Related to Horton Hospital Malaria Therapy Unit
Description:

‘We desire [in this report] to refer... to an entirely new field of enquiry which has lately become available in Europe and which, if scientifically tilled and harvested, promises to yield fruitful results. We refer, of course, to the field of enquiry opened up by the use of malaria as a method of treatment. The Commission is unanimously of opinion that, both in the immediate interest of the patients who undergo that treatment and in the ultimate interest of the millions of malaria sufferers in the world at large, it is essential that, in each country where the method is used, there should be central expert control and an officially organised arrangement by which a pure strain of a relatively innocuous organism cultivated in mosquitoes would be available for use. This means that a laboratory shall be established for the continuous provision of infected mosquitoes and that there shall be an official arrangement by which an expert member of the laboratory staff shall take the infected insects personally to the hospitals in which patients are to be treated, and shall have facilities for studying the course of the malarial attacks in those persons. We suggest that, wherever possible, the work in this laboratory should be carried out in close collaboration with the laboratory situated in the same district as the [a] malarious locality which has been selected for continuous routine observations of the natural course of the disease [recommended above] [10-11] among the general population. In this way, the factors concerned in the seasonal onset, course and decline of the natural disease (benign tertian, at least) among the population could be correlated with the more exact records of infection of anopheles month by month in the laboratory and the clinical manifestations of infected patients in the hospital. We can imagine no scheme of enquiry which would be likely to give more profitable results from the practical point of view, and no scheme which, in the present state of knowledge, would better justify the initial and recurring expense involved.’ (10-11)

 

‘Section II.

Arrangements for Studying Malaria

1. The Study of Artificial Infection of Mosquitoes and Man.

In the preceding Section, we stated the Commission’s opinion that the scientific study of malaria in all its aspects must be continuously pursued. To this end we recommended: (1) The establishment in each country of a laboratory for the provision of infected mosquitoes, which could be used, under expert supervision, for the malaria treatment of certain diseases; (2) the establishment in one or two malarious areas in each country an “observation station”, where certain routine epidemiological enquiries should be made at regular short intervals.

We hope that co-ordinated study along these two lines will be pursued continuously in every European country where necessary arrangements can be made. As a guide to those arrangements, we shall describe in this Section two or three of the laboratories and observational stations which members of the Commission visited during their European tours.

We shall begin by giving a brief account of the arrangements which have been made in England for the continuous provision of a supply of mosquitoes for inducing a pure infection in benign tertian malaria in patients to be treated. The work provides an opportunity of studying the clinical and parasitological features of malaria contracted in the natural way, as well as the circumstances governing the infection of mosquitoes and the factors which influence the persistence of the infective virus in those insects. The first results of a study on these lines were the subject of a special report to the Commission, which was published in 1926 as C.H./Malaria/57(1).

The hospital in which the arrangements are installed is in the Horton Mental Hospital at Epsom, near London. It is a hospital accommodating about 1,500 patients, and there are several other hospitals of the same size in the near neighbourhood. Therefore a considerable number of cases of general paralysis and other mental diseases which are to be treated with malaria are always available.

In the grounds of the hospital there is an isolated villa which has been allotted exclusively for the malarial treatment of patients. Fig. 4 is a photograph of this villa. [35-36]

[image of single-storey building – caption:

‘Figure 4. – Pavilion used for Malaria Treatment.

It contains two wards, each with seven beds, and several small rooms each with one or two beds. The total accommodation is for twenty patients. Fig. 5 is a photograph of one of the larger rooms.]

[image of three hospital beds in bright-looking room – caption:

‘Figure 5. - One of the Larger Wards’]

[36-37]

Each ward and small room is completely mosquito-proofed with double doors, as shown in Fig. 6, and with removable mosquito-proof window frames.

[image of covered, box-like structure around ward door – caption:

‘Figure 6. - Doors Protected against Mosquitoes’]

[37-38]

One of the medical officers of the hospital (Dr. Nicol), who is a psychiatrist, with considerable experience in the clinical and pathological study of malaria and in its treatments, devotes himself to the clinical care of the patients who pass through the course of treatment, and to a study of the disease in its clinical aspect and in its effect upon general paralysis and other mental conditions. He has under him a staff of nurses who have been specially trained in the nursing of malaria patients and the manner in which observations relating to the degree of fever and other clinical symptoms should be taken and recorded. Fig. 7 is a photograph of this staff.

[image – group of nurses (made and female) surrounding man in suit (Nicol?) – caption:

‘Figure 7. – Nurses Specially Trained in the Treatment of Malarial Patients.’]

[38-39]

Two small rooms in the building are equipped for the necessary laboratory work (Fig. 8), which is done by a senior laboratory assistant (Mr. P.G. Shute) who has been specially trained for the duty.

[image = corner of a room with shelves, miscellaneous equipment (inc. microscope, small mosquito ‘cages’), large box-like structure with sign above denoting ‘Infective Mosquitoes’ - caption:

‘Figure 8. – Laboratory.’]

The work is concerned only with benign tertian malaria parasite (P. vivax) and with A. maculipennis.

The strain of P. vivax, which has been in use since May 1925, was obtained from an otherwise healthy patient who contracted malaria in Madagascar. Before it was used for the infection of mosquitoes, it was proved to be an unmixed strain by direct blood inoculation into two patients. [39-40]

The mosquitoes (females of maculipennis) which are used are not bred from larvae but are collected in the adult stage from stables and other buildings in a country district where malaria does not occur. They are collected one by one in test-tubes, from which they are transferred to the mosquito cage shown in Fig. 9.

[image of box structure covered by material – caption:

‘Figure 9. – Mosquito Cage with Waterproof Cover’]

When about 300 have been caught, the waterproof cover shown in the photograph is drawn over the cage, which is then taken to the laboratory. After removing the waterproof cover, the cage is placed in the incubator at 23˚C. for 24 hours, in order that the blood in the stomachs of the mosquitoes may be digested quickly and that they may be ready to feed upon the infecting case.

The infecting case must be in the stage of the attack which is represented by the words “mosquitoes fed daily” in the following graphs: [40-41]

[images of malaria patient temperature graphs marked by times of mosquito feeding]

[41-42]

The two essential conditions are that the peripheral blood contains male and female gametes and that the gametes are ripe. The first is ascertained by finding these forms of the parasite in thin films of blood, the second by ascertaining that the male forms

[image of microscopic field with cells and dark patch – caption:

‘Figure 10. – Flagellated Male Parasite Partially Absorbed by a Polymorphonuclear Leucocyte.’]

[Image of male (Shute?) reaching into box covered by mesh – caption:

‘Figure 11. Capture of Mosquitoes in the Cage’]

[42-43]

“flagellate” readily (as in Fig. 10) in a “moist-chamber preparation” of freshly drawn blood.

[image of small jars covered with gauze mesh (mosquito cages) – caption:

‘Figure 12. – Glass Jars Used for Feeding Mosquitoes.’]

When the mosquitoes are to be fed on the infecting case, they are taken from the cage by catching them in a test-tube in the manner shown in Fig. 11. Then they are transferred from the test-tube to the glass jars shown in Fig. 12.

This is done in the following way: Tie a piece of paper over the open mouth of the jar. In this cover cut a half-circle valve of the same size as the mouth of a test-tube. Take the test tube that contains the mosquito and put its cotton-wool plug over the paper valve. Draw away the cotton-wool and at the same time push the mouth of the tube through the valve into the bottle. When the mosquito has flown into the bottle, draw out the tube and at the same time plug the valve with the cotton-wool. Transfer twenty mosquitoes in this way to each of four or five bottles. Then lay a piece of cotton mosquito-netting over the paper which closes the mouth of the bottle. Keep the mosquito-netting in place by laying the palm of the hand over it and carefully draw away the paper, thus leaving the netting as a cover to the mouth of the bottle. Tie the netting on tightly as in Fig. 12. [43-44]

The jars containing the mosquitoes are then placed on the leg of the patient in the manner shown in Fig. 13. A nurse keeps the mouths of the jars pressed closely against the skin during the period allowed for feeding, which is usually about twenty minutes. The mosquitoes bite readily through the netting which covers the mouths of the bottles.

[image of patient’s leg on bed with four mosquito jars resting on it – caption:

‘Figure 13. – Mosquitoes Biting Patient.’]

When the mosquitoes have fed, the jars are placed inside the mosquito cage and the mosquito-netting covers removed. The mosquitoes escape into the cage and the jars are taken out.

The cage is then placed in the incubator. The temperature at which the incubator is kept is 23˚C. By keeping a bowl of water in the incubator and by hanging wet cloths in it, the air is kept as nearly saturated with moisture as possible.

The procedure described is repeated daily, the mosquitoes being fed for at least five days on the infecting case. Afterwards they are fed every day or every other day on a patient who is awaiting treatment.

Some mosquitoes die every day. They are dissected to ascertain the progress of the malaria infection. When sporozoites are present in the salivary glands (which is usually between the tenth and fifteenth day after the first infective feed, but may be as long as the eighteenth or twentieth day) incubation at 23˚C. is discontinued, the group being kept instead either at room temperature or in an ice-box at 5˚ or [44-45] 6˚C. during the periods when the mosquitoes are not required for infecting patients.

In order to infect a patient, four or five mosquitoes are transferred from the cage to one of the glass jars and are allowed to bite the patient in the same manner as was described for the procedure of infecting the mosquitoes. Usually two or three of the mosquitoes bite within a few minutes.

If an infected batch of mosquitoes is kept in an ice-box during the intervals between successive feedings, some individuals will usually remain alive and infective for at least a month and occasionally much longer.’ (35-45)