall usage and restriction of broad-spectrum agents, is essential to minimize antimicrobial resistance. There are already data to suggest that reduction in the use of cephalosporins has reduced the incidence of C. difficile. Often a combination of different methods can be used together to reduce a particular risk (e.g. ventilator-associated pneumonia): the so-called ‘care bundle’ approach.




Classification of outbreaks

The type of outbreak has a bearing on public health measures that need to be instituted for its control.



Cases of some infectious diseases should be notified to the public health authorities so that they are aware of cases and outbreaks. Diseases that are notifiable in England and Wales are listed in Table 4.5.


Table 4.5 Diseases notifiable (to Local Authority Proper Officers) in England and Wales, under the Health Protection (Notification) Regulations 2010












Principles and basic mechanisms


Man constantly interacts with the world of microorganisms from birth to death. The majority cause no harm and some play a role in the normal functioning of the mouth, vagina and intestinal tract. However many microorganisms have the potential to produce disease. This may result from inoculation into damaged tissues, tissue invasion, a variety of virulence factors, or toxin production.





Pathogenesis


Figure 4.2 summarizes some of the steps that occur during the pathogenesis of infection. In addition, pathogens have developed a variety of mechanisms to evade host defences. For example, some pathogens produce toxins directed at phagocytes: Staphylococcus aureus (α-toxin), Streptococcus pyogenes (streptolysin) and Clostridium perfringens (α-toxin), while others such as Salmonella spp. and Listeria monocytogenes can survive within macrophages. Several pathogens possess a capsule that protects against complement activation (e.g. Strep. pneumoniae). Antigenic variation is an additional mechanism for evading host defences that is recognized in viruses (antigenic shift and drift in influenza), bacteria (flagella of salmonella and gonococcal pili) and protozoa (surface glycoprotein changes in Trypanosoma).






Tissue dysfunction or damage

Microorganisms produce disease by a number of well-defined mechanisms:





Exotoxins and endotoxins





Staphylococcus aureus presents an excellent example of the repertoire of microbial virulence. The clinical expression of disease varies according to site, invasion and toxin production and is summarized in Table 4.6. Furthermore, host susceptibility to infection may be linked to genetic or acquired defects in host immunity that may complicate intercurrent infection, injury, ageing and metabolic disturbances (Table 4.7).


Table 4.6 Clinical conditions produced by Staphylococcus aureus







Table 4.7 Examples of host factors that increase susceptibility to staphylococcal infections (predominantly Staphylococcus aureus)












a Often Staphylococcus epidermidis.




Metabolic and immunological consequences of infection






The inflammatory response


The inflammatory response is a fundamental biological response to a variety of stimuli including microorganisms or their products, such as endotoxin which acts on monocytes and macrophages. Non-phagocytic cells (lymphocytes, natural killer cells) are also involved. The release of cytokines, notably TNF-α, IL-1, IL-6 and interferon-γ, leads to the release of a cascade of other mediators involved in inflammation and tissue remodelling, such as interleukins, prostaglandins, leukotrienes and corticotropin. TNF is therefore responsible for many of the effects of an infection.


The biological behaviour of the pathogen and the consequent host response are responsible for the clinical expression of disease that often allows clinical recognition. The incubation period following exposure can be helpful (e.g. chickenpox 14–21 days). The site and distribution of a rash may be diagnostic (e.g. shingles), while symptoms of cough, sputum and pleuritic pain point to lobar pneumonia. Fever and meningismus characterize classical meningitis. Infection may remain localized or become disseminated and give rise to the sepsis syndrome and disturbances of protein metabolism and acid–base balance (see Ch. 16). Many infections are self-limiting and immune and non-immune host defence mechanisms will eventually clear the pathogens. This is generally followed by tissue repair, which may result in complete resolution or leave residual damage.




Approach to the patient with a suspected infection


Infectious diseases can affect any organ or system and can cause a wide variety of symptoms and signs. Fever is often regarded as the cardinal feature of infection, but not all febrile illnesses are infections and not all infectious diseases present with a fever. History-taking and examination should aim to identify the site(s) of infection and also the likely causative organism(s).




Mar 31, 2017 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Infectious diseases, tropical medicine and sexually transmitted infections
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