scrub typhus Like wild rodent plague, scrub typhus is a zoonosis in which humans are not involved. Well-defined areas, called mite islands, harbour rodents, mites and the Orientia, which is transmitted between them. A large number of rodents have been incriminated, including rats, and it is their system of burrows, runs and range of activity that determines the limit of the mite island. The rodents are fed upon by the larval stage of various Leptotrombiculid mites that need to take blood so that they can develop into a nymph and subsequently an adult. The larva climbs up on to grass or vegetation and awaits the passage of a rodent or any other passing mammal to which it attaches itself. Once it has fed, it drops off and continues its development in the soil. If during its feeding it sucks up O. tsutsugamushi, these develop in the nymph and adult and are passed on transovarially to infect the next generation of blood-sucking larvae. The mites appear unaffected by this infection, acting as a reservoir, hardly requiring the mammalian host except to provide a blood meal for their own continuity. Such is the balance of this arrangement that a mite island can persist undisturbed, causing harm to no one unless accidentally entered by humans. The larval mite will attack people just as it will attack birds and other mammals that come crashing through its hunting ground, transmitting the infection to its unusual host.

Scrub typhus is the disease of the wandering farmer, hunter or travelling army, passing through or camping in mite islands. These can be very small and localized or cover extensive areas, but generally, they are associated with transitional vegetation or fringe habitats, such as areas separating different vegetation zones (e.g. forest and grassland). Mite islands are nearly always the result of human activity, where forest is destroyed either for timber or in 'slash and burn' agriculture. The land regenerates as secondary growth, rats

Fig. 16.3. The transmission cycles and vectors of scrub, murine and epidemic

and other rodents move in and provide suitable conditions for the Leptotrombiculid mites.

murine typhus Scrub typhus has been given the alternative name of rural typhus, which adequately distinguishes it from urban typhus, the main characteristic of the flea-borne disease. Murine typhus is then a disease of towns and habitation, maintained there by domestic rodents, Rattus rattus and R. norvegicus. In contrast to scrub typhus, the mammal in murine typhus is the reservoir of the disease and the common rat flea X. cheopis acts only as a transmitter. Many other mammals have been found infected -mice, cats, opossums, shrews and skunks -but the key in all these alternative sites is always the domestic rat.

The flea becomes infected by biting the host, the infection appearing not to have any effect on the flea and does not shorten its lifespan. R. typhi is not transmitted by the bite of the flea, but is passed in its faeces. If infected faeces are rubbed into an abrasion or inhaled as an aerosol, other rats become infected. The body of the flea is also highly contagious and if crushed, the organism is liberated. While X. cheopis is the main vector, the organism has been isolated from Pulex irritans, the common human flea, lice, mites and ticks. These probably do not form an important means of transmission, but could explain epidemics where X. cheopis is not found.

Humans are infected by their close association with domestic rodents. When a flea is squashed or scratched into an abrasion, its tissue juices or faeces contaminate the wound. The habit of some people when catching fleas of crushing them between their teeth is also a potential method of infection. However, it would seem that the direct attack by the essentially healthy rat flea is uncommon and the more important method of transmission is from an aerosol of organisms in the flea faeces. These are carried on the rats' fur or sent into the air when disturbed. R. typhi can be inhaled, swallowed or enter through other mucus membranes, such as the conjunctiva. Murine typhus is common where rats live in constant contact with humans.

epidemic typhus While scrub typhus and murine typhus are zoonoses, epidemic typhus is an infection where only humans and the body louse, Pediculus humanus corporis, are involved. The louse can spend its entire life cycle on the same host, laying its eggs in the seams of clothing and finding all the food and shelter it requires. Female lice lay some 5-10 eggs per day, which hatch in 6-9 days depending on temperature. If the clothes are kept on the body, then the temperature is maintained and hatching takes place rapidly, but if they are removed and cooled down, development may take 2-3 weeks. One month is the maximum period they can survive, so clothes that are not worn for this length of time will be free of lice.

The egg hatches into a nymph, which in all respects resembles a small adult, and sucks blood. Three nymphal stages are passed through before it becomes an adult louse. Lice, both males and females, can only survive by taking blood meals and if deprived, can last no longer than 10 days. They are sensitive to temperature and will abandon a dead person as well as one with a high fever. The lifespan of an adult louse is about 1 month and during this time, a female may lay some 200-300 eggs.

R. prowazekii is ingested in the blood meal and can infect both males, females and all nymphal stages. The rickettsiae develop in the epithelial lining cells of the stomach, which they distend to such an extent that rupture takes place, liberating them back into the damaged gut lumen. These are then passed into the louse faeces in which they can survive for 100 days or more. The damage caused to the louse can be sufficiently severe to kill it within 10 days and this helps to explain why few lice are found on a person suffering from typhus.

Humans become infected by scratching the louse faeces into abrasions or the puncture wound left by the feeding parasite, or if the lice is crushed on the skin or in the mouth. Dried lice faeces can remain viable for a considerable period of time and fine particles that are inhaled or enter the conjunctiva can be a potential hazard to those not infested with lice.

Lice thrive in conditions of deprivation and poverty, where clothing is worn without changing and people live in close proximity to each other. Lice cannot travel far, or survive for long without a blood meal, so it is the crowding together of people that allows lice to crawl across and infest a new host. Where clothing is changed or washed, or the ambient temperature is high, body lice do not occur and typhus is not found. But, in times of human disruption brought about by war, famine or social upheaval, the crowding together of people, in conditions of poor sanitation, provides the stage for an outbreak of typhus. A similar situation can occur in the highland areas of tropical countries, where people live close to each other to keep warm.

Various claims have been made for nonhuman reservoirs of R. prowazekii, but humans appear to be an adequate reservoir and the louse an ideal vector. The difficulty is what happens to the organism when an epidemic has subsided? The probable answer is found in Brill-Zinsser disease, more suitably called recurrent typhus. In this condition, people are found to have R. prowazekii in their bodies long after they had the disease. The organism remains dormant until some event causes a breakdown in host resistance and overt disease reappears. Cases have been found 20 and 40 years after the person was in a typhus area and where lice have been absent for this length of time. But if lice are fed on these cases, they become infected and can transmit epidemic typhus.

Incubation period is 1-2 weeks (up to 3 weeks in scrub typhus). The incubation period is related to the infecting dose.

Period of communicability Lice can become infected during the febrile illness, which may last for 2 weeks, but since lice will leave a febrile person, it is probably only during the earlier part of the illness. A chronic carrier (with Brill-Zinsser disease) can infect lice for up to 40 years. Lice excrete rickettsiae 2-6 days after an infected blood meal, but continue to be a source of infection for weeks after they have died. Fleas in murine typhus remain infected for life (about 1 year).

Occurrence and distribution Like plague, typhus is a disease of history, particularly associated with the conflicts of man. When the anger of man causes war, disruption of civilizations, famine and refugees, then the disease of war, typhus, enters into the attack. At the present time, it is a particular risk of refugee camps.

Epidemic typhus can occur in highland areas, particularly during the rainy season with outbreaks occurring in Rwanda, Burundi, Ethiopia, Guatemala, Bolivia and Peru. The three countries in Africa have reported the most cases in recent times.

Murine typhus is endemic in Pakistan, India and the Malaysian peninsula, but may become epidemic in any part of the world where rats are found, such as in ports.

'Mite or typhus islands' are found in East, South and Southeast Asia, including Siberia, China, Japan, Thailand, Pakistan, Australia and Pacific Islands.

Control and prevention of scrub typhus is by the wearing of clothing treated with repellents or insecticides to prevent the larval mite from attacking humans. Long trousers tucked into boots with high lace-up sides, or gaiters to cover the gap, impregnated with diethyltoluamide, dimethylphthalate or a synthetic pyrethroid. Repellents should also be smeared on to arms and necks because it is these sites that are attacked when working in the undergrowth. If an area of scrub typhus is known and it is desired to clear it permanently, then the undergrowth should be cut down and burnt, leaving the ground to thoroughly dry out before being safe to use. A less permanent method is to spray the area with insecticides. Tetracycline can be taken as a prophylactic by those at particular risk, but such methods are never reliable.

Control of murine typhus is the same as forplague (Section 16.1) where the subject is covered in more detail. Essentially, it is the control of fleas and rats with the use of insecticide powders to kill the fleas first,

Box 16.1 Rat control.

The control of rats can be by cats, traps or poisoning. Rat protection with shields and guards should be used after rats have been removed. A well-trained cat can be most efficient. Trapping is an effective means of rat control if carried out properly. Traps can be made out of scrap pieces of metal and are, therefore, simply manufactured in developing countries. A knowledge of the rat runs is gained and the trap left baited, but unsprung. Once the bait has been taken, then the trap is set. Traps must be visited regularly, all dead rats disposed of (by burning) and set again.

Poisoning can be either with acute or chronic poisons. The number of poisons is considerable and where available, it is preferable to solicit professional advice. Poisons strong enough to kill rats are also able to kill other animals that may consume them. They are also dangerous to humans, especially children, so proper safety precautions must be observed. Zinc phosphate is a useful acute poison. A good bait should be used, such as broken maize or rice mixed in a proportion of 1:10 using cooking oil to dissolve it. Alternatively, it can be mixed with water and bait, then dried out before applying to the traps. There is a danger from the dust and gases produced when preparing baits, so mask and gloves should be used. Copper sulphate is an antidote and can be administered in 0.25g portions orally, every 10min until vomiting is induced. The most commonly used chronic poison is Warfarin, which is mixed with bait in a ratio of 1:19. With chronic poisons, the baitshould first be placed and only if it is taken, mixed with poison on subsequent applications. Gassing is very effective as it kills both rats and fleas at the same time, but strict precautions must be observed. Rodents living in burrows can be gassed, blocking all exits; hydrogen cyanide gas is most commonly used.

followed by measures against rats. Buildings should be protected against re-infestation and new structures built with rat-proofing (Box 16.1).

Control of epidemic typhus is control of the louse. In an epidemic, this is most effectively done by blowing an insecticide powder into people's clothing. This can be by a blower with a long nozzle that is pushed up the arms of clothing, down through necks and up trousers and skirts. The clothing should be thoroughly treated remembering that the lice live between the underclothing and body. Temephos (2%), propoxur (1%), permethrin (0.5%) or other synthetic pyr-ethroids can be used. Samples of lice should be tested for insecticidal resistance before and during mass treatments. Since it is conditions of overcrowding that generate epidemics, it is often not too difficult to disinfect large numbers of people in a comparatively short time. Dead bodies should be dusted with insecticides before burial. A long-term preventive method is to treat underclothing with insecticides in the same way as mosquito nets are treated, to give a target dose of 0.65-1 g/m2 permethrin. Clothes can be washed, but treatment should be repeated every 6 weeks.

Prophylactic antibiotics, generally tetracycline, can be given to contacts to reduce the extent of the reservoir. Treatment centres should be set up to discover cases early and antibiotics given.

Vaccines have been successful in controlling epidemics, but they suffer from various disadvantages. A killed vaccine (Cox) is painful when injected and does not give complete immunity, whereas a live, attenuated vaccine appears to give solid immunity for over 5 years, but must be prepared carefully as virulence can increase. Vaccines can either be used for mass administration in the face of epidemics or be given to individuals at increased risk, such as medical personnel.

In the long term, typhus will only disappear when all lice are removed. People should be encouraged to wash themselves and their clothes. Clothes must be boiled or washed at over 70°C, which is a higher temperature than most washing machines achieve. Ironing clothes kills both adults and eggs.

Treatment should be commenced as soon as possible, even before the diagnosis is confirmed, as speed is of the essence if treatment is to be effective. A single dose of

200 mg doxycycline, irrespective of age, is the treatment of choice. Alternatively, tetracycline at a dose of 500 mg four times a day may be given, and where both of these are unavailable, chloramphenicol may be used. Careful nursing is of utmost importance.

Surveillance is the cornerstone of prevention by conducting louse surveys at clinics, prisons, institutions and collections of people. Cases of proven or suspect epidemic louse-borne typhus should be notified to WHO. All contacts of a case should be placed under surveillance for 14 days.

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