Infectious disease: transmission and control

Transmission and the points at which it can be interrupted

An infectious disease persists only if its pathogen passes between hosts. Control therefore targets one or more parts of the transmission chain: the source of infection, the route between hosts, or host susceptibility. The most effective combination depends on the pathogen and its route of transmission.

The examples below are cholera (faecal-oral transmission), malaria (a mosquito vector), tuberculosis (airborne transmission) and HIV (infected body fluids). For each disease, distinguish prevention of transmission from treatment of an infected person.

Describe the drawing

A four-row table of case-study diseases. Cholera, caused by Vibrio cholerae, spreads in water and food contaminated with faeces. Malaria, caused by four Plasmodium species, spreads through the bite of an infected female Anopheles mosquito. Tuberculosis, caused by Mycobacterium tuberculosis and Mycobacterium bovis, spreads in coughed droplets and in unpasteurised milk. HIV spreads in body fluids through sex, shared needles and from mother to child. A note names the four Plasmodium species and singles out falciparum as the most dangerous.

The routes fall into a short list. Direct contact and body fluids: HIV passes only when infected fluid meets a mucous membrane or broken skin. Droplets: coughs and sneezes launch aerosols that another person inhales, which is how tuberculosis and influenza move through a shared room. Water and food: the faecal-oral route, where sewage reaches something that will be drunk or eaten, carries cholera. Vectors: an organism, usually biting, ferries the pathogen from blood to blood. Some pathogens add durable spores that wait in soil or dust for years, which is how tetanus enters a cut and how fungal diseases cross a field.

Transmission

The passage of a pathogen from an infected host to an uninfected one, directly or through an intermediate such as water, food or a vector.

Vector

An organism that carries a pathogen between hosts without suffering the disease itself; the female Anopheles mosquito is the vector of malaria.

Carrier (of infection)

An infected person with no symptoms who still sheds the pathogen and can pass it on.

Endemic

Describes a disease permanently established in a region or population, as malaria is across much of the tropics.

Living conditions multiply every route at once. Overcrowding shortens the distance a droplet has to travel; missing sanitation connects sewage to drinking water; malnutrition weakens the immune response that would otherwise end an infection early. These diseases therefore concentrate in the poorest places, and control measures are classified on an economic axis as well as a biological and a social one.

Cholera: faecal-oral transmission

Vibrio cholerae leaves one host in faeces and enters the next by mouth. Where sewage and drinking water are kept apart, cholera is close to impossible; where a flood, an earthquake or a war camp mixes them, one infected arrival can seed an epidemic within days, because a single water source serves thousands of mouths.

Two features increase transmission. Many infected people are carriers, shedding the bacterium with mild symptoms or none, so the number of sources exceeds the number of visible cases. And the watery diarrhoea produced by the toxin, several litres a day, contains large numbers of V. cholerae, which reaches the water supply where sanitation is absent.

The classic demonstration that control does not need a cure is John Snow's, in London in 1854, thirty years before the bacterium was identified. He mapped the cholera deaths of Soho, found them clustered around one public water pump in Broad Street, and had the pump handle removed, although deaths were already falling by then. Snow knew nothing about the organism; he had found the route.

Modern control is the same insight with better tools. The engineering that separates sewage from drinking water is expensive once and effective for a century. Oral vaccines exist and work, though protection fades within a few years, so they are used to blunt outbreaks and to protect travellers. And for whoever is infected anyway, oral rehydration solution turns a disease that can be fatal within a day into one that is usually survived, at very low cost.

Malaria: transmission by a mosquito vector

Four species of the protoctist Plasmodium cause almost all human malaria: P. falciparum, P. vivax, P. ovale and P. malariae. Falciparum is the dangerous one, responsible for most deaths; vivax and ovale can hide dormant in the liver and relapse months or years later; malariae runs the mildest, longest course. Name the four species and identify P. falciparum as the one causing most severe disease.

The parasite cannot pass from person to person. It needs two hosts, and the second is the female Anopheles mosquito, female because only females take blood meals. Biting an infected person, she takes up the parasite's sexual stages with the blood. They develop in her gut and then move to her salivary glands, which takes one to two weeks, and from then on every time she feeds the infective stages travel in with her saliva. In the person they multiply first in the liver, then in red blood cells, whose synchronised bursting gives the periodic waves of fever.

A two-host cycle gives control two targets, and the vector is the easier one. Insecticide-treated bed nets exploit the fact that Anopheles feeds mostly at night: the net blocks the bite, and the insecticide kills the mosquito that lands on it. Indoor spraying does the same for the walls she rests on after feeding. Draining or covering standing water removes the still pools her larvae need, and stocking ponds with larvae-eating fish is biological control in the strict sense, one organism deployed against another.

Resistance has developed to each antimalarial drug in turn. Artemisinin, isolated from sweet wormwood, is given as a combination with a second drug on purpose: a parasite carrying a mutation against one drug is still met by the other, so resistant lines are far slower to establish. Vaccines reached the clinic only in the 2020s and protect partially, because Plasmodium moves through liver, blood and mosquito stages that each present different antigens. The antigens therefore change with life stage as well as by mutation, which is a more difficult case than influenza's antigenic variation.

Describe the drawing

The malaria parasite's life cycle drawn as a single loop across a dashed vertical line that separates the person on the left from the mosquito on the right. Down the left: sporozoites go in with the saliva at a bite, multiply in liver cells, then in red blood cells that burst in step to give the fever, and gametocytes circulate. The loop crosses to the mosquito when those gametocytes are taken up in a blood meal by a female Anopheles, runs up her gut where gametes fuse and an oocyst develops, and reaches her salivary glands, from where it crosses back at the next bite. Four numbered control measures are set against the steps they interrupt: bed nets and spraying at the bite, larval control against the vector itself, artemisinin at the red cell stage and a partial vaccine at the liver stage. The four species are named, falciparum first as the dangerous one.

Tuberculosis: two species, two routes

Tuberculosis is caused by Mycobacterium tuberculosis, and also by Mycobacterium bovis, whose usual hosts are cattle. The two organisms give the disease two routes, and each route has its own control.

M. tuberculosis travels in droplets. An untreated person with active TB coughs the bacterium into shared air, and infection is a matter of dose and time. Hours in the same poorly ventilated room, night after night, is the classic setting, so the disease tracks overcrowded housing, prisons and shelters. Most people infected never become ill. The bacterium survives inside macrophages, walled into granulomas, and waits. Malnutrition, age or an untreated HIV infection can release it decades later, which is one of the ways the two pandemics feed each other.

Once the disease is active, the bacteria multiply, the centres of the granulomas break down and lung tissue is destroyed. The person has a persistent cough, sometimes bringing up blood, with fever, night sweats and weight loss. Untreated, the bacteria can spread to other organs, and the disease is often fatal.

M. bovis travels in unpasteurised milk and close contact with cattle. The control is agricultural rather than medical: herds are tested and infected animals slaughtered, and pasteurisation heats milk enough to denature the bacterium's proteins. In countries that do both, M. bovis disease in people has almost disappeared, an entire transmission route closed without a single patient treated.

Treatment exists and is long: a combination of antibiotics taken for six months or more, because the bacterium grows slowly and shelters inside cells. The length of the course creates a risk of resistance. A patient who stops at two months, when symptoms have gone, leaves behind the least susceptible bacteria, mutants that arose by chance, and the infection that relapses is resistant to those drugs. Multi-drug-resistant TB is the accumulated result, and control programmes respond by funding supervised courses, with a health worker watching each dose swallowed, rather than handing over a bottle of tablets. The BCG vaccine gives partial protection, strongest against severe childhood forms, so it contributes to a control programme without preventing all infection.

HIV: transmission in body fluids

The human immunodeficiency virus passes only in body fluids: unprotected sex, transfused blood and shared needles, and from mother to child in pregnancy, birth or breast milk. It does not survive drying, is not carried by insects and does not cross intact skin, so shaking hands, sharing cups and sharing air do not transmit it. Much of the stigma attached to the disease has followed from inaccurate beliefs about these boundaries.

Each route has a corresponding control. Condoms place a barrier between fluids. Donated blood is screened, subject to the testing-window limitation noted with ELISA. Needle exchanges supply sterile equipment to people who inject drugs, and substantially reduce transmission. Antiretroviral drugs given in pregnancy cut mother-to-child transmission from roughly one in four to under one in a hundred.

Antiretroviral drugs do not clear the infection. The virus integrates its genome into the T-helper cells that would coordinate a response against it, and replication resumes if the drugs are stopped. The drugs hold replication low enough that the immune system remains intact and AIDS does not develop. A person with a sustained undetectable viral load does not transmit the virus sexually, so treatment also functions as prevention.

There is at present no vaccine. The virus mutates its surface antigens rapidly within a single infected person, and it infects the T-helper cells on which a vaccine response would depend. With no cure and no vaccine, control acts on transmission, and global estimates of new infections have fallen since a peak in the 1990s.

The evolutionary race between pathogens and hosts

Pathogens and their hosts evolve in response to each other. A host whose defences destroy a pathogen more effectively is more likely to survive and reproduce, so selection favours better defences. A pathogen that escapes those defences reproduces and is transmitted more, so selection favours better evasion. Each change on one side alters the selection pressure on the other, and neither side stays ahead for long. This is the evolutionary race, also called an arms race. The two sides do not change at the same speed. A bacterium can divide in under an hour and one infected cell can release thousands of virus particles, while a human generation takes about 25 years. So most of the change that can be seen is on the pathogen's side.

Evolutionary race

The continuing coevolution of a pathogen and its host, in which better host defences select for better pathogen evasion, and the reverse.

Evasion mechanism

A feature of a pathogen that lets it avoid or survive the host's immune response, such as antigenic variation or surviving inside a phagocyte.

The evidence for the theory is the evasion mechanisms pathogens show. Each one only makes sense as the product of selection by an immune system: a way of escaping antibodies can only have been selected in a pathogen population that was exposed to antibodies. The four diseases in this lesson supply most of the cases examiners use.

Selection acts on the host too, and the clearest human example comes from malaria. The allele for sickle-cell haemoglobin causes sickle-cell disease in people with two copies, but people with one copy are partly protected against severe falciparum malaria. The allele is common where malaria has long been endemic and rare elsewhere, so the parasite has changed allele frequencies in human populations. The host's other answer works within one lifetime: the millions of different lymphocyte receptors produced in each person mean there is usually a lymphocyte complementary to a new antigen, even one that did not exist a year earlier.

Medicine has joined the race on the host's side. Each antibiotic and antimalarial drug is a new selection pressure, and resistance to each has followed. Vaccines and drugs can be changed far faster than human genes can, so the influenza vaccine is redesigned every year.

Biological, social and economic control measures

Every measure described above is biological, social or economic, and control programmes that rely on one category alone are less effective.

Describe the drawing

Three stacked panels sorting disease control measures onto axes. The biological panel lists vaccines including BCG for tuberculosis with none yet for HIV, antibiotics for the bacterial diseases, antiretroviral drugs, artemisinin combinations, insecticide-treated bed nets and pasteurising milk. The social panel lists clean water and sewage treatment, condoms and needle exchange, ventilated housing and contact tracing, testing and slaughtering infected cattle herds, and draining standing water. The economic panel lists funding TB courses and lifelong HIV drugs, subsidising nets and drugs, and investing in water infrastructure.

Biological measures act on the pathogen or its vector: vaccines, drugs, insecticides, fish that eat larvae, pasteurisation. Social measures change what people do and where they live: sanitation, ventilation, condom use, contact tracing, testing and slaughtering infected herds, education. Economic measures decide whether the first two happen at all: a net costs a few pounds and a sewage system costs millions, and the populations that need them most can afford them least.

The axes depend on one another. A bed net is a biological object; whether a family sleeps under it every night is social; whether they own one is economic. A six-month antibiotic course is biological; finishing it is social; being able to miss work for clinic visits is economic. Disease and poverty act on each other in both directions: illness reduces work and schooling, so expenditure on control has an economic return as well as a health benefit.

Malaria control: ethics, and how a method is validated

Every method of controlling endemic malaria has social and economic consequences, set out above. Most also raise ethical questions, about who bears the risk, who decides and who benefits, and none is adopted widely until the scientific community has tested it.

Insecticide spraying. DDT sprayed on the inside walls of houses was central to the eradication campaigns of the 1950s and 1960s, which removed malaria from several countries. DDT persists in the environment and accumulates along food chains, and it was banned for farm use in many countries from the 1970s. The Stockholm Convention of 2001 still allows it for indoor spraying against malaria vectors where no safe, effective and affordable alternative exists.

The ethical question has two parts. How should a known benefit to people at risk of a disease that kills children be weighed against harm to the environment and possible long-term effects on health? And who has the right to decide? Countries without malaria banned DDT, and some countries with it have argued for keeping it.

Drugs given to whole communities. Mass drug administration gives antimalarial drugs to everyone in an area, including people who are not ill, to clear the parasite from the population quickly. It exposes healthy people to side effects, raises the selection pressure for drug resistance, and needs consent from a whole community rather than from one patient.

Vaccines. The first malaria vaccines recommended for children, RTS,S in 2021 and R21 in 2023, protect only partly and need four doses. With a fixed budget, choosing between a partly effective vaccine and more bed nets decides which children are protected, which makes it an ethical decision as well as an economic one.

Genetically modified mosquitoes. Mosquitoes have been modified so that their offspring die or cannot carry the parasite, and gene drives are being developed that would spread such a change through a wild population. Released mosquitoes cannot be recalled and do not stop at borders, so a decision taken in one place affects people who were not consulted, and the effect on ecosystems of removing a mosquito species is uncertain.

Trials in people. New methods are tested where malaria is common, among people who are often poor and may have little health care outside the trial. Informed consent, what the control group receives, and whether the people who took part will have the method after the trial ends are the standard questions.

A control method is accepted only after the scientific community has tested it, in stages. It is tried in the laboratory and in small field trials, then in large field trials. Transmission happens across a whole community, so many malaria trials randomise whole villages or districts, not individuals. This is a cluster-randomised trial: some villages receive the new method, others continue with existing measures, and the number of cases, or of child deaths, is compared.

The results are submitted to a journal and checked by other scientists in the field before publication, which is peer review. One trial in one place is not enough, so trials are repeated in other countries and seasons, and systematic reviews pool the results of every comparable trial. Expert committees of the World Health Organization then review the whole body of evidence before recommending a method.

Insecticide-treated bed nets were validated this way. A series of community trials in several African countries in the 1990s found that they reduced deaths in children. Systematic reviews of those trials confirmed it, and the nets became a World Health Organization recommendation. Validation does not end there. Mosquitoes resistant to the insecticides on nets, and Plasmodium resistant to drugs, can make a validated method less effective, so resistance is monitored and the evidence is reviewed again.

Cluster-randomised trial

A trial in which whole groups, such as villages, are allocated at random to the new method or the comparison, used where a method acts on a community.

Peer review

The checking of a scientific paper's methods, results and conclusions by other scientists in the same field before it is published.

Mass drug administration

Giving a drug to everyone in an area, whether or not they are ill, to reduce transmission.